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Satta E, Strollo F, Borgia L, Guarino G, Romano C, Masarone M, Marfella R, Gentile S. Urinary L-FABP: A Novel Biomarker for Evaluating Diabetic Nephropathy Onset and Progression. A Narrative Review. Diabetes Ther 2025; 16:1107-1124. [PMID: 40178792 PMCID: PMC12085547 DOI: 10.1007/s13300-025-01731-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 03/17/2025] [Indexed: 04/05/2025] Open
Abstract
Patients with diabetes mellitus (DM) are at risk of developing diabetic nephropathy (DN), a condition whose onset and progression are linked to increased morbidity and mortality. Therefore, early recognition is crucial. Presently, this relies on the albumin excretion rate (AER) and glomerular filtration rate (GFR). Nevertheless, DN eventually affects patients with normal AER and GFR. Thus, further easy-to-handle biomarkers of DN onset/worsening are needed. Liver-type fatty acid-binding protein (L-FABP) has been associated with renal damage and could help predict/diagnose DN. We performed a literature selection to evaluate the performance of urinary excretion of such biomarker (urinary-L-FABP:uL-FABP) in predicting/diagnosing DN and its progression in diabetes. We evaluated 635 publications, 21 of which were included. Of these, 14 have cross-sectional design/arms and ten longitudinal design/arms. Cross-sectional studies showed uL-FABP to correlate with DN onset and severity in type-1 DM and type-2 DM, besides being higher than in healthy controls in the case of normoalbuminuria. Longitudinal studies showed baseline uL-FABP to predict DN onset in normoalbuminuric patients with T1DM and DN progression independently of diabetes type. The results suggest that uL-FABP is a marker of tubular damage detectable before increased albumin excretion and can represent the earliest sign of DN. Indeed, it discloses its onset and often predicts its severity in T2DM and patients with T1DM. Currently, uL-FABP can be routinely assessed and, being available as a point-of-care fast-test kit, may also become an easy-to-handle diagnostic tool for outpatients. In conclusion, uL-FABP represents a user-friendly biomarker of DN and can even predict DN progression in T2DM and T1DM over time.
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Affiliation(s)
- Ersilia Satta
- Nefrocenter Research Network, Cava de´ Tirreni, Italy
| | - Felice Strollo
- Department of Endocrinology and Diabetes, IRCCS San Raffaele Pisana, Rome, Italy
| | - Luisa Borgia
- Bioethics, DISVA, Department of Life and Environmental Sciences, Biological Sciences Faculty, Marche Polytechnic University, 22, Piazza Roma, 60121, Ancona, Italy
| | - Giuseppina Guarino
- Nefrocenter Research Network, Cava de´ Tirreni, Italy
- Department of Precision Medicine, Campania University "Luigi Vanvitelli", Naples, Italy
| | | | - Mario Masarone
- Department of Medicine, Surgery and Odontostomatology "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
| | - Raffaele Marfella
- Department of Precision Medicine, Campania University "Luigi Vanvitelli", Naples, Italy
| | - Sandro Gentile
- Nefrocenter Research Network, Cava de´ Tirreni, Italy
- Department of Precision Medicine, Campania University "Luigi Vanvitelli", Naples, Italy
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Soltani-Fard E, Taghvimi S, Karimi F, Vahedi F, Khatami SH, Behrooj H, Deylami Hayati M, Movahedpour A, Ghasemi H. Urinary biomarkers in diabetic nephropathy. Clin Chim Acta 2024; 561:119762. [PMID: 38844018 DOI: 10.1016/j.cca.2024.119762] [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: 04/18/2024] [Revised: 06/01/2024] [Accepted: 06/03/2024] [Indexed: 06/10/2024]
Abstract
Diabetic nephropathy (DN), a significant consequence of diabetes, is associated with adverse cardiovascular and renal disease as well as mortality. Although microalbuminuria is considered the best non-invasive marker for DN, better predictive markers are needed of sufficient sensitivity and specificity to detect disease in general and in early disease specifically. Even prior to appearance of microalbuminuria, urinary biomarkers increase in diabetics and can serve as accurate nephropathy biomarkers even in normoalbuminuria. In this review, a number of novel urine biomarkers including those reflecting kidney damage caused by glomerular/podocyte damage, tubular damage, oxidative stress, inflammation, and intrarenal renin-angiotensin system activation are discussed. Our review also includes emerging biomarkers such as urinary microRNAs. These short noncoding miRNAs regulate gene expression and could be utilized to identify potential novel biomarkers in DN development and progression. .
