Endocan Concentration in Kidney Transplant Recipients

Introduction

Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Elevated endocan levels are connected with endothelial activation/damage, neo-angiogenesis, and inflammation or carcinogenesis.

Viral Hepatitis Infections in Chronic Kidney Disease Patients and Renal Transplant Recipients

Within the last few decades, the incidence and prevalence of both hepatitis B and C infections have decreased among kidney disease patients. Significant advances have been made in the prevention of hepatitis B and C virus transmission in these high-risk populations; however, the transmission risk is still not negligible. Viral hepatitis infections represent a significant problem among kidney disease patients; patients on regular dialysis, as well as renal transplant recipients (RTRs) due to their epidemiological, virological, and clinical features. Chronic hepatitis B and C have a strong impact on the clinical course of kidney disease as well as on the clinical course after kidney transplantation. The purpose of this review is to focus on the epidemiology, transmission modes, natural courses, and treatment options of hepatitis B and C infections in both chronic kidney disease patients and RTRs.     

Liver Transplant Recipients With End-Stage Renal Disease Largely Benefit From Kidney Transplantation

Background

The incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD.

Characteristics of Testosterone Deficiency Syndrome in Men With Chronic Kidney Disease and Male Renal Transplant Recipients: A Cross-Sectional Study

Objectives

Testosterone deficiency syndrome (TDS) is common among male patients with chronic kidney disease (CKD). We compared the characteristics of TDS in men with CKD versus renal transplantation (RT) with those of age-matched normal controls.

Materials and Methods

The 129 patients were: RT recipients (n = 25) group I, CKD patients (n = 37) group II, and controls (n = 67). We performed estimates of testosterone, hemoglobin (Hgb), hematocrit (Hct), glucose, creatinine, and lipid profile. Self-assessment questionnaires—International Index of Erectile Function (IIEF), Aging Males' Symptoms (AMS), Center for Epidemiologic Studies Depression Scale—were used to evaluate erectile function, testosterone deficiency, and depression, respectively. We also investigated morning erection as well as the presence and duration of erectile dysfunction (ED).

Results

Group I (RT) showed significantly higher serum testosterone levels than group II (CKD), who displayed significantly worse erectile function, more severe testosterone deficiency symptoms, and a greater trend toward depression. Similarly, the prevalences of ED and TDS were significantly greater in group II than group I. Group I and controls differed significantly only in the results of serologic tests, such as serum creatinine, Hgb, and glucose and lipid profiles, but not in serum testosterone levels, scores of self-assessment questionnaires, or prevalence of ED or TDS. Serum testosterone levels correlated significantly with scores on the IIEF and AMS questionnaires in both group II and controls, but not group I.

Conclusions

RT recipients showed higher serum testosterone levels and a lower prevalence of TDS with milder symptom severity than CKD patients. RT recipients beyond the early acute posttransplant period, displayed serum testosterone levels and TDS prevalence similar to those of healthy controls. Unlike CKD patients and normal controls, serum testosterone did not significantly influence TDS symptoms in RT recipients.     

Differences in Cardiac Structure Assessed by Echocardiography Between Renal Transplant Recipients and Chronic Kidney Disease Patients

BackgroundCardiovascular disease (CVD) is the leading cause of death in predialysis chronic kidney disease (CKD) and dialysis patients as well as in renal transplant recipients (RTRs). Left ventricular hypertrophy (LVH) starts early during the course of CKD and is a strong predictor of CVD in this population. Regression of LVH after a successful renal transplantation remains a debatable issue among investigators, whereas there is little data comparing echocardiographic measurements between patients with predialysis CKD and RTRs.AimThe aim of this study was to compare echocardiographic measurements of LV structure and function between predialysis CKD patients and RTRs of similar renal function level.Patients and MethodsWe conducted a case control study with individual (1:2) matching from the Renal Transplant and the predialysis CKD Outpatient Clinic. For each of the 36 RTRs, two matched for gender, age and estimated glomerular filtration rate (eGFR) predialysis CKD outpatients (72 patients) were included. All patients underwent transthoracic echocardiography and LV mass, LV mass index [LVM and LVMI = LVM/BSA g/m²] and indices of systolic function were measured. In a subgroup of 12 RTRs we retrospectively assessed and compared the LVMI measurements at three different time points, during predialysis, dialysis and post transplant period.ResultsThe prevalence of LVH was 33% in RTRs and 52% in CKD patients (ns). RTRs had significantly lower LVM and LVMI levels compared with predialysis CKD patients (P = .006 and P = .008) while the other echocardiographic indices did not differ. In the subgroup of 12 RTRs, post-transplant LVMI levels (105 ± 25 g/m²) were significantly lower in comparison with predialysis (147 ± 57 g/m²) and dialysis LVMI levels (169 ± 72 g/m²) (P = .01, P = .01, respectively).ConclusionRTRs had significantly lower LVMI compared with predialysis CKD patients of similar age, renal function, hemoglobin and blood pressure level.     

