Kodali, Lavanya

Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is diagnosed through histological examination of kidney biopsy samples, which reveal the infiltration of mononuclear cells into the allograft tissue. Corticosteroids serve as the primary treatment for TCMR, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin. ABMR occurs due to the binding of antibodies to graft endothelial cells. The most common treatment for ABMR is plasmapheresis, although its efficacy is still a subject of debate. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also utilized to varying degrees, but their efficacy remains questionable. Management decisions for ABMR depend on the timing of the rejection episode and the presence of chronic changes. In managing both TCMR and ABMR, it is crucial to optimize immunosuppression and address adherence. However, further research is needed to explore newer therapeutics and evaluate their efficacy.

AbstractIntroductionInfections are known complications of solid‐organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection.MethodsThis is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment.ResultsWe identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver‐kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients.ConclusionsInfections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver‐kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow‐up in kidney transplant patients. image

Abstract Background. There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function.Methods. We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020 with DGF to determine factors associated with DGF duration as well as the impact of DGF duration on 1) acute rejection, BKV infection, progression of fibrosis on protocol biopsy, and death censored graft survival 2) resource utilization, including hospital length of stay and readmissions. DGF duration was assessed at three 14-day intervals: <14 DGF days, 14-27 DGF days, >28 DGF days.Results. There were 1714 DDKT were included, 59.4% (n=1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted >28 days. Conclusions. Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting <28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival. Trial Registration. Retrospective study approved by Mayo Clinic IRB.

AbstractBackground and objectivesWe aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT).Materials and methodsA total of 172 recipients received a kidney from donors with acute kidney injury stage 3 (AKIN3) requiring RRT. We compared the study group to 528 recipients who received a kidney from donors with AKIN stage 3 not on RRT and 463 recipients who received < 85% Kidney Donor Profile Index (KDPI) AKIN stage 0 kidney.ResultsThe study group donors were younger compared to the 2 control groups. Despite higher DGF in the study group, the length of hospital stay and acute rejection were similar. Death censored graft survival (96% AKIN3‐RRT vs. 97%AKIN3 no RRT vs. 96% KDPI < 85% AKIN0,P = 0.26) and patient survival with functioning graft at 1 year (95% across all groups,P = 0.402) were similar. The estimated glomerular filtration rate were similar across the 3 groups after first month. Interstitial fibrosis and tubular atrophy score ≥ 2 on protocol biopsy at time 0, 4 and 12 months were similar. Primary nonfunction was rare and associated with high KDPI.ConclusionsTransplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes.