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Background: Under the current kidney allocation system, pediatric candidates listed prior to age 18 receive priority for high-quality deceased donor organs. This has resulted in a decline in living donor transplantation in pediatrics, despite superior outcomes of living donor transplantation. Due to a young age at transplantation, most pediatric kidney transplant recipients require re-transplantation. The effects of a previously failed deceased donor vs a previously failed living donor on re-transplant candidates are unknown., Methods: Using the United Network for Organ Sharing database, we examined 2772 re-transplant recipients aged 18-30 years at time of relisting for second KT from 2000 to 2018 with history of prior pediatric KT (age ≤ 18 years)., Results: PFLDKT recipients compared to those with PFDDKT had shorter median waiting times and dialysis time regardless of their second donor type (14.0 vs 20.3 months, and 19.1 vs 34.5 months, respectively). PFLDKT recipients had higher re-transplant rates (adjusted HR 1.17, 95% CI 1.09-1.27, and adjusted HR 1.05, 95% CI 0.95-1.15 when calculating from time of relisting and time of returning to dialysis, respectively). PFDDKT recipients were more likely to have higher median PRA levels (90% vs 73%)., Conclusions: Re-transplant candidates who received a previous deceased donor as a child had a higher level of sensitization, longer waiting time, and dialysis exposure compared to those with PFLDKT. Among primary pediatric kidney transplant candidates, consideration should be considered for living donor transplantation, despite the priority for deceased donor organs, to avoid increased sensitization and longer waiting times for with re-transplantation., (© 2020 Wiley Periodicals LLC.)

Improving long-term transplant and patient survival is still an ongoing challenge in kidney transplant medicine. Our objective was to identify the subsequent risks of new-onset diabetes after transplant (NODAT) and acute rejection (AR) in the first year post-transplant in predicting mortality and transplant failure. A total of 4687 patients without preexisting diabetes (age 2-20 years, 2004-2010) surviving with a functioning transplant for longer than 1 year with at least one follow-up report were identified from the OPTN/UNOS database as of September 2014. Study population was stratified into four mutually exclusive groups: Group 1, patients with a history of AR; Group 2, NODAT+; Group 3, NODAT+ AR+; and Group 4, the reference group (neither). Multivariate regression was used to analyze the relative risks for the outcomes of transplant failure and mortality. The median follow-up time was 1827 days after 1 year post-transplant. AR was associated with an increased risk of adjusted graft and death-censored graft failure (HR 2.87, CI 2.48-3.33, P < .001 and HR 2.11, CI 1.81-2.47, P < .001), respectively. NODAT and AR were identified in 3.5% and 14.5% of all study patients, respectively. AR in the first year post-transplant was a major risk factor for overall and death-censored graft failure, but not mortality. However, NODAT was not a risk factor on graft survival or mortality., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: There have been no well defined guidelines to determine whether a kidney transplant should be offered to liver transplant candidates who have chronic kidney disease (CKD) or prolonged acute kidney injury while awaiting a liver transplant. This article provides a review of current literature on risk factors for CKD progression after liver transplantation alone (LTA) in patients with pretransplant renal dysfunction and the utility of cystatin C (Cyst C) to assess renal function in cirrhotic patients. Studies evaluating risk factors for transplant futility are also discussed. Based on available literature and existing consensus guidelines, a proposed algorithm for simultaneous liver-kidney transplantation (SLKT) or LTA is formulated., Recent Findings: In LTA recipients with pretransplant renal dysfunction, diabetes mellitus and type 2 hepatorenal syndrome are associated with CKD progression posttransplant. Coexisting diabetes and stages 3-4 CKD increase end-stage renal disease risk. Cyst C may be a better marker of renal function in cirrhotics. In LTA recipients, very high MELD scores and the concomitant presence of multiple comorbidities increase liver transplant futility risk. Similar studies in SLKT recipients are lacking., Summary: Pretransplant diabetes status should be incorporated into future guidelines for SLKT, whereas simultaneous kidney transplantation should be deferred in highest acuity SLKT candidates with high kidney transplant futility risk. Cyst C-based equations may allow clinicians to better select the most appropriate candidates for SLKT or LTA. Further studies are needed., Competing Interests: The authors declare no conflict of interest.

