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Lapsiwala B, Nathani PS, Bhalodia A, Rangan A, Khan F, Rajpopat P, Vaghani U, Kanagala SG, Bali A, Naik R, Chandramohan D, Desai R. Prevalence and Impact of Chronic Kidney Disease on Outcomes and Recurrence of Takotsubo Syndrome - A Comprehensive Review. Am J Med Sci 2025:S0002-9629(25)01037-7. [PMID: 40412618 DOI: 10.1016/j.amjms.2025.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 05/06/2025] [Accepted: 05/14/2025] [Indexed: 05/27/2025]
Abstract
Takotsubo Syndrome (TTS) is a condition that usually affects the left ventricle (LV), primarily in the apical region characterized by transient left ventricular dysfunction triggered by a variety of stresses. Patients with TTS often present clinically as acute coronary syndrome (ACS) making the diagnosis challenging. TTS can lead to serious adverse events, such as cardiac arrhythmias, cardiogenic shock, and thromboembolic events, which can worsen an already poor prognosis. Chronic kidney disease (CKD) is a well-established risk factor for cardiovascular disease, and TTS prognosis is worsened when kidney function is compromised. With a prevalence of 6.7% among TTS patients, CKD increases the morbidity and mortality risks in TTS patients. Moreover, CKD exacerbates TTS recurrence, with risk factors including female sex, advanced age, and diabetes mellitus. Clinical management of TTS in CKD patients requires comprehensive evaluation and tailored interventions. While ACE inhibitors and angiotensin receptor blockers may mitigate recurrence risk, optimization of dialysis treatments and management of comorbidities are paramount.This review synthesizes current literature to elucidate the prevalence, recurrence, pathophysiological mechanisms, clinical implications, and management strategies of CKD in TTS patients.
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Affiliation(s)
| | | | - Ami Bhalodia
- Internal Medicine, Hamilton Medical Center, Dalton, GA, USA
| | - Anvitha Rangan
- Landmark Medical Center/New York Medical College, NY, NY, USA
| | - Fazal Khan
- St. Francis Emory Healthcare, Columbus, GA, USA
| | | | - Utsav Vaghani
- Smt. N.H.L Municipal Medical College, Ahmedabad, Gujarat, India
| | | | - Atul Bali
- Department of Nephrology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA, USA
| | - Roopa Naik
- Department of Hospital Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA, USA
| | - Deepak Chandramohan
- Department of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Lee WJA, Shao SC, Hsieh MHC, Liao TC, Lin SJ, Lai ECC. Adverse renal events between ranibizumab and aflibercept in patients with diabetic macular oedema in Taiwan: a comparative cohort study. Br J Ophthalmol 2025:bjo-2024-325509. [PMID: 40147840 DOI: 10.1136/bjo-2024-325509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 03/05/2025] [Indexed: 03/29/2025]
Abstract
AIMS To assess and compare the risk of adverse renal events among patients with diabetic macular oedema (DME) who were treated with either intravitreal ranibizumab or aflibercept in Taiwan. METHODS We conducted a population-based retrospective cohort study and employed a target trial emulation framework using Taiwan's National Health Insurance Database from 2011 to 2018.Patients aged over 20 years diagnosed with DME and receiving treatment with either intravitreal aflibercept or ranibizumab were included. We applied propensity score methods to ensure balance in the baseline characteristics between the two treatment groups. The primary outcomes were the adverse renal events, specifically acute renal injury and hospitalisation due to renal events. We employed Cox proportional hazards models to estimate the HRs associated with these outcomes. RESULTS A total of 6330 patients receiving ranibizumab and 1258 patients receiving aflibercept were included in this study. The incidence rates of adverse renal events were 102.2 and 138.7 per 1000 person-years for ranibizumab and aflibercept, respectively. Patients treated with intravitreal aflibercept had a significantly higher risk of experiencing a composite of adverse renal events (HR: 1.42; 95% CI: 1.24 to 1.63), compared with those treated with ranibizumab, and specifically also a higher risk of acute kidney injury (HR: 1.32; 95% CI: 1.08 to 1.63) and hospitalisation due to renal events (HR: 1.43; 95% CI: 1.25 to 1.64). CONCLUSION In comparison to ranibizumab, the intravitreal use of aflibercept was associated with a greater risk of adverse renal events. These findings provide a solid foundation for future studies to validate these results further.
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Affiliation(s)
- Wan-Ju Annabelle Lee
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan
- Population Health Data Center, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chieh Shao
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Population Health Data Center, National Cheng Kung University, Tainan, Taiwan
- Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Miyuki Hsing-Chun Hsieh
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Population Health Data Center, National Cheng Kung University, Tainan, Taiwan
| | - Tzu-Chi Liao
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Population Health Data Center, National Cheng Kung University, Tainan, Taiwan
| | - Swu-Jane Lin
- University of Illinois Chicago, Chicago, Illinois, USA
| | - Edward Chia-Cheng Lai
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Population Health Data Center, National Cheng Kung University, Tainan, Taiwan
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Pekhale K, Tiwari V, Hussain M, Bridges CC, Croteau DL, Levi M, Rosenberg AZ, Santo B, Yang X, Kulikowicz T, Wang XX, Lee JH, Bohr VA. Cockayne syndrome mice reflect human kidney disease and are defective in de novo NAD biosynthesis. Cell Death Differ 2025:10.1038/s41418-025-01522-7. [PMID: 40374849 DOI: 10.1038/s41418-025-01522-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 04/11/2025] [Accepted: 04/30/2025] [Indexed: 05/18/2025] Open
Abstract
Cockayne Syndrome (CS) is a premature aging disorder caused by mutations in the CSA and CSB genes involved in DNA metabolism and other cellular processes. CS patients display many features including premature aging, neurodegeneration, and kidney abnormalities. Nicotinamide dinucleotide (NAD+) deprivation has been observed in CS patient-derived cells. NAD+ has essential roles in regulating cellular health, stress responses, and renal homeostasis. While kidney dysfunction is a common feature in CS patients, its molecular pathogenesis is not understood. Here, we report that severe kidney pathology is present in CS A and B mice. We find that the NAD+ biosynthetic pathways are impaired in kidneys from these mice. Using human renal tubular epithelial cells, we show that CSA/B downregulation causes persistent activation of the ATF3 transcription factor on the quinolinate phosphoribosyl transferase gene locus, a rate-limiting enzyme in de novo NAD+ biosynthesis in the kidney, causing impaired transcription and deficient NAD+ homeostasis.
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Affiliation(s)
- Komal Pekhale
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
- Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Vinod Tiwari
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
| | - Mansoor Hussain
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
| | - Christy C Bridges
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, 31404, USA
| | - Deborah L Croteau
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
- Computational Biology & Genomics Core, Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
| | - Moshe Levi
- Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA
| | - Avi Z Rosenberg
- Department of Pathology Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Briana Santo
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Xiaoping Yang
- Department of Pathology Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Tomasz Kulikowicz
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
| | - Xiaoxin X Wang
- Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA
| | - Jong-Hyuk Lee
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
- Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, 31404, USA.
- Center for Gerontology, Mercer University, Macon, GA, 31207, USA.
| | - Vilhelm A Bohr
- DNA repair section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
- Danish Center for Healthy Aging, University of Copenhagen, 2200, Copenhagen, Denmark.
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4
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Young KZ, Loveless I, Su WTK, Veenstra J, Yin C, Dimitrion P, Krevh R, Zhou L, She R, Pan M, Levin AM, Young A, Samir E, Dai A, Ge J, Huggins RH, de Guzman Strong C, Lim HW, Ozog DM, Hamzavi I, Adrianto I, Mi QS. A diverse hidradenitis suppurativa cohort: A retrospective cross-sectional study of 13,130 patients from a large US health care system database from 1995 to 2022. J Am Acad Dermatol 2025; 92:487-494. [PMID: 39532232 PMCID: PMC11859765 DOI: 10.1016/j.jaad.2024.10.073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 10/11/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Most epidemiological studies of hidradenitis suppurativa (HS) have described homogeneous patient populations. OBJECTIVE To characterize demographics, modifiable health behaviors, and comorbidities of HS patients within a diverse cohort. METHODS A retrospective cross-sectional study of 13,130 HS patients within a health care system was conducted. RESULTS A female sex bias of ∼3:1 in all racial/ethnic subgroups was observed. Black/African American (AA) patients had a lower age at HS diagnosis than White patients (37.1 years vs 39.4 years, P < .001). A higher proportion of Black/AA females than White females with HS had body mass index in the obese range (69.9% vs 56.5%; P = .03). In contrast, fewer Black/AA males with HS had a body mass index in the obese range compared to White males (51.4% vs 61.0%; P < .001). More Black/AA patients than White patients with HS had congestive heart failure (odds ratio (OR) = 2.10, confidence interval (CI) = 1.19-3.78; P < .05), chronic pulmonary disease (OR = 1.34; CI = 1.02-1.78; P < .05), diabetes with chronic complication (OR = 1.73; CI = 1.16-2.60; P < .05), renal disease (OR = 2.66; CI = 1.67-4.34; P < .05), and Charlson comorbidity index score ≥4 (OR = 1.67; CI = 1.09-2.58; P < .05). Furthermore, male patients were more likely than female patients to have renal disease (OR = 2.62; CI = 1.66-4.14; P < .05). LIMITATIONS A single-center study. CONCLUSION Subgroups of HS patients had significant differences in demographics, risk factors, and comorbid conditions.
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Affiliation(s)
- Kelly Z Young
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Ian Loveless
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan; Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan
| | - Wan-Ting K Su
- Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan; Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan
| | - Jesse Veenstra
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Congcong Yin
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan
| | - Peter Dimitrion
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan; Cancer Biology Graduate Program, School of Medicine, Wayne State University, Detroit, Michigan
| | - Rachel Krevh
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan
| | - Li Zhou
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan; Department of Biochemistry, Microbiology, and Immunology, School of Medicine, Wayne State University, Detroit, Michigan; Department of Internal Medicine, Henry Ford Health, Detroit, Michigan
| | - Ruicong She
- Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan
| | - Mingming Pan
- Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan
| | - Albert M Levin
- Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan; Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan
| | - Albert Young
- Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Eglal Samir
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Andrea Dai
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - James Ge
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Richard H Huggins
- Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Cristina de Guzman Strong
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Henry W Lim
- Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - David M Ozog
- Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan
| | - Iltefat Hamzavi
- Department of Dermatology, Henry Ford Health, Detroit, Michigan.
| | - Indra Adrianto
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan.
| | - Qing-Sheng Mi
- Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, Michigan; Henry Ford Health + Michigan State University Health Sciences, East Lansing, Michigan; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, Michigan; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Dermatology, Henry Ford Health, Detroit, Michigan; Cancer Biology Graduate Program, School of Medicine, Wayne State University, Detroit, Michigan; Department of Biochemistry, Microbiology, and Immunology, School of Medicine, Wayne State University, Detroit, Michigan; Department of Internal Medicine, Henry Ford Health, Detroit, Michigan.
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Aiff H, Attman PO, Golic M, Ramsauer B, Schön S, Steingrimsson S, Svedlund J. Prospects for lithium treated patients with severe renal impairment. Int J Bipolar Disord 2025; 13:5. [PMID: 39953220 PMCID: PMC11828763 DOI: 10.1186/s40345-025-00372-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 01/29/2025] [Indexed: 02/17/2025] Open
Abstract
OBJECTIVES To study the prospects for lithium treated patients who develop end stage renal disease (ESRD) and the role of renal replacement therapy (RRT). METHODS Retrospective analysis of survival, somatic comorbidity, lithium treatment and eligibility for renal replacement therapy in adult patients with at least one eGFR < 30 ml/min/1.73 m2. Subjects were selected from our laboratory database (s-Lithium and s-creatinine) from 1980 to 2017. RESULTS 620 (14%) of 4396 patients with a lithium history had at least one measurement of eGFR < 30 ml/min/1.73 m2. 302 (49%) patients had a transient decrease in renal function with subsequent improvement, 135 (22%) patients died with acute renal failure, while 153 (25%) developed chronic kidney disease stage 4 (CKD4) and 33 (5%) required RRT. RRT-treated patients represent only a fraction of the total ESRD population. Median survival time from the debut of CKD4 was 13.9 years in patients < 65 years and 4.4 years in older patients. 100 of the 153 patients with CKD4 continued lithium treatment. There was no significant difference in survival after the debut of CKD4 between the patients who stopped lithium treatment and those who continued. CONCLUSIONS A measurement of eGFR < 30 ml/min/1.73 m2 reflects a significant loss of renal function. In half of the patients it was due to a transient functional disturbance without long-term consequences. A quarter of patients had acute renal failure and died within days while the remaining quarter progressed to CKD4. Despite irreversible renal damage, patient survival can be counted in several years after debut of renal insufficiency with appropriate care including RRT. As the treating psychiatrist, it is important to consult with nephrology when renal function starts to deteriorate, to optimise somatic treatment.
