Heilman, Raymond L.

ABSTRACTBackgroundAlternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post‐transplant, coupled with a lack of follow‐up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4 months post‐transplantation, and explore any differences in follow‐up surveillance biopsies compared to a non‐TMA group.DesignThis is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4 months post‐transplantation were compared to a propensity matched non‐TMA group.ResultsThirty‐one patients developed TMA within 4 months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four‐month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non‐TMA group. However, at 1 year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non‐TMA,p = 0.083); however, death censored graft survival was significantly lower in the TMA group (p < 0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4 months and at 1 year as compared to the non‐TMA group.ConclusionEarly onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes.

Introduction. The impact of renal allograft rejection treatment on infection development has not been formally defined in the literature. Methods. We conducted a retrospective cohort study of 185 rejection (case) and 185 nonrejection (control) kidney transplant patients treated at our institution from 2014 to 2020 to understand the impact of rejection on infection development. Propensity scoring was used to match cohorts. We collected data for infections within 6 months of rejection for the cases and 18 months posttransplant for controls. Results. In 370 patients, we identified 466 infections, 297 in the controls, and 169 in the cases. Urinary tract infections (38.9%) and cytomegalovirus viremia (13.7%) were most common. Cumulative incidence of infection between the case and controls was 2.17 (CI 1.54–3.05); p<0.001. There was no difference in overall survival (HR 0.90, CI 0.49–1.66) or graft survival (HR 1.27, CI 0.74–2.20) between the groups. There was a significant difference in overall survival (HR 2.28, CI 1.14–4.55; p=0.019) and graft survival (HR 1.98, CI 1.10–3.56; p=0.023) when patients with infection were compared to those without. Conclusions. As previously understood, rejection treatment is a risk factor for subsequent infection development. Our data have defined this relationship more clearly. This study is unique, however, in that we found that infections, but not rejection, negatively impacted both overall patient survival and allograft survival, likely due to our institution’s robust post-rejection protocols. Clinicians should monitor patients closely for infections in the post-rejection period and have a low threshold to treat these infections while also restarting appropriate prophylaxis.

BACKGROUND: Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited. STUDY DESIGN: This was a single-center study of deceased donor kidney transplants from 2010 to 2022. The study cohort consisted of recipients of deceased donor kidney transplants from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: 1 to 2 dialysis days, 3 to 4 dialysis days, and 5 or more dialysis days. RESULTS: During this period, 765 AKI deceased donor transplants were performed, of which 230 were from donors on dialysis. The median dialysis duration was 2 days with a maximum of 13 days. Across the 3 groups, there were no differences in recipient age (p = 0.23) or dialysis vintage (p = 0.70). Donor age (p = 0.86) and kidney donor profile index (p = 0.57) were comparable between the groups. Recipients of deceased donor kidney transplants from donors on dialysis 5 or more days had lower terminal creatinine levels (p = 0.003) and longer cold ischemia times (p = 0.04). Posttransplant, the median length of hospital stay was 3 days for all groups (p = 0.75). There were no differences in delayed graft function occurrence (94.4% vs 86.8% vs 92.1%, p = 0.19), duration of delayed graft function (p = 0.56), or readmissions (p = 0.99). At 1 year posttransplant, the estimated glomerular filtration rate (p = 0.76), patient survival (p = 0.82), or death-censored graft survival (p = 0.28) were comparable. CONCLUSIONS: Excellent outcomes have been observed in AKI deceased donor kidney transplants, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.

