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There is little published information on the natural history and the treatment of immune complex membrano-proliferative glomerulonephritis (IC-MPGN) of unknown cause in the transplanted kidney.From 01/2004 to 12/2018, 41 patients had the diagnosis of post-transplant idiopathic IC-MPGN and were included in the study.The mean age of the cohort at the time of transplant was 50 ± 13 years. The most common presentation was increased proteinuria, followed by kidney dysfunction. Fewer than 50% of patients had hematuria at presentation. 25 patients (61%) had no change in their baseline immunosuppression after the diagnosis of idiopathic IC-MPGN. Eight patients (19.5%) received steroids alone, and 8 patients (19.5%) received rituximab with (7) or without (1) steroids. The patients who received rituximab had better uncensored graft survival than the patients who received no treatment (p = 0.02), but the benefit of steroids compared to no treatment did not reach statistical significance (p = 0.05). The multivariate analysis retained eGFR 30 mL/min/1.73m2 at time of diagnosis (HR = 3.30, p = 0.02; 95% Cl 1.15 - 9.46) as a significant predictor of graft loss. In this analysis, treatment of idiopathic IC-MPGN was associated with lower graft loss (HR = 0.22, p = 0.02; 95% Cl 0.06 - 0.78).To the best of our knowledge, this is the largest clinic-pathological series of post-transplant idiopathic IC-MPGN. Treatment of idiopathic IC-MPGN may be associated with better graft outcomes.

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., The presence of pretransplant donor‐specific antibody (DSA) represents a significant barrier to kidney transplantation for highly sensitized patients as they are less likely to undergo transplants compared with their nonsensitized counterparts. The goal of this study was to compare outcomes among patients of varying immunologic risk, based on the level of pre‐transplant 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). Also, 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).

Background Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD. Methods Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated. Results Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21). Conclusions CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population

BACKGROUND Since 2007, the National Living Donor Assistance Center has provided the most financial support to US living donors meeting specific income criteria by reimbursing travel, meal, and lodging expenses. In 2019, the National Kidney Registry started providing lost wages, travel, and lodging reimbursement via their Donor Shield program. Donor Shield is automatically provided to donors who participate in kidney paired donation through the National Kidney Registry or who donate at a Donor Shield Direct center, without any income restrictions. METHODS The support donors across the United States received from the Donor Shield program between January 2019 and February 2020 was studied. RESULTS During the study period, 326 (25.9%) of the 1260 donors covered by Donor Shield, from 46 programs received reimbursements amounting to a total of $647 384.45, with $472 389.97 (73.0%) covering lost wages. Median reimbursement per donor was $1813.80 (range, $44.0-$165.63). Eighty-one percent of 108 reimbursed donors who were surveyed reported that the lack of these reimbursements would have posed a financial hardship, and 4% said they would have been unable to donate without this support. CONCLUSIONS Expansion of lost wages reimbursement programs to all donors in the United States would be an important step toward achieving financial neutrality for this unique population and could also help meet the growing demand for transplantable organs by increasing living donation rates.

Living kidney donors incur a small increased risk of ESKD, of which predonation GFR is an important determinant. As a result, kidney function assessment is central to the donor candidate evaluation and selection process. This article reviews the different methods of GFR assessment, including eGFR, creatinine clearance, and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. eGFR obtained using the 2009 CKD Epidemiology Collaboration equation that, although the best of estimating estimations, tends to underestimate levels and has limited accuracy, especially near-normal GFR values. In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of the evaluation. Measured GFR is considered the gold standard, although there is some variation in performance characteristics, depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion. GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria. The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cutoff of

Secondary hyperoxaluria is associated with poor kidney allograft outcomes after the kidney transplant. Calcium oxalate (CaOx) deposition is common in early allograft biopsies leading to acute tubular necrosis and poor kidney allograft function. Though treatment options for secondary hyperoxaluria are limited, it is crucial to identify patients at increased risk of oxalate nephropathy after the transplant.Recent data suggest that significant changes in renal replacement therapies and dietary modifications in high-risk patients can prevent kidney allograft damage from the calcium oxalate deposition leading to improve allograft outcomes.The accurate and timely diagnosis of secondary oxalate nephropathy in kidney transplant recipients is paramount to preserving graft function in the long-term. This review will discuss the incidence, risk factors, prevention, and management of oxalate nephropathy in the kidney allograft.