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Affiliation(s)
- Harald Aiff
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
- Psykiatri Affektiva, Department of Psychiatry, Region Västra Götaland, Gothenburg, Sweden.
| | - Per-Ola Attman
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Psykiatri Affektiva, Department of Psychiatry, Region Västra Götaland, Gothenburg, Sweden
| | - Mihaela Golic
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Department of Psychiatry, Region Halland, Varberg, Sweden
| | - Bernd Ramsauer
- Department of Nephrology, Skaraborg Hospital, Skövde, Sweden
| | - Staffan Schön
- Swedish Renal Registry, Jönköping County Hospital, Jönköping, Sweden
| | - Steinn Steingrimsson
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Psykiatri Affektiva, Department of Psychiatry, Region Västra Götaland, Gothenburg, Sweden
| | - Jan Svedlund
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Psykiatri Affektiva, Department of Psychiatry, Region Västra Götaland, Gothenburg, Sweden
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Kitai Y, Toriu N, Yoshikawa T, Sahara Y, Kinjo S, Shimizu Y, Sato Y, Oguchi A, Yamada R, Kondo M, Uchino E, Taniguchi K, Arai H, Sasako T, Haga H, Fukuma S, Kubota N, Kadowaki T, Takasato M, Murakawa Y, Yanagita M. Female sex hormones inversely regulate acute kidney disease susceptibility throughout life. Kidney Int 2025; 107:68-83. [PMID: 39503698 DOI: 10.1016/j.kint.2024.08.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 08/16/2024] [Accepted: 08/27/2024] [Indexed: 11/08/2024]
Abstract
While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice increases susceptibility to kidney ischemia reperfusion injury partly via downregulation of insulin-like growth factor 1 receptor (IGF-1R) expression in proximal tubules. Adult mice ovariectomized pre-pubertally (at postnatal day 21) showed strong tolerance to kidney ischemia, which was partly reversed by the administration of 17β-estradiol, while adult mice ovariectomized post-pubertally (at 8 weeks of age) were vulnerable to kidney ischemia. Kidney tubular IGF-1R protein expression decreased during postnatal growth but was highly expressed in adult mice ovariectomized pre-pubertally and in infant mice, which might be partly explained by different expression of an E3 ligase (MDM2) of IGF-1R. Mice deficient of Igf-1r in proximal tubules (iIGF-1RKO mice) during postnatal kidney growth showed increased susceptibility to ischemic injury. RNA-seq and western blotting analysis using proximal tubular cells from pre-pubertally ovariectomized iIGF-1RKO and control mice revealed altered expression of cell cycle-associated molecules such as cyclin D1. These results suggest that Igf-1r deletion during postnatal growth renders proximal tubular cells susceptible to ischemia possibly via altered cell cycle regulation. Thus, our findings provide evidence that exposure to pubertal sex hormones leads to increased susceptibility to kidney ischemia, which is partly mediated by modulation of IGF-1R signaling.
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Affiliation(s)
- Yuichiro Kitai
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naoya Toriu
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahisa Yoshikawa
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoshiki Sahara
- Laboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Laboratory of Molecular Cell Biology and Development, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
| | - Sonoko Kinjo
- DNA Data Analysis Laboratory, Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Shizuoka, Japan
| | - Yoko Shimizu
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuki Sato
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Medical Innovation Center TMK project, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akiko Oguchi
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
| | - Ryo Yamada
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Makiko Kondo
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Eiichiro Uchino
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Keisuke Taniguchi
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroyuki Arai
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayoshi Sasako
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - Shingo Fukuma
- Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naoto Kubota
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Takashi Kadowaki
- Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Toranomon Hospital, Tokyo, Japan
| | - Minoru Takasato
- Laboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Laboratory of Molecular Cell Biology and Development, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
| | - Yasuhiro Murakawa
- RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
| | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.
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7
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Zhang Q, Yang L, Zhou L, Xin X. Nonlinear association of sex hormone-binding globulin levels and chronic kidney disease, an analysis based on the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Ren Fail 2024; 46:2409341. [PMID: 39378118 PMCID: PMC11463009 DOI: 10.1080/0886022x.2024.2409341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 08/16/2024] [Accepted: 09/20/2024] [Indexed: 10/10/2024] Open
Abstract
Studies on the relationship between serum sex hormone-binding globulin (SHBG) levels and chronic kidney disease (CKD) remain limited and inconclusive. Therefore, this study aims to evaluate the effects of SHBG on CKD in a nationally representative population. We included a total of 7713 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Multivariate logistic regression models were utilized to evaluate the association between SHBG levels and CKD, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Additionally, we employed a restricted cubic-spline regression model to explore potential dose-response associations. Among the participants, 4030 (52.2%) were women, and CKD was observed in 13.50% (1043/7713). After adjusting for various variables, SHBG levels were found to be associated with the risk of CKD (OR: 1.24; 95% CI: 1.11-1.38), indicating a 24% higher risk of CKD for SHBG levels (log2-transformed). A comparison between the highest quartile (Q4) and the lowest quartile (Q1) of SHBG levels revealed an OR of 1.51 (95% CI: 1.17-1.95) for CKD prevalence. Notably, while the association between SHBG and the risk of CKD disappeared when SHBG levels were <46.1 nmol/l, it existed when SHBG levels exceeded 46.1 nmol/l. Taken together, these findings indicate nonlinear correlations between serum SHBG levels and CKD, with the inflection point occurring at approximately 46.1 nmol/l, which suggest that SHBG levels could serve as a useful marker for assessing CKD risk, with potential applications in early detection and management strategies.
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Affiliation(s)
- Qi Zhang
- Department of Gynaecology and Obstetrics, Ganzhou Maternal and Child Health Hospital, Ganzhou, China
| | - Li Yang
- Department of Gynaecology and Obstetrics, Ganzhou Maternal and Child Health Hospital, Ganzhou, China
| | - Lin Zhou
- Department of Gynaecology and Obstetrics, Ganzhou Maternal and Child Health Hospital, Ganzhou, China
| | - Xiaoqin Xin
- Department of Clinical Laboratory, Ganzhou People’s Hospital, Ganzhou, China
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Ahmed HA, Shaaban AA, Ibrahim TM, Makled MN. G protein-coupled estrogen receptor activation attenuates cisplatin-induced CKD in C57BL/6 mice: An insight into sex-related differences. Food Chem Toxicol 2024; 194:115079. [PMID: 39491767 DOI: 10.1016/j.fct.2024.115079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 10/17/2024] [Accepted: 10/29/2024] [Indexed: 11/05/2024]
Abstract
Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) post-cisplatin therapy. This study aims at investigating the potential effect of G1 compound, a GPER agonist, on attenuating cisplatin-induced CKD. To induce CKD in male, intact female, and ovariectomized (OVX) mice, CKD was induced by injecting two cycles of 2.5 mg/kg cisplatin with a 16-day recovery period between cycles). G1 (50 or 100 μg/kg was administered daily for 6 weeks. Severity of renal damage was more pronounced in males than females. Interestingly, OVX resulted in renal damage that is non-significant compared to males and significantly higher than females. G1 improved renal function and blood flow as evidenced by reduction of serum creatinine and elevation of creatinine clearance, NO production, and reduction of ET1. This renoprotective effect could be attributed to its immunomodulatory effect regulated by TGF-β that shifted the balance to favor anti-inflammatory cytokine production (increased IL-10) rather than pro-inflammatory cytokines (decreased Th17 expression). Reduction of TGF-β activation also inhibited epithelial-to-mesenchymal transition that eventually ameliorated CKD development. Antioxidant potential of G1 has been demonstrated by upregulation of Nrf2 and subsequent antioxidant enzymes. These data suggest that G1 could be a promising therapeutic tool to attenuate CP-induced CKD.
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Affiliation(s)
- Hala A Ahmed
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt
| | - Ahmed A Shaaban
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt
| | - Tarek M Ibrahim
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt
| | - Mirhan N Makled
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt.
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9
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Johnson-Martínez JP, Diener C, Levine AE, Wilmanski T, Suskind DL, Ralevski A, Hadlock J, Magis AT, Hood L, Rappaport N, Gibbons SM. Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function. Cell Rep Med 2024; 5:101646. [PMID: 39019013 PMCID: PMC11293344 DOI: 10.1016/j.xcrm.2024.101646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 02/22/2024] [Accepted: 06/14/2024] [Indexed: 07/19/2024]
Abstract
Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of gut microbial genera, blood metabolites, and variation in lifestyle factors across BMF categories. These differences relate to inflammation, heart health, liver function, and kidney function. Causal mediation analysis indicates that the association between lower BMF and reduced kidney function is partially mediated by the microbially derived toxin 3-indoxyl sulfate (3-IS). This result, in a generally healthy context, suggests that the accumulation of microbiota-derived toxins associated with abnormal BMF precede organ damage and may be drivers of chronic, aging-related diseases.
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Affiliation(s)
- Johannes P Johnson-Martínez
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
| | - Christian Diener
- Institute for Systems Biology, Seattle, WA 98109, USA; Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Anne E Levine
- Institute for Systems Biology, Seattle, WA 98109, USA; Seattle Children's Hospital, Seattle, WA 98105, USA
| | | | | | | | - Jennifer Hadlock
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Biomedical Informatics, University of Washington, Seattle, WA 98104 USA
| | | | - Leroy Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Phenome Health, Seattle, WA 98109, USA; Department of Immunology, University of Washington, Seattle, WA 98195, USA; Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA 98195, USA; Center for Phenomic Health, Buck Institute for Research on Aging, Novato, CA 94945, USA
| | - Noa Rappaport
- Institute for Systems Biology, Seattle, WA 98109, USA; Phenome Health, Seattle, WA 98109, USA; Center for Phenomic Health, Buck Institute for Research on Aging, Novato, CA 94945, USA
| | - Sean M Gibbons
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; eScience Institute, University of Washington, Seattle, WA 98195, USA.
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10
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Umer EK, Abebe AT, Kebede YT, Bekele NT. Burden and risk profile of acute kidney injury in severe COVID-19 pneumonia admissions: a Finding from Jimma University medical center, Ethiopia. BMC Nephrol 2024; 25:109. [PMID: 38504176 PMCID: PMC10953204 DOI: 10.1186/s12882-024-03522-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 02/25/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a serious complication of the Corona Virus Disease of 2019 (COVID-19). However, data on its magnitude and risk factors among hospitalized patients in Ethiopia is limited. This study aimed to determine the magnitude of AKI and associated factors among patients admitted for severe COVID-19 pneumonia. METHODS An institution-based retrospective cross-sectional study was conducted among 224 patients admitted to Jimma University Medical Center in Ethiopia for severe COVID-19 pneumonia from May 2020 to December 2021. Systematic random sampling was used to select study participants. Medical records were reviewed to extract sociodemographic, clinical, laboratory, therapeutic, and comorbidity data. Bivariable and multivariable logistic regressions were performed to examine factors associated with AKI. The magnitude of the association between the explanatory variables and AKI was estimated using an adjusted odds ratio (AOR) with a 95% confidence interval (CI), and significance was declared at a p-value of 0.05. RESULTS The magnitude of AKI was 42% (95% CI: 35.3-48.2%) in the study area. Mechanical ventilation, vasopressors, and antibiotics were required in 32.6, 3.7, and 97.7% of the patients, respectively. After adjusting for possible confounders, male sex (AOR 2.79, 95% CI: 1.3-6.5), fever (AOR 6.5, 95% CI: 2.7-15.6), hypoxemia (AOR 5.1, 95% CI: 1.4-18.9), comorbidities (AOR 2.8, 95% CI: 1.1-7.0), and severe anemia (AOR 10, 95% CI: 1.7-65.7) remained significantly associated with higher odds of AKI. CONCLUSION The burden of AKI among patients with severe COVID-19 pneumonia is high in our setting. Male sex, abnormal vital signs, chronic conditions, and anemia can identify individuals at increased risk and require close monitoring and prevention efforts.
