Kidney Transplant Outcomes in Amyloidosis: US National Database Study.

BACKGROUND: We aimed to assess contemporary transplant outcomes among kidney recipients with amyloidosis, as the treatment and prognosis of amyloidosis have shown improvement over time. METHODS: Using the US Organ Procurement and Transplantation Network database, we initially evaluated the changes in patient and graft survival among kidney recipients with amyloidosis from 2002 to 2021. We then compared transplant outcomes between recipients with amyloidosis versus those with diabetic and nondiabetic causes of kidney failure, creating 1:4 matches with highly similar characteristics separately for deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) during the last decade (2012-2021). RESULTS: We identified 643 kidney recipients with amyloidosis during 2002-2021. Patient and death-censored graft survival improved over time. In the matching analysis for 207 DDKT and 166 LDKT recipients with amyloidosis during 2012-2021, patient survival was not significantly different between amyloidosis and diabetes groups in both DDKT (log-rank, P = 0.057) and LDKT (P = 0.99). Compared with the nondiabetes group, patient survival in the amyloidosis group was not significantly different for DDKTs (P = 0.56) but was significantly lower for LDKTs (P = 0.04). Death-censored graft failure risk was not significantly different between amyloidosis and diabetes or nondiabetes groups for both DDKTs (P = 0.78 and 0.75) and LDKTs (P = 0.40 and 0.24). CONCLUSIONS: In this well-matched cohort study, we found no significant differences in patient and graft survival between kidney recipients with amyloidosis and those with diabetes. Similarly, these outcomes were not significantly different between those with amyloidosis versus nondiabetic causes, except for patient survival of LDKT recipients.

Liver Outcome in Renal Transplant Recipients Who Acquired Hepatitis C Infection From an Infected Graft: Study Based on Liver Biopsy Findings.

Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.

Association of donor hepatitis C virus infection status and risk of BK polyomavirus viremia after kidney transplantation.

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring.

Association between ezetimibe usage and hepatitis C RNA levels in uninfected kidney transplant recipients who received hepatitis C infected kidneys.

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.

Robotic-assisted Kidney Transplantation With Simultaneous Bilateral Nephrectomies Is an Efficient, Feasible, and Safe Way to Manage Patients With Renal Failure Secondary to Adult Polycystic Kidney Disease.

Kidney transplantation has become the standard of care for end-stage renal disease secondary to adult polycystic kidney disease. Open surgical techniques remain the gold standard, although minimally invasive methods have gained traction in recent years. Native nephrectomy is frequently needed secondary to size or symptoms. Continued developments in surgical technology have allowed for the introduction of computer-assisted surgery (Robotics). We aim to describe the feasibility, safety, and efficiency of simultaneous laparoscopic bilateral nephrectomy and robotic-assisted kidney transplantation to treat end-stage renal kidney transplantation secondary to polycystic kidney disease. In this initial experience, 3 patients underwent kidney transplantation with a simultaneous bilateral nephrectomy. All patients tolerated the procedure well with no postoperative blood transfusions, dialysis, or surgical site infections. Simultaneous laparoscopic bilateral nephrectomy and robotic-assisted kidney transplantation may be feasible, safe, and efficient techniques. Complications were minimal, with short hospital stays. Supplemental Video; http://links.lww.com/TXD/A352.

Transplantation of liver from hepatitis C-infected donors to hepatitis C RNA-negative recipients: Histological and virologic outcome.