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Affiliation(s)
- Elahe Soltani-Fard
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Sina Taghvimi
- Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | | | - Farzaneh Vahedi
- Biomedical and Microbial Advanced Technologies Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | | | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran.
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Han YZ, Du BX, Zhu XY, Wang YZY, Zheng HJ, Liu WJ. Lipid metabolism disorder in diabetic kidney disease. Front Endocrinol (Lausanne) 2024; 15:1336402. [PMID: 38742197 PMCID: PMC11089115 DOI: 10.3389/fendo.2024.1336402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/09/2024] [Indexed: 05/16/2024] Open
Abstract
Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.
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Affiliation(s)
- Yi-Zhen Han
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Bo-Xuan Du
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xing-Yu Zhu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yang-Zhi-Yuan Wang
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Hui-Juan Zheng
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wei-Jing Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Takagi A, Kusunoki Y, Ohigashi M, Osugi K, Inoue C, Inoue M, Tsunoda T, Kadoya M, Konishi K, Katsuno T, Koyama H. Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study. Acta Diabetol 2024; 61:413-423. [PMID: 38006524 DOI: 10.1007/s00592-023-02214-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 11/08/2023] [Indexed: 11/27/2023]
Abstract
AIMS Glomerular damage and proximal tubular damage play an important role in the pathogenesis of diabetic kidney disease. This study aimed to investigate the relationship between the urinary markers of proximal tubular injury, including urinary liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABP/Cr) and urinary N-acetyl-β-D-glucosaminidase-to-creatinine ratio (uNAG/Cr), and glycemic control status. METHODS This cross-sectional study included 245 and 39 patients with type 2 diabetes mellitus (T2DM) and non-T2DM (NDM), respectively. The participants of this study were fitted with retrospective CGM, and glycemic control indices, such as time in range (TIR) and glycemia risk index (GRI), were calculated. RESULTS The results were presented as medians (interquartile ranges). The uL-FABP/Cr was significantly higher in the microalbuminuria than in the normo-albuminuria group [4.2 (2.7-7.1) and 2.2 (1.4-3.4) μg/gCr, respectively, P < 0.001], while the uNAG/Cr in the normo-albuminuria group [6.3 (4.5-10.1) U/gCr] was significantly higher than that in the NDM group [5.3 (3.8-6.3) U/gCr, P = 0.048] but significantly lower than that in the microalbuminuria group [9.2 (6.4-11.1) U/gCr, P = 0.004]. The multivariate logistic regression analysis indicated that CGM-derived TIR was significantly associated with the urinary albumin-to-creatinine ratio [uAlb/Cr, odds ratio (OR) 0.985, 95% confidence interval (CI) 0.971-0.998, P = 0.029] and uNAG/Cr (OR 0.973, 95% CI 0.957-0.989, P = 0.001) independent of renal function. GRI was similarly associated with uAlb/Cr and uNAG/Cr. CONCLUSION The findings of this study indicated that uNAG/Cr was elevated before albuminuria development and was associated with CGM-derived TIR and GRI.