Conversion to Everolimus in Kidney Transplant Recipients With Decreased Renal Function

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1–3 mg/d that was sufficient to achieve the recommended levels of 3–8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.     

Serum Procalcitonin Correlates With Renal Function and Immune Components in Early-Stage Renal Transplant Recipients

BackgroundIn renal transplantation, monitoring procalcitonin (PCT) in the early post-transplant period can be a promising method for early tracking of infectious complications. However, the correlation between PCT and infection-related factors and immune components and renal function remains unclear.Patients and methodsBetween November 2017 and December 2018, 62 early-stage renal transplant recipients were selected, and 4 mL peripheral blood samples were collected to detect the changes of specific immune cells and cytokines. Our study was in compliance with the Helsinki Congress and the Declaration of Istanbul; no prisoners were used, and participants were neither paid nor coerced in our study.ResultsAccording to serum PCT levels, recipients were divided into a high group (PCT ≥ 0.5 ng/mL) and a low group (PCT < 0.5 ng/mL). Compared with the low group, creatinine, cystatin C, urea, T helper type (Th) 22 cells, IL-22 + Th17 cells, interleukin (IL)-22, tumor necrosis factor alpha, and IL-17A increased while estimated glomerular filtration rate (eGFR) was decreased in the high group. In addition, PCT was significantly correlated with eGFR in the high group.ConclusionsSerum PCT is related with renal function and seems to be associated with immune components in early-stage renal transplant recipients.     

Prevalence of Chronic Kidney Disease Is Extremely High in Heart Transplant Recipients

Patients with cardiovascular disease often have renal dysfunction from concomitant diabetes mellitus, hypertension, or congestive heart failure. Glomerular filtration rate (GFR) less than 60 mL/min is predictive of premature death due to cardiovascular disease. The objective of the present study was to assess the prevalence of kidney dysfunction in 162 heart transplant recipients using estimated GFR according to the Cockcroft-Gault and the simplified Modification of Diet in Renal Disease (MDRD) formulas or creatinine clearance (24-hour urine collection). Normal serum creatinine concentrations were noted in 46% of patients. Mean (SD) GFR was 62.92 (31.04) mL/min using the Cockcroft-Gault formula, 55.38 (26.74) mL/min using the MDRD formula, and 62.62 (35.61) mL/min according to creatinine clearance. Using the Cockcroft-Gault formula, a diagnosis of stage 2 chronic kidney disease (CKD) (GFR 60–89 mL/min) was made in 92 patients (56.8%), stage 3 (GFR 30–59 mL/min) in 62 patients (38.3%), and stage 4 (GFR 15–29 mL/min) in 14 patients (8.6%). Using the MDRD formula, stage 2 CKD was present in 52 patients (28.5%), stage 3 in 77 (51.1%), and stage 4 in 28 (17.3%). According to creatinine clearance, stage 2 CKD was noted in 10 patients (6.2%), stage 3 in 114 (73.3%), and stage 4 in 21 (13.0%). We conclude that the prevalence of CKD is extremely high in heart transplant recipients. Evaluation of renal function is important to select the appropriate technique to reduce cardiovascular risk. A multidisciplinary approach in heart transplant recipients should include a nephrologist.     

Serum Adipokine Levels in Renal Transplant Recipients

Background

Metabolic syndrome (MS) is a common complication in renal transplant (RTx) recipients. This study aimed to explore the alterations and interrelationship of various adipokines in RTx recipients with and without MS.

Methods

RTx recipients followed at our hospital were randomly selected for the cross-sectional study of MS. The modified Adult Treatment Panel III criteria adopted for Asian populations were used to define MS. Overnight fasting blood samples were obtained for determination of adipokines, including adiponectin, leptin, resistin, and visfatin. Univariate and multivariate logistic regressions were performed to determine parameters that were associated with serum adipokine levels. Pearson correlation analysis was performed between adipokines.