Background/aims: We examined post-transplant survival among obese kidney candidates who were temporarily designated waitlist inactive (status 7) due to their weight., Methods: Using OPTN/United Network for Organ Sharing data, patient and graft survival of adult status 7 recipients with a registration body mass index (BMI) ≥30 kg/m(2) (n = 328) were compared to all others (controls; n = 74,066). Status 7 recipients were then matched to controls to assess whether pre-transplant weight loss was associated with a survival benefit., Results: Median BMI at registration (38 vs. 27 kg/m(2), p < 0.001) and transplant (36 vs. 27 kg/m(2), p < 0.001) and reduction in BMI while waitlisted (-5.0 vs. 0.0%, p < 0.001) were higher among status 7 than controls. Patient (status 7: 87.3%; control: 89.3%; p = 0.90) and graft survival (status 7: 82.9%; control: 81.6%; p = 0.75) were similar over 4 years. There was no association between status 7 and mortality (HR 0.96, 95% CI 0.59-1.57) or graft loss (HR 0.95, 95% CI 0.66-1.38) in the overall population nor between matched status 7 recipients and controls (patient survival: 86.0 vs. 87.5%, p = 0.20; graft survival: 82.6 vs. 77.2%, p = 0.61)., Conclusion: Among obese status 7 kidney candidates previously considered too obese for transplant, patient and graft survival were comparable to the general transplant population. No difference in survival was observed with pre-transplant weight loss.

This Phase III randomized trial examined efficacy and safety of a novel once-daily extended-release tacrolimus formulation (LCP-Tacro [LCPT]) versus twice-daily tacrolimus in de novo kidney transplantation. Primary efficacy end point was proportion of patients with treatment failure (death, graft failure, biopsy-proven acute rejection or lost to follow-up) within 12 months. Starting doses were, LCPT: 0.17 mg/kg/day and tacrolimus twice-daily: 0.1 mg/kg/day; 543 patients were randomized, LCPT: n = 268; tacrolimus twice-daily: n = 275. At 12 months treatment failure was LCPT: 18.3% and tacrolimus twice-daily: 19.6%; the upper 95% CI of the treatment difference was +5.27%, below the predefined +10% noninferiority criteria. There were no significant differences in the incidence of individual efficacy events or adverse events. Target tacrolimus trough levels were more rapidly achieved in the LCPT group. Following initial dose, 36.6% of patients in the LCPT group had rapidly attained trough levels within 6-11 ng/mL versus 18.5% of tacrolimus twice-daily patients; majority of tacrolimus twice-daily patients (74.7%) had troughs <6 ng/mL compared with 33.5% in the LCPT group. Overall, cumulative study dose was 14% lower for LCPT. Results suggest that use of once-daily LCPT in de novo kidney transplantation is efficacious and safe. Lower LCPT dose reflects the improved absorption provided by the novel formulation., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Candidates may be active or temporarily inactive (status 7) on the kidney transplant waiting list. One reason candidates may be inactive is for a "weight currently inappropriate for transplantation." We hypothesized that many of these candidates would not achieve active status., Methods: Using OPTN/UNOS data from 2006 to 2012, we used competing risks methods to determine the cumulative incidence of conversion to active status (activation), death, and delisting before conversion among 1679 obese adult kidney candidates designated as status 7 because of a weight inappropriate for transplantation. Fine and Gray competing risks regression was performed to characterize factors associated with conversion to active status in the overall study population and of transplantation among a subgroup of activated candidates., Results: At 6 years, the cumulative incidence of activation was 49%, of death before conversion was 15%, and of delisting was 21%. Higher body mass index (BMI) was strongly associated with a decreased subhazard of activation (BMI ≥45 versus 30-34.9, sHR: 0.22; 95% CI, 0.16-0.33). Female sex, diabetic end-stage renal disease, history of a previous transplant, panel reactive antibodies less than 80%, dialysis dependence at listing, and UNOS region 5 were negatively associated with activation. Among activated candidates, the cumulative incidence of transplantation at 6 years after initial waitlisting was 61%., Conclusion: Our findings indicate that half of obese status 7 candidates with a weight inappropriate for transplantation will not achieve active waitlist status. BMI at listing had a strong association with conversion to active status; comorbid factors and regional variation also impact activation.