BACKGROUND: The virologic and histologic outcomes of a hepatitis C virus (HCV)-infected liver graft into an HCV-negative recipient are not well understood. We aimed to evaluate the sustained virologic response (SVR) rate and the liver histology at 1 year post-Orthotopic liver transplantation (OLT) with an HCV-infected graft. METHODS: A total of 33 patients received the HCV antibody (Ab)+/nucleic acid amplification test (NAT)+ graft. Of these patients, 23 were HCV-negative recipients and 10 were HCV-positive recipients. The 1-year biopsy data were available for 24 patients: 15 patients in HCV-negative group who received an HCV Ab+/NAT+graft and 9 patients in HCV-positive group who received an HCV Ab+/NAT+ graft. Patients with (+) HCV ribonucleic acid (RNA) were started on direct-acting antiviral (DAA) treatment approximately 107 days after OLT using either a Glecaprevir-Pibrentasvir or Sofosbuvir-Velpatasvir or Sofosbuvir-Ledipasvir. RESULTS: All patients (n = 33) were treated with DAA and achieved SVR. The 1-year post-OLT liver biopsies were available in 24 patients: 9 patients had F1 and F2 fibrosis and 17 patients had minimal to moderate inflammation. There was no statistical difference in fibrosis and inflammation between the HCV-negative vs. HCV-positive recipients. All patients who received the NAT+ graft developed viremia and subsequently achieved SVR with treatment. CONCLUSION: At 1 year protocol liver biopsy, patients had inflammation consistent with viral hepatitis despite the successful eradication of HCV.

Association between serum osteoprotegerin level and mortality in kidney transplant recipients - a prospective observational cohort study.

Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1 pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.

Predialysis Potassium Variability and Postdialysis Mortality in Patients With Advanced CKD.

INTRODUCTION: Patients with advanced non-dialysis-dependent chronic kidney disease (NDD-CKD) are prone to potassium (K) imbalances due to reduced kidney function. Both hypo- and hyperkalemia are associated with increased mortality; however, it is unclear if K variability before dialysis initiation is associated with outcomes after dialysis initiation. METHODS: We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 1, 2007, through March 31, 2015, who had at least 1 K measurement each year over a 3-year period before transition (3-year prelude). For each patient, a linear mixed-effects model was used to regress K over time (in years) over the 3-year prelude to derive K variability (square root of the average squared distance between the observed and estimated K). The main outcomes of interest were 6-month all-cause and cardiovascular mortality after dialysis initiation. Multivariable Cox and Fine-Gray competing risk regression adjusted for 3-year prelude K intercept, K slope (per year), demographics, smoking status, comorbidities, length of hospitalizations, body mass index, vascular access type, medications, average estimated glomerular filtration rate, and number of K measurements over the 3-year prelude were used to assess the association of K variability (expressed as quartiles) with all-cause and cardiovascular mortality, respectively. RESULTS: Higher prelude K variability was associated with higher multivariable-adjusted risk of all-cause mortality but not cardiovascular mortality (adjusted hazard/subhazard ratios [95% confidence interval] for highest quartile [vs. lowest] of K variability, 1.14 [1.03-1.25] and 0.99 [0.85-1.16] for all-cause and cardiovascular mortality, respectively). CONCLUSION: Higher K variability is associated with higher all-cause mortality after dialysis initiation.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes.

RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

Donor hepatitis C antibody positivity misclassifies kidney donor profile index in non-hepatitis C-infected donors: time to revise the kidney donor profile index - a retrospective cohort study.

The kidney donor profile index (KDPI) defines an hepatitis C (HCV) positive donor based on HCV antibody (Ab) and/or nucleic acid amplification test (NAT) positivity, with donors who are not actively infected (Ab+/NAT-) also classified as HCV positive. From Scientific Registry of Transplant Recipients dataset, we identified HCV-negative recipients, who received a kidney transplant from HCV Ab+/NAT- (n = 116) and HCV Ab-/NAT- (n = 25 574) donor kidneys. We then compared recipients' estimated glomerular filtration rate (eGFR) at 6 months in matched cohorts, using combined exact matching (based on KDPI) and propensity score matching. We created two separate matched cohorts: for the first cohort, we used the allocation KDPI, while for the second cohort we used an optimal KDPI, where the HCV component of KDPI was considered negative in Ab+/NAT- patients. The mean ± SD age of the allocation KDPI-matched cohort at baseline was 59 ± 10 years, 69% were male, 61% were white. Recipients' eGFR at 6 months after transplantation was significantly higher in the HCV Ab+/NAT- group compared to the HCV Ab-/NAT- group (61.1 ± 17.9 vs. 55.6 ± 18.8 ml/min/1.73 m2 , P = 0.011) in the allocation KDPI-matched cohort, while it was similar (61.8 ± 19.5 vs. 62.1 ± 20.1 ml/min/1.73 m2 , P = 0.9) in the optimal KDPI-matched cohort. Recipients who received HCV Ab positive, but NAT-negative donor kidneys did not experience worse 6-month eGFR than correctly matched HCV Ab-/NAT- recipients.