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Affiliation(s)
- Ayako Takagi
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yoshiki Kusunoki
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Mana Ohigashi
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Keiko Osugi
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Chikako Inoue
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Maki Inoue
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Taku Tsunoda
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Manabu Kadoya
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Kosuke Konishi
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Tomoyuki Katsuno
- Department of Occupational Therapy, School of Rehabilitation, Hyogo Medical University, Nishinomiya, Hyogo, Japan
| | - Hidenori Koyama
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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Kongtasai T, Paepe D, Mortier F, Marynissen S, Meyer E, Duchateau L, Daminet S. Urinary liver-type fatty acid-binding protein in clinically healthy elderly cats: Evaluation of its potential to detect IRIS stage 1 chronic kidney disease and borderline proteinuria. Vet Med Sci 2022; 9:3-12. [PMID: 36418182 PMCID: PMC9856989 DOI: 10.1002/vms3.1003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Urinary liver-type fatty acid-binding protein (uL-FABP) is a promising biomarker to detect early chronic kidney disease (CKD) in cats. Few healthy cats show increased uL-FABP for unknown reasons. OBJECTIVES The objective of this study was to evaluate uL-FABP in a large healthy elderly cat population comparing cats with and without International Renal Interest Society (IRIS) stage 1 CKD and with and without borderline proteinuria. METHODS This was a cross-sectional study. One hundred ninety-six clinically healthy client-owned cats of ≥7 years old were subdivided based on two criteria: (1) having either IRIS stage 1 CKD or no evidence of CKD and (2) having borderline proteinuria or no proteinuria. Urinary L-FABP was measured using a validated commercially available feline L-FABP ELISA. RESULTS Overall, uL-FABP was detectable in 6/196 (3%) healthy elderly cats. For the first subdivision, nine (5%) cats had IRIS stage 1 CKD, 184 cats had no evidence CKD and three cats were excluded. All cats with IRIS stage 1 CKD had uL-FABP concentrations below the detection limit, whereas 6/184 (3%) cats without IRIS stage 1 CKD had detectable uL-FABP concentrations (median 1.79 ng/ml, range 0.79-3.66 ng/ml). For the second subdivision, 47 (24%) cats had borderline proteinuria, 147 cats had no proteinuria and two cats were excluded. One of the borderline proteinuric cats had a detectable uL-FABP concentration, whereas the other five cats with detectable uL-FABP concentrations were non-proteinuric. CONCLUSION With the current assay, the screening potential of uL-FABP as an early biomarker for feline CKD is limited as uL-FABP was rarely detected in clinically healthy elderly cats independently of the presence of either IRIS stage 1 CKD or borderline proteinuria.
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Affiliation(s)
- Thirawut Kongtasai
- Small Animal DepartmentFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium,Department of Clinical Sciences and Public HealthFaculty of Veterinary MedicineMahidol UniversityNakhon PathomThailand
| | - Dominique Paepe
- Small Animal DepartmentFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - Femke Mortier
- Small Animal DepartmentFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - Sofie Marynissen
- Small Animal DepartmentFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - Evelyne Meyer
- Department of PharmacologyToxicology and BiochemistryFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - Luc Duchateau
- Department of NutritionGenetics and EthologyFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
| | - Sylvie Daminet
- Small Animal DepartmentFaculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
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Zhang L, Xue S, Wu M, Dong D. Performance of urinary liver-type fatty acid-binding protein in diabetic nephropathy: A meta-analysis. Front Med (Lausanne) 2022; 9:914587. [PMID: 36117980 PMCID: PMC9479543 DOI: 10.3389/fmed.2022.914587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 08/09/2022] [Indexed: 12/02/2022] Open
Abstract
Aims Diabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage renal failure. Thus, early diagnostic markers for diabetic patients are urgently needed to improve the prognosis of DN and predict DN progression. Materials and methods PubMed, MEDLINE, EMBASE, and Scopus were searched for publications until February 24, 2021. Review Manager 5.4 software was used for meta-analysis. We performed the heterogeneity test using the I2 statistic: P < 0.1 and I2> 50% meant statistical significance. Results We included 13 studies. The urinary liver-type fatty acid-binding protein (uL-FABP) concentrations in the normal albuminuria group were significantly higher than those in the normal control group without diabetes mellitus (DM) [P = 0.009, SMD 1.72, 95% CI (0.44, 2.99)]. Urinary F-LABP levels were elevated in the macroalbuminuria group compared with those in the microalbuminuria group with DM [P = 0.002, SMD 2.82, 95% CI (1.03, 4.61)]. Urinary L-FABP levels were also significantly increased in the progression and CKD groups compared with non-progression and CKD subjects with DM [P = 0.02, P < 0.00001, respectively]. Furthermore, uL-FABP concentrations were positively correlated with the albumin-to-creatinine ratio and systolic blood pressure in patients with DM [Summary Fisher’s Z = 0.58 P < 0.00001; Summary Fisher’s Z = 0.24 P < 0.0001, respectively] and negatively correlated with estimated glomerular filtration rate in patients with DM [Summary Fisher’s Z = −0.36, P < 0.0001]. Conclusion Urinary L-FABP may be a potential marker for the detection of all stages of DN and for the prediction of the progression and severity of DN in patients with type 1 and 2 DM.