Serum albumin is an indicator of overall health status, but it remains unclear how pre-transplant hypoalbuminemia is associated with early post-transplant outcomes.This study included all adult kidney transplant recipients (KTRs) at our center from 01/01/2001-12/31/2017 with serum albumin measured within 30 days before transplantation. KTRs were grouped based on pretransplant albumin level normal (≥4.0 g/dL), mild (≥3.5 - 4.0g/dL), moderate (≥3.0 - 3.5g/dL), or severe hypoalbuminemia (3.0g/dL). Outcomes of interest included: length of hospital stay (LOS), readmission within 30 days, delayed graft function(DGF), and re-operation related to post-transplant surgical complications. We also analyzed rejection, graft failure, and death within 6 months post-transplant.A total of 2807 KTRs were included 43.6% had normal serum albumin, 35.3% mild, 16.6% moderate, and 4.5% severe hypoalbuminemia. Mild and moderate hypoalbuminemia were associated with a shorter LOS by 1.22 (p 0.001) and 0.80 days (p = 0.01), respectively, compared to normal albumin. Moderate (HR: 0.58; 95% CI: 0.37-0.91; p = 0.02) and severe hypoalbuminemia (HR: 0.21; 95% CI: 0.07-0.68; p = 0.01) were associated with significantly lower rates of acute rejection within 6 months post-transplant.Patients with pre-transplant hypoalbuminemia have post-transplant outcomes similar to those with normal serum albumin, but with a lower risk of acute rejection based on the degree of hypoalbuminemia.

Studies conducted in the northern United States found cytomegalovirus (CMV) disease after liver transplantation follows a seasonal pattern, with increased incidence in fall and winter. This has not been evaluated in kidney transplant recipients. Improved understanding of CMV seasonality may help guide use of preventative therapies.We evaluated adult patients receiving a kidney transplant at our center in Wisconsin from January 1, 1995 to December 31, 2018. CMV event was defined as quantifiable viral replication with clinical signs or symptoms suspicious for CMV per current consensus recommendations. Seasons were divided as follows: winter (December-February), spring (March-May), summer (June-August), and fall (September-November). The primary objective was to evaluate the annual distribution of CMV disease and determine whether this differed by season.There were 6151 kidney transplants in the study period. A total of 913 patients had 1492 episodes of CMV. Median time from transplant to first detection was 5.51 months (interquartile range [IQR] 2.87-11.7). The observed overall incidence exceeded the expected incidence in winter (+.7%), spring (+5.5%), and fall (+3.4%) and was less than expected in summer (-9.5%) (p = .18). The incidence of CMV during summer, however, was 21% less than expected (p = .001) in recipients who were CMV positive (R+) at the time of transplantation. No such difference was observed in CMV negative recipients (R-; p = .58).CMV after kidney transplant appears to be less common during the summer season in patients who were R+ at transplant but does not follow seasonal variation in R-. Reasons for this are unclear but are likely related to CMV-specific cell-mediated immunity. These findings may have clinical implications, particularly the use of non-pharmacologic strategies to improve response to antiviral therapy.

Introduction Peritoneal dialysis (PD) has been used increasingly in past decade. Many of these patients undergo transplantation and may require dialysis for delayed graft function (DGF). The outcomes of DGF based on the post-transplantation dialysis modality are not well known. Methods We retrospectively reviewed all adult kidney transplant recipients (KTRs) from the University of Wisconsin School of Medicine and Public Health who developed DGF between November 2015 and April 2019. Patients were divided into those who received hemodialysis (HD) or PD during the DGF period. Immediate graft explant, DGF among living donor KTRs, or those requiring just a single dialysis treatment were excluded. Results Of 224 KTRs with DGF during the study period, 167 fulfilled our selection criteria. There were 16 patients in the PD and 151 in the HD group. Baseline characteristics were similar between the two groups, except diabetes was more prevalent in the HD group. Five of 16 PD patients had to be transitioned to HD. There was no difference in DGF duration, hospital length of stay, infectious or surgical complications, rejection at various time periods, graft function at last follow-up, or graft failure. In multivariate analysis, only rejection within the first year of transplantation (hazard ratio [HR]: 4.26; 95% confidence interval [CI]: 1.20–15.08; P = 0.02) and post-surgical complications (HR: 3.79; 95% CI: 1.03– 13.91; P = 0.04) were associated with death-censored graft failure (DCGF). The use of PD for treatment of DGF was not associated with DCGF. Conclusions In carefully selected patients, PD can be continued safely for DGF without any effect on short-term or long-term transplant outcomes., Graphical abstract