Kidney transplantation has become a preferred treatment for end-stage renal disease (ESRD) as transplant recipients enjoy freedom from dialysis and improvement in both quality and quantity of life. More patients are being placed on the transplant waiting list, although the waiting list patients still only represent a very small fraction of ESRD patients. The characteristics of both waitlisted and transplanted patients have changed considerably in the last decade, as the ESRD population has aged and waiting list times have increased. Over the last 10 years, we have witnessed an increasingly severe shortage of kidney donors. Even with increasing efforts of the transplant community to expand the donor pool by including larger numbers of high risk deceased donor transplants, the overall number of kidney transplants has remained relatively stable. Those who do receive transplants, however, benefit from excellent transplant outcomes. The use of paired exchange/chain transplant donors has increased the living donor pool significantly and with outstanding results. Belatacept, a costimulation blockage drug, represents a new class of transplant immunosuppression. It has been used sparingly in the first few years of its approval. Most kidney transplant patients are still maintained on immunosuppressive agents that were approved almost two decades ago. In the next decade, we will certainly continue to deal with an organ shortage as the number of eligible and waitlisted patients is likely to increase. Effective and efficient organ allocation policies will be increasingly necessary to address this scarcity. Optimizing the transplant candidate work-up, improving maintenance of waitlisted patients, and providing optimal post-transplant medical care will be vital to the continued success of kidney transplantation.

Background: Studies from older cohorts of kidney recipients have observed that recipients with sickle cell disease (SCD) have lower patient survival compared with age- and race-matched controls. We examined whether survival has improved among SCD recipients in the current era., Methods: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing data, all black/African-American kidney recipients were stratified according to transplant year into an early (1988-99) and recent era (2000-11). Patient and allograft survival among SCD recipients and those with other diagnoses were compared (early era: SCD n = 67, others n = 20 694; recent era: SCD n = 106, others n = 34 428). A secondary-matched cohort analysis compared patient and allograft survival between SCD recipients matched to recipients with other diagnoses based on recipient and donor age, gender and donor type (deceased versus living)., Results: Patient survival at 6 years was lower among SCD recipients in the early era compared with other diagnoses (55.7 versus 78.0%; P < 0.001). Six-year patient survival among sickle cell recipients improved in the recent era (69.8%; P versus early era = 0.04), although still trended toward lower survival compared with other diagnoses (80.0%; P = 0.07). Multivariate Cox proportional hazard models revealed an increased mortality risk with SCD in both eras [early: hazard ratio (HR) = 3.12; 95% confidence interval (CI): 2.15-4.54; recent: HR: 2.03; 95% CI: 1.31-3.16]. Patient survival among matched SCD recipients in the recent era was comparable to diabetic recipients (SCD: 73.1%, diabetes: 74.1%; P = 0.44)., Conclusions: Patient survival has improved among contemporary sickle cell recipients compared with an earlier cohort and is comparable to a matched cohort of diabetic kidney recipients. Appropriately selected SCD patients may receive kidney transplants with reasonable survival outcome.

Pancreas transplant alone (PTA) is usually performed in type 1 diabetic patients with preserved renal function to correct severe metabolic complications. One of the major concerns is renal failure after PTA. Here, we reported the cumulative incidence of kidney failure requiring kidney transplantation (KF/KT) among PTA recipients in the United States. Using the Organ Procurement Transplant Network/ United Network for Organ Sharing database, all primary adult PTA recipients with estimated baseline glomerular filtration rate (by the Modification of Diet in Renal Disease equation) >or=60 mL/min/1.73m2 were selected (n=1085). KF/ KT after PTA was defined as: wait-listing for or receiving a kidney alone (KA) or simultaneous pancreas kidney (SPK) transplant. The median follow-up time was 1185 days (25-75%: 524-2183). Ten years post PTA, 120 (11.1%) patients developed KF/KT; of those, 70 (6.5%) subsequently received a KA/SPK transplant (56 received KA and 14 received SPK) and 50 (4.6%) recipients were listed without receiving a transplant. The cumulative incidence of KF/KT after PTA at 1, 3, and 5 years after PTA was 0.3, 2.5, and 9.7%, respectively. In conclusion, KF/KT after PTA was not uncommon (9.7% at 5 years), and prospective PTA recipients should be aware of the risks of kidney failure after transplantation.

Background: Delayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF., Methods: Linking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF., Results: Patients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ≥13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34)., Conclusions: Pre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF., (© 2012 John Wiley & Sons A/S.)