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Affiliation(s)
- Li Zhang
- Department of Nephrology, The First Hospital of Jilin University, Changchun, China
| | - Shuai Xue
- Thyroid Surgery Department, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Meiyan Wu
- Department of Nephrology, The First Hospital of Jilin University, Changchun, China
| | - Dan Dong
- Department of Nephrology, The First Hospital of Jilin University, Changchun, China
- *Correspondence: Dan Dong,
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Mitrofanova A, Burke G, Merscher S, Fornoni A. New insights into renal lipid dysmetabolism in diabetic kidney disease. World J Diabetes 2021; 12:524-540. [PMID: 33995842 PMCID: PMC8107981 DOI: 10.4239/wjd.v12.i5.524] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/31/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs, including the kidney. Research suggests that impaired cholesterol metabolism, increased lipid uptake or synthesis, increased fatty acid oxidation, lipid droplet accumulation and an imbalance in biologically active sphingolipids (such as ceramide, ceramide-1-phosphate and sphingosine-1-phosphate) contribute to the development of diabetic kidney disease (DKD). Currently, the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production, oxidative stress, inflammation, or cell death. Therefore, control of renal lipid dysmetabolism is a very important therapeutic goal, which needs to be archived. This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.
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Affiliation(s)
- Alla Mitrofanova
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
- Department of Surgery, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
| | - George Burke
- Department of Surgery, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
- Diabetes Research Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
| | - Sandra Merscher
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
| | - Alessia Fornoni
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
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Kongtasai T, Meyer E, Paepe D, Marynissen S, Smets P, Mortier F, Demeyere K, Vandermeulen E, Stock E, Buresova E, Defauw P, Duchateau L, Daminet S. Liver-type fatty acid-binding protein and neutrophil gelatinase-associated lipocalin in cats with chronic kidney disease and hyperthyroidism. J Vet Intern Med 2021; 35:1376-1388. [PMID: 33723886 PMCID: PMC8162613 DOI: 10.1111/jvim.16074] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 01/28/2021] [Accepted: 02/04/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats. OBJECTIVE To evaluate urinary and serum L-FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine (131 I) treatment. ANIMALS Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) 131 I treatment. METHODS Cross-sectional and longitudinal study. Serum L-FABP (sL-FABP), serum NGAL (sNGAL), urinary L-FABP (uL-FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min-max). RESULTS CKD cats had significantly higher sL-FABP (13.50 [3.40-75.60] ng/ml) and uL-FABP/Cr (4.90 [0.97-2139.44] µg/g) than healthy cats (4.25 [1.34-23.25] ng/ml; P = .01 and 0.46 [0.18-9.13] µg/g; P < .001, respectively). Hyperthyroid cats at T0 had significantly higher uL-FABP/Cr (0.94 [0.15-896.00] µg/g) than healthy cats (P < .001), thereafter uL-FABP/Cr significantly decreased at T2 (0.54 [0.10-76.41] µg/g, P = .002). For the detection of CKD, uL-FABP/Cr had 100% (95% confidence interval [CI], 66.4-100.0) sensitivity and 93.2% (95% CI, 81.3-98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups. CONCLUSIONS AND CLINICAL IMPORTANCE L-FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL-FABP to predict azotemia after treatment in hyperthyroid cats remains unknown.
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Affiliation(s)
| | - Evelyne Meyer
- Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Dominique Paepe
- Small Animal Department, Ghent University, Merelbeke, Belgium
| | | | - Pascale Smets
- Small Animal Department, Ghent University, Merelbeke, Belgium
| | - Femke Mortier
- Small Animal Department, Ghent University, Merelbeke, Belgium
| | - Kristel Demeyere
- Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Eva Vandermeulen
- Department of Medical Imaging of Domestic Animals, Ghent University, Merelbeke, Belgium
| | - Emmelie Stock
- Department of Medical Imaging of Domestic Animals, Ghent University, Merelbeke, Belgium
| | - Eva Buresova
- Davies Veterinary Specialists, Higham Gobion, United Kingdom
| | - Pieter Defauw
- Lumbry Park Veterinary Specialists, Alton, United Kingdom
| | - Luc Duchateau
- Biometrics Research Group, Ghent University, Merelbeke, Belgium
| | - Sylvie Daminet
- Small Animal Department, Ghent University, Merelbeke, Belgium
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McLeod DJ, Sebastião YV, Ching CB, Greenberg JH, Furth SL, Becknell B. Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy. Pediatr Nephrol 2020; 35:1907-1914. [PMID: 32444926 PMCID: PMC7502482 DOI: 10.1007/s00467-020-04602-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/01/2020] [Accepted: 05/05/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. METHODS Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. RESULTS In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). CONCLUSIONS In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.
