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Background. There are limited data about the risk factors for weight changes and the association of significant weight changes with graft and metabolic outcomes after simultaneous pancreas and kidney (SPK) transplantation. Methods. We included all SPK recipients with both allografts functioning for at least 6 mo post-transplant and categorized them based on the weight changes from baseline to 6 mo post-transplant. We analyzed risk factors for significant weight gain (SWG) and significant weight loss (SWL) over 6 mo post-transplant, as well as outcomes including pancreas uncensored graft failure, pancreas death-censored graft failure (DCGF), composite pancreas graft outcomes of DCGF, use of an antidiabetic agent, or hemoglobin A1C >6.5%, and kidney DCGF. Results. Of 280 SPK recipients, 153 (55%) experienced no significant weight change, 57 (20%) SWG, and 70 (25%) SWL. At 6 mo post-transplant, mean weight changes were 1.2% gain in the no significant weight change group, 13.4% gain in SWG, and 9.6% loss in the SWL groups. In multivariate analysis, the only factor associated with decreased risk for weight gain was older recipient age (aOR, 0.97; 95% confidence intervals, 0.95-0.99). Importantly, SWG or SWL were not associated with pancreas graft failure, P-DCGF, or K-DCGF. Interestingly in the adjusted model, SWG at 6 mo was associated with a lower risk for composite outcomes (HR, 0.35; 95% confidence intervals, 0.14-0.85). Conclusions. Forty-five percent of SPK recipients had significant weight changes by 6 mo post-transplant, but only 20% exhibited SWG. Likely because of proper management, weight changes were not associated with poor outcomes post-SPK transplant.

Backgrounds. Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies. Methods. SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A– based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or 6.5. Results. One hundred eighty-three SPK recipients were included: A+β– (n = 72), A–β– (n = 42), A–β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non–death-censored pancreas graft failure for A+β– recipients compared with other groups: A–β– (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A–β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes. Conclusions. In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.

Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.

Background. Kidney transplant centers lack consistent diagnostic malnutrition tools. The Academy of Nutrition and Dietetics and American Society of Parenteral Nutrition Adult Malnutrition Criteria (AMC) is the widely accepted and utilized tool by Registered Dietitian Nutritionists (RDNs) to diagnose malnutrition. Methods. In this single-center, retrospective observational study, we evaluated the outcomes of prekidney transplant malnutrition based on Academy of Nutrition and Dietetics and American Society of Parenteral Nutrition AMC, as well as the individual components of the AMC, on posttransplant outcomes including length of stay, delayed graft function (DGF), early readmission, cardiovascular events, acute rejection, death-censored graft failure, and death. Bivariable and multivariable logistic regression models were used to assess the association of malnutrition or its components with outcomes of interest. Results. A total of 367 recipients were included, of whom 36 (10%) were malnourished (23 moderately and 13 severely) at pretransplant evaluation. In adjusted models, pretransplant malnutrition was significantly associated with increased risk for early readmission (adjusted odds ratio 2.86; 95% confidence interval: 1.14-7.21; P = 0.03) and with DGF (adjusted odds ratio 8.33; 95% confidence interval: 1.07-64.6; P = 0.04). Muscle depletion was also associated with an increased risk for readmission and with DGF. Fat depletion and reduced functionality in the adjusted model were only associated with increased risk for readmission. Conclusions. Malnutrition could be an important consideration for selecting kidney transplant recipients because it was associated with poor clinical outcomes. A multidisciplinary approach with the involvement of RDNs to outline a nutrition intervention plan may help mitigate some of the poor outcomes.