Results

A total of 280 RTx recipients were enrolled for the study. Seventy-three cases (26.1%) fulfilled the criteria of MS. A significantly higher serum leptin level was found in MS patients (16.61 ± 13.90 vs 8.00 ± 7.42 μg/mL; P < .0001). There was no significant difference in serum levels of adiponectin, resistin, and visfatin between the 2 groups. Serum adiponectin level was positively correlated with serum resistin (r = 0.422; P < .0001) and visfatin levels (r = 0.224; P < .0001). Serum resistin level was positively correlated with serum visfatin level. All but serum visfatin level were negatively correlated with estimated glomerular filtration rate. Univariate logistic regression revealed the following variables to be associated with serum leptin level: metabolic syndrome, sex, body weight, waist circumference, body mass index (BMI), hypertension, serum creatinine, fasting blood sugar, Hb_A1c, serum triglyceride, and uric acid. Multivariate analysis revealed that sex, body weight, BMI, and serum creatinine were associated with serum leptin level.

Conclusions

Compared with RTx recipients without MS, patients with MS were associated with significantly higher serum leptin levels and similar adiponectin, resistin, and visfatin levels. A close interrelationship was also found in the serum levels of these adipokines.     

The Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Formulas Versus Measured or Estimated Creatinine Clearance in Kidney Transplant Recipients

Background

Estimation of glomerular filtration rate (eGFR) after renal transplantation is performed with the use of methods that are standardized for a population of nontransplantation patients with chronic kidney disease. The aim of the study was to compare the performance of GFR estimation formulas in renal transplant recipients.

Methods

The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were compared with measured creatinine clearance or clearance estimated by the Cockroft-Gault (C-G) formula. The influence of age, body mass index, and eGFR on the relative performance of these formulas also was studied by subgroups analysis.

Results

Mean measured or estimated creatinine clearance overestimates the values of GFR calculated using the MDRD or CKD-EPI equation. This was statistically significant (P < .05) in whole-study population and in subgroups of patients at age above 25 years, with body mass index above 25, and in a subgroup with eGFR-MDRD <50 mL/min/m². The mean bias from creatinine clearance was 7.46 mL/min for MDRD, 4.4 mL/min for CKD-EPI and −1.65 mL/min for C-G formula. There was a statistically significant (P < .05) negative correlation between eGFR value and bias from creatinine clearance for all 3 methods of estimation. The correlation coefficient was −0.4 for MDRD, −0.36 for CKD-EPI, and −0.46 for C-G clearance.

Conclusions

Measured and estimated creatinine clearance overestimate values of eGFR calculated by the MDRD or CKD-EPI formula in a population of kidney transplant recipients, especially in subjects with obesity and worse renal function. Accuracy of analyzed GFR estimation formulas decreases with deterioration of renal graft function.     

Mineral and Bone Disease in Kidney Transplant Recipients

Purpose of Review

Despite metabolic improvements following kidney transplantation, transplant recipients still often suffer from complex mineral and bone disease after transplantation.

Recent Findings

The pathophysiology of post-transplant disease is unique, secondary to underlying pre-transplant mineral and bone disease, immunosuppression, and changing kidney function. Changes in modern immunosuppression regimens continue to alter the clinical picture. Modern management includes reducing cumulative steroid exposure and correcting the biochemical abnormalities in mineral metabolism. While bone mineral density screening appears to help predict fracture risk and anti-osteoporotic therapy appears to have a positive effect on bone mineral density, more data regarding specific treatment is necessary.

Summary

Patients with mineral and bone disease after kidney transplantation require special care in order to properly manage and mitigate their mineral and bone disease. Recent changes in clinical management of transplant patients may also be changing the implications on patients’ mineral and bone disease.

     

Treatment With Ezetimibe in Kidney Transplant Recipients With Uncontrolled Dyslipidemia

Introduction

Cardiovascular disease is the leading cause of death in kidney transplant recipients. Hyperlipidemia is a cardiovascular risk factor present in over 70% of recipients. Ezetimibe has proved effective for the treatment of dyslipidemia in these patients.

Aim

To evaluate the efficacy and safety of treatment with ezetimibe in kidney transplant recipients with uncontrolled hyperlipidemia.

Materials and methods

We undertook a prospective study of 25 kidney transplant recipients with dyslipidemia who started treatment with 10 mg of ezetimibe. Statins were being taken by 96% of these patients. Monotherapy was used in one case. Measurements were made at baseline and after 3, 6, and 12 months of the lipid and hepatic profiles, CPK, lactose dehydrogenase, renal function and levels of immunosuppressive agents.