Background: Recent studies show a survival advantage with kidney transplant in elderly patients compared with those on dialysis therapy., Study Design: In our present study, we examined and compared the association of expanded criteria donor (ECD) kidney and living kidney donation with the outcome of kidney transplant across different ages, including elderly recipients., Setting & Participants: Using the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplant patients. Mortality and death-censored transplant failure risks were estimated by Cox proportional regression analyses during follow-up with a median of 3.9 years., Predictors: ECD kidney and living kidney donation and age compared with others., Outcomes: Mortality and death-censored transplant failure risk., Results: Patients were aged 45 ± 16 years and included 40% women and 19% patients with diabetes. Compared with transplant recipients 55 to younger than 65 years, the fully adjusted death-censored transplant failure risk was higher in patients 75 years and older (HR, 1.30; 95% CI, 1.09-1.56), 35 to younger than 55 years (HR, 1.13; 95% CI, 1.08-1.17), and 18 to younger than 35 years (HR, 1.64; 95% CI, 1.57-1.71). Compared with non-ECD kidneys, ECD kidneys were significant predictors of mortality in nonelderly patients (18-<35 years: HR, 1.46 [95% CI, 1.19-1.77]; 35-<55 years: HR, 1.23 [95% CI, 1.14-1.32]; and 55-<65 years: HR, 1.26 [95% CI, 1.15-1.38]) and patients 65 to younger than 70 years (HR, 1.20; 95% CI, 1.05-1.36), but not in other groups of elderly patients (HRs of 1.12 [95% CI, 0.93-1.36] for 70-<75 years and 1.04 [95% CI, 0.74-1.47] for ≥75 years). Similar results were found for risk of transplant loss. Compared with deceased donor kidneys, a living donor kidney was associated with better survival in all age groups and lower transplant loss risk in patients younger than 70 years., Limitations: Unmeasured confounders cannot be adjusted for., Conclusions: For deceased donors, ECD kidneys are not associated with increased mortality or transplant failure in recipients older than 70 years. For all types of donors, the persistent association between living donor kidneys and lower all-cause mortality across all ages suggests that, if possible, elderly patients gain longevity from living donor kidney transplant., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Over the past two decades, most guidelines have advocated early initiation of dialysis on the basis of studies showing improved survival in patients starting dialysis early. These recommendations led to an increase in the proportion of patients initiating dialysis with an estimated glomerular filtration rate (eGFR) >10 ml/min/1.73 m(2), from 20% in 1996 to 52% in 2008. During this period, the percentage of patients starting dialysis with an eGFR ≥15 ml/min/1.73 m(2) increased from 4% to 17%. However, recent studies have failed to substantiate a benefit of early dialysis initiation and some data have suggested worse outcomes for patients starting dialysis with a higher eGFR. Several reasons for this seemingly paradoxical observation have been suggested, including the fact that patients requiring early dialysis are likely to have more severe symptoms and comorbidities, leading to confounding by indication, as well as biological mechanisms that causally relate early dialysis therapy to adverse outcomes. Patients with a failing renal allograft who reinitiate dialysis encounter similar problems. However, unique factors associated with a failed allograft means that the optimal timing of dialysis initiation in failed transplant patients might differ from that in transplant-naive patients with chronic kidney disease. In this Review, we discuss studies of dialysis initiation and compare risks and benefits of early versus late initiation and reinitiation of dialysis therapy.

Background and Objectives: The association between pretransplant body composition and posttransplant outcomes in renal transplant recipients is unclear. It was hypothesized that in hemodialysis patients higher muscle mass (represented by higher pretransplant serum creatinine level) and larger body size (represented by higher pretransplant body mass index [BMI]) are associated with better posttransplant outcomes., Design, Setting, Participants, & Measurements: Linking 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, 10,090 hemodialysis patients were identified who underwent kidney transplantation from July 2001 to June 2007. Cox regression hazard ratios and 95% confidence intervals of death and/or graft failure were estimated., Results: Patients were 49 ± 13 years old and included 49% women, 45% diabetics, and 27% African Americans. In Cox models adjusted for case-mix, nutrition-inflammation complex, and transplant-related covariates, the 3-month-averaged postdialysis weight-based pretransplant BMI of 20 to <22 and < 20 kg/m(2), compared with 22 to <25 kg/m(2), showed a nonsignificant trend toward higher combined posttransplant mortality or graft failure, and even weaker associations existed for BMI ≥ 25 kg/m(2). Compared with pretransplant 3-month- averaged serum creatinine of 8 to <10 mg/dl, there was 2.2-fold higher risk of combined death or graft failure with serum creatinine <4 mg/dl, whereas creatinine ≥14 mg/dl exhibited 22% better graft and patient survival., Conclusions: Pretransplant obesity does not appear to be associated with poor posttransplant outcomes. Larger pretransplant muscle mass, reflected by higher pretransplant serum creatinine level, is associated with greater posttransplant graft and patient survival.