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Affiliation(s)
- Ebrahim Kelil Umer
- Department of Internal Medicine, Adama Hospital Medical College, Adama, Ethiopia
| | - Abel Tezera Abebe
- School of Medicine, Faculty of Medical Sciences, Institute of Health, Jimma University, Jimma, Ethiopia.
| | - Yabets Tesfaye Kebede
- School of Medicine, Faculty of Medical Sciences, Institute of Health, Jimma University, Jimma, Ethiopia
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11
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Johnson-Martínez JP, Diener C, Levine AE, Wilmanski T, Suskind DL, Ralevski A, Hadlock J, Magis AT, Hood L, Rappaport N, Gibbons SM. Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.03.04.531100. [PMID: 36945445 PMCID: PMC10028848 DOI: 10.1101/2023.03.04.531100] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
Bowel movement frequency (BMF) has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome and inflammatory bowel disease. Lower BMF (constipation) can lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, the connections between BMF, gut microbial metabolism, and the early-stage development and progression of chronic disease remain underexplored. Here, we examined the phenotypic impact of BMF variation in a cohort of generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data. We showed significant differences in microbially-derived blood plasma metabolites, gut bacterial genera, clinical chemistries, and lifestyle factors across BMF groups that have been linked to inflammation, cardiometabolic health, liver function, and CKD severity and progression. We found that the higher plasma levels of 3-indoxyl sulfate (3-IS), a microbially-derived metabolite associated with constipation, was in turn negatively associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. Causal mediation analysis revealed that the effect of BMF on eGFR was significantly mediated by 3-IS. Finally, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which indicate several common-sense strategies for mitigating constipation and diarrhea. Overall, we suggest that aberrant BMF is an underappreciated risk factor in the development of chronic diseases, even in otherwise healthy populations.
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Affiliation(s)
- Johannes P. Johnson-Martínez
- Institute for Systems Biology, Seattle, WA 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
| | | | - Anne E. Levine
- Institute for Systems Biology, Seattle, WA 98109, USA
- Seattle Children’s Hospital, Seattle, WA 98105, USA
| | | | | | | | | | | | - Leroy Hood
- Institute for Systems Biology, Seattle, WA 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
- Phenome Health, Seattle, WA 98109
- Department of Immunology, University of Washington, Seattle, WA 98195, USA
- Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA 98195, USA
| | - Noa Rappaport
- Institute for Systems Biology, Seattle, WA 98109, USA
| | - Sean M. Gibbons
- Institute for Systems Biology, Seattle, WA 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
- Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
- eScience Institute, University of Washington, Seattle, WA 98195, USA
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12
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Starr MC, Barreto E, Charlton J, Vega M, Brophy PD, Ray Bignall ON, Sutherland SM, Menon S, Devarajan P, Akcan Arikan A, Basu R, Goldstein S, Soranno DE. Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference. Pediatr Nephrol 2024; 39:941-953. [PMID: 37792076 PMCID: PMC10817846 DOI: 10.1007/s00467-023-06154-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/08/2023] [Accepted: 08/29/2023] [Indexed: 10/05/2023]
Abstract
BACKGROUND In the past decade, there have been substantial advances in our understanding of the pathobiology of pediatric acute kidney injury (AKI). In particular, animal models and studies focused on the relationship between kidney development, nephron number, and kidney health have identified a number of heterogeneous pathophysiologies underlying AKI. Despite this progress, gaps remain in our understanding of the pathobiology of pediatric AKI. METHODS During the 26th Acute Disease Quality Initiative (ADQI) Consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations for opportunities to advance translational research in pediatric AKI. The current state of research understanding as well as gaps and opportunities for advancement in research was discussed, and recommendations were summarized. RESULTS Consensus was reached that to improve translational pediatric AKI advancements, diverse teams spanning pre-clinical to epidemiological scientists must work in concert together and that results must be shared with the community we serve with patient involvement. Public and private research support and meaningful partnerships with adult research efforts are required. Particular focus is warranted to investigate the pediatric nuances of AKI, including the effect of development as a biological variable on AKI incidence, severity, and outcomes. CONCLUSIONS Although AKI is common and associated with significant morbidity, the biologic basis of the disease spectrum throughout varying nephron developmental stages remains poorly understood. An incomplete understanding of factors contributing to kidney health, the diverse pathobiologies underlying AKI in children, and the historically siloed approach to research limit advances in the field. The recommendations outlined herein identify gaps and outline a strategic approach to advance the field of pediatric AKI via multidisciplinary translational research.
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Affiliation(s)
- Michelle C Starr
- Department of Pediatrics, Division of Nephrology, Indiana University School of Medicine, Riley Hospital for Children, 1044 W. Walnut Street, Indianapolis, IN, 46202, USA
- Pediatric and Adolescent Comparative Effectiveness Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Erin Barreto
- Department of Pharmacy, Mayo Clinic, Rochester, MN, USA
| | - Jennifer Charlton
- Department of Pediatrics, Division of Nephrology, University of Virginia, Charlottesville, VA, USA
| | - Molly Vega
- Renal and Apheresis Services, Texas Children's Hospital, Houston, TX, USA
| | - Patrick D Brophy
- Department of Pediatrics, Golisano Children's Hospital, University of Rochester, Rochester, NY, USA
| | - O N Ray Bignall
- Department of Pediatrics, Division of Nephrology and Hypertension, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, USA
| | - Scott M Sutherland
- Department of Pediatrics, Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA
| | - Shina Menon
- Division of Pediatric Nephrology, Seattle Children's Hospital and University of Washington, Seattle, WA, USA
| | - Prasad Devarajan
- Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
| | - Ayse Akcan Arikan
- Department of Pediatrics, Divisions of Critical Care and Nephrology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | - Rajit Basu
- Department of Pediatrics, Division of Critical Care, Northwestern University, Chicago, IL, USA
| | - Stuart Goldstein
- Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
| | - Danielle E Soranno
- Department of Pediatrics, Division of Nephrology, Indiana University School of Medicine, Riley Hospital for Children, 1044 W. Walnut Street, Indianapolis, IN, 46202, USA.
- Department of Bioengineering, Purdue University, West Lafayette, IN, USA.
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13
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Yamao Y, Oami T, Yamabe J, Takahashi N, Nakada TA. Machine-learning model for predicting oliguria in critically ill patients. Sci Rep 2024; 14:1054. [PMID: 38212363 PMCID: PMC10784288 DOI: 10.1038/s41598-024-51476-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 01/05/2024] [Indexed: 01/13/2024] Open
Abstract
This retrospective cohort study aimed to develop and evaluate a machine-learning algorithm for predicting oliguria, a sign of acute kidney injury (AKI). To this end, electronic health record data from consecutive patients admitted to the intensive care unit (ICU) between 2010 and 2019 were used and oliguria was defined as a urine output of less than 0.5 mL/kg/h. Furthermore, a light-gradient boosting machine was used for model development. Among the 9,241 patients who participated in the study, the proportions of patients with urine output < 0.5 mL/kg/h for 6 h and with AKI during the ICU stay were 27.4% and 30.2%, respectively. The area under the curve (AUC) values provided by the prediction algorithm for the onset of oliguria at 6 h and 72 h using 28 clinically relevant variables were 0.964 (a 95% confidence interval (CI) of 0.963-0.965) and 0.916 (a 95% CI of 0.914-0.918), respectively. The Shapley additive explanation analysis for predicting oliguria at 6 h identified urine values, severity scores, serum creatinine, oxygen partial pressure, fibrinogen/fibrin degradation products, interleukin-6, and peripheral temperature as important variables. Thus, this study demonstrates that a machine-learning algorithm can accurately predict oliguria onset in ICU patients, suggesting the importance of oliguria in the early diagnosis and optimal management of AKI.
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Affiliation(s)
- Yasuo Yamao
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan
| | - Takehiko Oami
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan
| | | | - Nozomi Takahashi
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan
| | - Taka-Aki Nakada
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan.
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14
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Loban K, Morgan R, Kute V, Bhalla AK, Sandal S. Are Differences in Living Kidney Donation Rates a Sex or a Gender Disparity? EXP CLIN TRANSPLANT 2024; 22:28-36. [PMID: 38385370 DOI: 10.6002/ect.mesot2023.l21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2024]
Abstract
Sex-disaggregated data reveal significant disparities in living kidney donation, with more female than male living kidney donors in most countries and proportions over 60% in some countries. We summarize the present state of knowledge with respect to the potential drivers of this disparity and argue that it is primarily driven by gender-related factors. First, we present the differences between sex and gender and then proceed to summarize the potential medical reasons that have been proposed to explain why males are less likely to be living kidney donors than females, such as the higher prevalence of kidney failure in males. We then present counterarguments as to why biological sex differences are not enough to explain lower living kidney donation among males, such as a higher prevalence of chronic kidney disease among females, which could affect donation rates. We argue that gender differences likely provide a better explanation as to why there are more women than men living kidney donors and explore the role of economic and social factors, as well as gender roles and expectations, in affecting living kidney donation among both men and women. We conclude with the need for a gender analysis to explain this complex psychosocial phenomenon in living kidney donation.
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Affiliation(s)
- Katya Loban
- From the Research Institute of the McGill University Health Centre and the Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada
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15
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Öztürk E, Ganidağlı S, Öztürk ZA. Colistin treatment in older adults: why should we know more? Curr Med Res Opin 2023; 39:1481-1487. [PMID: 37738213 DOI: 10.1080/03007995.2023.2262380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 09/20/2023] [Indexed: 09/24/2023]
Abstract
OBJECTIVES We aimed to investigate the risk factors of colistin-associated nephrotoxicity in patients older than 65 years treated in the palliative care unit. METHODS 119 palliative care patients who received intravenous colistimethate for at least 7 days were included in the study. The estimated glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Data were obtained from the hospital information system. RESULTS The mean age of the participants was 76.7 ± 9.9 years and 49.4% were female. Of the 119 patients, 57 had colistin-induced nephropathy (CIN) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The rate of CIN was higher in women than in men. The baseline phosphate level was higher in the CIN (+) group than in the CIN (-) group. The lower GFR values in patients with pneumonia persisted at days 14 and 30, whereas the lower GFR in patients without pneumonia did not. According to multivariate logistic regression, female gender and baseline phosphate level ≥ 4.5 mg/dl were found as independent variables for the development of nephropathy. CONCLUSIONS The creatinine levels of the patients with pneumonia and CIN did not improve after nephrotoxicity, whereas the creatinine levels of the other patients without pneumonia and CIN did. Female gender and baseline phosphate were independent risk factors for CIN. Prolonged kidney failure may lead to a more difficult clinical follow-up process for clinicians. Therefore, clinicians should be aware of persistent renal insufficiency in older patients with pneumonia receiving colistimethate.
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Affiliation(s)
- Ercüment Öztürk
- Department of Internal Medicine, Division of Geriatric Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
| | - Sencer Ganidağlı
- Department of Internal Medicine, Division of Geriatric Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
| | - Zeynel Abidin Öztürk
- Department of Internal Medicine, Division of Geriatric Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
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16
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Sarray S, Lamine LB, Dallel M, Ezzidi I, Sellami N, Turki A, Moustafa AEEA, Mtiraoui N. Association of matrix metalloproteinase-2 gene variants with diabetic nephropathy risk. J Gene Med 2023; 25:e3553. [PMID: 37312425 DOI: 10.1002/jgm.3553] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/11/2023] [Accepted: 05/30/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Diabetic nephropathy is a highly destructive microvascular complication of diabetes. Genetic predisposition is involved in the pathogenesis of diabetic nephropathy, with multiple allelic polymorphisms associated with the development and progression of the disease, thereby increasing the overall risk. To date, no study is available that shows the association of matrix metalloproteinase-2 (MMP-2) gene polymorphisms with diabetic nephropathy risk. Thus, we investigated the potential genetic influence of MMP-2 promoter variants in the development of diabetic nephropathy in type 2 diabetic patients. METHODS In total, 726 type 2 diabetic patients and 310 healthy controls were included in the study and genotyped for MMP-2, -1306C/T, -790T/G, -1575G/T and -735C/T by real-time PCR. The analysis of the outcomes was performed assuming three genetic models. The threshold for statistical significance was set at 0.05. RESULTS The results showed that the minor allele frequency of the -790T/G variant was significantly higher in patients with and without nephropathy compared to controls. Furthermore, the distribution analysis revealed a significant association of the -790T/G variant, in all genetic models, with increased risk of diabetic nephropathy that persisted after adjusting for key covariates. No significant associations between MMP-2, -1306C/T, -1575G/T, -735C/T and the risk of diabetic nephropathy were detected. Haplotype analysis identified two risk haplotypes GCGC and GTAC associated with diabetic nephropathy. CONCLUSIONS The present study is the first to demonstrate the allelic and genotypic association of the MMP-2-790T/G variant and two haplotypes with an increased risk of diabetic nephropathy in a Tunisian population with type 2 diabetes.