Association of age with risk of first and subsequent allograft failure and mortality among young kidney transplant recipients in the USA - a retrospective cohort study.

Adolescent age may be a high-risk period for kidney allograft failure. However, the knowledge on this topic is limited mostly to the first transplant. Among 20 960 patients aged ≤21 years at the first kidney transplantation from the US Renal Data System, we evaluated the association of age at the first kidney transplant with risk for the first and subsequent graft failures (1st, 2nd, and 3rd) using the conditional risk set model for recurrent time-to-event data. The median age was 15 (interquartile range: 9-18) years, and 18% received transplants twice or more during a median follow-up of 9.7 years. The risk for graft failures was highest in 16 to <18 years old with an adjusted hazard ratio (aHR) of 1.93 (95% CI, 1.73-2.15; reference: <3 years). When separately analyzed, the highest risk was observed in 17, 19, and 21 years old for the first, second, and third transplant, respectively. Those 16 to <18 years were also strongly associated with the highest risk for death after returning to dialysis (aHR, 4.01; 95% CI, 2.82-5.71). Adolescent recipients remain at high risk for allograft failure for a long time, which may result in high mortality risk, even though they surpass this high-risk period soon after the first transplant.

KDOQI US Commentary on the 2018 KDIGO Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C.

The first KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection was published in 2008. The ensuing decade bore witness to remarkable advances in the treatment of HCV infection following the approval of direct-acting antiviral (DAA) agents that deliver cure rates routinely >95%. In this context, the KDIGO organization correctly recognized the need for an updated HCV guideline that would be relevant to the treatment of HCV-infected patients with kidney disease in the DAA era. The current NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) commentary provides an in-depth review and perspective on the 2018 KDIGO guideline. Of note, the KDIGO work group made significant updates to guideline chapters 2 and 4 as a direct result of the availability of DAAs. The intent of this commentary is to provide useful interpretation for nephrologists and other practitioners caring for HCV-infected patients with chronic kidney disease, including dialysis patients and kidney transplant recipients. The availability of DAA agents that are safe and highly effective has created new opportunities, such as the transplantation of kidneys from HCV-infected kidney donors. The ability to treat HCV infection in patients with kidney disease will have a significant impact on the care of our patients and should favorably influence long-term outcomes as well.

Predialysis coronary revascularization and postdialysis mortality.

Objectives: Coronary artery bypass grafting (CABG) is associated with better survival than percutaneous coronary intervention (PCI) in patients with mild-to-moderate chronic kidney disease (CKD) and End-Stage Renal Disease (ESRD). However, the optimal strategy for coronary artery revascularization in advanced CKD patients who transition to ESRD is unclear. Methods: We examined a contemporary national cohort of 971 US veterans with incident ESRD, who underwent first CABG or PCI up to 5 years prior to dialysis initiation. We examined the association of a history of CABG versus PCI with all-cause mortality following transition to dialysis, using Cox proportional hazards models adjusted for time between procedure and dialysis initiation, socio-demographics, comorbidities and medications. Results: 582 patients underwent CABG and 389 patients underwent PCI. The mean age was 66±8 years, 99% of patients were male, 79% were white, 19% were African Americans, and 84% were diabetics. The all-cause post-dialysis mortality rates after CABG and PCI were 229/1000 patient-years (PY) [95% CI: 205-256] and 311/1000PY [95% CI: 272-356], respectively. Compared to PCI, patients who underwent CABG had 34% lower risk of death [multivariable adjusted Hazard Ratio (95% CI) 0.66 (0.51-0.86), p=0.002] after initiation of dialysis. Results were similar in all subgroups of patients stratified by age, race, type of intervention, presence/absence of myocardial infarction, congestive heart failure and diabetes. Conclusion: CABG in advanced CKD patients was associated lower risk of death after initiation of dialysis compared to PCI.

Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: Single center experience.

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

Acute kidney injury following coronary revascularization procedures in patients with advanced CKD.

BACKGROUND: Previous studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD. METHODS: We examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses. RESULTS: A total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P < 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P < 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P < 0.001]. CONCLUSION: CABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.

Association of Pretransplant Renal Function With Liver Graft and Patient Survival After Liver Transplantation in Patients With Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is one of the top 3 indications for liver transplantation (LT) in Western countries. It is unknown whether renal dysfunction at the time of LT has any effect on post-LT outcomes in recipients with NASH. From the United Network for Organ Sharing-Standard Transplant Analysis and Research data set, we identified 4088 NASH recipients who received deceased donor LT. We divided our recipients a priori into 3 categories: group 1 with estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 at the time of LT and/or received dialysis within 2 weeks preceding LT (n = 937); group 2 with recipients who had eGFR ≥30 mL/minute/1.73 m2 and who did not receive renal replacement therapy prior to LT (n = 2812); and group 3 with recipients who underwent simultaneous liver-kidney transplantation (n = 339). We examined the association of pretransplant renal dysfunction with death with a functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models. The mean ± standard deviation age of the cohort at baseline was 58 ± 8 years, 55% were male, 80% were Caucasian, and average exception Model for End-Stage Liver Disease score was 24 ± 9. The median follow-up period was 5 years (median, 1816 days; interquartile range, 1090-2723 days). Compared with group 1 recipients, group 2 recipients had 19% reduced trend for risk for death with a functioning graft (subhazard ratio [SHR], 0.81; 95% confidence interval [CI], 0.64-1.02) and similar risk for graft loss (SHR, 1.25; 95% CI, 0.59-2.62), whereas group 3 recipients had similar risk for death with a functioning graft (SHR, 1.23; 95% CI, 0.96-1.57) and graft loss (SHR, 0.18; 95% CI, 0.02-1.37) using an adjusted competing risk regression model. In conclusion, recipients with preserved renal function before LT showed a trend toward lower risk of death with a functioning graft compared with SLKT recipients and those with pretransplant severe renal dysfunction in patients with NASH.

Radical versus partial nephrectomy, chronic kidney disease progression and mortality in US veterans.

Background: Partial nephrectomy is considered the preferred care for localized kidney tumors and may yield better patient and kidney survival and similar oncological outcomes compared with radical nephrectomy. We sought to reexamine these hypotheses in a large nationally representative cohort of US veterans who underwent radical or partial nephrectomy. Methods: We identified 7073 US veterans who had a partial or radical nephrectomy between 2004 and 2013. We collected data on estimated glomerular filtration rate (eGFR) prior to admission for nephrectomy surgery, immediately after surgery and 180 days postsurgery. We evaluated the association of nephrectomy type and eGFR at different time points with long-term mortality risk in adjusted survival models. Results: Patients who underwent radical (compared to partial) nephrectomy had a 2-fold greater decline in eGFR (-21.8 ± 17.7 versus -10.3 ± 17.4 mL/min/1.73 m2) immediately after surgery. This larger drop in eGFR resulted in a larger proportion of radical nephrectomy patients having an eGFR <60 mL/min/1.73 m2 at ≥180 days postsurgery. Radical (compared to partial) nephrectomy patients also exhibited a 2.2-fold higher mortality [adjusted death hazard ratio 2.21 (95% confidence interval 1.91-2.55)]. Low eGFRs prior to surgery and 180 days postsurgery were associated with higher risk of postnephrectomy death. Conclusions: Worse postnephrectomy kidney function and higher mortality were observed with radical nephrectomy, and a low presurgical eGFR and a greater decrease in eGFR postsurgery were associated with worse mortality irrespective of the type of nephrectomy. Additional studies are needed to examine predictors of postnephrectomy outcomes.

Inflammatory Markers and Outcomes in Kidney Transplant Recipients.