Background and Objectives: Type 2 diabetic patients with end-stage renal disease may receive a simultaneous pancreas-kidney (SPK) transplant. However, outcomes are not well described. Risks for death and graft failure were examined in SPK type 2 diabetic recipients., Design, Setting, Participants, & Measurements: Using the United Network for Organ Sharing database, outcomes of SPK transplants were compared between type 2 and type 1 diabetic recipients. All primary SPK adult recipients transplanted between 2000 and 2007 (n=6756) were stratified according to end-stage pancreas disease diagnosis (type 1: n=6141, type 2: n=582). Posttransplant complications and risks for death and kidney/pancreas graft failure were compared., Results: Of the 6756 SPK transplants, 8.6% were performed in recipients with a type 2 diabetes diagnosis. Rates of delayed kidney graft function and primary kidney nonfunction were higher in the type 2 diabetics. Five-year overall and death-censored kidney graft survival were inferior in type 2 diabetics. After adjustment for other risk factors, including recipient (age, race, body weight, dialysis time, and cardiovascular comorbidities), donor, and transplant immune characteristics, type 2 diabetes was not associated with increased risk for death or kidney or pancreas failure when compared with type 1 diabetic recipients., Conclusions: After adjustment for other risk factors, SPK recipients with type 2 diabetes diagnosis were not at increased risk for death, kidney failure, or pancreas failure when compared with recipients with type 1 diabetes., (Copyright © 2011 by the American Society of Nephrology)

Wegener's granulomatosis (WG) is the leading cause of rapidly progressive glomerulonephritis-induced end-stage renal disease (ESRD). In this study, we compared transplant outcomes between recipients with ESRD caused by WG to recipients with ESRD secondary to other causes. Using OPTN/UNOS data from 1996 to 2007, 919 recipients with WG were identified. Post-transplant outcomes included rates of delayed graft function, acute rejection within one-yr post-transplant, overall and death-censored graft survival, and patient survival and were compared between recipients with ESRD secondary to WG versus ESRD from other causes. Recipients with ESRD because of WG had superior unadjusted and adjusted rates of graft loss, patient death, and functional graft loss (adjusted hazard ratio [HR] 0.711, 0.631, and 0.625 respectively, p < 0.001). When we compared the WG cohort to a non-WG, non-diabetic population, the HR for graft loss was still significant, but patient death and death-censored graft loss were not. Subgroup analysis of recipients aged over 60 confirmed that WG recipients had better unadjusted outcomes. This study supports the notion that renal transplantation is an effective treatment option for patients with ESRD secondary to WG. They fare similarly, if not better, than other patients., (© 2010 John Wiley & Sons A/S.)

The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and Objectives: Transplant options for type I diabetics with end-stage renal disease include simultaneous pancreas-kidney (SPKT), living donor kidney (LDKT), and deceased donor kidney transplant (DDKT). It is unclear whether SPKT offers a survival benefit over LDKT in the current era of transplantation. The authors compared outcomes of kidney transplant recipients with type I diabetes using data from the Organ Procurement and Transplant Network/United Network for Organ Sharing., Design, Setting, Participants, & Measurements: Adult (age 20 to 59) type I diabetics who received a solitary first-time kidney transplant between 2000 and 2007 were studied. Outcomes included overall kidney graft and patient survival. Multivariate analysis was performed using a stepwise Cox proportional hazards model., Results: Kidney graft survival was better for recipients of LDKT compared with SPKT (P = 0.008), although patient survival was similar (P = 0.346). On multivariate analysis, LDKT was associated with lower adjusted risks over 72 mo follow-up of kidney graft failure (HR 0.71; 95% CI 0.61 to 0.83) and patient death (HR 0.78; 95% CI 0.65 to 0.94) versus SPKT. Compared with DDKT, SPKT had superior unadjusted kidney graft and patient survival, partly due to favorable SPKT donor and recipient factors., Conclusions: Despite more transplants from older donors and among older recipients, LDKT was associated with superior outcomes compared with SPKT and was coupled with the least wait time and dialysis exposure. LDKT utilization should be considered in all type I diabetics with an available living donor, particularly given the challenges of ongoing organ shortage.

Background: Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival., Methods and Results: We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain <1.0 kg and > or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively., Conclusions: In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.