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Affiliation(s)
- Sameh Sarray
- Arabian Gulf University, Manama, Bahrain
- Faculty of Sciences, University Tunis EL Manar, Tunis, Tunisia
| | - Laila Ben Lamine
- Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
| | - Meriem Dallel
- Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
| | - Intissar Ezzidi
- Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
- Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia
| | - Nejla Sellami
- Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
| | - Amira Turki
- Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
| | | | - Nabil Mtiraoui
- Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia
- Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia
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17
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Kumar P, Brooks HL. Sex-specific epigenetic programming in renal fibrosis and inflammation. Am J Physiol Renal Physiol 2023; 325:F578-F594. [PMID: 37560775 PMCID: PMC11550885 DOI: 10.1152/ajprenal.00091.2023] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 07/18/2023] [Accepted: 07/31/2023] [Indexed: 08/11/2023] Open
Abstract
The growing prevalence of hypertension, heart disease, diabetes, and obesity along with an aging population is leading to a higher incidence of renal diseases in society. Chronic kidney disease (CKD) is characterized mainly by persistent inflammation, fibrosis, and gradual loss of renal function leading to renal failure. Sex is a known contributor to the differences in incidence and progression of CKD. Epigenetic programming is an essential regulator of renal physiology and is critically involved in the pathophysiology of renal injury and fibrosis. Epigenetic signaling integrates intrinsic and extrinsic signals onto the genome, and various environmental and hormonal stimuli, including sex hormones, which regulate gene expression and downstream cellular responses. The most extensively studied epigenetic alterations that play a critical role in renal damage include histone modifications and DNA methylation. Notably, these epigenetic alterations are reversible, making them candidates for potential therapeutic targets for the treatment of renal diseases. Here, we will summarize the current knowledge on sex differences in epigenetic modulation of renal fibrosis and inflammation and highlight some possible epigenetic therapeutic strategies for CKD treatment.
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Affiliation(s)
- Prerna Kumar
- Department of Physiology, School of Medicine, Tulane University, New Orleans, Louisiana, United States
| | - Heddwen L Brooks
- Department of Physiology, School of Medicine, Tulane University, New Orleans, Louisiana, United States
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18
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Golomb D, Shemesh A, Goldberg H, Hen E, Atmana F, Barkai E, Shalom B, Cooper A, Raz O. Effect of gender on presentation and outcome of renal colic. Urologia 2023; 90:653-658. [PMID: 36635856 DOI: 10.1177/03915603221150039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To examine gender-related differences in the presentation, management, and outcomes of patients admitted to the emergency department ED with ureteral stones. METHODS Retrospective analysis of all patients admitted to the ED at our institution, found to have a ureteral stone on CT. Clinical, laboratory, imaging parameters, and outcomes were collected. RESULTS 778 patients were admitted with ureteral stones between January 2018 and December 2020. 78% (n = 609) were males and 22% (n = 169) were females. The mean ages were 49.4 (SD 14.4) and 51.6 (SD 15.7) in males and females, respectively (p = 0.08). Female patients presented with a higher body temperature (p = 0.01), pulse rate (p < 0.0001), nausea and vomiting (p < 0.0001), elevated serum C-reactive protein (CRP) (p = 0.002) compared to males. The prevalence of elevated serum creatinine was higher in males (p < 0.0001). Alpha-blockers were recommended on discharge in 54.8% (334) of males, compared to only 29.6% (50) of females (p < 0.0001). Spontaneous stone expulsion was significantly higher in males compared to females (p = 0.01). CONCLUSIONS Our results demonstrate that gender does effect presentation and outcome of patients presenting with renal colic. Females were found to have elevated infectious parameters, more nausea and vomiting and a higher incidence of positive urine cultures. Males admitted to the ED were found to have significantly higher serum creatinine levels. Medical expulsive therapy (MET) with alpha-blockers was prescribed significantly less in female patients, which may have resulted in a lower spontaneous stone expulsion rate.
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Affiliation(s)
- Dor Golomb
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Amit Shemesh
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Hanan Goldberg
- Department of Urology, State University of New York, Upstate Medical University, Syracuse, NY, USA
| | - Eyal Hen
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Fahed Atmana
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Eyal Barkai
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Ben Shalom
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Amir Cooper
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
| | - Orit Raz
- Department of Urology, Samson Assuta Ashdod University Hospital, Ashdod, Israel
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19
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Zeng B, Zhou J, Peng D, Dong C, Qin Q. The prevention and treatment of COVID-19 in patients treated with hemodialysis. Eur J Med Res 2023; 28:410. [PMID: 37814329 PMCID: PMC10563282 DOI: 10.1186/s40001-023-01389-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 09/21/2023] [Indexed: 10/11/2023] Open
Abstract
Patients treated with hemodialysis are often immunocompromised due to concomitant disease. As a result, this population is at high risk of infection and mortality from COVID-19. In addition to symptomatic treatment, a series of antiviral drugs targeting COVID-19 are now emerging. However, these antivirals are used mainly in mild or moderate patients with high-risk factors for progression to severe disease and are not available as pre- or post-exposure prophylaxis for COVID-19. There is a lack of clinical data on the use of anti-COVID-19 drugs, especially in patients treated with hemodialysis, therefore, vaccination remains the main measure to prevent SARS-CoV-2 infection in these patients. Here, we review the clinical features and prognosis of patients on hemodialysis infected with SARS-CoV-2, the main anti-COVID-19 drugs currently available for clinical use, and the safety and efficacy of anti-COVID-19 drugs or COVID-19 vaccination in patients treated with hemodialysis. This information will provide a reference for the treatment and vaccination of COVID-19 in patients treated with hemodialysis and maximize the health benefits of these patients during the outbreak.
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Affiliation(s)
- Binyu Zeng
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
- International Science and Technology Innovation Cooperation Base for Early Clinical Trials of Biological Agents in Hunan Province, Changsha, China
| | - Jia Zhou
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
- International Science and Technology Innovation Cooperation Base for Early Clinical Trials of Biological Agents in Hunan Province, Changsha, China
| | - Daizhuang Peng
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
- International Science and Technology Innovation Cooperation Base for Early Clinical Trials of Biological Agents in Hunan Province, Changsha, China
| | - Chengmei Dong
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
- International Science and Technology Innovation Cooperation Base for Early Clinical Trials of Biological Agents in Hunan Province, Changsha, China
| | - Qun Qin
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
- International Science and Technology Innovation Cooperation Base for Early Clinical Trials of Biological Agents in Hunan Province, Changsha, China.
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20
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Alhamad MA, Almulhim MY, Alburayh AA, Alsaad RA, Alhajji AM, Alnajjar JS, Alhashem SS, Salah G, Al Sahlawi M. Factors Affecting Adherence to Hemodialysis Therapy Among Patients With End-Stage Renal Disease Attending In-Center Hemodialysis in Al-Ahsa Region, Saudi Arabia. Cureus 2023; 15:e46701. [PMID: 38022334 PMCID: PMC10630638 DOI: 10.7759/cureus.46701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2023] [Indexed: 12/01/2023] Open
Abstract
Background Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are global health concerns, with ESRD requiring renal replacement therapy (RRT). Hemodialysis is a prevalent modality for RRT. However, access to hemodialysis is challenging for rural patients due to geographical barriers and limited nephrology services. This research aims to identify factors influencing adherence to hemodialysis sessions among rural ESRD patients, addressing travel, healthcare infrastructure, and socioeconomic factors. Materials and methods A cross-sectional study of 154 participants was conducted from July 06 to September 10, 2023 at Al-Jaber Dialysis Center in Al-Ahsa, Saudi Arabia. It included adult CKD patients on hemodialysis who were interviewed to assess factors influencing hemodialysis adherence using a structured questionnaire. Results Our study assessed hemodialysis adherence in 154 patients in Al-Ahsa, Saudi Arabia. Gender distribution was nearly equal (male = 54.5%), with the majority aged 41-60, married, and residing in downtown areas. Hypertension (43.9%) and diabetes (32.3%) were the prevalent comorbidities. Most patients received thrice-weekly dialysis (96.15%), with family cars as the primary transportation mode (55.2%). Hypertension (43.3%) and diabetic nephropathy (40.9%) were the leading causes of CKD. Approximately 26% missed dialysis, with health issues and transportation difficulties being common reasons. Notably, adherence correlated with female gender, lower education, and family car transportation mode. Social support significantly influenced adherence, highlighting its importance in maintaining hemodialysis adherence. Conclusion Our study identified various sociodemographic and dialysis-related factors influencing adherence among hemodialysis patients in the Al-Ahsa region, Saudi Arabia. Notably, factors such as gender, education level, and transportation means significantly influenced adherence. Adequate family and social support were associated with better adherence. These findings highlight the importance of tailored interventions addressing these factors to enhance hemodialysis adherence and ultimately improve patient outcomes in this population.
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Affiliation(s)
| | - Mohammed Y Almulhim
- Nephrology, King Faisal University, Al-Ahsa, SAU
- Internal Medicine, College of Medicine, King Faisal University, Al-Ahsa, SAU
| | | | | | | | | | | | - Ghassan Salah
- Nephrology, King Fahad General Hospital, Al-Ahsa, SAU
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21
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Chen W, Feng J, Ji P, Liu Y, Wan H, Zhang J. Association of hyperhomocysteinemia and chronic kidney disease in the general population: a systematic review and meta-analysis. BMC Nephrol 2023; 24:247. [PMID: 37612681 PMCID: PMC10463317 DOI: 10.1186/s12882-023-03295-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 08/11/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Increasing evidence shows that an elevated homocysteine(Hcy) level is associated with an increased risk of chronic kidney disease (CKD). This study systematically evaluated the correlation between homocysteine level and the incidence of CKD reported in cohort and cross-sectional studies. METHODS We searched electronic databases and reference lists for relevant articles. 4 cohort studies and 7 cross-sectional studies including 79,416 patients were analyzed in a meta-analysis. Hyperhomocysteinemia was defined as a Hcy level > 15 µmol/L, which was the criterium used in previous studies. Meta-analyses were conducted of literature searches from online databases such as PubMed, Embase, Cochrane and Scopus. Computed pooled adjusted odds ratios with corresponding 95% confidence intervals (95% CI) were used to estimate the risk of new-onset CKD according to Hcy levels in the general population. RESULTS People with high Hcy levels were more likely to suffer from CKD than people with normal Hcy levels (pooled OR, 2.09; 95% CI, 1.72-2.55). This positive relationship persisted across different study types such as cohort studies (summary OR, 2.2; 95% CI, 1.55-3.13) and cross-sectional studies (summary OR, 2.07; 95% CI, 1.63-2.63). CONCLUSIONS People with hyperhomocysteinemia have a higher incidence of CKD, Hyperhomocysteinemia may also be an independent risk factor for CKD in the general population.
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Affiliation(s)
- Wei Chen
- Guangxi Health Commission key Laboratory of Emergency and Critical Medicine, The Second Affiliated Hospital of Guangxi, Medical University, Nanning, China
| | - Jihua Feng
- Guangxi Health Commission key Laboratory of Emergency and Critical Medicine, The Second Affiliated Hospital of Guangxi, Medical University, Nanning, China
| | - Pan Ji
- Guangxi Health Commission key Laboratory of Emergency and Critical Medicine, The Second Affiliated Hospital of Guangxi, Medical University, Nanning, China
| | - Yani Liu
- Guangxi Health Commission key Laboratory of Emergency and Critical Medicine, The Second Affiliated Hospital of Guangxi, Medical University, Nanning, China
| | - Huan Wan
- Guangxi Health Commission key Laboratory of Emergency and Critical Medicine, The Second Affiliated Hospital of Guangxi, Medical University, Nanning, China
| | - Jianfeng Zhang
- Guangxi Health Commission key Laboratory of Emergency and Critical Medicine, The Second Affiliated Hospital of Guangxi, Medical University, Nanning, China.
