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.

The Burden of Chronic Kidney Disease in Renal Transplant Recipients

The National Kidney Foundation has developed guidelines for the diagnosis and classification of chronic kidney disease (CKD) but it is not known whether these are applicable to renal transplant recipients. This study determined the prevalence of CKD according to the stages defined in the guidelines, the complications related to CKD and whether the prevalence of complications was related to CKD stage in 459 renal transplant recipients. CKD was present in 412 patients (90%) and 60% were in CKD Stage 3 with a glomerular filtration rate (GFR) between 30 and 59 mL/min/1.73 m2. The prevalence of anemia increased from 0% in Stage 1 to 33% in Stage 5 (p<0.001). Hypertension was present in 86% and increased from 60% in Stage 1 to 100% in Stage 5 (p=0.02). The number of anti-hypertensives per patient increased from 0.7 in Stage 1 to 2.3 in Stage 5 (p<0.001). The number of CKD complications per patient increased from 1.1 in Stage 1 to 2.7 in Stage 5 (p<0.001). We conclude that CKD and the complications of CKD are highly prevalent in renal transplant recipients. The classification of renal transplant patients by CKD stage may help clinicians identify patients at increased risk and target appropriate therapy to improve outcomes.     

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.     

Native Nephrectomy in Renal Transplant Recipients With Autosomal Dominant Polycystic Kidney Disease

Introduction

Patients with autosomal dominant polycystic kidney disease (ADPKD) represent about 10% of kidney transplant recipients (KTR) and have unique needs regarding acceptance for this procedure. Whether native kidney nephrectomy (NKN) affects kidney transplantation (KT) outcomes remains a matter of debate, and more data is needed to establish a standard approach to KTR with ADPKD.

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.     

Risk of End‐Stage Renal Disease Among Liver Transplant Recipients With Pretransplant Renal Dysfunction

Guidelines recommend restricting simultaneous liver–kidney (SLK) transplant to candidates with prolonged dialysis or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² for 90 days. However, few studies exist to support the latter recommendation. Using Scientific Registry of Transplant Recipients and Medicare dialysis data, we assembled a cohort of 4997 liver transplant recipients from February 27, 2002–January 1, 2008. Serial eGFRs were calculated from serum creatinines submitted with MELD reports. We categorized recipients by eGFR patterns in the 90 days pretransplant: Group 1 (eGFR always >30), Group 2 (eGFR fluctuated), Group 3 (eGFR always <30) and Group 4 (short‐term dialysis). For Group 2, we characterized fluctuations in renal function using time‐weighted mean eGFR. Among liver‐alone recipients in Group 3, the rate of end‐stage renal disease (ESRD) by 3 years was 31%, versus <10% for other groups (p < 0.001). In multivariable Cox regression, eGFR Group, diabetes (HR 2.65, p < 0.001) and black race (HR 1.83, p = 0.02) were associated with ESRD. Among liver‐alone recipients in Group 2, only diabetics with time‐weighted mean eGFR <30 had a substantial ESRD risk (25.6%). In summary, among liver transplant candidates not on prolonged dialysis, SLK should be considered for those whose eGFR is always <30 and diabetic candidates whose weighted mean eGFR is <30 for 90 days.     

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.     

Hazards of Stroke in Renal Transplant Recipients and Patients With End-Stage Renal Disease

BackgroundSeveral comparison studies have suggested that kidney transplant (KT) could reduce stroke risk in patients with end-stage renal disease (ESRD). To avoid the selection criteria bias of using dialysis patients as control groups, we compared the risk of stroke between KT recipients and comparable propensity score-matched dialysis patients.MethodsWe used Taiwan's National Health Insurance Research Database to identify patients with newly diagnosed ESRD between 2000 and 2009. We separated them into 2 groups: a KT group and a non-KT dialysis-only group. To evaluate the stroke outcome, we compared each patient with KT to a patient on dialysis without KT using propensity score matching.ResultsIn total, 2735 KT recipients and 10,940 propensity score-matched dialysis patients were identified. The incidence rates of overall stroke were 9.1 and 23.4 per 1000 person-years in KT recipients and non-KT dialysis patients. Compared with the propensity score-matched dialysis patients, the patients who received KT exhibited significantly lower overall stroke risk, hemorrhagic stroke, and ischemic stroke, the adjusted hazard ratios were 0.37 (95% CI, 0.31–0.45), 0.19 (95% CI, 0.12–0.29), and 0.46 (95% CI, 0.37–0.56), respectively (all P < .001).ConclusionsThrough a propensity score-matched cohort, this study confirms that KT is associated with a reduced risk of stroke more than dialysis alone in patients with newly diagnosed ESRD.     

Outcomes of Recipients With Pancreas Transplant Alone Who Develop End‐Stage Renal Disease

Recipients of pancreas transplant alone (PTA) may be at increased risk for developing end‐stage renal disease (ESRD). The survival experience of PTA recipients developing ESRD has not been described. Furthermore, the relative survival of these patients as compared to diabetics on chronic dialysis is unknown. We studied all adult PTA recipients from January 1, 1990 to September 1, 2008 using the Scientific Registry of Transplant Recipients. Each PTA recipient developing ESRD was matched to 10 diabetics on chronic dialysis from the United States Renal Data System. Cox proportional hazards models were fitted to determine the relation between ESRD and mortality among PTA recipients, and the relation between PTA and mortality among diabetics on chronic dialysis. There were 1597 PTA recipients in the study, of which 207 developed ESRD. Those with ESRD had a threefold increase in mortality versus those without (adjusted hazard ratio 3.28 [95% confidence interval: 2.27, 4.76]). There was no significant difference in the risk of death among PTA recipients with ESRD versus diabetics on dialysis. PTA recipients developing ESRD are three times more likely to die than PTA recipients without ESRD; however, the risk of death in these patients was similar to diabetics on chronic dialysis without PTA.     

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.

     

Potential Advantages and Limitations of Applying the Chronic Kidney Disease Classification to Kidney Transplant Recipients

The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) classification of Chronic Kidney Disease (CKD) characterizes patients by their level of kidney function and includes kidney transplant recipients (KTRs). Most KTRs have stage > or = 3 CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2) and may benefit from aggressive CKD care. Recent modifications to the K/DOQI CKD classification reflect the recognition of KTRs as a unique subset of CKD patients in whom the presentation, progression and implications of CKD may vary from those in nontransplant CKD populations. Currently, there is limited information about how adopting the CKD classification in KTRs will influence clinical management and outcomes. Appropriately designed studies are needed to develop transplant-specific CKD treatment recommendations, and to ensure patient, health provider and payer acceptance of the continued need for aggressive CKD care after transplantation. Education and implementation strategies will be required to ensure appropriate integration of the CKD classification and treatment guidelines into existing posttransplant care programs. The CKD classification thus represents an exciting potential strategy to improve clinical outcomes that should be adopted, further studied and modified to incorporate considerations unique to KTRs.