Background: Fabry disease is a rare but important cause of end-stage renal disease (ESRD) among young men. Postkidney transplantation outcomes among patients with Fabry disease remain controversial., Methods: Using data from Organ Procurement Transplant Network/United Network for Organ Sharing, 197 kidney transplant recipients with ESRD because of Fabry disease from 1987 to 2007 were identified. We compared rates of graft loss and death with those of kidney transplant recipients with other (non-Fabry) causes of ESRD. Fabry patients were then compared with a 10:1 matched cohort of transplant recipients with other causes of ESRD., Results: Five-year graft survival was superior among Fabry patients (74%) compared with those with other causes of ESRD (69%), but was similar to those in the matched cohort (P=0.64). Five-year patient survival among Fabry patients (81%) was similar to those with other causes of ESRD (P=0.33), but was inferior to the matched cohort (90%). Cox multivariate analysis revealed that Fabry patients had a 40% lower risk of returning to dialysis compared with both matched and unmatched cohorts, but had a higher risk of death (2.15; 1.52-3.02) compared with the matched cohort., Conclusion: This analysis of 197 kidney transplant recipients with Fabry indicates that they have superior graft survival and similar patient survival compared with patients with other causes of ESRD. However, Fabry patients had a higher risk of death compared with a matched cohort of patients with other causes of ESRD. This requires further investigation and may suggest a need for further attention to the minimization of cardiovascular death in this group of patients.

Background: The organ shortage has resulted in more use of older deceased donor kidneys. Data are limited on the impact of donor aged 70 years and older on transplant outcomes. We examined patient and graft outcomes of renal transplant from expanded criteria donors (ECDs) aged 70 years and older, using the Organ Procurement Transplant Network/United Network of Organ Sharing database., Methods: We identified 601 deceased donor transplants from donors older than 70 years from 2000 to 2005. The follow-up time was until May 2007. Allograft and patient survival were compared between recipients of transplants from older ECDs (age > or =70) and younger ECDs (age 50-69). The relative risk of graft loss and patient death were determined using multivariate models., Results: The adjusted relative risks of overall graft loss (hazards ratio [HR] 1.37; 95% confidence interval [CI] 1.19-1.58), death-censored graft loss (HR 1.32; 95% CI 1.09-1.61), and patient death (HR 1.37; 95% CI 1.15-1.64) were greater among recipients of transplants from older ECD kidneys. The relative risk of patient death was lower when older ECD kidneys were transplanted into recipients older than 60 compared with recipients aged 41 to 60. In contrast, the relative risk of death-censored graft loss was not increased when older ECD kidneys were transplanted into recipients older than 60., Conclusions: Transplants from older ECD kidneys are associated with a higher risk of graft loss and patient death. The risk was highest when older ECD kidneys were transplanted into recipients younger than 60 years.

Background: Clinical data are lacking concerning concomitant administration of everolimus and tacrolimus in renal transplant recipients., Methods: In a prospective, multicenter, open-label, exploratory, randomized, 6-month study, 92 de novo renal transplant patients received everolimus, steroids, and basiliximab with low or standard tacrolimus exposure. The primary objective was to compare renal function at 6 months after transplant., Results: Mean 6-month serum creatinine (primary safety variable) was 112+/-31 micromol/L (1.26+/-0.35 mg/dL) and 127+/-50 micromol/L (1.44+/-0.57 mg/dL) in the low and standard tacrolimus groups, respectively, (n.s.); mean estimated GFR (Nankivell) was 75.3+/-16.6 mL/min and 72.5+/-15.2 mL/min (n.s.). Biopsy-proven acute rejection occurred in 13 patients: seven (14%) in the low tacrolimus group and six (14%) in the standard tacrolimus group, n.s. One graft was lost in the standard tacrolimus group. No patients died., Conclusions: Tacrolimus exposure reduction in the presence of everolimus, steroids and basiliximab induction results in good efficacy in de novo renal transplant recipients with very well-preserved renal function. Additional studies are warranted because between-group comparisons were limited by the relatively small differences in tacrolimus exposure in the 2 arms; trough levels were toward the upper end of the low-exposure ranges and toward the bottom of the standard-exposure ranges.

Background: Patients on maintenance dialysis typically show a suboptimal immune response to hepatitis B virus vaccine compared with the non-uraemic population. Some authors have claimed that dialysis mode has an impact on the immune response to hepatitis B virus vaccine but consistent information is lacking on this issue., Aim: To evaluate the relationship between dialysis mode and immune response to hepatitis B vaccine in dialysis population by performing a systematic review with a meta-analysis of clinical trials., Method: We used the random effects model of DerSimonian and Laird; sources of heterogeneity in effect estimates were explored by performing sensitivity analyses., Results: The relative risk of failure to respond to hepatitis B vaccine among patients who underwent maintenance haemodialysis vs. peritoneal dialysis was the end point of interest. We identified 14 clinical trials involving 1211 unique patients on maintenance dialysis. Pooling of study results did not show a significant decreased risk of response to hepatitis B vaccine among haemodialysis patients (overall risk ratio: 1.0, 95% confidence intervals: 0.92-1.1). The P-value was 0.13 for our test of study heterogeneity., Conclusion: There is no significant link between dialysis mode and seroresponse to hepatitis B virus vaccine in dialysis population.