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22
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Yang M, Yang Y, Xu Y, Wu Y, Lin J, Mai J, Fang K, Ma X, Zou C, Lin Q. Development and Validation of Prediction Models for All-Cause Mortality and Cardiovascular Mortality in Patients on Hemodialysis: A Retrospective Cohort Study in China. Clin Interv Aging 2023; 18:1175-1190. [PMID: 37534232 PMCID: PMC10392814 DOI: 10.2147/cia.s416421] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 07/22/2023] [Indexed: 08/04/2023] Open
Abstract
Purpose This study aimed to develop two predictive nomograms for the assessment of long-term survival status in hemodialysis (HD) patients by examining the prognostic factors for all-cause mortality and cardiovascular (CVD) event mortality. Patients and methods A total of 551 HD patients with an average age of over 60 were included in this study. The patients' medical records were collected from our hospital and randomly allocated to two cohorts: the training cohort (n=385) and the validation cohort (n=166). We employed multivariate Cox assessments and fine-gray proportional hazards models to explore the predictive factors for both all-cause mortality and cardiovascular event mortality risk in HD patients. Two nomograms were established based on predictive factors to forecast patients' likelihood of survival for 3, 5, and 8 years. The performance of both models was evaluated using the area under the curve (AUC), calibration plots, and decision curve analysis. Results The nomogram for all-cause mortality prediction included seven factors: age ≥ 60, sex (male), history of diabetes and coronary artery disease, diastolic blood pressure, total triglycerides (TG), and total cholesterol (TC). The nomogram for cardiovascular event mortality prediction included three factors: history of diabetes and coronary artery disease, and total cholesterol (TC). Both models demonstrated good discrimination, with AUC values of 0.716, 0.722 and 0.725 for all-cause mortality at 3, 5, and 8 years, respectively, and 0.702, 0.695, and 0.677 for cardiovascular event mortality, respectively. The calibration plots indicated a good agreement between the predictions and the decision curve analysis demonstrated a favorable clinical utility of the nomograms. Conclusion Our nomograms were well-calibrated and exhibited significant estimation efficiency, providing a valuable predictive tool to forecast prognosis in HD patients.
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Affiliation(s)
- Min Yang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Yaqin Yang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Yuntong Xu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Yuchi Wu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Jiarong Lin
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Jianling Mai
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Kunyang Fang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Xiangxia Ma
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Chuan Zou
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
| | - Qizhan Lin
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
- Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China
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23
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Sleiman J, Soler Pujol G, Montañez E, Roatta V, Laham G. Access to treatment in chronic kidney disease, dialysis and transplantation. Is there gender equality? Front Med (Lausanne) 2023; 10:1176975. [PMID: 37415763 PMCID: PMC10321413 DOI: 10.3389/fmed.2023.1176975] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 06/01/2023] [Indexed: 07/08/2023] Open
Abstract
Sex and gender are often used as synonyms. However, while sex describes only a biological state, gender is a dynamic concept that takes into account psychosocial and cultural aspects of human existence that can change according to place and time. Inequality in medicine has been described in several areas. Among them, gender inequality has been disregarded for many years and is now a matter of concern. Chronic kidney disease (CKD) is a growing epidemic worldwide, affecting approximately 10% of the population. Although both men and women are affected, gender equality, especially in access to different treatments, is a matter of concern. We decided to investigate gender equality in patients with CKD. To this end, we conducted a literature narrative review to determine whether gender inequalities were found in CKD patients in general and in access to different treatment modalities in particular. A non-language restricted search was performed until November 30th 2022 in PubMed, SciELO, Trip Database, Google Scholar, MEDES y MEDLINE. We also investigated the situation in this regard in our country. We found that CKD is more prevalent in women than men, nevertheless this prevalence decreases along the CKD stages to the point that more men reach end stage kidney disease (ESKD) and dialysis. Access to transplant (ATT) is higher in men than in women although posttransplant survival shows no gender differences. Finally, most series have shown that women are more frequently Kidney transplantation (KT) living donors than men. Results in our country are similar to the published literature with the exception of a higher proportion of men as KT living donors. As in other areas, gender inequality in Nephrology has been largely overlooked. In this review we have highlighted gender differences in CKD patients. Gender inequality in Nephrology exists and needs to be looked upon in order to reach a personalized clinical approach.
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24
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Cooper KM, Colletta A, Moulton K, Ralto KM, Devuni D. Kidney disease in patients with chronic liver disease: Does sex matter? World J Clin Cases 2023; 11:3980-3992. [PMID: 37388789 PMCID: PMC10303604 DOI: 10.12998/wjcc.v11.i17.3980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/30/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
Kidney disease in patients with liver disease is serious and increases mortality. Up to 50% of patients hospitalized experience an episode of acute kidney injury. In general, men with liver disease are thought to be at increased risk of kidney disease. However, this association should be considered with caution because most studies use creatinine-based inclusion criteria, which is negatively biased against women. In this review, we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.
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Affiliation(s)
- Katherine M Cooper
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Alessandro Colletta
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kristen Moulton
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kenneth M Ralto
- Department of Medicine, Division of Renal Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Deepika Devuni
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
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25
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Allam S, Elsakka EGE, Ismail A, Doghish AS, Yehia AM, Elkady MA, Mokhlis HA, Sayed SM, Abd Elaziz AI, Hashish AA, Amin MM, El Shahat RM, Mohammed OA. Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats. Life Sci 2023; 323:121697. [PMID: 37061126 DOI: 10.1016/j.lfs.2023.121697] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 04/17/2023]
Abstract
AIM this study aims to explore the effect of androgen receptor (AR) blockade by flutamide on some renal pathologic changes such as inflammation, apoptosis, and fibrosis in male rats. MAIN METHODS Firstly, we investigated the potential effect of AR blockade on renal inflammatory intermediates including IL-1β, IL-6, TNF-α, NF-Қβ proteins, and the renal gene expression of NF-Қβ. Besides inflammation, we also assessed the apoptosis pathways including the caspases 3 & 9, mTOR, pAKT proteins, and BAX gene expression. Besides inflammation and apoptosis pathways, we also investigated the effect of androgen blockade on renal fibrosis intermediates including vimentin, TGFβ-1, α-SMA, MMP-9, collagen type-III, collagen type-IV, and the renal expression of the col1A1 gene. Besides previous pathological pathways, we assessed the expression of chloride channel protein-5 (ClC-5), as an important regulator of many renal pathological changes. Finally, we assessed the impact of previous pathological changes on renal function at biochemical and pathological levels. KEY FINDINGS We found that AR blockade by flutamide was associated with the down-regulation of renal inflammation, apoptosis, and fibrosis markers. It was associated with expression down-regulation of IL-1β & IL-6, TNF-α, NF-Қβ, caspases 3 & 9, mTOR, MMP-9, collagens, TGFβ-1, and α-SMA. Away from down-regulation, we also found that AR blockade has upregulated ClC-5 and pAKT proteins. SIGNIFICANCE AR is a major player in androgens-induced nephrotoxicity. AR blockade downregulates renal fibrosis, inflammation, and apoptosis pathways. It may be helpful as a strategy for alleviation of renal side effects associated with some drugs. However; this needs further investigations.
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Affiliation(s)
- Shady Allam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, 32511 Menoufia, Egypt
| | - Elsayed G E Elsakka
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.
| | - Ahmed Ismail
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
| | - Amr Mohamed Yehia
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Mohamed A Elkady
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Hamada Ahmed Mokhlis
- Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Sara M Sayed
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (girls) Al-Azhar University, Nasr City, Cairo, Egypt
| | - Adel I Abd Elaziz
- Department of Pharmacology, Faculty of Medicine (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Abdullah A Hashish
- Basic Medical Sciences Department, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Mona M Amin
- Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Rehab M El Shahat
- Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Osama A Mohammed
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt; Department of Clinical Pharmacology, Faculty of Medicine, Bisha University, Bisha 61922, Saudi Arabia
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26
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Phengpol N, Thongnak L, Lungkaphin A. The programming of kidney injury in offspring affected by maternal overweight and obesity: role of lipid accumulation, inflammation, oxidative stress, and fibrosis in the kidneys of offspring. J Physiol Biochem 2023; 79:1-17. [PMID: 36264422 DOI: 10.1007/s13105-022-00927-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 10/05/2022] [Indexed: 11/29/2022]
Abstract
Maternal overweight and obesity are considered important factors affecting fetal development with many potential consequences for offspring after delivery, including the increased risk of obesity and diabetes mellitus. Maternal obesity promotes adiposity in the offspring by increasing fat deposition and expansion in the body of the offspring. The expansion of adipose tissue changes adipokine levels, including a decrease in adiponectin and an increase in leptin. In addition to changes in adipokine levels, there are also increases in pro-inflammatory cytokines, pro-fibrotic cytokines, and reactive oxygen species, leading to oxidative stress in the offspring. These contribute to the promotion of insulin resistance in offspring, which is associated with kidney injury. Interestingly, maternal obesity can also promote renal lipid accumulation, which could activate inflammatory processes and promote renal oxidative stress and renal fibrosis. These alterations in the kidneys of the offspring imply that a mother being overweight/obese can program the development of kidney disease in offspring. This review will discuss the effects of a mother being overweight or obese on their offspring and the consequences with regard to the kidneys of their offspring. With a focus on the molecular mechanisms, including renal inflammation, renal oxidative stress, renal fibrosis, and renal lipid metabolism in offspring born to overweight and obese mothers, the causative mechanisms and perspective of these conditions will be included.
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Affiliation(s)
- Nichakorn Phengpol
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Laongdao Thongnak
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Anusorn Lungkaphin
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. .,Functional Food Research Center for Well-Being, Chiang Mai University, Chiang Mai, Thailand. .,Functional Foods for Health and Disease, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. .,Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, Thailand.
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27
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Impact of hypertension and diabetes on the onset of chronic kidney disease in a general Japanese population. Hypertens Res 2023; 46:311-320. [PMID: 36171326 DOI: 10.1038/s41440-022-01041-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 08/19/2022] [Accepted: 08/25/2022] [Indexed: 02/07/2023]
Abstract
Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.
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28
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Liu J, Liu Z, Sun W, Luo L, An X, Yu D, Wang W. Role of sex hormones in diabetic nephropathy. Front Endocrinol (Lausanne) 2023; 14:1135530. [PMID: 37143724 PMCID: PMC10151816 DOI: 10.3389/fendo.2023.1135530] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Accepted: 03/22/2023] [Indexed: 05/06/2023] Open
Abstract
Diabetic nephropathy (DN) is the most common microvascular complication in diabetes and one of the leading causes of end-stage renal disease. The standard treatments for patients with classic DN focus on blood glucose and blood pressure control, but these treatments can only slow the progression of DN instead of stopping or reversing the disease. In recent years, new drugs targeting the pathological mechanisms of DN (e.g., blocking oxidative stress or inflammation) have emerged, and new therapeutic strategies targeting pathological mechanisms are gaining increasing attention. A growing number of epidemiological and clinical studies suggest that sex hormones play an important role in the onset and progression of DN. Testosterone is the main sex hormone in males and is thought to accelerate the occurrence and progression of DN. Estrogen is the main sex hormone in females and is thought to have renoprotective effects. However, the underlying molecular mechanism by which sex hormones regulate DN has not been fully elucidated and summarized. This review aims to summarize the correlation between sex hormones and DN and evaluate the value of hormonotherapy in DN.
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Affiliation(s)
- Jiahui Liu
- Public Research Platform, First Hospital of Jilin University, Changchun, Jilin, China
| | - Zhe Liu
- College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Weixia Sun
- Nephrology Department, First Hospital of Jilin University, Changchun, Jilin, China
| | - Ling Luo
- Public Research Platform, First Hospital of Jilin University, Changchun, Jilin, China
| | - Xingna An
- Public Research Platform, First Hospital of Jilin University, Changchun, Jilin, China
| | - Dehai Yu
- Public Research Platform, First Hospital of Jilin University, Changchun, Jilin, China
- *Correspondence: Dehai Yu, ; Wanning Wang,
| | - Wanning Wang
- Nephrology Department, First Hospital of Jilin University, Changchun, Jilin, China
- *Correspondence: Dehai Yu, ; Wanning Wang,
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Jing H, Liao M, Tang S, Lin S, Ye L, Zhong J, Wang H, Zhou J. Predicting the risk of acute kidney injury after cardiopulmonary bypass: development and assessment of a new predictive nomogram. BMC Anesthesiol 2022; 22:379. [PMID: 36476178 PMCID: PMC9727998 DOI: 10.1186/s12871-022-01925-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a common and severe complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to establish a model to predict the probability of postoperative AKI in patients undergoing cardiac surgery with CPB. METHODS We conducted a retrospective, multicenter study to analyze 1082 patients undergoing cardiac surgery under CPB. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the AKI model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the previously mentioned model. Finally, we used multiple methods to evaluate the accuracy and clinical applicability of the model. RESULTS Age, gender, hypertension, CPB duration, intraoperative 5% bicarbonate solution and red blood cell transfusion, urine volume were identified as important factors. Then, these risk factors were created into nomogram to predict the incidence of AKI after cardiac surgery under CPB. CONCLUSION We developed a nomogram to predict the incidence of AKI after cardiac surgery. This model can be used as a reference tool for evaluating early medical intervention to prevent postoperative AKI.