BACKGROUND: Increased levels of TNF-α and IL6 are associated with inflammation and cardiovascular disease among patients with normal kidney function. However, little is known about their association with outcomes in kidney transplant recipients. METHODS: We collected sociodemographic, clinical and laboratory parameters, medical and transplant history from 977 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary study. Serum cytokine levels were measured at baseline. Associations between serum TNF-α and IL6 values and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. RESULTS: The mean ± SD age of the study population was 51 ± 13 years, 57% were men, 21% were diabetics. Median serum TNF-α and IL6 concentrations were significantly higher in patients who died with a functioning graft as compared with those who did not die during the follow-up period (TNF-α: median, 1.92 pg/mL; interquartile range [IQR], 1.43-2.67 pg/mL vs median, 2.25 pg/mL; IQR, 1.63-3.08 pg/mL, P < 0.001; and for IL6: median, 1.91 pg/mL; IQR, 1.21-3.02 pg/mL vs median, 2.81 pg/mL; IQR, 1.65-4.97 pg/mL, P < 0.001). Higher serum TNF-α and IL6 levels were associated with higher mortality risk in both unadjusted and fully adjusted models: TNF-α: hazard ratios (HRs)(1 pg/ml increments), 1.24; 95% confidence interval (CI), 1.13-1.36 and HRs(1 pg/ml increments), 1.19; 95% CI, 1.08-1.32; IL6: HRs(1 pg/ml increments), 1.06; 95% CI, 1.03-1.09 and HRs(1 pg/ml increments), 1.03; 95% CI, 0.99-1.06, respectively. Compared with patients whose serum TNF-α or IL6 levels were in the lowest tertile, those in the middle tertile had similar mortality risk (TNF-α: HR, 1.09; 95% CI, 0.74-1.61; IL6: HR, 1.05; 95% CI, 0.68-1.62), but patients in the highest tertile reported higher risk of mortality: TNF-α: HR, 1.45; 95% CI, 1.01-2.09; IL6: HR, 1.55; 95% CI, 1.04-2.32 in multivariable adjusted models. CONCLUSIONS: In prevalent kidney transplant recipients, serum TNF-α and IL6 were independently associated with death with a functioning graft.

The effect of ambient temperature and humidity on interdialytic weight gains in end-stage renal disease patients on maintenance hemodialysis.

PURPOSE: Interdialytic weight gain (IDWG) is both a measure of dietary compliance and a well-established predictor of future adverse outcomes in dialysis patients. The impact of environmental conditions on IDWG in end-stage renal disease is little studied to date. METHODS: We retrospectively reviewed IDWG for 100 consenting chronic end-stage renal disease patients undergoing thrice weekly in-center hemodiafiltration under three different climatic conditions in a Central European city: Weekend_1 was humid (93 %) and warm (24 °C); Weekend_2 was dry (38 %) and hot (33 °C); and Weekend_3 was dry (30 %) and warm (24 °C). RESULTS: The cohort's mean age was 60.9 ± 14.7 years, all were Eastern European, and 56 % were men. Residual urine output measured 100 [25-75 % quartiles: 0, 612] mL/day, single-pool Kt/V 1.4 ± 0.25, and albumin 40.1 ± 3.9 g/L. Mean IDWGs measured as follows: Weekend_1 ("humid-warm"): 2973 ± 1386 mL; Weekend_2 ("dry-hot"): 2685 ± 1368 mL and Weekend_3 ("dry-warm"): 2926 ± 1311 mL. Paired-samples testing for difference showed higher fluid gains on the humid-warm (239 mL; 95 % CI 21-458 mL; p = 0.032) and on the dry-warm weekends (222 mL; 95 % CI -8 to 453 mL, p = 0.059), when compared to the dry-hot weekend. Under the latter, dry-hot climatic condition, residual urine output lost its significance to impact IDWG during multiple regression analysis. CONCLUSION: While excess temperature may impact IDWG to a small degree, air humidity does not; the least weight gains occurred on the dry-hot weekend. However, the effects of both were minimal under continental summer conditions and are unlikely to explain large excesses of individual session-to-session variations.

Candidate Surrogate End Points for ESRD after AKI.

AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%-40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.