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Purpose: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

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.

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 <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality., 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.

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1-year graft survival for both organs was not different. At last follow-up, uncensored and death-censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Antibody-mediated rejection (AMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical AMR based on the donor-specific antibody (DSA) testing may result in better outcomes., Methods: We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between March 1, 2013 and December 31, 2016. Patients were divided into 3 groups: clinical AMR (n = 118), subclinical AMR (n = 25), or no rejection on protocol biopsy (controls; n = 77)., Results: Both clinical and subclinical AMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (P = ns). Mean follow-up after AMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical AMR groups, respectively (P < 0.001). Graft outcomes were similar in the subclinical rejection and control groups. In adjusted Cox regression analysis, only clinical rejection (hazards ratio [HR], 4.31; 95% confidence interval [CI], 1.01-18.94; P = 0.05) and sum chronicity scores (HR, 1.16; 95% CI, 1.01-1.35; P = 0.03) were associated with increased risk of graft failure, while estimated glomerular filtration rate at time of biopsy (HR, 0.98; 95% CI, 0.96-0.99; P = 0.01) was associated with decreased risk of graft failure., Conclusions: Our study suggests that early diagnosis and treatment of subclinical AMR using DSA monitoring may improve outcomes after kidney transplantation.

The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28-2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31-3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65-5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12-4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale & Objective: Recent studies suggest that metabolic acidosis is associated with mortality and graft failure in kidney transplant recipients. However, it is unknown whether serum bicarbonate (measured as total carbon dioxide [tCO 2 ] in serum) levels predict cardiovascular events (CVEs) following kidney transplantation., Study Design: Observational cohort study., Settings & Participants: Single-center study of 2,128 kidney transplant recipients free of CVEs during the first 13.5 months following transplantation., Predictor: tCO 2 level at 1 year posttransplantation., Outcomes: Ischemic, arrhythmic, and heart failure CVEs and death from any cause., Analytical Approach: Independent associations were assessed using multivariable proportional hazards regression models. Restricted cubic spline Poisson models were used to explore nonlinear associations. Linear spline proportional hazards models were used to assess associations at different tCO 2 levels., Results: The prevalence of metabolic acidosis defined as tCO 2 level < 24 mEq/L was 38.8% (n=826). There were 384 recipients with a CVE and 610 deaths during a median follow-up of 4.0 years. CVEs included 241 ischemic, 137 arrhythmic, and 150 heart failure events. tCO 2  level < 20 mEq/L was associated with increased risk for CVEs (adjusted HR [aHR], 2.00; 95% CI, 1.29-3.10) compared to the reference category of tCO 2 level of 24.0 to 25.9 mEq/L. This association was primarily due to ischemic CVEs (aHR, 2.28; 95% CI, 1.34-3.90). For every 1 mEq/L lower tCO 2 level for those with tCO 2 < 24 mEq/L, risks for all CVEs and ischemic events were 17% and 15% higher, respectively (aHR for all CVEs of 0.83 [95% CI, 0.74-0.94] and aHR for ischemic CVEs of 0.85 [95% CI, 0.74-0.99]). Notably, tCO 2 level < 20 mEq/L, compared to tCO 2 level of 24.0 to 25.9 mEq/L, was independently associated with all-cause mortality (aHR, 1.43; 95% CI, 1.02-2.02). For every 1-mEq/L lower tCO 2 level for those with tCO 2 < 24 mEq/L, there was 17% higher risk for death (aHR, 0.83; 95% CI, 0.75-0.92)., Limitations: Single-center observational study., Conclusions: Metabolic acidosis is an independent risk factor for ischemic CVEs after kidney transplantation. It is unknown whether correction of acidosis improves outcomes in these patients., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)