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Affiliation(s)
- Huan Jing
- grid.413107.0The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan Avenue West, Tianhe District, Guangdong Province Guangzhou City, China
| | - Meijuan Liao
- grid.452881.20000 0004 0604 5998The First People’s Hospital of Foshan, 81 Lingnan Avenue, Chancheng District, Guangdong Province Foshan City, China
| | - Simin Tang
- grid.413107.0The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan Avenue West, Tianhe District, Guangdong Province Guangzhou City, China
| | - Sen Lin
- grid.452881.20000 0004 0604 5998The First People’s Hospital of Foshan, 81 Lingnan Avenue, Chancheng District, Guangdong Province Foshan City, China
| | - Li Ye
- grid.452881.20000 0004 0604 5998The First People’s Hospital of Foshan, 81 Lingnan Avenue, Chancheng District, Guangdong Province Foshan City, China
| | - Jiying Zhong
- grid.452881.20000 0004 0604 5998The First People’s Hospital of Foshan, 81 Lingnan Avenue, Chancheng District, Guangdong Province Foshan City, China
| | - Hanbin Wang
- grid.452881.20000 0004 0604 5998The First People’s Hospital of Foshan, 81 Lingnan Avenue, Chancheng District, Guangdong Province Foshan City, China
| | - Jun Zhou
- grid.413107.0The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan Avenue West, Tianhe District, Guangdong Province Guangzhou City, China
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Văcăroiu IA, Calangiu F, Tănase G, Isac S, Georgescu DE, Dragoș D, Cobilinschi C, Chiperi LV, Ionescu D, Balcangiu-Stroescu AE, Călinoiu AL, Tulin R, Bălan DG. Biomarkers Involved in the Mineral-Bone Disorders Secondary to Chronic Hemodialysis. Intern Med 2022; 19:17-25. [DOI: 10.2478/inmed-2022-0225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Abstract
Introduction. Chronic kidney disease (CKD) is one of the most prevalent public health problems of the elderly population. End-Stage Renal Disease (ESRD)’s most common treatment is dialysis. There are some dissimilarities between the sexes that are apparent in the status and the possible outcomes of CKD. This study aims to shed some light on these somewhat overlooked wwwvariations and their implications.
Materials and methods. We conducted an observational study on subjects with CKD, undergoing hemodialysis for at least 2 years. For participation, we selected an equal number of men and women, which were divided into 2 groups according to gender. Plasma levels of the following parameters were monitored: creatinine, urea, bicarbonate, phosphorus, calcium, alkaline phosphatase, vitamin D, FGF-23 and TNF-alpha. The differences of the variables between the two groups were evaluated using TTEST and CORREL test.
Results. A significant correlation was between the plasma levels of FGF-23 and gender (p =0.02). Regarding the plasmatic levels of urea, besides the expected difference in pre- and post- dialysis levels, we obtained a significant correlation between its post-dialysis value and gender (p =0.045). In regard to the plasmatic levels of the alkaline phosphatase, there was a significant correlation between its value and gender (p =0.01).
Conclusions. There is a significant correlation between the plasmatic levels of creatinine, urea, alkaline phosphatase, vitamin D, FGF-23 and gender. Women present lower levels of creatinine and urea, while men present lower plasmatic levels of vitamin D, alkaline phosphatase and FGF-23.
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Affiliation(s)
| | - Filip Calangiu
- “Prof. Dr. Al. Trestioreanu” Oncology Institute , Bucharest , Romania
| | - Georgiana Tănase
- “Prof. Dr. Al. Trestioreanu” Oncology Institute , Bucharest , Romania
| | - Sebastian Isac
- “Carol Davila” University of Medicine and Pharmacy , Bucharest , Romania
- Fundeni Clinical Institute , Bucharest , Romania
| | | | - Dorin Dragoș
- “Carol Davila” University of Medicine and Pharmacy , Bucharest , Romania
- University Emergency Hospital Bucharest , Romania
| | - Claudia Cobilinschi
- “Carol Davila” University of Medicine and Pharmacy , Bucharest , Romania
- “Sfânta Maria” Clinical Hospital , Bucharest , Romania
| | | | - Dorin Ionescu
- “Carol Davila” University of Medicine and Pharmacy , Bucharest , Romania
| | | | | | - Raluca Tulin
- “Carol Davila” University of Medicine and Pharmacy , Bucharest , Romania
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Larkin BP, Nguyen LT, Hou M, Glastras SJ, Chen H, Faiz A, Chen J, Wang R, Pollock CA, Saad S. Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease. Diabetes Obes Metab 2022; 24:1939-1949. [PMID: 35635331 PMCID: PMC9544807 DOI: 10.1111/dom.14778] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 05/09/2022] [Accepted: 05/25/2022] [Indexed: 11/29/2022]
Abstract
AIM To determine, using a mouse model of obesity, whether low-dose hydralazine prevents obesity-related chronic kidney disease (CKD). METHODS From 8 weeks of age, male C57BL/6 mice received a high-fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water, for 24 weeks. Biometric and metabolic variables, renal function and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed. RESULTS The HFD-fed mice developed obesity, with glucose intolerance, hyperinsulinaemia and dyslipidaemia. Obesity increased albuminuria and glomerulosclerosis, which were significantly ameliorated by low-dose hydralazine in the absence of a blood pressure-lowering effect. Obesity increased renal global DNA methylation and this was attenuated by low-dose hydralazine. HFD-induced changes in methylation of individual loci were also significantly reversed by low-dose hydralazine. Obese mice demonstrated increased markers of kidney fibrosis, inflammation and oxidative stress, but these markers were not significantly improved by hydralazine. CONCLUSION Low-dose hydralazine ameliorated HFD-induced albuminuria and glomerulosclerosis, independent of alterations in biometric and metabolic variables or blood pressure regulation. Although the precise mechanism of renoprotection in obesity is unclear, an epigenetic basis may be implicated. These data support repurposing hydralazine as a novel therapy to prevent CKD progression in obese patients.
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Affiliation(s)
- Benjamin P. Larkin
- Renal Research Laboratory, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
| | - Long T. Nguyen
- Renal Research Laboratory, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
| | - Miao Hou
- Department of CardiologyChildren′s Hospital of Soochow UniversitySuzhouJiangsuChina
| | - Sarah J. Glastras
- Renal Research Laboratory, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
- Department of DiabetesEndocrinology and Metabolism, Royal North Shore HospitalSydneyAustralia
| | - Hui Chen
- School of Life Sciences, Faculty of ScienceUniversity of Technology SydneySydneyAustralia
| | - Alen Faiz
- School of Life Sciences, Faculty of ScienceUniversity of Technology SydneySydneyAustralia
| | - Jason Chen
- Department of Anatomical PathologyRoyal North Shore HospitalSt LeonardsNew South WalesAustralia
| | - Rosy Wang
- Renal Research Laboratory, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
| | - Carol A. Pollock
- Renal Research Laboratory, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
| | - Sonia Saad
- Renal Research Laboratory, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
- School of Life Sciences, Faculty of ScienceUniversity of Technology SydneySydneyAustralia
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32
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Park Y, Lee SJ. Analysis of the Association between Metabolic Syndrome and Renal Function in Middle-Aged Patients with Diabetes. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:11832. [PMID: 36142104 PMCID: PMC9517400 DOI: 10.3390/ijerph191811832] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/16/2022] [Accepted: 09/16/2022] [Indexed: 06/16/2023]
Abstract
This study investigated the effects of metabolic syndrome on the estimated glomerular filtration rate in middle-aged participants with diabetes to provide basic data to enable the development of education programs for middle-aged people to prevent diabetic kidney disease. This cross-sectional descriptive study analyzed data obtained in the 2nd year of the 8th Korea National Health and Nutrition Examination Survey in 2020 and enrolled 279 participants aged 40-65 years who were diagnosed with diabetes. Multilevel stratified cluster sampling was used to improve the representativeness of the samples and the accuracy of parameter estimation. The risk factors of metabolic syndrome and the risk of elevated eGFR were analyzed using regression analysis and the correlation between the variables was determined using Pearson's correlation analysis. Middle-aged participants with diabetes whose eGFR was <90 showed a significant difference in their risk for metabolic syndrome based on sex, age, disease duration, and total cholesterol concentrations. Systolic blood pressure and waist circumference in men, and waist circumference and HDL cholesterol level in women were identified as risk factors that contribute to the increasing prevalence of metabolic syndrome.
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Affiliation(s)
- Yoonjin Park
- Department of Nursing, Joongbu University, Geumsan-gun 32713, Korea
| | - Su Jung Lee
- School of Nursing, Research Institute of Nursing Science, Hallym University, Chuncheon-si 24252, Korea
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Liao KW, Chien LC, Chen YC, Kao HC. Sex-specific differences in early renal impairment associated with arsenic, lead, and cadmium exposure among young adults in Taiwan. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:52655-52664. [PMID: 35274206 PMCID: PMC8911167 DOI: 10.1007/s11356-022-19521-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/25/2022] [Indexed: 05/06/2023]
Abstract
Exposure to a single metal has been reported to damage renal function in humans. However, information regarding the association between multiple-metal exposure and markers for early renal impairment in different sexes among the young adult Taiwanese population is scarce. We assessed the association between exposure to arsenic (As), cadmium (Cd), and lead (Pb), and early renal impairment markers using urinary microalbumin (MA), β2-microglobulin (β2MG), and N-acetyl-beta-D-glucosaminidase (NAG) by analyzing 157 young adults aged 20‒29 years, in Taiwan. Inductively coupled plasma mass spectrometry was used to determine urinary As, Cd, and Pb levels. Regression models were applied to different sex groups. The results showed that after adjusting for potential confounding factors and each metal, urinary Cd levels were significantly positively associated with urinary MA (β = 0.523, 95% CI: 0.147-0.899) and β2MG (β = 1.502, 95% CI: 0.635-2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (β = 0.161, 95% CI: 0.027-0.296) in females. This study thus indicates that the effect of exposure to metals (especially Cd) on early renal impairment among young adults in Taiwan is sex-specific. Our study results could contribute toward developing early intervention programs for decreasing the incidence of renal dysfunction. Further studies are warranted to confirm our findings and clarify the potential mechanisms involved.
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Affiliation(s)
- Kai-Wei Liao
- School of Food Safety, College of Nutrition, Taipei Medical University, 250 Wu-Xing Street, Taipei, 11031, Taiwan.
- Research Center of Food Safety Inspection and Function Development, Taipei Medical University, Taipei, Taiwan.
| | - Ling-Chu Chien
- School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan
| | - Yang-Ching Chen
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ho-Ching Kao
- Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan
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Tang WH, Hung WC, Wang CP, Wu CC, Hsuan CF, Yu TH, Hsu CC, Cheng YA, Chung FM, Lee YJ, Lu YC. The Lower Limit of Reference of Urinary Albumin/Creatinine Ratio and the Risk of Chronic Kidney Disease Progression in Patients With Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne) 2022; 13:858267. [PMID: 35721762 PMCID: PMC9200995 DOI: 10.3389/fendo.2022.858267] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/02/2022] [Indexed: 11/24/2022] Open
Abstract
A urine albumin/creatinine ratio (UACR) <30 mg/g is considered to be normal, while increased risk of incident hypertension and cardiovascular disease mortality in subjects with high normal UACR level had been observed. However, a mild elevated but normal UACR level was associated with the risk of initiating chronic kidney disease (CKD) is uncertain. We investigated whether higher normal UACR is associated with the risk of developing CKD. A total of 4821 subjects with type 2 diabetes mellitus (T2DM), an estimated glomerular filtration rate >60 ml/min/1.73 m2 and UACR <30 mg/g enrolled in a diabetes disease management program between 2006 and 2020 were studied. The optimal cutoff point for baseline UACR as a predictor for progression to CKD according to the 2012 KDIGO definition was calculated using receiving operating characteristic curve analysis. After a mean of 4.9 years follow-up, the CKD risk progression increased in parallel with the quartiles of baseline UACR <30 mg/g (p for trend <0.0001). UACR cutoff points of 8.44 mg/g overall, 10.59 mg/g in males and 8.15 mg/g in females were associated with the risk of CKD progression. In multivariate Cox regression analysis, the hazard ratios for the association between UACR (>8.44 mg/g, >10.9 mg/g, >8.15 mg/g in overall, male, and female patients, respectively) and the risk of CKD progression were significant. This study demonstrated that a cutoff UACR value of >10 mg/g could significantly predict the cumulative incidence and progression of CKD in patients with T2DM.