Delayed graft function (DGF) is a common complication among deceased donor kidney transplant recipients (DDKTs) and is associated with worse outcomes. The effect on outcomes of concordance versus discordance in DGF between two different recipients of kidneys from the same donor is largely unknown.We reviewed all adult DDKTs for which both kidneys were transplanted to two different recipients at our center between 2014-2019. DDKTs were divided into four groups based on the DGF status: concordance no DGF (cc-no-DGF); discordance no DGF(dd-no-DGF); discordance DGF (dd-DGF) and concordance in DGF (cc-DGF). Acute rejection (AR) and death censored graft failure (DCGF) were outcomes of interest.A total of 578 DDKTs fulfilled our selection criteria, 280were in cc-no-DGF, 83 in dd-no-DGF, 83 in dd-DGF, and 132 in cc-DGF. Compared to cc-no-DGF, in univariate analysis, dd-DGF was associated with an increased risk of AR (HR: 1.60; 95% CI: 1.0-2.56) but cc-DGF was not (HR: 1.01; 95% CI: 0.63-1.62). dd-DGF was not associated with an increased risk of AR in multivariate analysis. In multivariate analysis, dd-DGF was associated with an increased risk of DCGF (HR: 2.70; 95% CI: 1.05-6.93) but cc-DGFwas not (HR: 2.36; 95% CI: 0.97-5.70).Discordance in DGF is associated with worse outcomes and may need closefollow-up and monitoring to improve the outcomes.

Third-party vascular allografts (VAs) are an invaluable resource in kidney and pancreas transplantation when vascular reconstruction is needed and additional vessels from the organ donor are not available. We report the largest single-center experience to date on VA use, at a high-volume U.S. transplant center. Over a 7-year period, VAs were used for vascular reconstruction of 65 kidneys and 5 pancreases, in 69 recipients. The renal vein required reconstruction more often with right kidney transplantation (72.5% vs 27.5%, P < .001), and the renal artery required reconstruction more often with left kidney transplantation (67.6% vs 32.4%, P = .003). Eleven patients (15.9%) developed anti-VA de novo HLA donor-specific antibodies (dnDSAs) at a median time after transplantation of 19.0 months. Higher number of HLA mismatches between the VA donor and the recipient, and development of anti-organ allograft dnDSAs were significant predictors of anti-VA dnDSA development. Those with anti-VA dnDSAs had a higher rate of organ allograft rejection (45.4% vs 13.8%, P = .03) compared to those without, but there was no significant difference in incidence of vascular complications or graft outcomes. VAs can help circumvent challenging surgical situations. Anti-VA dnDSAs do not adversely affect organ allograft outcomes; however, they can contribute to HLA sensitization in the recipients.

We surveyed US transplant centers to assess practices regarding the evaluation and selection of living kidney donors based on metabolic, cardiovascular, and substance use risk factors. Our companion article describes renal aspects of the evaluation. Response rate was 31%. Compared with 2005, programs have become more accepting of hypertensive candidates: 65% in 2017% vs 41% in 2005 consider candidates with hypertension well controlled with 1 medication. One notable exception is black hypertensive candidates, who are frequently excluded regardless of severity. The most common body mass index (BMI) cutoff remains 35 kg/m2 , and fewer programs now consider candidates with BMI >40 kg/m2 . A 2-hour oral glucose tolerance test of ≥140 mg/dL remains the most common criterion for exclusion of prediabetic candidates. One quarter to one third of programs exclude based on isolated cardiac abnormalities, such as mild aortic stenosis; a similar proportion consider these candidates only if older than 50 years. Cigarette or marijuana smoking are infrequently criteria for exclusion, although 45% and 37% programs, respectively, require cessation 4 weeks prior to surgery. In addition to providing an overview of current practices in living kidney donor evaluation, our study highlights the importance of research evaluating outcomes with various comorbidities to guide practice.

We surveyed US transplant programs to assess practices used to assess kidney health in living kidney donor candidates in 2017; the response rate was 31%. In this report, we focus on the kidney; a companion piece focuses on the metabolic and cardiovascular aspects of candidate evaluation. Compared to 2005, programs have become more stringent in accepting younger candidates and less stringent in accepting older candidates. The 24-hour creatinine clearance remains the mainstay for kidney function assessment, with 74% continuing to use a value below 80 mL/min/1.73 m2 for exclusion and 22% using age-based criteria. ApoL1 genotyping is obtained routinely or selectively by 45%, half of which use the high-risk genotype as an absolute exclusion criterion. For history of symptomatic stones, 49% accept if there is no current radiographic evidence of stones and urine profile is low risk, 80%-95% consider candidates with unilateral asymptomatic stones, but only 33%-48% consider if stones are bilateral. In addition, 14% use the risk assessment tool developed by Grams et al routinely for decision-making, and 42% use it sometimes. Also, 57% reported not having yet determined a risk threshold for acceptable postdonation risk above which candidates are excluded. Contemporary practice variation underscores the need for better evidence to guide the donor selection process.