Hepatitis C virus (HCV) is common in certain solid organ transplant recipients, most notably in those undergoing liver or kidney transplantation. Infection typically antedates transplantation but may have been acquired at the time of transplantation via infected blood products or organs. A more rapid and aggressive course of HCV-related infection and liver disease is the major concern in organ transplant recipients compared with immunocompetent patients. HCV-related liver disease is an important cause of morbidity and mortality in patients with end-stage renal disease treated by dialysis or transplantation. The outcome of HCV infection in renal and liver transplant recipients has been extensively investigated, whereas literature on HCV-related liver disease among patients with orthotopic heart transplantation is scanty. This article reviews the literature concerning the treatment of HCV-related liver disease in renal and orthotopic heart transplantation.

Background: The natural history of hepatitis C virus infection among patients on long-term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life-expectancy is substantially diminished by end-stage renal disease., Aim: To conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus infection on the survival of patients receiving chronic dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point., Methods: We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality with hepatitis C virus across the published studies., Results: We identified four clinical trials (2341 unique patients); three (75%) of them were prospective, cohort studies; the fourth was a case-control study. Pooling of study results demonstrated that presence of antihepatitis C virus antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for relative risk was 1.57 with a 95% confidence interval (CI) of 1.33-1.86. A test for homogeneity of the relative risks across the four studies gave a P-value of 0.77. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among antihepatitis C virus-positive than -negative dialysis patients., Conclusions: This meta-analysis demonstrates that antihepatitis C virus-positive patients on dialysis have an increased risk of mortality compared with hepatitis C virus-negative patients. The excess risk of death in hepatitis C virus-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. Clinical trials with extended follow-up are currently under way to assess the effect of hepatitis C virus treatment on the excess risk of mortality in this population.

Background: Patients on maintenance dialysis typically show a suboptimal immune response to hepatitis B virus vaccine compared with the non-uraemic population. A variety of inherited or acquired factors have been implicated in this diminished response. Age-associated changes in immune status may contribute to decreased vaccine efficacy in older individuals although contradictory results have been reported in individuals with normal kidney function., Aims: To evaluate the relationship between age and immune response to hepatitis B vaccine in patients with end-stage renal disease by performing a systematic review of the literature with a meta-analysis of clinical trials., Method: We used the random effects model of DerSimonian and Laird; sources of heterogeneity in effect estimates were explored by performing sensitivity analyses., Results: We identified 17 clinical trials (1800 unique patients); six (35%) were controlled studies. Pooling of study results demonstrated a significantly decreased risk of response to hepatitis B vaccine among older dialysis patients (overall risk ratio: 0.74; 95% confidence intervals: 0.70-0.79). The P-value was 0.0139 for our test of study heterogeneity. A lowered risk of response to hepatitis B vaccine persisted after exclusion of trials based on plasma-derived vaccines; it was present even when 'older' individuals were defined as being as 50 years (RR: 0.85, 95% CI: 0.75-0.96) or more (cut-off 60 years RR: 0.75; 95% CI: 0.66-0.85). An effect of age on seroprotection rate was present in all clinical reports, irrespective of the geographic origin of the study group: Europe (RR: 0.76; 95% CI: 0.70-0.83) North America (RR: 0.67; 95% CI: 0.60-0.74) or other countries (RR: 0.83; 95% CI: 0.71-0.97). Additional doses of vaccine did not appear to have an impact on RR of response by age., Conclusions: Our meta-analysis showed a clear association between older age and impaired response to hepatitis B virus vaccine in end-stage renal disease patients. Such a relationship is biologically plausible. Vaccination schedules with adapted vaccine doses and frequent serum testing for loss of immunity against hepatitis B virus are recommended in elderly patients on maintenance dialysis.

In the last several years, numerous studies on the natural history and outcomes of viral hepatitis in dialysis and transplantation have been reported. Despite these, the management of hepatitis C virus or hepatitis B virus-related liver disease in end-stage renal disease continues to be an area of controversy. This article aims to address the current therapeutic options for patients with renal disease and chronic viral hepatitis.