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Affiliation(s)
- Daryl J McLeod
- Section of Urology, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
- Center for Surgical Outcomes Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
| | - Yuri V Sebastião
- Center for Surgical Outcomes Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Christina B Ching
- Section of Urology, Nationwide Children's Hospital, Columbus, OH, 43205, USA
- Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Jason H Greenberg
- Department of Pediatrics, Section of Nephrology, Yale University School of Medicine, New Haven, CT, 06510, USA
| | - Susan L Furth
- Department of Pediatrics, Division of Nephrology, Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA
| | - Brian Becknell
- Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA
- Department of Pediatrics, Section of Nephrology, Nationwide Children's Hospital, Columbus, OH, 43205, USA
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Hikasa S, Shimabukuro S, Hideta K, Higasa S, Sawada A, Tokugawa T, Tanaka K, Yanai M, Kimura T. Utility of urinary liver-type fatty acid-binding protein as a predictor of renal dysfunction in Japanese patients with HIV receiving tenofovir disoproxil fumarate with low urinary β2 microglobulin levels: a retrospective observational study. J Pharm Health Care Sci 2019; 5:12. [PMID: 31183158 PMCID: PMC6551878 DOI: 10.1186/s40780-019-0140-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 05/07/2019] [Indexed: 11/23/2022] Open
Abstract
Background Tenofovir disoproxil fumarate (TDF) is known to reduce estimated glomerular filtration rate (eGFR). It is clinically important to identify patients at high risk for renal dysfunction as early as possible. Among the tubular markers, urinary β2 microglobulin (Uβ2MG) is a well-known biomarker of TDF-related tubulopathy. However, renal dysfunction has often been occurred in patients receiving TDF with low Uβ2MG levels. Recently, urinary liver-type fatty acid–binding protein (UL-FABP) was suggested to be predictor of the progression of renal dysfunction. Thus, we focused on UL-FABP in patients receiving TDF with low Uβ2MG levels. Methods A retrospective, observational, single-center study, between January 2013 and December 2016, was conducted. Two renal end points (> 25% decrement in eGFR and > 20 mL/min/1.73 m2 decrement relative to the baseline) were assessed. To estimate the effect of UL-FABP on time to the first event, log-rank test was performed. Results A total of 24 Japanese outpatients with human immunodeficiency virus receiving TDF were enrolled. The outcome each occurred in two patients during the follow-up period. UL-FABP levels ≥4.0 μg/g creatinine was significantly associated with > 25% decrement and > 20 mL/min/1.73 m2 decrement (p = 0.006 and 0.001, respectively). Conclusion Based on our preliminary analysis, UL-FABP levels ≥4.0 μg/g creatinine predict renal dysfunction in patients receiving TDF with low Uβ2MG levels.
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Affiliation(s)
- Shinichi Hikasa
- 1Department of pharmacy, The Hospital of Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Shota Shimabukuro
- 1Department of pharmacy, The Hospital of Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Kyoko Hideta
- 1Department of pharmacy, The Hospital of Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Satoshi Higasa
- 2Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Akihiro Sawada
- 2Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Tazuko Tokugawa
- 2Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Kuniyoshi Tanaka
- 1Department of pharmacy, The Hospital of Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Mina Yanai
- 1Department of pharmacy, The Hospital of Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
| | - Takeshi Kimura
- 1Department of pharmacy, The Hospital of Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan
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11
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Abstract
Diabetic kidney disease (DKD) remains one of the leading causes of reduced lifespan in diabetes. The quest for both prognostic and surrogate endpoint biomarkers for advanced DKD and end-stage renal disease has received major investment and interest in recent years. However, at present no novel biomarkers are in routine use in the clinic or in trials. This review focuses on the current status of prognostic biomarkers. First, we emphasise that albuminuria and eGFR, with other routine clinical data, show at least modest prediction of future renal status if properly used. Indeed, a major limitation of many current biomarker studies is that they do not properly evaluate the marginal increase in prediction on top of these routinely available clinical data. Second, we emphasise that many of the candidate biomarkers for which there are numerous sporadic reports in the literature are tightly correlated with each other. Despite this, few studies have attempted to evaluate a wide range of biomarkers simultaneously to define the most useful among these correlated biomarkers. We also review the potential of high-dimensional panels of lipids, metabolites and proteins to advance the field, and point to some of the analytical and post-analytical challenges of taking initial studies using these and candidate approaches through to actual clinical biomarker use.
