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Feng X, Zhou R, Jiang Q, Wang Y, Yu C. Analysis of cadmium accumulation in community adults and its correlation with low-grade albuminuria. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 834:155210. [PMID: 35421478 DOI: 10.1016/j.scitotenv.2022.155210] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 12/30/2021] [Accepted: 04/08/2022] [Indexed: 05/22/2023]
Abstract
OBJECTIVE To investigate the effects of chronic non-occupational exposure to cadmium (Cd) on renal injury in residents living in the urban areas of China. METHODS In this cross-sectional study, we recruited 1000 participants in Shanghai from August 2015 to August 2017 and collected data on their socio-demographic characteristics, lifetime occupation, and lifestyle factors. The urinary Cd, urinary albumin, urinary creatinine, serum creatinine, urea, and uric acid levels were tested, and 683 participants completed those measurements. RESULTS The median urinary Cd concentration of this study population was 0.77 μg/g. The urinary Cd concentration was significantly higher in the female, older, and lower body mass index populations. There were 148 participants with dominant albuminuria who had higher urinary Cd levels than those without dominant albuminuria (0.98 vs. 0.72 μg/g; P < 0.001). Among participants without dominant albuminuria, there were 134 participants with low-grade albuminuria (13.84 ≤ ACR < 30 mg/g) and 401 participants who had normal urinary albumin excretion (ACR < 13.84 mg/g). Compared with those who had normal urinary albumin excretion, those with low-grade albuminuria had significantly higher urinary Cd levels (0.83 vs. 0.69 μg/g; P < 0.001). Among those without dominant albuminuria, participants in the highest quartile of urinary Cd were more likely to have low-grade albuminuria than those in the lowest quartile (Odd's ratio = 2.98; P < 0.001). Further adjustment for age, sex, and BMI or other potential confounding factors did not change the magnitudes of the associations. Moreover, we conducted multivariable stepwise linear regression analysis within 134 low-grade albuminuria participants and demonstrated that urinary Cd concentration (P < 0.001) were independent determinants of urine albumin after adjusting for relevant confounders. CONCLUSION The urinary Cd levels observed in Chinese urban adults are substantial and associated with an increased risk of low-grade albuminuria. Our findings suggest that potential sources of environmental Cd exposure should be explored, and the associated renal toxicity should be studied in more detail in future.
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Affiliation(s)
- Xuefang Feng
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.
| | - Rong Zhou
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China
| | - Qian Jiang
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China
| | - Yanan Wang
- Department of Nephrology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China
| | - Chen Yu
- Department of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.
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2
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Mottola C, Girerd N, Duarte K, Aarnink A, Giral M, Dantal J, Garrigue V, Mourad G, Buron F, Morelon E, Ladrière M, Kessler M, Frimat L, Girerd S. Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation. Clin Kidney J 2020; 13:791-802. [PMID: 33125000 PMCID: PMC7577768 DOI: 10.1093/ckj/sfaa044] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 03/10/2020] [Indexed: 12/22/2022] Open
Abstract
Background The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT. Methods The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFRMDRD) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients. Results Both 3-month eGFRMDRD and proteinuria were independent predictors of return to dialysis (all P < 0.05) and there was a strong correlation between eGFR at 3 and 12 months (Spearman’s ρ = 0.76). The predictive accuracy of the 3-month eGFR was within a similar range and did not differ significantly from the 12-month eGFR in either the derivation cohort [C-index 62.6 (range 57.2–68.1) versus 66.0 (range 60.1–71.9), P = 0.41] or the validation cohort [C-index 69.3 (range 66.4–72.1) versus 71.7 (range 68.7–74.6), P = 0.25]. Conclusion The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.