Kidney transplant recipients (KTR) present unique characteristics, including disease vintage, immunosuppression, and single functioning kidneys. We conducted preliminary analyses to assess the impact of coronavirus disease 2019 (COVID-19) on outcomes in KTR compared to nontransplant patients.We evaluated published information in peer-reviewed journals between January 1, 2020, and April 24, 2020, with available data on acute kidney injury (AKI), renal replacement therapy (RRT), intensive care unit (ICU) stay, and death and compared clinical outcomes in KTR vs nontransplant recipients with COVID-19.A total of 19 published articles were identified, including a total of 88 KTR and 5342 nontransplant patients. The sample size varied between 2 and 2634. Mean age was 58.6 years vs 58.9 years in KTR vs nontransplant patients. Patient-level incidence of AKI (27.5% vs 13.3%, P .001), RRT (15.4% vs 3.3%, P .001), ICU stay (34.1% vs 15.1%, P .001), and death (22.7% vs 16.2%, P = .10) was higher in KTR, representing relative risks of 2.06 (1.44, 2.96), 4.72 (2.62, 8.51), 2.25 (1.67, 3.03), and 1.41 (0.95, 2.08), respectively.Early results suggest that the KTR are at significantly higher risk of AKI, RRT, and ICU stay from SARS-CoV-19 infection compared to the general population. The risk of death may not be significantly different.

Background Kidney allograft biopsy is the gold standard for diagnosis of rejection. Under the current extraordinary circumstances of the coronavirus disease 2019 (COVID-19), where social distancing is key to limiting the spread of the virus, the model used to provide care to transplant recipients has undergone a very rapid transformation. In the spirit of medical distancing, we have been using the donor-derived cell-free DNA test for screening for rejection. Methods This manuscript describes our experience with this approach between March 15th and May 20th, 2020. Results This test was obtained for-cause in 23 patients and for monitoring in 9 patients. Normal results aided in foregoing biopsy in 63% of the patients where the test was obtained in the outpatient setting. The test is neither 100% sensitive nor specific for rejection; however, when used in combination with the available clinical information, can be used for determining whether bringing in a transplant recipient into a medical facility is necessary. Conclusions In the event the COVID-19 becomes a long-term challenge for our community, non-invasive biomarkers such as the donor-derived cell-free DNA may become more relevant than ever in enhancing our ability to care for our transplant patients while maximizing the distancing measures.

Purpose of review Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplant recipients. This article provides a summary of the clinical research relating to donor-specific antibodies (DSA) and ABMR in kidney transplant recipients at the University of Wisconsin-Madison Transplant Center. Recent findings Over 40% of the kidney transplant candidates on the UNOS waitlist are sensitized, and both preformed and de novo DSA are associated with increased risk of rejection and graft loss. We have developed graded induction-desensitization treatment and monitoring protocols based on the degree of immunologic risk. We have also implemented standard treatment and surveillance strategies for patients with ABMR. Additional important observations from our studies include high rates of ABMR in patients with positive C4d staining in postreperfusion biopsies and rise in DSA at 1 week after transplant, and increased risk of kidney allograft failure in patients with de novo DSA and ABMR, as well as in patients with HLA-DSA undetectable ABMR. We also found worse outcomes with de novo DSA following simultaneous pancreas--kidney and liver--kidney transplantation. Notably, favorable long-term graft outcomes were observed in patients with DSA who do not present the classic histopathological findings of ABMR. Summary In order to improve long-term outcomes for kidney transplant recipients, further research focusing on the pathogenic mechanisms elicited by HLA and non-HLA DSA, and novel therapies targeting these pathways is needed.

Clinical application of biomarkers is an integral component of transplant care. Clinicians and scientists alike are in search of better biomarkers than the current serologic (serum creatinine, donor-specific antibodies), urine-derived (urinalysis, urine protein), and histologic ones we now use. The science behind recent biomarker discovery spans across multiple molecular biologic disciplines, including transcriptomics, proteomics, and metabolomics. Innovative methodology and integration of basic and clinical approaches have allowed researchers to unearth molecular phenomena preceding clinical disease. Biomarkers can be classified in several ways. In this review, we have classified them via their origin and outcome: Primarily immunologic, i.e., representative of immune regulation and dysfunction and non-immunologic, pertaining to delayed graft function, cardiovascular events/mortality, infection, malignancy, post-transplant diabetes, graft, and patient survival. Novel biomarker uses to guide the diagnosis and management of transplant-related outcomes is a promising area of research. However, the use of biomarkers to predict outcomes after kidney transplantation is not well studied. In this review, we summarize the recent studies illustrating biomarker use and transplant outcomes.

