Serum Total Homocysteine and Cardiovascular Disease Occurrence in Chronic, Stable Renal Transplant Recipients: A Prospective Study

Abstract. Renal transplant recipients have disproportionately high rates of arteriosclerotic outcomes, and recent studies provided controlled evidence that clinically stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia. Few studies suggest that hyperhomocysteinemia may be a cardiovascular risk factor in renal transplant recipients. In the study presented here, the association between atherosclerotic events and homocysteine concentrations was examined in 207 stable renal transplant recipients. The role of hyperhomocysteinemia was analyzed with respect to other known cardio-vascular risk factors. The mean follow-up was 21.2 ± 1.9 mo (range, 14 to 26). Mean total homocysteine (tHcy) was 21.1 ± 9.5 μmol/L and median concentration was 19 μmol/L. Seventy percent of patients (n = 153) were hyperhomocysteinemic (values >15 μmol/L). tHcy correlated negatively with folate concentration (r = -0.3; P <0.01). tHcy was closely related to creatinine concentration (r = 0.54; P < 0.001). Cardiovascular disease events (CVE) including death were observed in 30 patients (14.5%; 7.34 events per 1000 person-months of follow-up). Fasting tHcy values were higher in patients who experienced CVE (31.5 ± 10.3 versus 17.8 ± 7.5; P < 0.001). Cox regression analysis showed that tHcy was a risk factor for cardiovascular complications (relative risk [RR] 1.06; 95% confidence interval (95% CI), 1.04 to 1.09; P < 0.0001). This corresponds to an increase in RR for CVE of 6% per μmol/L increase in tHcy concentration. Age (RR 1.55; 95% CI, 1.09 to 2.19; P < 0.01) and creatinine concentration (RR 1.34; 95% CI, 1.08 to 1.66; P < 0.01) were also independent predictor for CVE. This study demonstrates that elevated fasting tHcy is an independent risk factor for the development of CVE in chronic stable renal transplant recipients. Randomized, place-bo-controlled homocysteine studies of the effect of tHcy lowering on CVE rates are urgently required in this patient population.

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Decreased Serum Retinol Is Associated with Increased Mortality in Renal Transplant Recipients

Clinical Chemistry ◽

10.1373/clinchem.2006.084699 ◽

2007 ◽

Vol 53 (10) ◽

pp. 1841-1846 ◽

Cited By ~ 4

Author(s):

Grainne M Connolly ◽

Ronan Cunningham ◽

A Peter Maxwell ◽

Ian S Young

Keyword(s):

Renal Transplant ◽

Vitamin A ◽

Cox Regression ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Serum Retinol ◽

Cox Regression Analysis ◽

All Cause Mortality ◽

Retinol Concentration

Abstract Background: Vitamin A plays a central role in epithelial integrity and immune function. Given the risk of infection after transplantation, adequate vitamin A concentrations may be important in patients with a transplant. We assessed whether there was an association between retinol concentration and all-cause mortality in renal transplant recipients. Methods: We recruited 379 asymptomatic renal transplant recipients between June 2000 and December 2002. We measured serum retinol at baseline and collected prospective follow-up data at a median of 1739 days. Results: Retinol was significantly decreased in those renal transplant recipients who had died at follow-up compared with those who were still alive at follow-up. Kaplan–Meier analysis showed that retinol concentration was a significant predictor of mortality. In multivariate Cox regression analysis, decreased retinol concentration remained a statistically significant predictor of all-cause mortality after adjustment for traditional cardiovascular risk factors, high-sensitivity C-reactive protein, and estimated glomerular filtration rate. Conclusions: Serum retinol concentration is a significant independent predictor of all-cause mortality in renal transplantation patients. Higher retinol concentration might impart a survival advantage via an antiinflammatory or anti-infective mechanism.

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Hyperhomocysteinaemia: a significant risk factor for cardiovascular disease in renal transplant recipients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/9.8.1103 ◽

1994 ◽

Vol 9 (8) ◽

pp. 1103-1108 ◽

Cited By ~ 113

Author(s):

Z. A. Massy ◽

B. Chadefaux-Vekemans ◽

A. Chevalier ◽

C. A. Bade ◽

T. B. Drüeke ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Factor ◽

Renal Transplant ◽

Significant Risk ◽

Significant Risk Factor ◽

Renal Transplant Recipients ◽

Transplant Recipients

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Hyperhomocyst(e)inemia as an independent risk factor for cardiovascular disease in renal transplant recipients

Transplantation Journal ◽

10.1097/00007890-199806270-00308 ◽

1998 ◽

Vol 65 (12) ◽

pp. S75

Author(s):

Didier DUCLOUX ◽

Christophe RUEDIN ◽

Roger GIBEY ◽

Jean-Michel REBIBOU ◽

Catherine BRESSON-VAUTRIN ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Factor ◽

Renal Transplant ◽

Independent Risk Factor ◽

Renal Transplant Recipients ◽

Transplant Recipients

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Is low pre-transplant parathyroid hormone a risk marker for cardiovascular disease in long-term follow-up of renal transplant recipients?

Clinical and Experimental Nephrology ◽

10.1007/s10157-018-1543-9 ◽

2018 ◽

Vol 22 (5) ◽

pp. 1188-1197 ◽

Cited By ~ 2

Author(s):

Elin Isaksson ◽

Martin Almquist ◽

Astrid Seeberger ◽

Gunnar Sterner

Keyword(s):

Cardiovascular Disease ◽

Parathyroid Hormone ◽

Renal Transplant ◽

Risk Marker ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Long Term Follow Up

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Sclerostin is an independent risk factor for all-cause mortality in kidney transplant recipients

Clinical and Experimental Nephrology ◽

10.1007/s10157-020-01956-y ◽

2020 ◽

Vol 24 (12) ◽

pp. 1177-1183

Author(s):

Shufei Zeng ◽

Torsten Slowinski ◽

Wolfgang Pommer ◽

Ahmed A. Hasan ◽

Mohamed M. S. Gaballa ◽

...

Keyword(s):

Risk Factor ◽

Renal Transplant ◽

Kidney Transplant ◽

Independent Risk Factor ◽

Cox Regression ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Kaplan Meier ◽

All Cause Mortality

Abstract Background Sclerostin is a hormone contributing to the bone-vascular wall cross talk and has been implicated in cardiovascular events and mortality in patients with chronic kidney disease (CKD). We analyzed the relationship between sclerostin and mortality in renal transplant recipients. Methods 600 stable renal transplant recipients (367men, 233 women) were followed for all-cause mortality for 3 years. Blood and urine samples for analysis and clinical data were collected at study entry. We performed Kaplan–Meier survival analysis and Cox regression models considering confounding factors such as age, eGFR, cold ischemia time, HbA1c, phosphate, calcium, and albumin. Optimal cut-off values for the Cox regression model were calculated based on ROC analysis. Results Sixty-five patients died during the observation period. Nonsurvivors (n = 65; sclerostin 57.31 ± 30.28 pmol/L) had higher plasma sclerostin levels than survivors (n = 535; sclerostin 47.52 ± 24.87 pmol/L) (p = 0.0036). Kaplan–Meier curve showed that baseline plasma sclerostin concentrations were associated with all-cause mortality in stable kidney transplant recipients (p = 0.0085, log-rank test). After multiple Cox regression analysis, plasma levels of sclerostin remained an independent predictor of all-cause mortality (hazard ratio, 1.011; 95% CI 1.002–1.020; p = 0.0137). Conclusions Baseline plasma sclerostin is an independent risk factor for all-cause mortality in patients after kidney transplantation.

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P1650HIGH-DENSITY LIPOPROTEIN PARTICLES AND THEIR RELATIONSHIP TO POSTTRANSPLANTATION DIABETES IN RENAL TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1650 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sara Sokooti Oskooei ◽

Tamas Szili-Torok ◽

Jose L Flores-Guerrero ◽

Maryse C.J. Osté ◽

António W Gomes-Neto ◽

...

Keyword(s):

Renal Transplant ◽

Lower Risk ◽

Cox Regression ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Cox Proportional Hazards ◽

Relative Mass ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Cox Regression Analysis

Abstract Background and Aims It is established that high concentrations of High-Density Lipoprotein (HDL) are associated with low risk of type 2 diabetes and posttransplantation diabetes mellitus (PTDM). However, HDL particles vary by size, density, and biological action. The aim of our study was to determine the association between different HDL particles with the development of PTDM in renal transplant recipients (RTRs). Method We included 351 stable outpatient adult RTR with a functioning graft ≥1 year from the Tranplantlines Food and Nutrition Study(NCT02811835). HDL particle concentration and size were measured by 1H-NMR spectroscopy using a Vantera® NMR Clinical Analyzer (LabCorp, Raleigh, NC). HDL size was weighted averages derived from the sum of the diameter of each subclass multiplied by its relative mass percentage. Estimated ranges of HDL diameter for the HDL subclasses were as follows: large HDL particles, 9.6–13 nm; medium HDL particles, 8.1–9.5 nm; and small HDL particles, 7.4–8.0 nm. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of HDL particles with PTDM. Results During 5.2 (IQR, 4.1–5.8) years of follow-up, 39 (11%) RTR developed PTDM. In a multivariable Cox regression analysis, higher HDL cholesterol was associated with a lower risk of PTDM development, after adjustment for age, sex and BMI (hazard ratio[HR] 0.55, 95% CI 0.36-0.83 per 1SD mg/dL; P=0.005). Moreover, among different HDL indices; HDL size, and large HDL were inversely associated with PTDM, after adjustment for age, sex, and BMI ([ HR 0.48, 95% CI 0.31-0.76 per 1SD nm; P=0.002], and [HR 0.63, 95% CI 0.47-0.84 per 1SD µmol/L; P=0.002], respectively ). However medium HDL and small HDL were not associated with risk of developing PTDM ([ HR 0.88, 95% CI 0.64-1.23 per 1SD µmol/L; P=0.48], and [HR 1.14, 95% CI 0.85-1.52 per µmol/L; P=0.37], respectively ). In additional models, the association remained significant for HDL cholesterol, HDL size, and large HDL after adjustment for other confounders including, the lifestyle, use of medication, kidney function and transplantation-specific parameters. In the last model after adjustment for age, sex, BMI, triglycerides, systolic blood pressure, and fasting plasma glucose, association were similar for HDL cholesterol, HDL size, and large HDL ([ HR 0.61, 95% CI 0.40-0.94 per 1SD mg/dL; P=0.024], [HR 0.58, 95% CI 0.36-0.93 per 1SD nm; P=0.025], and [HR 0.68, 95% CI 0.50-0.93 per 1SD µmol/L; P=0.017]. Conclusion In this study, we found that higher concentrations of HDL cholesterol, large HDL, and higher HDL size were associated with a lower risk of developing PTDM in RTRs, independent of established risk factors for PTDM development.