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Affiliation(s)
- Clément Mottola
- Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
| | - Nicolas Girerd
- INSERM U1116, Clinical Investigation Centre, Lorraine University, Vandoeuvre-lès-Nancy, France.,Cardiovascular and Renal Clinical Trialists (INI-CRCT) F-CRIN Network, Nancy, France
| | - Kevin Duarte
- INSERM U1116, Clinical Investigation Centre, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Alice Aarnink
- Department of Immunology and Histocompatibility, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
| | - Magali Giral
- CRTI UMR 1064, Inserm, Nantes University, Nantes, France.,ITUN, Nantes University Hospital, RTRS Centaure, Nantes, France
| | - Jacques Dantal
- CRTI UMR 1064, Inserm, Nantes University, Nantes, France.,ITUN, Nantes University Hospital, RTRS Centaure, Nantes, France
| | - Valérie Garrigue
- Department of Nephrology and Kidney Transplantation, Montpellier University Hospital, Montpellier, France
| | - Georges Mourad
- Department of Nephrology and Kidney Transplantation, Montpellier University Hospital, Montpellier, France
| | - Fanny Buron
- Department of Nephrology and Kidney Transplantation, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Emmanuel Morelon
- Department of Nephrology and Kidney Transplantation, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Marc Ladrière
- Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
| | - Michèle Kessler
- Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
| | - Luc Frimat
- Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France.,Cardiovascular and Renal Clinical Trialists (INI-CRCT) F-CRIN Network, Nancy, France
| | - Sophie Girerd
- Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France.,INSERM U1116, Clinical Investigation Centre, Lorraine University, Vandoeuvre-lès-Nancy, France.,Cardiovascular and Renal Clinical Trialists (INI-CRCT) F-CRIN Network, Nancy, France
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3
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Hernández D, Alonso-Titos J, Armas-Padrón AM, Lopez V, Cabello M, Sola E, Fuentes L, Gutierrez E, Vazquez T, Jimenez T, Ruiz-Esteban P, Gonzalez-Molina M. Waiting List and Kidney Transplant Vascular Risk: An Ongoing Unmet Concern. Kidney Blood Press Res 2019; 45:1-27. [PMID: 31801144 DOI: 10.1159/000504546] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 11/01/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is an important independent risk factor for adverse cardiovascular events in patients waitlisted for kidney transplantation (KT). Although KT reduces cardiovascular risk, these patients still have a higher all-cause and cardiovascular mortality than the general population. This concerning situation is due to a high burden of traditional and nontraditional risk factors as well as uremia-related factors and transplant-specific factors, leading to 2 differentiated processes under the framework of CKD, atherosclerosis and arteriosclerosis. These can be initiated by insults to the vascular endothelial endothelium, leading to vascular calcification (VC) of the tunica media or the tunica intima, which may coexist. Several pathogenic mechanisms such as inflammation-related endothelial dysfunction, mineral metabolism disorders, activation of the renin-angiotensin system, reduction of nitric oxide, lipid disorders, and the fibroblast growth factor 23-klotho axis are involved in the pathogenesis of atherosclerosis and arteriosclerosis, including VC. SUMMARY This review focuses on the current understanding of atherosclerosis and arteriosclerosis, both in patients on the waiting list as well as in kidney transplant recipients, emphasizing the cardiovascular risk factors in both populations and the inflammation-related pathogenic mechanisms. Key Message: The importance of cardiovascular risk factors and the pathogenic mechanisms related to inflammation in patients waitlisted for KT and kidney transplant recipients.
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Affiliation(s)
- Domingo Hernández
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain,
| | - Juana Alonso-Titos
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | | | - Veronica Lopez
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Mercedes Cabello
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Eugenia Sola
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Laura Fuentes
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Elena Gutierrez
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Teresa Vazquez
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Tamara Jimenez
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Pedro Ruiz-Esteban
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Miguel Gonzalez-Molina
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
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4
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Paoletti E, Citterio F, Corsini A, Potena L, Rigotti P, Sandrini S, Bussalino E, Stallone G. Everolimus in kidney transplant recipients at high cardiovascular risk: a narrative review. J Nephrol 2019; 33:69-82. [DOI: 10.1007/s40620-019-00609-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 04/05/2019] [Indexed: 12/20/2022]
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Girerd S, Frimat L, Ducloux D, Le Meur Y, Mariat C, Moulin B, Mousson C, Rieu P, Dali-Youcef N, Merckle L, Lepage X, Rossignol P, Girerd N, Jaisser F. EPURE Transplant (Eplerenone in Patients Undergoing Renal Transplant) study: study protocol for a randomized controlled trial. Trials 2018; 19:595. [PMID: 30376884 PMCID: PMC6208100 DOI: 10.1186/s13063-018-2956-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 10/01/2018] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Despite advances in immunosuppressive therapy, kidney graft survival has failed to improve during the last decades. Ischemia/reperfusion injury (IRI) is one of the main pathophysiological mechanisms underlying delayed graft function, which is associated with poor long-term graft survival. Due to organ shortage, the proportion of grafts from expanded criteria donors (ECDs) is ever growing. These grafts may particularly benefit from IRI prevention. In preclinical models, mineralocorticoid receptor antagonists (MRAs) have been shown to efficiently prevent IRI. This study aims to assess the effect of MRA administration in the early phase of kidney transplantation (KT) among recipients of ECD grafts on mid-term graft function. METHODS/DESIGN This is a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients on hemodialysis and undergoing a single or a dual KT from an ECD will be eligible for inclusion. We plan to randomize 132 patients. Included patients will be randomized (1:1) to receive either eplerenone 25 mg every 12 h during 4 days (the first dose being administered just prior to KT) or placebo. The primary outcome is graft function at 3 months, assessed by glomerular filtration rate (GFR, in mL/min/1.73m2) measured using iohexol clearance. Secondary outcomes include (1) proportion of patients with either dialysis dependency or a GFR < 30 mL/min/1.73m2 at 3 months, (2) proportion of patients with immediate, slow, or delayed graft function, (3) proteinuria at 3 months, (4) occurrence of hyperkalemia during the first week following KT, (5) length of hospital stay for the KT, and (6) occurrence of biopsy-proven acute rejection in the first 3 months following KT. Estimated GFR, graft, and patient survival will also be collected at 1, 3, and 10 years via the national database of organ recipients. DISCUSSION Improvement of ECD grafts is a public health priority, since better ECD outcomes could eventually limit organ shortage. MRA administration in the early phase of KT may prevent IRI and subsequently improve mid-term graft function. The trial will also assess the safety of MRA administration in this population, primarily the absence of threatening hyperkalemia. TRIAL REGISTRATION ClinicalTrials.gov, NCT02490904 . Registered on 1 July 2015.