Results

A significant reduction was noted in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. No patient had changes in the hepatic profile, increased CPK and lactose dehydrogenase levels, or important adverse effects. Renal function remained stable, with no significant variations in plasma levels of the different immunosuppressive agents.

Conclusions

The use of ezetimibe associated with statins is an efficient and safe therapeutic alternative for the treatment of poorly controlled dyslipidemia in recipients of a kidney graft.     

Increased Asymmetric Dimethylarginine Serum Levels are Associated With Acute Rejection in Kidney Transplant Recipients

Asymmetric dimethylarginine (ADMA) has been identified as a marker of endothelial dysfunction and an independent risk factor for cardiovascular events in uremic subjects. This study evaluated ADMA plasma levels in kidney transplant recipients. ADMA levels were serially measured during the first year posttransplantation in 41 recipients treated with cyclosporine regimen (CY), sirolimus (SIR), or low-dose cyclosporine plus everolimus (E). Homocysteine, C reactive protein (CRP), nitric oxide (NO), and standard routine laboratory analyses were determined serially. ADMA significantly increased at 6 months posttransplantation, but was significantly lower among patients on SIR or E. NO was only slightly reduced in patients with increased ADMA levels. Interestingly, ADMA was significantly increased during the first 4 days posttransplantation in patients who experienced acute rejection during the first 6 months after transplantation. The same group of patients demonstrated higher levels of CRP and systolic blood pressure before transplantation. Our results demonstrated that ADMA was increased in patients on CY at 6 months. When increased soon after transplantation ADMA may be associated with episodes of acute rejection in kidney transplant recipients. The presence of elevated systolic blood pressure, as well as CRP and ADMA levels, suggested a role for endothelial dysfunction in the development of acute rejection episodes among deceased donor kidney transplant recipients.     

Early Prediction of Cardiovascular Disease in Kidney Transplant Recipients

Cardiovascular disease (CVD) is frequent after kidney transplantation (KT). This study investigated CVD prediction in KT by information available before KT or within 6 months after KT. The study cohort consisted of 629 patients with KT in 2005–10 and with adult age at KT. The end point was incidence up to 2015 of CVD (coronary heart disease, cerebrovascular disease, peripheral artery disease). Graft failure, non-CVD death with functioning graft, and loss to follow-up were considered competing events. CVD prediction was investigated for 34 variables by means of competing-risks regression. Follow-up range was 0.28–10.00 years (mean ± SD, 7.30 ± 3.10). First incident event was CVD in 103 patients and competing events in 146 patients. In the multivariable model for pre-KT variables only, CVD predictors were male sex (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.06–2.66), diabetic nephropathy (HR, 6.63; 95% CI, 1.81–24.35), pre-KT dialysis for ≥5 years (HR, 1.52; 95% CI, 1.02–2.27), pre-KT CVD (HR, 4.87; 95% CI, 2.84–8.35), and age at KT ≥45 years (HR, 2.98; 95% CI, 1.83–4.87). In the model for pre-KT and post-KT variables together, the sole post-KT CVD predictor was estimated glomerular filtration rate <60 mL/min at the 6-month visit (HR, 1.75; 95% CI, 1.11–2.77). Diabetic nephropathy, pre-KT dialysis, pre-KT CVD, and age at KT predicted 91.2% of incident CVD. Early available information effectively predicted CVD in KT independently from competing events.     

Clinical Significance of Serum Visfatin in Renal Transplant Recipients

Chronic antibody-mediated rejection is the most common cause of late graft loss in renal transplant recipients. Visfatin is a pre-B cell colony-enhancing factor secreted by activated lymphocytes. We hypothesize that visfatin may play a role in the augmentation of B cell colonies and facilitate antibody-mediated rejection. Renal transplant recipients were randomly selected for the study. Fasting blood samples were obtained for the assay of visfatin. The participants were prospectively followed up for 3 years. A total of 146 patients were recruited for the study and were divided into 3 groups according to tertile of serum visfatin level. At the end of follow-up, 6 patients had graft loss, including 1 graft loss in tertile 1, 3 in tertile 2, and 2 in tertile 3 (P?=?.60). Fourteen patients experienced at least 1 episode of acute rejection, while 21 patients were diagnosed as having chronic rejection. The distribution of acute rejection was 10.2% in tertile 1, 10.2% in tertile 2, and 8.3% in tertile 3 (P?=?.94); chronic rejection occurred in 10.2%, 16.3%, and 16.7%, respectively (P?=?.59). We conclude that serum visfatin level was not correlated with either graft failure or patient mortality in a 3-year observation period.