Background: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. Methods: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. Results: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin Conclusion: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Background There is limited information about the utility of donor-specific antibody (DSA) against Human Leukocyte Antigen (HLA) monitoring and the role of protocol kidney biopsy for de-novo DSA (dnDSA) in simultaneous liver and kidney (SLK) transplant recipients. Methods We analyzed SLK recipients transplanted between 01/2005 and 12/2017 who had DSA checked post-transplant. Patients were divided into two groups based on whether they developed dnDSA post-transplant (dnDSA+) or not (dnDSA-). Kidney graft rejection ± 45 days of dnDSA and a kidney death censored graft survival were the primary endpoints. Results A total of 83 SLK recipients fulfilled our selection criteria. Of those, 23 were dnDSA+ and 60 were dnDSA-. 22 of 23 dnDSA+ patients had DSA against class II HLA, predominantly against DQ. 15 recipients underwent kidney biopsy ± 45 days of dnDSA. Six of these were clinically indicated due to kidney graft dysfunction. The other nine had a protocol kidney biopsy only due to dnDSA, and 6 of these 9 had a rejection. Also, 3 recipients had sequential biopsies of both the kidney and liver grafts. Among those with sequential biopsies of both grafts, there was a difference between the organs in the rate and types of rejections. At last follow up, dnDSA was not associated with graft failure of either the kidney or liver. Conclusion Although our study was limited by a small sample size, it suggests the potential utility of DSA monitoring and protocol kidney biopsy for dnDSA.

Among kidney transplant recipients, the duration of pretransplant dialysis is significantly associated with worse post-transplant outcomes. However, data on the outcomes of preemptive simultaneous pancreas and kidney (SPK) are limited. We analyzed primary SPK recipients transplanted between January 2000 and December 2017. Patients were divided into two groups based on pretransplant dialysis history of preemptive versus non-preemptive. Patient and survival of grafts were outcomes of interest. Of the 644 recipients, 174 (27%) were preemptive and 470 (73%) were not. Most of the baseline characteristics were similar between the groups. In the univariable analysis, the non-preemptive transplant was associated with 54% increased risk for kidney death-censored graft failure (DCGF; HR: 1.54; 95% CI: 1.01-2.35; P = 0.05). There was a 29% increased risk after adjustment for confounding factors (HR: 1.29; 95% CI: 0.83-2.02; P = 0.26), although this association was not statistically significant. Similarly, there was a 16% increased risk of pancreas DCGF in univariable analysis and 1% after adjustment, which was also not statistically significant. When outcomes were based on the duration of pretransplant dialysis, the duration was not associated with either patient survival or survival of either graft in K-M analysis. In SPK recipients, with pretransplant dialysis history, there was a tendency toward inferior graft survival, mainly for the kidney more than the pancreas.

Background The first simultaneous pancreas and kidney (SPK) transplant was performed in 1966. Early procedures were associated with significant morbidity and mortality and were performed in very low numbers in select patients. Methods This study includes all recipients of an SPK at the University of Wisconsin-Madison between 1986 and 1993, who were actively followed and had a functional pancreas allograft for >25 years as of October 31, 2018. Results A total of 291 SPK were performed during the study period; of these, 39 patients still had a functional graft at last follow up and 9 (18.8%) pancreas grafts were lost due to patient death or graft failure after >25 years. At last follow up, all 39 patients with functional pancreas graft had at least one comorbidity, such as hypertension, hyperlipidemia, or coronary artery disease. Twenty-seven required enteric conversion; 11 patients experienced renal allograft failure (10 underwent a repeat kidney transplant); and 6 required amputation of part of the lower extremity. In the Cox regression analysis, bladder drained pancreas was associated with lower probability of prolonged pancreas graft survival (hazard ratio: 0.52; confidence interval: 0.32-0.85; P = 0.01). Conclusions With careful and detailed follow-up and attention to complications, some recipients of pancreas grafts have outstanding outcomes. As the number of pancreas recipients with prolonged graft survival may be rising, healthcare providers should be aware of the management of complications associated with this unique group of patients.

Living kidney donation is widely practiced throughout the world. During the past 2 decades, various groups have provided guidance about the evaluation and care of living donors. However, during this time, our knowledge in the field has advanced substantially and many agreed on the need for a comprehensive, unifying document. KDIGO (Kidney Disease: Improving Global Outcomes) addressed this issue at an international level with the publication of its clinical practice guideline on the evaluation and care of living kidney donors. The KDIGO work group extensively reviewed the available literature and wrote a series of guideline recommendations using various degrees of evidence when available. As has become recent practice, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) convened a work group to provide a commentary on the KDIGO guideline, with a focus on how these recommendations apply in the context of the United States. In the United States, the United Network for Organ Sharing (UNOS) guides and regulates the practice of living kidney donation. While the KDIGO guideline for the care of living kidney donors and UNOS policy are similar in most aspects of the care of living kidney donors, several important areas are not consistent or do not align with common practice by US transplantation programs in areas in which UNOS has not set specific policy. For the time being, and recognizing the value of the KDIGO guidelines, US transplantation programs should continue to follow UNOS policy.