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Affiliation(s)
- Sophie Girerd
- Transplant Unit, Nephrology Department, Nancy University Hospital, Lorraine University, Vandoeuvre-lès-Nancy, France. .,INSERM U1116, Clinical Investigation Center, Lorraine University, Vandoeuvre-lès-Nancy, France. .,INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France.
| | - Luc Frimat
- Transplant Unit, Nephrology Department, Nancy University Hospital, Lorraine University, Vandoeuvre-lès-Nancy, France.,INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France
| | - Didier Ducloux
- INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France.,Transplant Unit, Nephrology Department, Besançon University Hospital, Bourgogne Franche-Comté University, Besançon, France
| | - Yannick Le Meur
- Department of Nephrology, Brest University Hospital, Brest University, Brest, France
| | - Christophe Mariat
- Transplant Unit, Nephrology Department, Saint-Etienne University Hospital, Jean Monnet University, Saint-Etienne, France
| | - Bruno Moulin
- INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France.,Nephrology and Transplantation Department, Strasbourg University Hospital, Strasbourg University, Strasbourg, France
| | - Christiane Mousson
- Transplant Unit, Nephrology Department, Dijon University Hospital, Bourgogne Franche-Comté University, Dijon, France
| | - Philippe Rieu
- INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France.,Transplant Unit, Nephrology Department, Reims University Hospital, Reims Champagne-Ardenne University, Reims, France
| | - Nassim Dali-Youcef
- Department of Biochemistry and Molecular Biology, Strasbourg University Hospital, Strasbourg University, Strasbourg, France.,Department of functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/ CNRS UMR 7104/ INSERM U 964/ Strasbourg University, 1 rue Laurent Fries, 67404, Illkirch, France
| | - Ludovic Merckle
- INSERM U1116, Clinical Investigation Center, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Xavier Lepage
- INSERM U1116, Clinical Investigation Center, Lorraine University, Vandoeuvre-lès-Nancy, France
| | - Patrick Rossignol
- INSERM U1116, Clinical Investigation Center, Lorraine University, Vandoeuvre-lès-Nancy, France.,INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France
| | - Nicolas Girerd
- INSERM U1116, Clinical Investigation Center, Lorraine University, Vandoeuvre-lès-Nancy, France.,INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France
| | - Frédéric Jaisser
- INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN network, Nancy, France.,INSERM, UMRS 1138, Team 1, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes University, Paris, France
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6
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Lam NN, Klarenbach S, Quinn RR, Hemmelgarn B, Tonelli M, Ye F, Ravani P, Bello AK, Brennan DC, Lentine KL. Renal Function, Albuminuria, and the Risk of Cardiovascular Events After Kidney Transplantation. Transplant Direct 2018; 4:e389. [PMID: 30498766 PMCID: PMC6233669 DOI: 10.1097/txd.0000000000000828] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Accepted: 07/18/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The risk of mortality and graft loss is higher in kidney transplant recipients with reduced estimated glomerular filtration rate (eGFR) and albuminuria. It is unclear whether these markers are also associated with cardiovascular events. METHODS We examined linked healthcare databases in Alberta, Canada to identify kidney transplant recipients between 2002 and 2013 who had at least 1 outpatient serum creatinine and albuminuria measurement at 1-year posttransplant. We determined the relationship between categories of eGFR and albuminuria and the risk of subsequent cardiovascular events. RESULTS Among 1069 eligible kidney transplant recipients, the median age was 52 years, 37% were female, and 52% had eGFR ≥60 mL/min per 1.73 m2. Over a median follow-up of 6 years, the adjusted rate of all-cause mortality and cardiovascular events was 2.7-fold higher for recipients with eGFR 15-29 mL/min per 1.73 m2 and heavy albuminuria compared to recipients with eGFR ≥60 mL/min per 1.73 m2 and normal albuminuria (rate ratio, 2.7; 95% confidence interval, 1.3-5.7). Similarly, recipients with heavy albuminuria had a threefold increased risk of all-cause mortality and heart failure compared with recipients with eGFR ≥60 mL/min per 1.73 m2 and normal albuminuria. CONCLUSIONS These findings suggest that eGFR and albuminuria should be used together to determine the risk of cardiovascular outcomes in transplant recipients.