Background. Recurrence of glomerulonephritis (GN) is a significant contributor to long-term allograft failure among kidney transplant recipients (KTRs) with kidney failure because of GN. Accumulating evidence has revealed the role of vitamin D in both innate and adaptive immunity. Although vitamin D deficiency is common among KTRs, the association between 25-hydroxyvitamin D (25[OH]D) and GN recurrence in KTRs remains unclear. Methods. We analyzed data from KTRs with kidney failure caused by GN who received a transplant at our center from 2000 to 2019 and had at least 1 valid posttransplant serum 25(OH)D measurement. Survival analyses were performed using a competing risk regression model considering other causes of allograft failure, including death, as competing risk events. Results. A total of 67 cases of GN recurrence were identified in 947 recipients with GN followed for a median of 7.0 y after transplant. Each 1 ng/mL lower serum 25(OH)D was associated with a 4% higher hazard of recurrence (subdistribution hazard ratio [HR]: 1.04; 95% confidence interval [CI], 1.01-1.06). Vitamin D deficiency (≤20 ng/mL) was associated with a 2.99-fold (subdistribution HR: 2.99; 95% CI, 1.56-5.73) higher hazard of recurrence compared with vitamin D sufficiency (≥30 ng/mL). Results were similar after further adjusting for concurrent urine protein–creatinine ratio, serum albumin, and estimated glomerular filtration rate (eGFR). Conclusions. Posttransplant vitamin D deficiency is associated with a higher hazard of GN recurrence in KTRs. Further prospective observational studies and clinical trials are needed to determine any causal role of vitamin D in the recurrence of GN after kidney transplantation. More in vitro and in vivo experiments would be helpful to understand its effects on autoimmune and inflammation processes.

Background. Posttransplant erythrocytosis (PTE) is a well-known complication of kidney transplantation. However, the risk and outcomes of PTE among simultaneous pancreas-kidney transplant (SPKT) recipients are poorly described. Methods. We analyzed all SPKT recipients at our center between 1998 and 2021. PTE was defined as at least 2 consecutive hematocrit levels of >51% within the first 2 y of transplant. Controls were selected at a ratio of 3:1 at the time of PTE occurrence using event density sampling. Risk factors for PTE and post-PTE graft survival were identified. Results. Of 887 SPKT recipients, 108 (12%) developed PTE at a median of 273 d (interquartile range, 160–393) after transplantation. The incidence rate of PTE was 7.5 per 100 person-years. Multivariate analysis found pretransplant dialysis (hazard ratio [HR]: 3.15; 95% confidence interval [CI], 1.67-5.92; P

Background. Kidney transplant outcomes have dramatically improved since the first successful transplant in 1954. In its early years, kidney transplantation was viewed more skeptically. Today it is considered the treatment of choice among patients with end-stage kidney disease. Methods. Our program performed its first kidney transplant in 1966 and recently performed our 12 000th kidney transplant. Here, we review and describe our experience with these 12 000 transplants. Transplant recipients were analyzed by decade of date of transplant: 1966–1975, 1976–1985, 1986–1995, 1996–2005, 2006–2015, and 2016–2022. Death-censored graft failure and mortality were outcomes of interest. Results. Of 12 000 kidneys, 247 were transplanted from 1966 to 1975, 1147 from 1976 to 1985, 2194 from 1986 to 1995, 3147 from 1996 to 2005, 3046 from 2006 to 2015, and 2219 from 2016 to 2022 compared with 1966–1975, there were statistically significant and progressively lower risks of death-censored graft failure at 1 y, 5 y, and at last follow-up in all subsequent eras. Although mortality at 1 y was lower in all subsequent eras after 1986–1995, there was no difference in mortality at 5 y or the last follow-up between eras. Conclusions. In this large cohort of 12 000 kidneys from a single center, we observed significant improvement in outcomes over time. Kidney transplantation remains a robust and ever-growing and improving field.