AbstractBackgroundUrinary Tract Infections are the most common post‐transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy.MethodsThe study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant.ResultsThe mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3–2.7, diabetes mellitus (OR 2.479, 1.687–3.645), and deceased donation (OR 1.69, 1.098–2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06–3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36–6.02) and a trend toward higher rejection risk.ConclusionAsymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

(1) Background: Acute kidney injury (AKI) kidneys have high non-utilization rates due to concerns regarding unfavorable outcomes. In this paper, we aimed to review the past, present, and future opinions on AKI kidneys. (2) Methods: A PubMed search was conducted for topics relevant to AKI kidney transplantation. (3) Results: Current short- and long-term data on AKI kidneys have demonstrated good outcomes including favorable graft function and survival. The role of procurement biopsies is controversial, but they have been shown to be beneficial in AKI kidneys by allowing clinicians to differentiate between reversible tubular injury and irreversible cortical necrosis. Machine perfusion has also been applied to AKI kidneys and has been shown to reduce delayed graft function (DGF). The incidence of DGF increases with AKI severity and its management can be challenging. Strategies employed to counteract this have included early initiation of dialysis after kidney transplantation, early targeting of adequate immunosuppression levels to minimize rejection risk, and establishment of outpatient dialysis. (4) Conclusions: Despite good outcomes, there continue to be barriers that impact AKI kidney utilization. Successful strategies have included use of procurement biopsies or machine perfusion and expectant management of DGF. With increasing experience, better use of AKI kidneys can result in additional opportunities to expand the donor pool.

AbstractIntroductionExpedited out‐of‐sequence deceased donor kidney allocation is a strategy to avoid discards after early placement attempts have been unsuccessful. Our study aimed to assess outcomes and characteristics of these transplanted kidneys.MethodsKDPI matching was performed between expedited allocation (EA) and standard allocation (SA) deceased donor kidney transplants performed at our center.ResultsBetween 2018 and 2021, there were 225 EA offers, and 189 (84%) were transplanted. EA recipients were older (p = .007) and had shorter dialysis vintage (p < .0001). EA kidneys were likely to be nationally allocated (p < .001), have AKI (p < .0001) and longer CIT (p < .0001). There were no differences in EA and SA time‐zero kidney biopsies (ci, p = .07; ct, p = .89; cv, p = .95; ah, p = .79). EA kidneys had more DGF (p = .0006), but there were no differences in DGF duration (p = .83), hospital length of stay (p = .43), 1‐ and 2‐year eGFR (p = .16, p = .99), patient (p = .34), or death‐censored graft (p = .66) survival.ConclusionDuring this study period, our center transplanted 189 kidneys through EA following local‐regional declines. These kidneys often came from AKI donors and had more DGF but had similar outcomes to KDPI‐matched SA kidneys. Although it has been suggested that EA has the potential to worsen transplant disparities, transplant center level decisions on organ acceptance contribute to these variations.

AbstractThe objective of this study was to compare the long‐term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single‐center study, conducted from 2003 to 2022, had a median follow‐up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5‐year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

Patients with failed renal allografts have associated increased morbidity and mortality. The individualization of immunosuppression taper is the key element in managing these patients to avoid graft intolerance and sensitization while balancing the risk of continued immunosuppression. Most patients with uncomplicated chronic allograft failure do not require allograft nephrectomy (AN), and there is no clear evidence that it improves outcomes. The AN procedure is associated with variable morbidity and mortality. It is reserved mainly for early technical graft failure or in symptomatic cases associated with allograft infection, malignancy, or graft intolerance syndrome. It may also be considered in those who cannot tolerate immunosuppression and are at high risk for graft intolerance. AN has been associated with an increased risk of sensitization due to inflammatory response from surgery, immunosuppression withdrawal with allograft failure, and retained endovascular tissue. Although it is presumed that for-cause AN after transplant failure is associated with sensitization, it remains unclear whether elective AN in patients who remain on immunotherapy may prevent sensitization. The current practice of immunosuppression taper has not been shown to prevent sensitization or increase infection risk, but current literature is limited by selection bias and the absence of medication adherence data. We discuss the management of failed allografts based on retransplant candidacy, wait times, risk of graft intolerance syndrome, and immunosuppression side effects. Many unanswered questions remain, and future prospective randomized trials are needed to help guide evidence-based management.