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Affiliation(s)
- Ngan N. Lam
- Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Scott Klarenbach
- Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Robert R. Quinn
- Division of Nephrology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Brenda Hemmelgarn
- Division of Nephrology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Marcello Tonelli
- Division of Nephrology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Feng Ye
- Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Pietro Ravani
- Division of Nephrology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Aminu K. Bello
- Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Daniel C. Brennan
- Center for Transplantation, Johns Hopkins School of Medicine, Baltimore, MD
| | - Krista L. Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO
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7
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Hernández D, Muriel A, Castro de la Nuez P, Alonso-Titos J, Ruiz-Esteban P, Duarte A, Gonzalez-Molina M, Palma E, Alonso M, Torres A. Survival in Southern European patients waitlisted for kidney transplant after graft failure: A competing risk analysis. PLoS One 2018. [PMID: 29513701 PMCID: PMC5841738 DOI: 10.1371/journal.pone.0193091] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Background Whether patients waitlisted for a second transplant after failure of a previous kidney graft have higher mortality than transplant-näive waitlisted patients is uncertain. Methods We assessed the relationship between a failed transplant and mortality in 3851 adult KT candidates, listed between 1984–2012, using a competing risk analysis in the total population and in a propensity score-matched cohort. Mortality was also modeled by inverse probability weighting (IPTW) competing risk regression. Results At waitlist entry 225 (5.8%) patients had experienced transplant failure. All-cause mortality was higher in the post-graft failure group (16% vs. 11%; P = 0.033). Most deaths occurred within three years after listing. Cardiovascular disease was the leading cause of death (25.3%), followed by infections (19.3%). Multivariate competing risk regression showed that prior transplant failure was associated with a 1.5-fold increased risk of mortality (95% confidence interval [CI], 1.01–2.2). After propensity score matching (1:5), the competing risk regression model revealed a subhazard ratio (SHR) of 1.6 (95% CI, 1.01–2.5). A similar mortality risk was observed after the IPTW analysis (SHR, 1.7; 95% CI, 1.1–2.6). Conclusions Previous transplant failure is associated with increased mortality among KT candidates after relisting. This information is important in daily clinical practice when assessing relisted patients for a retransplant.
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Affiliation(s)
- Domingo Hernández
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
- * E-mail:
| | - Alfonso Muriel
- Clinic Biostatistic Unit, Hospital Ramón y Cajal IRYCIS, CIBERESP, Universidad Autónoma, Madrid, Spain
| | | | - Juana Alonso-Titos
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Pedro Ruiz-Esteban
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Ana Duarte
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Miguel Gonzalez-Molina
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Eulalia Palma
- Nephrology Department, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain
| | - Manuel Alonso
- Transplant Coordination Center and Andalusian Health Service, Seville, Spain
| | - Armando Torres
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, REDinREN (RD16/0009/0031) and Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
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8
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Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link. Am J Med Sci 2017; 354:7-16. [DOI: 10.1016/j.amjms.2017.01.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 12/20/2016] [Accepted: 01/09/2017] [Indexed: 12/31/2022]
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9
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Lam NN, Tonelli M, Lentine KL, Hemmelgarn B, Ye F, Wen K, Klarenbach S. Albuminuria and posttransplant chronic kidney disease stage predict transplant outcomes. Kidney Int 2017; 92:470-478. [PMID: 28366228 DOI: 10.1016/j.kint.2017.01.028] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 12/22/2016] [Accepted: 01/19/2017] [Indexed: 02/01/2023]
Abstract
In 2012, the KDIGO guidelines updated the classification system for chronic kidney disease to include albuminuria. Whether this classification system predicts adverse clinical outcomes among kidney transplant recipients is unclear. To evaluate this, we conducted a retrospective study using linked databases in Alberta, Canada to follow kidney transplant recipients from 2002-2011. We examined the association between an estimated glomerular filtration rate (eGFR of 60 or more, 45-59, 30-44, 15-29 mL/min/1.73 m2) and albuminuria (normal, mild, heavy) at one year post-transplant and subsequent mortality and graft loss. There were 900 recipients with a functioning graft and at least one outpatient serum creatinine and urine protein measurement at one year post-transplant. The median age was 51.2 years, 38.7% were female, and 52% had an eGFR of 60 mL/min/1.73 m2 or more. The risk of all-cause mortality and death-censored graft loss was increased in recipients with reduced eGFR or heavier albuminuria. The adjusted incidence rate per 1000 person-years of all-cause mortality for recipients with an eGFR of 15-29 mL/min/1.73 m2 and heavy albuminuria vs. an eGFR 60 mL/min/1.73 m2 or more and normal protein excretion was 117 (95% confidence interval 38-371) vs. 15 (9-23) (rate ratio 8). Corresponding rates for death-censored graft loss were 273 (88-1203) vs. 6 (3-9) (rate ratio 49). Reduced eGFR and heavier albuminuria in kidney transplant recipients are associated with an increased risk of mortality and graft loss. Thus, eGFR and albuminuria may be used together to identify, evaluate, and manage transplant recipients who are at higher risk of adverse clinical outcomes.