Controlling the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major triumphs in the management of end-stage renal disease. However, HBV incidence and prevalence rates remain high in dialysis patients in less-developed countries, and HBV within dialysis units continues to spread in the industrialized world. Overall response rates to HBV vaccination are lower in dialysis patients than in the nondialysis population. Lamivudine is effective in the treatment of HBV infection in the dialysis setting. Presence of hepatitis B surface antigen (HbsAg) has a negative impact on patient survival after renal transplantation. Several issues remain unanswered with regard to the management of HBV infection in dialysis patients, including the management of lamivudine resistance and the optimal timing and duration of antiviral therapy. Liver biopsy prior to renal transplantation is crucial in order to identify and exclude patients with advanced fibrosis or even cirrhosis.

Background: The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue., Methods and Aims: We evaluated the efficacy and safety of initial interferon monotherapy in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses., Results: We have identified 14 clinical trials (269 unique patients); two were controlled studies. The mean overall estimate for sustained virological response (SVR) and drop-out rate was 37%[95% confidence interval (CI) 28-48] and 17% (95% CI 10-28), respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms (17%), neurological (21%) and gastrointestinal (18%). The overall weighted estimate for SVR in patients with hepatitis C virus genotype 1 was 30.6% (95% CI 20.9-48). In the sub-group of clinical trials (n = 5) with standard interferon administration (3 million units [MUI] thrice weekly, subcutaneous route, 24-week treatment), the overall mean estimate of SVR was 39% (95% CI 25-56). The studies were heterogeneous with regard to SVR and drop-out rate., Conclusions: Tolerance to initial interferon monotherapy was lower in dialysis than nonuremic patients with chronic hepatitis C. However, more than one-third of haemodialysis patients with chronic hepatitis C have been successfully treated with interferon. Longer duration of interferon monotherapy does not appear to have a beneficial effect on the response rate. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in dialysis population.

Hepatitis C virus (HCV) infection remains frequent among dialysis patients. The relationship between viral load and liver disease progression is currently a matter of debate; however, low HCV viral load (HCV RNA) is a well established predictor of successful antiviral treatment. Dialysis patients have immune compromise due to uremia; in spite of this, HCV viral load is not high and does not increase over time. A number of studies support the notion that this dynamics of HCV viral load may be related to lowering of HCV RNA titers during the HD procedure. It has been suggested that the intradialytic reduction of HCV is membrane-dependent; polysulphone (PS) and hemophan membranes appear more effective. Various mechanisms have been mentioned to explain the reduction of HCV RNA during hemodialysis (HD): adsorption of HCV onto dialysis membrane, HCV escape into spent dialysate, destruction of HCV particles or increased interferon (IFN) activity. Several investigators have noted that, at the end of the HD procedure, a virological rebound of HCV viremia occurs. Some suggestions have been made to minimize the risk for HCV escape into spent dialysate. However, controversial evidence on these issues exists: the HCV RNA reduction during HD procedures has not been seen in some studies and the relationship between the intra-dialytic reduction of HCV RNA titers and dialysis membrane is not completely understood. It is evident that additional long-term longitudinal studies by serial viral load estimations are needed to better define the dynamics of HCV viral load in the dialysis population.

Hepatitis C virus infection (HCV) is common in patients with end-stage renal disease (ESRD) and long observation periods have shown the detrimental effect of HCV infection on patient and graft survival after renal transplantation. At present, interferon is the most important agent for the treatment of hepatitis C in ESRD; however, limited information exists concerning the long-term response of patients who undergo renal transplantation after successful antiviral therapy. We describe the evolution of HCV infection in a dialysis patient with hepatitis C who was successfully treated with interferon alpha and then underwent renal transplantation. He received aggressive immunosuppression during the induction phase and for allograft rejection; however, regular screening showed complete absence of biochemical and virological relapse of HCV over a 6-year post-transplantation period. We conclude that interferon can offer excellent response in selected dialysis patients with hepatitis C. Alternative strategies with newer antiviral agents are currently under active investigation.

The purpose of this paper is to describe the ICED, summarize outcomes of prior studies in which it was used, and describe the adaptations that have lead to the present instrument. We will then demonstrate its use in quantifying the burden of comorbid conditions in a sample of hemodialysis and peritoneal dialysis patients from our center, and show the relationship between ICED levels and outcomes in peritoneal dialysis patients.