Background. Kidney transplant recipients (KTRs) are a vulnerable immunocompromised population at risk of severe COVID-19 disease and mortality after SARS-CoV-2 infection. We sought to characterize the post-infection sequelae in KTRs at our center. Methods. We studied all adult KTRs (with a functioning allograft) who had their first episode of SARS-CoV-2 infection between 04/2020 and 04/2022. Outcomes of interest included risk factors for hospitalization, all-cause mortality, COVID-19-related mortality, and allograft failure. Results. Of 979 KTRs with SARS-CoV-2 infection, 381 (39%) were hospitalized. In the multivariate analysis, risk factors for hospitalization included advanced age/year (HR: 1.03, 95% CI: 1.02–1.04), male sex (HR: 1.29, 95% CI: 1.04–1.60), non-white race (HR: 1.48, 95% CI: 1.17–1.88), and diabetes as a cause of ESKD (HR: 1.77, 95% CI: 1.41–2.21). SARS-CoV-2 Vaccination was associated with decreased risk of hospitalization (HR: 0.73, 95% CI: 0.59–0.90), all-cause mortality (HR: 0.52, 95% CI: 0.37–0.74), and COVID-19-related mortality (HR: 0.47, 95% CI: 0.31–0.71) in the univariate and multivariate analyses. Risk factors for both all-cause and COVID-19-related mortality in the multivariate analyses included advanced age, hospitalization, and respiratory symptoms for hospital admission. Furthermore, additional risk factors for all-cause mortality in the multivariate analysis included being a non-white recipient and diabetes as a cause of ESKD, with being a recipient of a living donor as protective. Conclusions. Hospitalization due to COVID-19-associated symptoms is associated with increased mortality. Vaccination is a protective factor against hospitalization and mortality.

BK polyomavirus (BKPyV) is a ubiquitous human polyomavirus and a major infection after kidney transplantation, primarily due to immunosuppression. BKPyV reactivation can manifest as viruria in 30%–40%, viremia in 10%–20%, and BK polyomavirus-associated nephropathy (BKPyVAN) in 1%–10% of recipients. BKPyVAN is an important cause of kidney graft failure. Although the first case of BKPyV was identified in 1971, progress in its management has been limited. Specifically, there is no safe and effective antiviral agent or vaccine to treat or prevent the infection. Even in the current era, the mainstay approach to BKPyV is a reduction in immunosuppression, which is also limited by safety (risk of de novo donor specific antibody and rejection) and efficacy (graft failure). However, recently BKPyV has been getting more attention in the field, and some new treatment strategies including the utilization of viral-specific T-cell therapy are emerging. Given all these challenges, the primary focus of this article is complications associated with BKPyV, as well as strategies to mitigate negative outcomes.

Despite the continued improvements in pancreas transplant outcomes in recent decades, a subset of recipients experience graft failure and can experience substantial morbidity and mortality. Here, we summarize what is known about the failed pancreas allograft and what factors are important for consideration of retransplantation. The current definition of pancreas allograft failure and its challenges for the transplant community are explored. The impacts of a failed pancreas allograft are presented, including patient survival and resultant morbidities. The signs, symptoms, and medical and surgical management of a failed pancreas allograft are described, whereas the options and consequences of immunosuppression withdrawal are reviewed. Medical and surgical factors necessary for successful retransplant candidacy are detailed with emphasis on how well-selected patients may achieve excellent retransplant outcomes. To achieve substantial medical mitigation and even pancreas retransplantation, patients with a failed pancreas allograft warrant special attention to their residual renal, cardiovascular, and pulmonary function. Future studies of the failed pancreas allograft will require improved reporting of graft failure from transplant centers and continued investigation from experienced centers.

Background. Delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs) is a well-known risk factor for allograft rejection, decreased graft survival, and increased cost. Although DGF is associated with an increased risk of rejection, it is unclear whether it also increases the risk of infection. Methods. We reviewed all adult DDKTRs at our center between 2010 and 2018. The primary outcomes of interest were BK viremia, cytomegalovirus viremia, pneumonia, and urinary tract infection (UTI) within the first year of transplant. Additional analysis was made with censoring follow-up at the time of allograft rejection. Results. A total of 1512 DDKTRs were included, of whom 468 (31%) had DGF. As expected, several recipient, donor, and baseline immunological characteristics differed by DGF status. After adjustment, DGF was significantly associated with an increased risk of BK viremia (hazard ratio: 1.34; 95% confidence interval, 1.0-1.81; P = 0.049) and UTI (hazard ratio: 1.70; 95% confidence interval, 1.31-2.19; P