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Affiliation(s)
- Ngan N Lam
- Department of Medicine, Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada.
| | - Marcello Tonelli
- Department of Medicine, Division of Nephrology, University of Calgary, Calgary, Alberta, Canada
| | - Krista L Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, Missouri, USA
| | - Brenda Hemmelgarn
- Department of Medicine, Division of Nephrology, University of Calgary, Calgary, Alberta, Canada
| | - Feng Ye
- Department of Medicine, Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada
| | - Kevin Wen
- Department of Medicine, Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada
| | - Scott Klarenbach
- Department of Medicine, Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada
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10
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Abstract
Solid organ transplantation is an effective treatment for patients with end-stage organ disease. The prevalence of cardiovascular diseases (CVD) has increased in recipients. CVD remains a leading cause of mortality among recipients with functioning grafts. The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors, metabolic sequelae of immunosuppressive agents, infection, and rejection. Risk modification must be weighed against the risk of mortality owing to rejection or infection. Aggressive risk stratification and modification before and after transplantation and tailoring immunosuppressive regimens are essential to prevent complications and improve short-term and long-term mortality and graft survival.
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Affiliation(s)
- Mrudula R Munagala
- Department of Cardiology, Newark Beth Israel Medical Center, 201 Lyons Avenue, Suite # L4, Newark, NJ 07112, USA.
| | - Anita Phancao
- Integris Baptist Medical Center, 3400 Northwest Expressway, Building C, Suite 200, Oklahoma City, OK 73112, USA
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Yanishi M, Kinoshita H, Yoshida T, Takayasu K, Yoshida K, Mishima T, Sugi M, Tsukaguchi H, Kawa G, Matsuda T. Comparison of live donor pre-transplant and recipient post-transplant renal volumes. Clin Transplant 2016; 30:613-8. [DOI: 10.1111/ctr.12727] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2016] [Indexed: 01/17/2023]
Affiliation(s)
- Masaaki Yanishi
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Hidefumi Kinoshita
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Takashi Yoshida
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Kenta Takayasu
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Kenji Yoshida
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Takao Mishima
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Motohiko Sugi
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Hiroyasu Tsukaguchi
- 2nd Department of Internal Medicine; Division of Nephrology; Kansai Medical University; Osaka Japan
| | - Gen Kawa
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
| | - Tadashi Matsuda
- Department of Urology and Andrology; Kansai Medical University; Osaka Japan
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Hernández D, Muriel A, Abraira V. Current state of clinical end-points assessment in transplant: Key points. Transplant Rev (Orlando) 2016; 30:92-9. [PMID: 26948088 DOI: 10.1016/j.trre.2016.02.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Accepted: 02/03/2016] [Indexed: 12/20/2022]
Abstract
Solid organ transplantation is the treatment of choice for patients with end-stage organ disease. However, organ transplantation can stress the cardiovascular system and decrease immune surveillance, leading to early mortality and graft loss due to multiple underlying comorbidities. Clinical end-points in transplant include death and graft failure. Thus, generating accurate predictive models through regression models is crucial to test for definitive clinical post-transplantation end-points. Survival predictive models should assemble efficient surrogate markers or prognostic factors to generate a minimal set of variables derived from a proper modeling strategy through regression models. However, a few critical points should be considered when reporting survival analyses and regression models to achieve proper discrimination and calibration of the predictive models. Additionally, population-based risk scores may underestimate risk prediction in transplant. The application of predictive models in these patients should therefore incorporate both classical and non-classical risk factors, as well as community-based health indicators and transplant-specific factors to quantify the outcomes in terms of survival properly. This review focuses on assessment of clinical end-points in transplant through regression models by combining predictive and surrogate variables, and considering key points in these analyses to accurately predict definitive end-points, which could aid clinicians in decision making.