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Affiliation(s)
- Wei-Hua Tang
- Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Yuli Branch, Hualien, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Chin Hung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chao-Ping Wang
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chin-Feng Hsuan
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, Kaohsiung, Taiwan
| | - Teng-Hung Yu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chia-Chang Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- The School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ya-Ai Cheng
- Department of Health Care Administration, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Fu-Mei Chung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | | | - Yung-Chuan Lu
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
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Collister D, Krakowsky Y, Potter E, Millar AC. Chronic Kidney Disease in the Transgender, Nonbinary, or Gender Diverse Person. Semin Nephrol 2022; 42:129-141. [PMID: 35718361 DOI: 10.1016/j.semnephrol.2022.04.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nephrologists are increasingly providing care to transgender, nonbinary, and gender diverse (TNBGD) individuals with chronic kidney disease. This narrative review discusses the care of TNBGD individuals from a nephrology perspective. TNBGD individuals are under-represented in the nephrology literature. TNBGD individuals are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Gender-affirming hormone therapy (GAHT) with estradiol in transfeminine individuals potentially increases the risk of venous thromboembolism and cardiovascular disease. GAHT with testosterone in transmasculine individuals potentially increases the risk of erythrocytosis and requires careful monitoring. GAHT modifies body composition and lean muscle mass, which in turn influence creatinine generation and excretion, which may impact the performance of estimated glomerular filtration rate (GFR) equations and the estimation of 24-hour urine values from spot urine albumin/protein to creatinine ratios. There are limited studies regarding TNBGD individuals with chronic kidney disease. Additional research is needed to evaluate the effects of GAHT on GFR and biomarkers of kidney function and the performance of the estimated GFR equation in TNBGD populations.
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Affiliation(s)
- David Collister
- Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada; Population Health Research Institute, Hamilton, Ontario, Canada.
| | - Yonah Krakowsky
- Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Surgery, Women's College Hospital, Toronto, Ontario, Canada
| | - Emery Potter
- Department of Surgery, Women's College Hospital, Toronto, Ontario, Canada; Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada
| | - Adam C Millar
- Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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Sridhar VS, Yau K, Benham JL, Campbell DJT, Cherney DZI. Sex and Gender Related Differences in Diabetic Kidney Disease. Semin Nephrol 2022; 42:170-184. [PMID: 35718364 DOI: 10.1016/j.semnephrol.2022.04.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diversity in sex and gender are important considerations in the pathogenesis, prognostication, research, and management of diabetic kidney disease (DKD). Sex and gender differences in the disease risk, disease-specific mechanisms, and outcomes in DKD may be attributed to biological differences between males and females at the cellular and tissue level, inconsistencies in the diagnostic and assessment tools used in chronic kidney disease and DKD, as well societal differences in the way men, women, and gender-diverse individuals self-manage and interact with health care systems. This review outlines key considerations related to the impact of sex on DKD, specifically elaborating on how they contribute to observed differences in disease epidemiology, pathogenesis, and treatment strategies. We also highlight the effect of gender on DKD progression and care.
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Affiliation(s)
- Vikas S Sridhar
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Kevin Yau
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Jamie L Benham
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - David J T Campbell
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta.
| | - David Z I Cherney
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta
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Chen D, Sun H, Lu C, Chen W, Guo VY. The association between hypertriglyceridemic-waist phenotype and chronic kidney disease: a cohort study and meta-analysis. Sci Rep 2022; 12:1935. [PMID: 35121773 PMCID: PMC8817025 DOI: 10.1038/s41598-022-05806-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 12/20/2021] [Indexed: 12/20/2022] Open
Abstract
Evidence on the association between hypertriglyceridemic-waist phenotype (HTGW) and chronic kidney disease (CKD) is limited and inconsistent. We aimed to explore such association among 7406 Chinese aged ≥ 45 years in a cohort setting, followed by a meta-analysis. Participants were categorized into four phenotypes: NTNW (normal triglycerides and normal waist circumference), NTGW (isolated enlarged waist circumference), HTNW (isolated high triglycerides), and HTGW (high triglycerides and enlarged waist circumference). We used multivariate logistic regression to determine the association between different phenotypes and risk of CKD in the cohort study. For meta-analysis, we searched relevant studies from Embase, Medline, PubMed, and Web of Science from dataset inception up to May 1, 2021. A random-effect model was used to estimate the pooled effect and I2 statistic was applied to evaluate heterogeneity. In the cohort study, compared to the NTNW phenotype, HTGW (OR 1.82, 95% CI 1.32 to 2.51, p < 0.01) and NTGW (OR 1.48, 95% CI 1.13 to 1.94, p = 0.004) were significantly associated with CKD risk after 4 years follow-up, but not for the HTNW phenotype. The meta-analysis also showed a positive association between HTGW phenotype and CKD risk (pooled OR 1.53, 95% CI 1.31 to 1.79, I2 = 62.4%). Assessment of triglyceridemic-waist phenotypes might help to identify individuals with high-risk of developing CKD.
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Affiliation(s)
- Dezhong Chen
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Second Road, Guangzhou, 510080, Guangdong, China
| | - Huimin Sun
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Second Road, Guangzhou, 510080, Guangdong, China
| | - Ciyong Lu
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Second Road, Guangzhou, 510080, Guangdong, China
| | - Weiqing Chen
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Second Road, Guangzhou, 510080, Guangdong, China
| | - Vivian Yawei Guo
- Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Second Road, Guangzhou, 510080, Guangdong, China.
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He W, Liu X, Hu B, Li D, Chen L, Li Y, Zhu K, Tu Y, Xiong S, Wang G, Fu B. Gender and Ethnic Disparities of Acute Kidney Injury in COVID-19 Infected Patients: A Literature Review. Front Cell Infect Microbiol 2022; 11:778636. [PMID: 35145920 PMCID: PMC8823179 DOI: 10.3389/fcimb.2021.778636] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/20/2021] [Indexed: 12/21/2022] Open
Abstract
Coronavirus disease 2019(COVID-19) has become a public health emergency of concern worldwide. COVID-19 is a new infectious disease arising from Coronavirus 2 (SARS-CoV-2). It has a strong transmission capacity and can cause severe and even fatal respiratory diseases. It can also affect other organs such as the heart, kidneys and digestive tract. Clinical evidence indicates that kidney injury is a common complication of COVID-19, and acute kidney injury (AKI) may even occur in severely ill patients. Data from China and the United States showed that male sex, Black race, the elderly, chronic kidney disease, diabetes, hypertension, cardiovascular disease, and higher body mass index are associated with COVID-19‐induced AKI. In this review, we found gender and ethnic differences in the occurrence and development of AKI in patients with COVID-19 through literature search and analysis. By summarizing the mechanism of gender and ethnic differences in AKI among patients with COVID-19, we found that male and Black race have more progress to COVID-19-induced AKI than their counterparts.
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Affiliation(s)
- Weihang He
- Reproductive Medicine Center, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaoqiang Liu
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Jiangxi Institute of Urology, Nanchang, China
| | - Bing Hu
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Dongshui Li
- Reproductive Medicine Center, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Luyao Chen
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yu Li
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ke Zhu
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Jiangxi Institute of Urology, Nanchang, China
| | - Yechao Tu
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Situ Xiong
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Gongxian Wang
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Jiangxi Institute of Urology, Nanchang, China
| | - Bin Fu
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Jiangxi Institute of Urology, Nanchang, China
- *Correspondence: Bin Fu,
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Is Compensation Prediction Score Valid for Contralateral Kidney After Living-Donor Nephrectomy in the United States? Transplant Proc 2022; 54:237-241. [PMID: 35031118 DOI: 10.1016/j.transproceed.2021.08.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 08/26/2021] [Indexed: 11/23/2022]
Abstract
BACKGROUND Compensation after living donor nephrectomy is well known, and a compensation prediction score (CPS) was made in Japan previously. The aim of this study was to perform external validation of CPS in the United States. METHODS We studied retrospectively 78 living donor nephrectomies in our institution. We defined a favorable compensation as a postdonation estimated glomerular filtration rate (eGFR) at 1 year of >60% of the predonation eGFR. We analyzed the living donors' clinical characteristics and outcomes and validated CPS score. RESULTS The median (range) donor age was 43 (21-63) years, and median body mass index was 26.9 (18.3-35.9) kg/m2. Forty-four percent of donors were White. The donor predonation eGFR was 105 (61-134) mL/min/1.73 m2, and the postdonation eGFR at 1 year was 73.2 (0-115) mL/min/1.73 m2. Eighty-three percent of donors had a favorable compensation. The CPS was 9.6 (1.6-15.6) and showed strong diagnostic accuracy for predicting favorable compensation (area under the curve, 0.788; 95% confidence interval, 0.652-0.924; P = .001). The CPS showed a significant positive correlation with the postdonation eGFR at 1 year (R = 0.54; P < .001). CONCLUSIONS In the United States, the CPS would be a valid tool with which to predict a favorable compensation of remnant kidney function.
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Neugarten J, Golestaneh L. Gender-dependent mechanisms of injury and repair. REGENERATIVE NEPHROLOGY 2022:303-318. [DOI: 10.1016/b978-0-12-823318-4.00023-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Moreno-Gómez-Toledano R, Arenas MI, Muñoz-Moreno C, Olea-Herrero N, Reventun P, Izquierdo-Lahuerta A, Antón-Cornejo A, González-Santander M, Zaragoza C, Saura M, Bosch RJ. Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166296. [DOI: https:/doi.org/10.1016/j.bbadis.2021.166296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Ren Q, Chen D, Liu X, Yang R, Yuan L, Ding M, Zhang N. Derivation and Validation of a Prediction Model of End-Stage Renal Disease in Patients With Type 2 Diabetes Based on a Systematic Review and Meta-analysis. Front Endocrinol (Lausanne) 2022; 13:825950. [PMID: 35360073 PMCID: PMC8960850 DOI: 10.3389/fendo.2022.825950] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/07/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES To develop and validate a model for predicting the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes. METHODS The derivation cohort was from a meta-analysis. Statistically significant risk factors were extracted and combined to the corresponding risk ratio (RR) to establish a risk assessment model for ESRD in type 2 diabetes. All risk factors were scored according to their weightings to establish the prediction model. Model performance is evaluated using external validation cohorts. The outcome was the occurrence of ESRD defined as eGFR<15 ml min-1 1.73 m-2 or received kidney replacement therapy (dialysis or transplantation). RESULTS A total of 1,167,317 patients with type 2 diabetes were included in our meta-analysis, with a cumulative incidence of approximately 1.1%. The final risk factors of the prediction model included age, sex, smoking, diabetes mellitus (DM) duration, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and triglyceride (TG). All risk factors were scored according to their weightings, with the highest score being 36.5. External verification showed that the model has good discrimination, AUC=0.807(95%CI 0.753-0.861). The best cutoff value is 16 points, with the sensitivity and specificity given by 85.33% and 60.45%, respectively. CONCLUSION The study established a simple risk assessment model including 8 routinely available clinical parameters for predicting the risk of ESRD in type 2 diabetes.
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Affiliation(s)
- Qiuyue Ren
- Department of Nephropathy, Wang Jing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Dong Chen
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinbang Liu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Ronglu Yang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Lisha Yuan
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Min Ding
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Ning Zhang
- Department of Nephropathy, Wang Jing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Ning Zhang,
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Moreno-Gómez-Toledano R, Arenas MI, Muñoz-Moreno C, Olea-Herrero N, Reventun P, Izquierdo-Lahuerta A, Antón-Cornejo A, González-Santander M, Zaragoza C, Saura M, Bosch RJ. Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166296. [PMID: 34718120 DOI: 10.1016/j.bbadis.2021.166296] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 02/06/2023]
Abstract
Bisphenol-A (BPA), a chemical -xenoestrogen- used in the production of the plastic lining of food and beverage containers, is present in the urine of almost the entire population. Recent studies have shown that BPA exposure is associated with podocytopathy, increased urinary albumin excretion (UAE), and hypertension. Since these changes are characteristic of early diabetic nephropathy (DN), we explored the renal effects of BPA and diabetes including the potential role of sexual dimorphism. Male and female mice were included in the following animals' groups: control mice (C), mice treated with 21.2 mg/kg of BPA in the drinking water (BPA), diabetic mice induced by streptozotocin (D), and D mice treated with BPA (D + BPA). Male mice form the D + BPA group died by the tenth week of the study due probably to hydro-electrolytic disturbances. Although BPA treated mice did not show an increase in serum creatinine, as observed in D and D + BPA groups, they displayed similar alteration to those of the D group, including increased in kidney damage biomarkers NGAL and KIM-1, UAE, hypertension, podocytopenia, apoptosis, collapsed glomeruli, as well as TGF-β, CHOP and PCNA upregulation. UAE, collapsed glomeruli, PCNA staining, TGF-β, NGAL and animal survival, significantly impaired in D + BPA animals. Moreover, UAE, collapsed glomeruli and animal survival also displayed a sexual dimorphism pattern. In conclusion, oral administration of BPA is capable of promoting in the kidney alterations that resemble early DN. Further translational studies are needed to clarify the potential role of BPA in renal diseases, particularly in diabetic patients.