Backgrounds:. It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients. Methods:. In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death. Results:. Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008). Conclusions:. We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

Background. Traditionally, antibody-mediated rejection (AMR) has been suspected mainly by a rise in serum creatinine (Scr) and confirmed by allograft biopsy. There is limited literature describing the trend of Scr after treatment, and how that trend might differ between patients with histological response and with no response to treatment. Methods. We included all cases of AMR at our program between March 2016 and July 2020 who had a follow-up biopsy after the index biopsy, with initial diagnosis of AMR. We trended the Scr and change in Scr (delta Scr) and its association with being a responder (microvascular inflammation, MVI ≤1) or nonresponder (MVI >1), as well as graft failure. Results. A total of 183 kidney transplant recipients were included, 66 in the responder group and 177 in the nonresponder group. The MVI scores and sum chronicity scores, along with transplant glomerulopathy scores, were higher in the nonresponder group. However, Scr at index biopsy was similar in responders (1.74 ± 0.70) versus nonresponders (1.83 ± 0.65; P = 0.39), as were the delta Scr at various time points. After adjustment for multiple variables, delta Scr was not associated with being a nonresponder. Also, delta Scr value at follow-up biopsy compared with index biopsy among responders was 0 ± 0.67 (P = 0.99) and among nonresponders was –0.01 ± 0.61 (P = 0.89). Being a nonresponder was significantly associated with an increased risk of graft failure at the last follow-up in univariate analysis but was not in multivariate analysis (hazard ratio 1.35; 95% confidence interval, 0.58-3.17; P = 0.49). Conclusions. We found that Scr is not a good predictor of the resolution of MVI, supporting the utility of follow-up biopsies after treatment of AMR.

Abstract Background The effect of low‐level pretransplant donor‐specific antibody (DSA) on kidney transplant outcomes is not well described. The goal of this study was to compare outcomes among patients of varying immunologic risk, based on the level of pretransplant DSA. Methods We retrospectively reviewed all adult kidney transplant recipients who had undergone a transplant at our center between January 2013 and May 2017. Patients were grouped as negative DSA (mean fluorescence intensity, [MFISUM 1000). Rejection, infection, graft, and patient survival were outcomes measured. Results Of 952 patients, 82.1% had negative DSA, 10.7% had low‐level DSA, and 7.1% had positive DSA. The positive DSA group had the highest rate of antibody‐mediated rejection (10.3%), followed by low‐level DSA (7.8%) and the negative DSA group (4.5%) (p = .034). The rate of BK viremia was highest in the positive DSA group (39.7%), followed by the low‐level group (30.4%) and the negative DSA group (25.6%), (p = .025). None of the other outcomes, including graft or patient survival, were different between the groups. Conclusion While low‐level DSA should not prevent proceeding with kidney transplantation, it should not be ignored. Future studies are needed to investigate the long‐term effects of varying levels of pre‐transplant DSA on outcomes.