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Affiliation(s)
- Domingo Hernández
- Department of Nephrology, Carlos Haya Regional University Hospital and University of Malaga, IBIMA, REDinREN (RD12/0021/0015). Avda. Carlos Haya s/n., 29010, Málaga, Spain.
| | - Alfonso Muriel
- Clinical Biostatistic Unit, Hospital Ramón y Cajal, IRYCIS, CIBERESP, Crta. Colmenar km 9.1, 28034, Madrid, Spain
| | - Víctor Abraira
- Clinical Biostatistic Unit, Hospital Ramón y Cajal, IRYCIS, CIBERESP, Crta. Colmenar km 9.1, 28034, Madrid, Spain
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López V, Cabello M, Ruíz-Esteban P, Sola E, Gutiérrez C, Jironda C, Burgos D, González-Molina M, Hernández D. Impact of Early Low-Grade Proteinuria and Allograft Dysfunction on Survival in Expanded Criteria Donor Kidney Transplant Recipients. Transplant Proc 2015; 47:2611-4. [PMID: 26680050 DOI: 10.1016/j.transproceed.2015.08.045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 08/18/2015] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Recent studies have demonstrated a relationship between low-grade proteinuria and worse graft survival, but this has not been fully studied in expanded criteria donor (ECD) kidney transplant recipients. AIM The aim of this study was to assess whether the combination of early low-grade proteinuria (<1 g/d) and allograft dysfunction at the third month post-transplantation predicts outcomes in terms of survival in ECD kidney transplant recipients. MATERIAL AND METHODS We studied a cohort of 269 ECD kidney transplant recipients subdivided into 4 groups according to clinically relevant proteinuria (300 mg/d) and median creatinine (Cr; 1.7 mg/dL; interquartile range, 1.4-2.1 mg/dL) at the third month post-transplantation: Group A (Cr <1.7 mg/dL and proteinuria <300 mg/24 h; n = 97), Group B (Cr <1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 38), Group C (Cr ≥1.7 mg/dL and proteinuria <300 mg/24 h; n = 79), and Group D (Cr ≥1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 55). RESULTS Death-censored graft survival was significantly lower in Group D compared with the rest (P < .007). Multivariate Cox regression analysis using fixed covariates showed that the combination of low-grade proteinuria and a lower estimated glomerular filtration rate (eGFR) as associated with graft failure (hazard rate [HR] 2.5, 95% confidence interval [CI], 1.09-5.97; P = .03). CONCLUSIONS The early association of low-grade proteinuria and allograft dysfunction represents an important risk factor for graft loss in ECD kidney transplant recipients. Strategies to optimize renal function could improve the outcome in this specific population.
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Affiliation(s)
- V López
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain.
| | - M Cabello
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - P Ruíz-Esteban
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - E Sola
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - C Gutiérrez
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - C Jironda
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - D Burgos
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - M González-Molina
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
| | - D Hernández
- Nephrology Department, Regional University Hospital of Malaga, Malaga Institute of Biomedical Research (IBIMA), University of Malaga, Malaga, Spain
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Zsom L, Wagner L, Fülöp T. Minimization vs tailoring: Where do we stand with personalized immunosuppression during renal transplantation in 2015? World J Transplant 2015; 5:73-80. [PMID: 26421259 PMCID: PMC4580929 DOI: 10.5500/wjt.v5.i3.73] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 06/13/2015] [Accepted: 07/11/2015] [Indexed: 02/05/2023] Open
Abstract
The introduction of novel immunosuppressive agents over the last two decades and the improvement of our diagnostic tools for early detection of antibody-mediated injury offer us an opportunity, if not a mandate, to better match the immunosuppression needs of the individual patients with side effects of the therapy. However, immunosuppressive regimens in the majority of programs remain mostly protocol-driven, with relatively little inter-program heterogeneity in certain areas of the world. Emerging data showing different outcomes with a particular immunosuppressive strategy in populations with varying immunological risks underscore a real potential for "personalized medicine" in renal transplantation. Studies demonstrating marked differences in the adverse-effect profiles of individual drugs including the risk for viral infections, malignancy and renal toxicity call for a paradigm shift away from a "one size fits all" approach to an individually tailored immunosuppressive therapy for renal transplant recipients, assisted by both screening for predictors of graft loss and paying close attention to dose or class-related adverse effects. Our paper explores some of the opportunities during the care of these patients. Potential areas of improvements may include: (1) a thorough assessment of immunological and metabolic risk profile of each renal transplant recipient; (2) screening for predictors of graft loss and early signs of antibody-mediated rejection with donor-specific antibodies, protocol biopsies and proteinuria (including close follow up of adverse effects with dose adjustments or conversions as necessary); and (3) increased awareness of the possible link between poor tolerance of a given drug at a given dose and non-adherence with the prescribed regimen. Altogether, these considerations may enable the most effective use of the drugs we already have.
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Santos J, Martins LS. Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker. World J Nephrol 2015; 4:345-53. [PMID: 26167457 PMCID: PMC4491924 DOI: 10.5527/wjn.v4.i3.345] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 05/06/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.