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Affiliation(s)
- Helen M Colhoun
- MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
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12
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Siddiqui K, Joy SS, Ilias S, Alzeer HS, Al-Rubeaan K. Urinary biomarkers reporting weakness and validation failure in Type 2 diabetic nephropathy: systematic review. Biomark Med 2018; 12:487-499. [PMID: 29697277 DOI: 10.2217/bmm-2017-0338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
For better identification of novel diagnostic urinary biomarker in Type 2 diabetic nephropathy (T2DN), methodological and reporting quality is as important as validity of biomarkers. The aim of this systematic review is to find out the best-reported diagnostic urinary biomarkers study in T2DN based on STARD criteria. We also analyzed the validity of urinary markers in the selected articles those followed STARD criteria. The diagnostic accuracy of urinary biomarkers on T2DN is not conclusive because of the poor reporting quality and differences in adjustment for conventional risk factors. For a proper validation of urinary biomarkers on T2DN, in future large well-designed longitudinal studies, with specific prediction analysis and validation of the biomarkers by adjusting with possible conventional risk factors.
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Affiliation(s)
- Khalid Siddiqui
- Department of Biochemistry, Strategic Center for Diabetes Research, King Saud University, Riyadh, Saudi Arabia
| | - Salini S Joy
- Department of Biochemistry, Strategic Center for Diabetes Research, King Saud University, Riyadh, Saudi Arabia
| | - Shumaila Ilias
- Department of Biochemistry, Strategic Center for Diabetes Research, King Saud University, Riyadh, Saudi Arabia
| | - Haya S Alzeer
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Khalid Al-Rubeaan
- Department of Biochemistry, Strategic Center for Diabetes Research, King Saud University, Riyadh, Saudi Arabia.,University Diabetes Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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13
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Papadopoulou-Marketou N, Kanaka-Gantenbein C, Marketos N, Chrousos GP, Papassotiriou I. Biomarkers of diabetic nephropathy: A 2017 update. Crit Rev Clin Lab Sci 2017; 54:326-342. [DOI: 10.1080/10408363.2017.1377682] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Nektaria Papadopoulou-Marketou
- Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece
- Department of Endocrinology, Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden
| | - Christina Kanaka-Gantenbein
- Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece
| | | | - George P. Chrousos
- Diabetes Centre of the Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece
| | - Ioannis Papassotiriou
- Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens, Greece
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14
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Ilyas Z, Chaiban JT, Krikorian A. Novel insights into the pathophysiology and clinical aspects of diabetic nephropathy. Rev Endocr Metab Disord 2017; 18:21-28. [PMID: 28289965 DOI: 10.1007/s11154-017-9422-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Diabetic nephropathy (DN) is a well-described complication of diabetes mellitus and the leading cause of end stage renal disease (ESRD). Although increased albuminuria has been the gold standard for screening, data suggests that renal damage starts long before the onset of clinically apparent increases in macro and even micro-albuminuria. Clinical practice guidelines for the prevention of DN have been traditionally focused on the control of serum glucose, blood pressure and dyslipidemia, with some focus on the renin-angiotensin-aldosterone system (RAAS) as a main target for successful therapy. Recent evidence has led to a better understanding of the underlying mechanisms of the pathophysiology of this disease and suggests that various novels pathways can be targeted to delay and even prevent the progression of DN. Hence a more comprehensive therapeutic approach to therapy is on the horizon, carrying the promise for a more successful and impactful management. This review will highlight new insights into the pathophysiology, clinical aspects and future diagnostic and therapeutic modalities for DN.