BK polyomavirus (BKV) is a common infection among kidney transplant recipients (KTR). Risk factors and outcomes based on donor characteristics remain largely unknown.In this study, we aimed to analyze the impact of donor factors through a paired kidney analysis. We included 289 pairs of adult deceased donor transplants (578 KTRs total); each pair had received kidneys from the same donor. Recipient pairs were divided into three groups: "no BK group" if neither KTR developed BK viremia (n = 336), "discordant" if the only one did (n = 176), and "concordant" if both did (n = 66). Acute rejection (AR), graft failure, and BK nephropathy (BKN) were outcomes of interest.Donors in the concordant group were younger, had lower kidney donor profile index (KDPI), and were less likely to be donor after circulatory death (DCD). In multivariate analyses, KTRs who had a donor with a higher body mass index (BMI) (hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99; p = .009) were less likely to develop BKV. Concordance was not associated with AR (HR: 0.83; 95% CI: 0.51-1.34; p = .45), graft failure (HR: 1.77; 95% CI: 0.42-7.50; p = .43), or BKN (HR: 1.02; 95% CI: 0.51-2.03; p = .96).Our study suggests lower donor BMI is associated with BKV infection, and concordance or discordance between paired kidney recipients is not associated with poor outcomes.

Cardiovascular events, including ischemic heart disease, heart failure, and arrhythmia, are common complications after kidney transplantation and continue to be leading causes of graft loss. Kidney transplant recipients have both traditional and transplant-specific risk factors for cardiovascular disease. In the general population, modification of cardiovascular risk factors is the best strategy to reduce cardiovascular events; however, studies evaluating the impact of risk modification strategies on cardiovascular outcomes among kidney transplant recipients are limited. Furthermore, there is only minimal guidance on appropriate cardiovascular screening and monitoring in this unique patient population. This review focuses on the limited scientific evidence that addresses cardiovascular events in kidney transplant recipients. Additionally, we focus on clinical management of specific cardiovascular entities that are more prevalent among kidney transplant recipients (ie, pulmonary hypertension, valvular diseases, diastolic dysfunction) and the use of newer evolving drug classes for treatment of heart failure within this cohort of patients. We note that there are no consensus documents describing optimal diagnostic, monitoring, or management strategies to reduce cardiovascular events after kidney transplantation; however, we outline quality initiatives and research recommendations for the assessment and management of cardiovascular-specific risk factors that could improve outcomes.

Management of immunosuppression in a kidney transplant recipient with a failed allograft is complex; continuation carries infectious and metabolic risks, and discontinuation can lead to sensitization.We evaluated risk factors for sensitization in 89 kidney or simultaneous kidney-pancreas recipients, whose kidney transplant failed after January, 2013 and who were subsequently re-evaluated for kidney transplantation.Among recipients with pre graft failure cPRA 50%, calcineurin inhibitor (CNI) continuation (OR .11, P = .003) and steroid continuation (OR .17, P = .04) were associated with significantly lower odds of developing an absolute increase in cPRA of ≥50%. Each additional HLA mismatch was associated with OR of 2.16 (P = .02). CNI use was associated with OR of .09 (P = .001) for increase in cPRA to ≥80% if pre graft failure cPRA was50%, and OR of .08 (P = .02) for increase in cPRA to ≥98% if pre graft cPRA was80%. Anti-metabolites were continued more often among recipients who had a50% increase (P = .006); however, the association was lost on multivariate analyses. Weaning off immunosuppression and higher number of HLA mismatches are associated with greater likelihood of sensitization.While both CNI and steroid continuation conferred some protection against increase in cPRA, CNI continuation was the only factor protecting against becoming highly sensitized.

Patients with end-stage renal disease (ESRD) are at a higher risk of needing hip or knee replacement (joint replacement) surgery due to the high prevalence of degenerative joint disease and other conditions. However, there remains a large debate about the timing of joint replacement surgery and whether it should be pre- vs post-transplant.We conducted a retrospective study analyzing all adult kidney transplant recipients (KTRs) at our university hospital who had undergone subsequent joint replacement between 2001 and 2017. Transplant-specific outcomes of acute rejection, death censored graft failure (DCGF), and patient death post-joint replacement surgery were outcomes of interest. Controls were selected at a 1:3 ratio based on the incidence density sampling of post-transplant interval.There were 101 KTRs in the joint replacement group and were compared with 281 controls. In the multivariate analysis, the need for joint replacement was not associated with acute rejection (HR: 1.59; 95% CI: 0.77-3.29; P = 0.21); DCGF (HR: 0.89; 95% CI: 0.49-1.60; P = 0.70) or patient death (HR: 0.84, 95% CI: 0.55-1.38, P = 0.42).In selected KTRs, joint replacement surgery was not associated with detrimental transplant-specific outcomes.