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Hernández D, Triñanes J, Salido E, Pitti S, Rufino M, González-Posada JM, Torres A. Artery Wall Assessment Helps Predict Kidney Transplant Outcome. PLoS One 2015; 10:e0129083. [PMID: 26066045 PMCID: PMC4466324 DOI: 10.1371/journal.pone.0129083] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 05/05/2015] [Indexed: 12/13/2022] Open
Abstract
Background Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation. Methods In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality. Results A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021). Conclusion A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.
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Affiliation(s)
- Domingo Hernández
- Nephrology Department, Carlos Haya Regional University Hospital and University of Málaga (IBIMA), REDinREN, Málaga, Spain
- * E-mail:
| | - Javier Triñanes
- Research Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Eduardo Salido
- Research Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Sergio Pitti
- Radiology Department, Hospital Universitario de Canarias, Tenerife, Spain
| | - Margarita Rufino
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
| | - José Manuel González-Posada
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
| | - Armando Torres
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
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17
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Does the KDIGO CKD risk stratification based on GFR and proteinuria predict kidney graft failure? Int Urol Nephrol 2014; 46:1857-65. [DOI: 10.1007/s11255-014-0761-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 06/03/2014] [Indexed: 10/25/2022]
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18
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Regression of cardiac growth in kidney transplant recipients using anti-m-TOR drugs plus RAS blockers: a controlled longitudinal study. BMC Nephrol 2014; 15:65. [PMID: 24755192 PMCID: PMC4005821 DOI: 10.1186/1471-2369-15-65] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 04/16/2014] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Left ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up. METHODS We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up. RESULTS Nineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P=0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P=0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P=0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P=0.019). CONCLUSIONS Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass.
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Smith-Palmer J, Kalsekar A, Valentine W. Influence of renal function on long-term graft survival and patient survival in renal transplant recipients. Curr Med Res Opin 2014; 30:235-42. [PMID: 24128389 DOI: 10.1185/03007995.2013.855189] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Renal function post kidney transplantation is an outcome of interest for both clinicians and regulators evaluating immunosuppressive treatments post-transplantation. The current review sought to provide a synopsis of currently available literature examining the relationship between post-transplantation renal function and long-term graft survival and patient survival. METHODS A systematic literature review was performed using the PubMed, EMBASE and Cochrane Library databases. The search strategy was designed based on high level Medical Subject Heading (MeSH) terms and designed to capture studies published in English to 2012 and identified a total of 2683 unique hits; for inclusion studies were required to have >100 patients. Following two rounds of screening, a total of 27 studies were included in the final review (26 of which were identified via the literature review and one study was identified via searches of the reference sections of included studies). RESULTS The consensus among studies was that lower post-transplantation GFR, in particular 12 month GFR, was consistently and significantly associated with an increased risk for overall graft loss, death-censored graft loss and all-cause mortality in both univariate and multivariate analyses. The magnitude of the association between reduced GFR and outcomes was greater for death-censored graft loss versus overall graft loss and for graft loss in comparison with overall patient mortality. The predictive utility of GFR alone in predicting long-term outcomes was reported to be limited. CONCLUSIONS Lower GFR and greater rates of decline in GFR post-transplantation are associated with an increased risk for graft loss (overall and death-censored) and all-cause mortality; however, the predictive utility of GFR alone in predicting long-term outcomes is limited.
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Affiliation(s)
- J Smith-Palmer
- Ossian Health Economics and Communications , Basel , Switzerland
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20
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Lezaic V, Dajak M, Radivojevic D, Ristic S, Marinkovic J. Cystatin C and serum creatinine as predictors of kidney graft outcome. Int Urol Nephrol 2013; 46:1447-54. [PMID: 24338493 DOI: 10.1007/s11255-013-0624-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 12/03/2013] [Indexed: 12/17/2022]
Abstract
PURPOSE Serum cystatin C (Cys C) was evaluated as a predictor of kidney graft failure progression, and its predictive ability was compared to other markers of graft function. METHODS The following kidney graft markers were determined in 91 patients who came for regular checkups of kidney graft function to our outpatient service in February 2008: Cys C, serum creatinine (sCr), 24-h proteinuria and 24-h urinary creatinine clearance (CCr). Glomerular filtration rate (eGFR) was estimated using sCr-based and Cys C formula. Patients were regularly monitored until February 2013 or to graft failure. RESULTS During follow-up, graft failure occurred in 21 recipients. The Cys C ≥2.65 mg/l discriminated patients with and without graft failure (sensitivity of 80.95% and specificity of 92.86%). According to c statistic, the highest performance was achieved for Cys C (0.874). In addition, Cys C area under the curve (AUC) was significantly better than CCr AUC (p = 0.007), 24-h proteinuria AUC (p = 0.03), eGFR estimated by the chronic kidney disease epidemiology collaboration (EPI) AUC (p = 0.05), but not better than sCr or eGFR AUCs calculated by other formulas. In the multivariable model, sCr, CCr, Cys C and eGFRs were predictors of graft failure. Combination of Cys C, sCr and logarithm of 24 h proteinuria (0.883) or Cys C, CCr and logarithm of 24-h proteinuria (0.884) had the highest AUC for predicting graft outcome that exceed insignificantly Cys C or sCr areas. CONCLUSIONS The most reliable predictors of graft outcome were Cys C, sCr and proteinuria. Because Cys C is unavailable in many transplant centers, from the practical point of view, sCr remains the most sensitive predictor of graft outcome.