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Affiliation(s)
- Zubair Ilyas
- Department of Internal Medicine, University of Illinois at Chicago, Advocate Christ Medical Center, Chicago, IL, USA
| | - Joumana T Chaiban
- Department of Internal Medicine, University of Illinois at Chicago, Advocate Christ Medical Center, Chicago, IL, USA
- Division of Endocrinology, Advocate Christ Medical Center, Chicago, IL, USA
| | - Armand Krikorian
- Department of Internal Medicine, University of Illinois at Chicago, Advocate Christ Medical Center, Chicago, IL, USA.
- Division of Endocrinology, Advocate Christ Medical Center, Chicago, IL, USA.
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15
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Urinary Markers of Tubular Injury in Early Diabetic Nephropathy. Int J Nephrol 2016; 2016:4647685. [PMID: 27293888 PMCID: PMC4884862 DOI: 10.1155/2016/4647685] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 04/26/2016] [Indexed: 01/08/2023] Open
Abstract
Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN.
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16
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Gluhovschi C, Gluhovschi G, Petrica L, Timar R, Velciov S, Ionita I, Kaycsa A, Timar B. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy. J Diabetes Res 2016; 2016:4626125. [PMID: 27413755 PMCID: PMC4927990 DOI: 10.1155/2016/4626125] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 05/12/2016] [Indexed: 12/12/2022] Open
Abstract
Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition-mainly cardiovascular ones-and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new "gold standard" biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.
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Affiliation(s)
- Cristina Gluhovschi
- Division of Nephrology, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
- *Cristina Gluhovschi:
| | | | - Ligia Petrica
- Division of Nephrology, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
| | - Romulus Timar
- Department of Diabetes and Metabolic Diseases, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
| | - Silvia Velciov
- Division of Nephrology, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
| | - Ioana Ionita
- Division of Hematology, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
| | - Adriana Kaycsa
- Department of Biochemistry, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
| | - Bogdan Timar
- Department of Diabetes and Metabolic Diseases, University of Medicine and Pharmacy “V. Babes”, 300041 Timisoara, Romania
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17
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Kamijo-Ikemori A, Kimura K. Urinary liver-type fatty acid binding protein and chronic kidney disease. Indian J Nephrol 2015; 25:263-4. [PMID: 26628789 PMCID: PMC4588319 DOI: 10.4103/0971-4065.150726] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Affiliation(s)
- A Kamijo-Ikemori
- Department of Internal Medicine, Division of Nephrology and Hypertension, Tokyo, Japan ; Department of Anatomy, Division of Nephrology and Hypertension, St. Marianna University School of Medicine, Kanagawa, Japan
| | - K Kimura
- Department of Internal Medicine, Tokyo Takanawa Hospital, Tokyo, Japan
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18
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Fiseha T. Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients. Biomark Res 2015; 3:16. [PMID: 26146561 PMCID: PMC4491239 DOI: 10.1186/s40364-015-0042-3] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Accepted: 06/26/2015] [Indexed: 02/06/2023] Open
Abstract
Diabetic nephropathy (DN) is a serious complication of diabetes associated with increased risk of mortality, and cardiovascular and renal outcomes. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney function and improve patient outcomes. Urinary biomarkers may be elevated in diabetic patients even before the appearance of microalbuminuria, and can be used as useful marker for detecting nephropathy in patients with normoalbuminuria (early DN). We reviewed some new and important urinary biomarkers, such as: Neutrophil gelatinase associated lipocalin (NGAL), N-acetyl-beta-glucosaminidase (NAG), Cystatin C, alpha 1-microglobulin, immunoglobulin G or M, type IV collagen, nephrin, angiotensinogen and liver-type fatty acid–binding protein (L-FABP) associated with early DN in type 2 diabetic patients. Our search identified a total of 42 studies that have been published to date. Urinary levels of these biomarkers were elevated in type 2 diabetic patients compared with non-diabetic controls, including in patients who had no signs indicating nephropathy (without microalbuminuria), and showed positive correlation with albuminuria. Despite the promise of these new urinary biomarkers, further large, multicenter prospective studies are still needed to confirm their clinical utility as a screening tool for early type 2 DN in every day practice.
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Affiliation(s)
- Temesgen Fiseha
- Department of Clinical Laboratory Science, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
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