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Urinary Taurine Excretion and Risk of Late Graft Failure in Renal Transplant Recipients

Nutrients ◽

10.3390/nu11092212 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2212

Author(s):

Adrian Post ◽

M. Yusof Said ◽

Antonio W. Gomes-Neto ◽

Jennifer van der Krogt ◽

Pim de Blaauw ◽

...

Keyword(s):

Renal Transplant ◽

Graft Failure ◽

Cox Regression ◽

Low Risk ◽

Renal Transplant Recipients ◽

Regression Analyses ◽

Transplant Recipients ◽

Taurine Supplementation ◽

Underlying Mechanisms

Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m2), urinary taurine excretion (533 (210–946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (β = 0.126; P = 0.001). During median follow-up for 5.3 (4.5–6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67–0.82); P < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation.

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Hyperhomocyst(e)inemia as an independent risk factor for cardiovascular disease in renal transplant recipients.

Transplantation Journal ◽

10.1097/00007890-199805131-00287 ◽

1998 ◽

Vol 65 (Supplement) ◽

pp. 151

Author(s):

Didier DUCLOUX ◽

Christophe RUEDIN ◽

Roger GIBEY ◽

Jean-Michel REBIBOU ◽

Catherine BRESSON-VAUTRIN ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Factor ◽

Renal Transplant ◽

Independent Risk Factor ◽

Renal Transplant Recipients ◽

Transplant Recipients

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Early postoperative C-terminal agrin fragment (CAF) serum levels predict graft loss and proteinuria in renal transplant recipients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0369 ◽

2016 ◽

Vol 54 (1) ◽

Cited By ~ 4

Author(s):

Dominik Steubl ◽

Anna Vogel ◽

Stefan Hettwer ◽

Susanne Tholen ◽

Peter B. Luppa ◽

...

Keyword(s):

Renal Transplant ◽

Predictive Value ◽

Cox Regression ◽

Univariate Analysis ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Long Term Outcomes

AbstractC-terminal agrin fragment (CAF), cleavage product of agrin, was previously correlated with kidney function in renal transplant patients. This article studies the predictive value of CAF for long-term outcomes in renal transplant recipients.In this observational cohort study, serum CAF, creatinine and blood-urea-nitrogen (BUN) concentrations and eGFR (CKD-EPI) were assessed 1–3 months after transplantation in 105 patients undergoing kidney transplantation. Cox regression models were used to analyse the predictive value of all parameters concerning all-cause mortality (ACM), graft loss (GL), doubling of creatinine/proteinuria at the end of follow-up.Median follow-up time was 3.1 years. The mean concentrations were 191.9±152.4 pM for CAF, 176±96.8 μmol/L for creatinine, 12.6±6.2 mmol/L for BUN and 44.9±21.2 mL/min for CKD-EPI formula, respectively. In univariate analysis CAF and BUN concentrations predicted ACM (CAF: HR=1.003, 1.1-fold risk, p=0.043; BUN: HR=1.037, 1.3-fold risk, p=0.006). Concerning GL, CAF (HR=1.006, 3.1-fold risk, p<0.001), creatinine (HR=2.396, 2.6-fold risk, p<0.001), BUN (HR=1.048, 1.7-fold risk, p=0.001) and eGFR (CKD-EPI) (HR=0.941, 0.45-fold risk reduction, p=0.006) showed a statistically significant association. CAF was the only parameter significantly associated with doubling of proteinuria (HR=1.005, 1.7-fold risk, p<0.001). In multiple regression analysis (CAF only) the association remained significant for GL and doubling of proteinuria but not ACM.Early postoperative serum CAF appears to be a useful tool for the assessment of long-term outcomes in renal transplant recipients. Most importantly it represents a promising predictor for the development of proteinuria.

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