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Affiliation(s)
- Visnja Lezaic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia,
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Gillis KA, Patel RK, Jardine AG. Cardiovascular complications after transplantation: treatment options in solid organ recipients. Transplant Rev (Orlando) 2013; 28:47-55. [PMID: 24412041 DOI: 10.1016/j.trre.2013.12.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Accepted: 12/01/2013] [Indexed: 12/14/2022]
Abstract
Premature cardiovascular disease is the commonest cause of death in solid organ transplant recipients, with coronary artery disease, sudden cardiac death and heart failure being highly prevalent. There are unique factors leading to CV disease in organ transplant recipients that include underlying comorbidities, and metabolic effects of immunosuppression. As a consequence management strategies developed in the general population may have limited benefit. In this review, we will focus on renal transplantation, where most research has been carried out and, despite incomplete understanding of the disease process, the incidence of cardiovascular disease appears to be falling.
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Rodrigo E, Ruiz JC, Fernández-Fresnedo G, Fernández MD, Piñera C, Palomar R, Monfá E, Gómez-Alamillo C, Arias M. Cystatin C and albuminuria as predictors of long-term allograft outcomes in kidney transplant recipients. Clin Transplant 2013; 27:E177-83. [PMID: 23373671 DOI: 10.1111/ctr.12082] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2012] [Indexed: 12/18/2022]
Abstract
Although cystatin C (Cys) and albuminuria (Alb) are predictors of end-stage renal disease in the general population, there are limited data about the performance of these markers alone or combined with respect to the prediction of the kidney transplant outcome. We assessed the ability of one-yr creatinine (Cr), MDRD equation, Cys, Hoek equation, Alb, the logarithm of albuminuria (LogAlb), and two products of these variables for predicting death-censored graft loss (DCGL) in 127 kidney transplant recipients. Mean follow-up time was 5.6 ± 1.7 yr. During this time, 18 patients developed DCGL. The area under the receiver operating characteristic curve for DCGL ranged from 71.1% to 85.4%, with Cys*LogAlb being the best predictor. Cys-based variables and variables combining LogAlb and renal function estimates have better discrimination ability than Cr-based variables alone. After multivariate analysis, quartiles of all one-yr variables (except of Cr and MDRD) were independent predictors for DCGL. Predictors combining Alb and a Cr- or Cys-based estimate of renal function performed better than those markers alone to predict DCGL. Cys-based predictors performed better than Cr-based predictors. Using a double-marker in kidney transplantation, it is possible to identify the highest risk group in which to prioritize specialty care.
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Affiliation(s)
- Emilio Rodrigo
- Nephrology Service, University Hospital "Marqués de Valdecilla", University of Cantabria, Fundación Marqués de Valdecilla-IFIMAV, Santander, Spain.
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Zitzner JR, Tambur AR. Role of ELISPOT Assays in Risk Assessment Pre- and Post-Kidney Transplantation. Cells 2012; 1:100-10. [PMID: 24710417 PMCID: PMC3901086 DOI: 10.3390/cells1020100] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Revised: 04/30/2012] [Accepted: 05/07/2012] [Indexed: 12/31/2022] Open
Abstract
Immunologic risk in kidney transplantation is typically minimized by avoiding, or at least limiting, the potential of donor specific humoral responses by testing for the presence of donor-specific antibodies (DSA). Additionally, selecting donor and recipient pairs with the least number of human leukocyte antigen (HLA) mismatches has been shown to play a role in transplant outcome. However, numerous other factors may play a role in the success of transplant outcome and patient health. Specifically, the use of T-cell allospecific ELISPOT assays have helped elucidate the role of pre-formed cellular responses as additional factors in post-transplant outcome. In this review, we will evaluate numerous uses of ELISPOT assays to assess the pre- and post-transplant immunologic risk of rejection episodes, graft survival and even viral susceptibility as well as the utility of ELISPOT assays in monitoring tolerance and withdrawal of immunosuppressive medications following kidney transplantation.
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Affiliation(s)
- Jennifer R Zitzner
- Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave., Tarry Building Suite 11-703, Chicago, IL 60611-3008, USA.
| | - Anat R Tambur
- Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave., Tarry Building Suite 11-703, Chicago, IL 60611-3008, USA.
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