Purpose To evaluate the association of conversion from valganciclovir to letermovir on cytomegalovirus-specific cellular immunity METHODS: Adult patients were included if they received a kidney or liver transplant between 8/1/2018-12/31/20, developed symptomatic, high-level CMV viremia and were converted to letermovir 480 mg daily as monotherapy after treatment with ganciclovir-derivatives for a minimum of 4 weeks and had subsequent CMV cell-mediated immunity (CMI) testing via ICS assay by flow cytometry (Viracor Eurofins T Cell Immunity Panel). Results Seven patients met inclusion criteria; 87.5% were male and recipients of a kidney transplant. All patients were CMV high risk (D+/R-). Mean time from transplant to CMV disease was 200±91 days. Peak viral load (VL) during CMV treatment was 540,341±391,211 IU/mL. Patients received a mean of 30±24 weeks (range:4-78 weeks) of therapy with ganciclovir-derivatives at induction doses prior to letermovir introduction. The median absolute lymphocyte count (ALC) at letermovir initiation was 400/uL (IQR 575) and the median VL was 51.6 (range: ND-490) IU/mL. Most patients (n = 5/7, 71.4%) experienced an increase in VL 1 and/or 2 weeks after conversion to letermovir. All patients had positive CMI per ICS assay after conversion. Patients received a mean of 10.3±6.9 weeks of letermovir prior to having a positive result. Median ALC at positivity was 900/uL. Immunosuppression was not further reduced from initiation of letermovir to demonstration of CMV CMI. No patient had progressive replication or breakthrough disease while maintained on letermovir and 3 patients (42.9%) underwent antiviral withdrawal without recurrence at last follow up. Conclusion In this case series of abdominal transplant recipients with severe or persistent CMV infection, patients developed CMV-specific CMI after conversion to letermovir monotherapy. This data suggests that using letermovir in place of valganciclovir for secondary prophylaxis may address the lack of efficacy previously seen with this approach, as well as the issues that plague antiviral withdrawal with systematic monitoring. Future prospective studies are needed to evaluate this effect in a more controlled research environment with serial CMI testing to elucidate the optimal duration of letermovir when used in this way This article is protected by copyright. All rights reserved.

Background. The clinical significance and appropriate management of graft pyelonephritis diagnosed by biopsy are poorly understood. Methods. We analyzed data from all patients with pyelonephritis on transplant kidney biopsy from January 1998 to December 2019. Patients were divided into 2 groups: those whose urinalysis was positive for urinary tract infection (UA+) and those whose urinalysis was negative (UA–). Results. There were a total of 101 patients with the diagnosis of pyelonephritis by biopsy during the study period. The mean time from transplant to pyelonephritis diagnosis was 3.3 ± 4 y. Thirty-six (35.6%) of the patients with pyelonephritis on biopsy had a negative UA. Out of 65 patients in the UA+ group, 54 (83%) received antibiotics. Only 12 of the UA– patients (33%) received antibiotics. The use of antibiotics in both the UA+ (P = 0.03) and UA– groups (P = 0.02) compared with no use of antibiotics was associated with better death-censored graft survival. On multivariate analysis, the use of antibiotics (hazard ratio = 0.22, P = 0.001, 95% confidence interval, 0.12-0.61) was associated with improved graft survival. Conclusion. The finding of pyelonephritis on a transplant kidney biopsy is almost always a surprise but is an important finding. Treatment with antibiotics, regardless of signs or symptoms of urinary tract infection, is associated with improved graft survival.

BACKGROUND: Despite the institution of a new Kidney Allocation System in 2014, A2/A2B to B transplantation has not increased as expected. The current Organ Procurement and Transplantation Network policy requires subtyping on two separate occasions, and in the setting of discrepant results, defaulting to the A1 subtype. However, there is significant inherent variability in the serologic assays used for blood group subtyping and genotyping is rarely done. METHODS: The National Kidney Registry, a kidney paired donation (KPD) program, performs serological typing on all A/AB donors, and in cases of non-A1/non-A1B donors, confirmatory genotyping is performed. RESULTS: Between 2/18/2018 and 9/15/2020, 13.0% (145) of 1,111 type A donors registered with the NKR were ultimately subtyped as A2 via genotyping. Notably, 49.6% (72) of these were subtyped as A1 at their donor center, and in accordance with OPTN policy, ineligible for allocation as A2. CONCLUSION: Inaccurate A2 subtyping represents a significant lost opportunity in transplantation, especially in KPD where A2 donors can not only facilitate living donor transplantation for O and highly sensitized candidates, but can also facilitate additional living donor transplants. This study highlights the need for improved accuracy of subtyping technique, and the need for policy changes encouraging optimal utilization of A2 donor kidneys.