Background. There is limited data exist on relative outcomes with T-depletion versus IL-2 receptor (IL2R) blockade induction in pancreas transplantation. Methods. We analyzed all patients who underwent simultaneous pancreas-kidney or pancreas transplant alone at our institution between January 1, 2011, and December 31, 2019. Results. Of 417 pancreas transplant recipients, 291 received induction with a T-depleting agent and 126 received induction with an IL2R blocker. No difference was detected in pancreas allograft death-censored (P = 0.7) or uncensored (P = 0.5) survival. Although pancreas rejection was more common overall (P = 0.03), this difference was no longer present in recipients at low immunologic risk (P = 0.08). Cytomegalovirus and bacterial infections were significantly more common in the patients who received T-cell depleting agents for induction (21% versus 11%, P = 0.03; 34% versus 23%, P = 0.04, respectively). On multivariate analysis, history of pancreas rejection (Hazard ratio (HR) = 4.7, P = 0.0001; 95% Confidence interval (CI), 2.16-10.12) and higher calculated panel reactive antibodies (HR = 1.01, P = 0.04; 95% CI, 1.0002-1.02) were associated with increased risk of pancreas allograft failure, but choice of induction was not (HR = 0.64, P = 0.3; 95% CI, 0.27-1.51). Further, on multivariate analysis, Cytomegalovirus infection was associated with increased risk of pancreas allograft rejection (HR = 1.78, P = 0.01; 95% CI, 1.11-2.87), but choice of induction was not (HR = 0.84, P = 0.46; 95% CI, 0.54-1.32). Similarly, bacterial infection was associated with increased risk of patient death (HR = 2.94, P = 0.04; 95% CI, 1.03-8.32). Conclusion. Our data suggest that IL-2 receptor blockade may be a reasonable choice of induction for pancreas transplant recipients at low immunologic risk.

Background. There is limited information on the value of short-term invasive and noninvasive monitoring in kidney transplant recipients (KTR) undergoing therapy for chronic active antibody-mediated rejection (cAMR). Methods. We describe response rates in patients with cAMR receiving pulse steroids/IVIG ± rituximab 3-mo after index biopsy. Results. The study included 82 consecutive KTR. Mean time from transplant to cAMR was 10 y. Mean peritubular capillaritis (ptc), glomerulitis (g), microvascular inflammation (MVI), C4d, and cg Banff scores were 1.1, 2.1, 3.2, 0.2, and 2, respectively. Mean estimated glomerular filtration rate (eGFR) and urine protein creatinine (UPC) ratio were 38 mL/min and 1.6 g/g, respectively. Thirty (37%) patients lost their allograft during the mean follow-up of 2.4 y. In patients treated with pulse steroids/IVIG (n = 41), response rates for eGFR, UPC, donor-specific antibodies (DSAs), and MVI were 27%, 49%, 7%, and 19%, respectively. In the pulse steroids/IVIG/rituximab group, response rates were 66%, 61%, 20%, and 69%, respectively. Univariate analysis identified response in eGFR (HR = 0.03; P = 0.001; 95% CI, 0.004-0.26), UPC (HR = 0.38; P = 0.01; 95% CI, 0.18-0.82), and DSA (HR = 0.11; P = 0.004; 95% CI, 0.02-0.49) as predictors of graft survival. Multivariate analysis only retained eGFR response (HR = 0.12; P = 0.01; 95% CI, 0.02-0.64). Conclusions. In cAMR, short-term response to treatment for kidney function and DSA was associated with graft survival, but the role of early surveillance biopsies needs further evaluation.

Background. Limited published data exist to guide patient monitoring after the treatment of T-cell mediated rejection (TCMR) of kidney allografts. Methods. We reviewed the kidney function and histological outcomes after treatment of 163 first episodes of biopsy-proven TCMR between January 1‚ 2015‚ and July 31‚ 2020. Results. Of the 146 patients treated with steroid pulse alone, complete histological response was seen in 83% of patients with borderline rejection, 82.5% with grade 1A, 67% with grade 1B, and 50% with grade IIA. Of the 17 patients treated with steroids plus antithymocyte globulin, the complete histological response rate was 100% with grade 1A, 75% with grade 1B, 100% with grade IIA, and 57% with grade IIB. Among the patients with complete response as assessed by kidney function, 14% only had a partial or no response histologically. Among patients with no kidney function response, 68% had a complete response histologically. Conclusion. We thus find that responses based on kidney function alone do not correlate well with histological responses. If further treatment had been based solely on changes in estimated glomerular filtration rate, a significant number of patients would have been subsequently undertreated or overtreated. These results support the use of protocol follow-up biopsies after the treatment of TCMR.