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Affiliation(s)
- Rafael Moreno-Gómez-Toledano
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - María I Arenas
- Universidad de Alcalá, Department of Biomedicine and Biotechnology, Alcalá de Henares, Spain
| | - Carmen Muñoz-Moreno
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - Nuria Olea-Herrero
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - Paula Reventun
- Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Adriana Izquierdo-Lahuerta
- University Rey Juan Carlos, Biochemistry and Molecular Biology Area, Department of Basic Sciences of Health, Alcorcon, Spain
| | - Alba Antón-Cornejo
- Clinical Analysis Service, Principe de Asturias Hospital, Alcalá de Henares, Spain
| | - Marta González-Santander
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - Carlos Zaragoza
- Unidad de Investigación Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)/Facultad de Medicina Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain; Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain
| | - Marta Saura
- Universidad de Alcalá, Laboratory of Pathophysiology of the Vascular Wall, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, IRICYS, Department of System Biology/Physiology Unit, Alcalá de Henares, Spain
| | - Ricardo J Bosch
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain.
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Sutherland MR, Malik W, Nguyen VB, Tran V, Polglase GR, Black MJ. Renal morphology and glomerular capillarisation in young adult sheep born moderately preterm. J Dev Orig Health Dis 2021; 12:975-981. [PMID: 33300490 DOI: 10.1017/s2040174420001208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman's spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman's space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.
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Affiliation(s)
- Megan R Sutherland
- Department of Anatomy and Developmental Biology and the Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Waleed Malik
- Department of Anatomy and Developmental Biology and the Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Vivian B Nguyen
- Department of Anatomy and Developmental Biology and the Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Vivian Tran
- Department of Anatomy and Developmental Biology and the Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Graeme R Polglase
- The Ritchie Centre, Department of Obstetrics and Gynaecology, Monash University and the Hudson Institute of Medical Research, Clayton, Victoria, Australia
| | - Mary Jane Black
- Department of Anatomy and Developmental Biology and the Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
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Bech SK, Qi H, Mariager CØ, Hansen ESS, Ilicak E, Zöllner FG, Laustsen C. The number of glomeruli and pyruvate metabolism is not strongly coupled in the healthy rat kidney. Magn Reson Med 2021; 87:896-903. [PMID: 34554602 DOI: 10.1002/mrm.29025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 08/23/2021] [Accepted: 09/07/2021] [Indexed: 11/10/2022]
Abstract
PURPOSE The number of glomeruli is different in men and women, as they also present different prevalence and progression of chronic kidney disease. A recent study has demonstrated a potential difference in renal metabolism between sexes, and a potential explanation could be the differences in glomeruli number. This study investigates the potential correlation between glomerular number and pyruvate metabolism in healthy kidneys. METHODS This study is an experimental study with rats (N = 12). We used cationized-ferritin MRI to visualize and count glomeruli and hyperpolarized [1-13 C]pyruvate to map the metabolism. Dynamic contrast-enhanced MRI was used to analyze kidney hemodynamics using gadolinium tracer. RESULTS Data showed no or subtle correlation between the number of glomeruli and the pyruvate metabolism. Minor differences were observed in the number of glomeruli (female = 24,509 vs. male = 26 350; p = .16), renal plasma flow (female = 606.6 vs. male= 455.7 ml/min/100 g; p = .18), and volume of distribution (female = 87.44 vs. male = 76.61 ml/100 ml; p = .54) between sexes. Mean transit time was significantly prolonged in males compared with females (female = 8.868 s vs. male = 10.63 s; p = .04). CONCLUSION No strong statistically significant correlation between the number of glomeruli and the pyruvate metabolism was found in healthy rat kidneys.
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Affiliation(s)
- Sabrina Kahina Bech
- MR Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Haiyun Qi
- MR Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | | | - Efe Ilicak
- Computer Assisted Clinical Medicine, Mannheim Institute for Intelligent Systems in Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Frank G Zöllner
- Computer Assisted Clinical Medicine, Mannheim Institute for Intelligent Systems in Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.,Cooperative Core Facility Animal Scanner ZI, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoffer Laustsen
- MR Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Feng S, Huang N, Xue M, Zhang P, Zhong Z, Guo Q, Li Z. Association between urinary VEGFA and renal pathology of IgA nephropathy patients. J Clin Lab Anal 2021; 35:e23995. [PMID: 34498313 PMCID: PMC8551689 DOI: 10.1002/jcla.23995] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/12/2021] [Accepted: 08/21/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes. METHODS Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated. RESULTS Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders. CONCLUSIONS Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.
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Affiliation(s)
- Shaozhen Feng
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
| | - Naya Huang
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
| | - Miaorong Xue
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
| | - Puhua Zhang
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
| | - Zhong Zhong
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
| | - Qunying Guo
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
| | - Zhijian Li
- Department of NephrologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Provincial Key Laboratory of NephrologyGuangzhouChina
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Larkin BP, Nguyen LT, Hou M, Glastras SJ, Chen H, Wang R, Pollock CA, Saad S. Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease. Front Cell Dev Biol 2021; 9:705263. [PMID: 34485290 PMCID: PMC8416283 DOI: 10.3389/fcell.2021.705263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 07/30/2021] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Maternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring. METHODS Female C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint. RESULTS Offspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress. CONCLUSION Gestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.
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Affiliation(s)
- Benjamin P. Larkin
- Renal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
| | - Long T. Nguyen
- Renal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
| | - Miao Hou
- Department of Cardiology, Children’s Hospital of Soochow University, Suzhou, China
| | - Sarah J. Glastras
- Renal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
- Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, NSW, Australia
| | - Hui Chen
- Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia
| | - Rosy Wang
- Renal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
| | - Carol A. Pollock
- Renal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
| | - Sonia Saad
- Renal Research Laboratory, Royal North Shore Hospital, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
- Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia
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Swann SA, Kaida A, Nicholson V, Brophy J, Campbell AR, Carter A, Elwood C, Gebremedhen T, Gormley R, King EM, Lee M, Lee V, Maan EJ, Magagula P, Nyman S, Pang D, Pick N, Povshedna T, Prior JC, Singer J, Tognazzini S, Murray MCM, Cote HCF. British Columbia CARMA-CHIWOS Collaboration (BCC3): protocol for a community-collaborative cohort study examining healthy ageing with and for women living with HIV. BMJ Open 2021; 11:e046558. [PMID: 34362800 PMCID: PMC8351488 DOI: 10.1136/bmjopen-2020-046558] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 07/22/2021] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Women living with HIV (WLWH) experience accelerated ageing and an increased risk of age-associated diseases earlier in life, compared with women without HIV. This is likely due to a combination of viral factors, gender differences, hormonal imbalance and psychosocial and structural conditions. This interdisciplinary cohort study aims to understand how biological, clinical and sociostructural determinants of health interact to modulate healthy ageing in WLWH. METHODS AND ANALYSIS The British Columbia Children and Women: AntiRetroviral therapy and Markers of Aging-Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CARMA-CHIWOS) Collaboration (BCC3) study will enrol WLWH (n=350) and sociodemographically matched HIV-negative women (n=350) living in British Columbia. A subset of BCC3 participants will be past participants of CARMA, n≥1000 women and children living with and without HIV, 2008-2018 and/or CHIWOS, n=1422 WLWH, 2013-2018. Over two study visits, we will collect biological specimens for virus serologies, hormones and biological markers as well as administer a survey capturing demographic and sociostructural-behavioural factors. Sociodemographics, comorbidities, number and type of chronic/latent viral infections and hormonal irregularities will be compared between the two groups. Their association with biological markers and psychostructural and sociostructural factors will be investigated through multivariable regression and structural equation modelling. Retrospective longitudinal analyses will be conducted on data from past CARMA/CHIWOS participants. As BCC3 aims to follow participants as they age, this protocol will focus on the first study visits. ETHICS AND DISSEMINATION This study has been approved by the University of British Columbia Children's and Women's Research Ethics Board (H19-00896). Results will be shared in peer-reviewed journals, conferences and at community events as well as at www.hivhearme.ca and @HIV_HEAR_me. WLWH are involved in study design, survey creation, participant recruitment, data collection and knowledge translation. A Community Advisory Board will advise the research team throughout the study.
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Affiliation(s)
- Shayda A Swann
- Experimental Medicine, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
| | - Angela Kaida
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Valerie Nicholson
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
- Epidemiology and Population Health, BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
| | - Jason Brophy
- Division of Infectious Diseases, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Amber R Campbell
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Oak Tree Clinic, BC Women's Hospital and Health Centre, Vancouver, British Columbia, Canada
| | - Allison Carter
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
- Faculty of Medicine, The Kirby Institute, Sydney, New South Wales, Australia
| | - Chelsea Elwood
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Obstetrics and Gynecology, BC Women's Hospital and Health Centre, Vancouver, British Columbia, Canada
| | - Tsion Gebremedhen
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Rebecca Gormley
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
- Epidemiology and Population Health, BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
| | - Elizabeth M King
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Medicine, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Melanie Lee
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Vonnie Lee
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Oak Tree Clinic, BC Women's Hospital and Health Centre, Vancouver, British Columbia, Canada
| | - Evelyn J Maan
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Oak Tree Clinic, BC Women's Hospital and Health Centre, Vancouver, British Columbia, Canada
| | - Patience Magagula
- Afro-Caribbean Positive Network of BC, Vancouver, British Columbia, Canada
| | - Sheila Nyman
- Bear Rock Consulting, Lone Butte, British Columbia, Canada
| | - Davi Pang
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Neora Pick
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Division of Infectious Diseases, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Tetiana Povshedna
- Pathology and Laboratory Medicine, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Jerilynn C Prior
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Centre for Menstrual Cycle and Ovulatory Research, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Joel Singer
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Shelly Tognazzini
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Melanie C M Murray
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Division of Infectious Diseases, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Helene C F Cote
- British Columbia Women's Hospital and Health Centre Women's Health Research Institute, Vancouver, British Columbia, Canada
- Pathology and Laboratory Medicine, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
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Huang Q, Zhang F, Liu S, Jiang Y, Ouyang D. Systematic investigation of the pharmacological mechanism for renal protection by the leaves of Eucommia ulmoides Oliver using UPLC-Q-TOF/MS combined with network pharmacology analysis. Biomed Pharmacother 2021; 140:111735. [PMID: 34020251 DOI: 10.1016/j.biopha.2021.111735] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/07/2021] [Accepted: 05/11/2021] [Indexed: 11/17/2022] Open
Abstract
Bark is the traditional medicinal component of Eucommia ulmoides Oliver (E. ulmoides). However, the demand for E. ulmoides medicinal materials seriously limits their sustainability. To alleviate resource constraints, the bioactivity of E. ulmoides leaves and its pharmacodynamic basis were investigated. In the present study, extracts of E. ulmoides leaves were found to display potential renal protective properties in rat glomerular mesangial (HBZY-1) cells treated with high levels of glucose, suggesting that they possess potential factors capable of treating diabetic nephropathy. Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively characterize the chemical components of E. ulmoides leaves. A total of 83 possible chemical components, including 12 iridoids, 13 flavonoids, 14 lignans, 20 phenylpropanoids, 14 phenolic acids, and 10 additional components, were identified in E. ulmoides leaves. Network pharmacology was used for a preliminary exploration of the potential mechanism of action of renal protection afforded by E. ulmoides leaves towards diabetic nephropathy. The network pharmacology results were verified using a series of biological experiments. The present study provided the basis for the comprehensive development and utilization of E. ulmoides leaves and the discovery of potential drugs.
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Affiliation(s)
- Qi Huang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 411000, Hunan, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Fengyu Zhang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Shao Liu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
| | - Yueping Jiang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
| | - Dongsheng Ouyang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 411000, Hunan, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
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DiNicolantonio JJ, McCarty MF, Barroso-Aranda J, Assanga S, Lujan LML, O'Keefe JH. A nutraceutical strategy for downregulating TGFβ signalling: prospects for prevention of fibrotic disorders, including post-COVID-19 pulmonary fibrosis. Open Heart 2021; 8:openhrt-2021-001663. [PMID: 33879509 PMCID: PMC8061562 DOI: 10.1136/openhrt-2021-001663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/30/2021] [Indexed: 12/14/2022] Open
Affiliation(s)
- James J DiNicolantonio
- Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA
| | | | | | - Simon Assanga
- Department of Research and Postgraduate Studies in Food, University of Sonora, Sonora, Mexico
| | | | - James H O'Keefe
- University of Missouri-Kansas City, Saint Lukes Mid America Heart Institute, Kansas City, Missouri, USA
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