Introduction Little is known aboutbiopsy findings and outcomes when kidney transplant recipients (KTRs) undergo biopsy for isolated proteinuria with stable serum creatinine (SCr). Methods We analyzed all KTRs who underwent biopsy for isolated proteinuria with stable SCr between January 2016 and June 2020. Patients were divided into three groups based on the biopsy findings: Active Rejection (AR), Glomerulonephritis (GN), and Other. Results A total of 130 KTRs fulfilled our selection criteria; 38 (29%) in the AR group, 26 (20%) in the GN group, and 66 (51%) in the Other group. Most baseline characteristics were similar between the groups. In multivariate analysis, higher HLA mismatch (HR per mismatch: 1.30; 95% CI:1.06-1.59; P = .01) and male gender (HR: .45; 95% CI .23-.89; P = .02) were associated with AR. There was no significant correlation between the degree of proteinuria and rejection (r = .05, P = .58) or GN (r = .07, P = .53). Graft survival was also similar between the groups. Likely due to the early diagnosis without a significant rise in SCr, outcomes were similar among all three groups. Conclusion Routine monitoring for proteinuria followed by a biopsy and appropriate management may help to identify early acute graft injury and prevent graft failure.

BACKGROUND Data on epidemiology and outcomes of cytomegalovirus (CMV) nephritis in kidney transplant patients are limited due to the rarity of this condition. METHODS A retrospective review of all kidney transplant recipients (KTR) (n = 6490) and biopsy-proven CMV nephritis between 1/1997 and 12/2020 was performed. RESULTS The prevalence of CMV nephritis was low: 13/6490 (0.2%). The diagnosis was made at a median of 7.0 months (range 2.6-15.6 months) after transplant. 6 of 13 (46%) patients were CMV (D+/R-). Median CMV DNA load at biopsy was 376,000, IU/mL (range 87,000-6,460,000 IU/mL). Main biopsy features were CMV glomerulitis (n = 7/13, 54%) followed by CMV tubulointerstitial nephritis (6/13; 46%). Mean eGFR at biopsy (22.7 ± 12 mL/min/1.73 m2 ) was significantly decreased compared to baseline eGFR (38.7 ± 18.5 mL/min/1.73 m2 , p = 0.02). The vast majority, 11 of 13 (85%), experienced graft failure including 5 of 13 (38%) death-censored. 5 of 13 (38%) patients were diagnosed with acute rejection: three had concurrent acute rejection, and two had rejection within 3 months of index biopsy, respectively. Patients with tubulointerstitial CMV nephritis were significantly more likely to have rejection at the time of biopsy (50% vs. 0%, p

Purpose Persistent viral replication resulting in ongoing cytomegalovirus (CMV) viremia despite adequate therapy is difficult to manage and associated with negative outcomes. We report a case series of kidney transplant recipients receiving adjunctive letermovir in combination with valganciclovir for refractory CMV. Methods Adult patients receiving a kidney or kidney-pancreas transplant were included if they developed CMV viremia and initiated letermovir 480 mg daily as part of a dual therapy regimen with valganciclovir 900 mg twice daily between 1/9/2020 and 31/12/2020. Included patients received ≥90 days of valganciclovir and had a detectable viral load less than 1000 Iu/ml (log10 Results Eight patients were included. Letermovir was added 223 ± 105 days after initiation of CMV treatment with ganciclovir derivatives. Median viral load at initiation was 139.7 (range: 73-355) IU/ml and did not clear or change significantly after 2, 4 and 12 weeks of adjunctive letermovir (132.5 [range: 34.5-513] IU/ml vs. 68.7 [range: 34.5-574] IU/ml vs. 78.3 [range: 34.5-347] IU/ml, p > 0.05). Tacrolimus was reduced by ∼30% in anticipation of a letermovir-tacrolimus drug interaction. Despite this reduction, mean tacrolimus serum levels two weeks after adjunctive letermovir increased by 43% (5.6 ± 1.6 ng/ml vs 8.0 ± 4.6 ng/ml). Conclusion In kidney and kidney-pancreas recipients with refractory CMV, the use of adjunctive letermovir did not result in viral clearance. Additionally, despite a mean tacrolimus dose reduction of 30% at letermovir initiation, serum concentrations increased by over 40%. Further investigation into the optimal approach to refractory CMV is needed.