IgA nephropathy recurrence after kidney transplantation is a common complication, which is most often detected histologically. Recurrence after transplant affects long-term graft survival, with prognosis being worse with increasing levels of proteinuria, a higher histological activity, and concurrent rejection. Treatment in kidney transplant patients is similar to that in native kidneys: using renin-angiotensin-aldosterone system (RAAS) blockade agents, steroids, and increased immunosuppression. Iptacopan, an inhibitor of alternative complement pathway factor B, has demonstrated reduction in proteinuria and complement activity in native IgAN. However, it has not been studied in recurrent IgAN after kidney transplant. We present a case of recurrent IgAN refractory to conventional therapy with clinical and histological improvement after treatment with iptacopan. A 39-year-old male patient underwent a deceased donor kidney transplantation. A 3-month biopsy showed features of recurrent IgAN in the transplanted kidney. Following treatment for rejection, subsequent biopsies demonstrated active IgAN with worsening proteinuria, which was treated with rituximab, cyclophosphamide, and steroids. Despite these interventions, there was no improvement in IgAN or proteinuria. At 40 months post-transplant, the patient was started on iptacopan, after which a follow-up biopsy showed resolution of active IgA activity. The patient has tolerated iptacopan well and has not had any adverse events or serious infections.

We conducted a retrospective review of adult kidney transplant recipients (KTRs) who received belatacept in addition to calcineurin inhibitors, antimetabolites, and corticosteroids for recurrent or refractory rejection or for persistent donor-specific antibodies (DSAs) unresponsive to standard therapy. Fifteen recipients were included. Kidney function remained stable on follow-up; median eGFR was 52 mL/min (R 23–91) at baseline and 54 mL/min (R 25–105) at 6 months (p = 0.15) after belatacept initiation. The DSA intensity declined significantly from a median of 4,990 mean fluorescence intensity (MFI) (R 0–23,305) at baseline to 1,644 MFI (R 0–6,903) at 3–6 months (p = 0.03). There was also a small reduction in biopsy-proven rejections from 85.7% to 63.6%. Infections occurred in most recipients (73.3%), with a majority arising more than 6 months after therapy initiation. Two patients developed post-transplant lymphoproliferative disorder (PTLD), each with either substantial prior exposure to lymphocyte-depleting agents or prolonged immunosuppression. Two deaths occurred, one related to PTLD and one to septic shock. These findings suggest that belatacept-based quadruple immunosuppression may reduce DSA and stabilize kidney function in patients with persistent alloimmunity, but without a statistically significant reduction in rejections. There is also a significant burden of infections and PTLD, highlighting the need for careful patient selection and caution before adopting this approach.

Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation, commonly diagnosed after patients present with nonspecific constitutional symptoms and/or transplant organ dysfunction. In this article, we report a case of a kidney transplant recipient who was found to have highly elevated circulating donor-derived cell-free DNA (dd-cfDNA) levels on routine serum surveillance for allograft rejection, initially without organ dysfunction or evidence of allograft rejection on biopsy. Later, for cause imaging revealed retroperitoneal lymphadenopathy and an allograft hilar mass, which was biopsied to show PTLD/diffuse large B cell lymphoma. The elevated circulating dd-cfDNA levels in this patient prompted targeted next-generation sequencing of the same 266 single-nucleotide polymorphisms used to detect dd-cfDNA on the diffuse large B cell lymphoma, which identified it as derived from the donor. The patient achieved complete remission with retained allograft kidney function after reduced immunosuppression and 6 cycles of immunochemotherapy. This case suggests that dd-cfDNA may be an early detection tool in rare but potentially life-threatening cases of donor-derived malignancy, such as donor-derived PTLD.

Acute thrombotic microangiopathy (TMA) developing in association with SARS-CoV-2 infection is a rare but recognized phenomenon in native kidneys. In the allograft kidney, a diagnosis of TMA has a broad etiologic differential, including antibody-mediated rejection and recurrent and de novo causes of TMA that affect the native kidney. Prior case reports have described plasma exchange or eculizumab use in patients with COVID-19-associated TMA. Herein, we describe the course of a kidney transplant patient with COVID-19-associated TMA with response to eculizumab that was sustained after medication withdrawal and review the literature on COVID-19-associated TMA of the allograft kidney.

Introduction:Causes of secondary oxalate nephropathy include enteric dysfunction and excessive intake of oxalate or oxalate precursors. During the COVID-19 pandemic, there has been a dramatic rise in sales of supplements and vitamin C, during which time we observed an apparent increase in the proportion of ingestion-associated oxalate nephropathy. Methods:We retrospectively reviewed secondary oxalate nephropathy and compared pre-pandemic (2018-2019) and pandemic (2020-early 2022) time periods. Results:We identified 35 patients with kidney biopsy proven (30 native, 5 allograft) oxalate nephropathy at a single academic institution. Supplement-associated oxalate nephropathy comprised a significantly higher proportion of cases during COVID-19 pandemic compared with the preceding 2 years (44% vs. 0%, P = 0.002), and was associated with use of vitamin C, dietary changes, and supplements. Oxalate nephropathy in the kidney allograft, in contrast, remained associated with enteric hyperoxaluria, antibiotic use, and dehydration. Many patients had diabetes mellitus (57%), hypertension (40%) and/or pre-existing chronic kidney disease (CKD, 49%). Of 9 patients in which the potentially causative ingestion was identified and removed, 8 experienced improvement in kidney function. Conclusion:There was a shift toward supplements rather than enteric hyperoxaluria as a leading cause of secondary oxalate nephropathy during the COVID-19 pandemic. Kidney outcomes are better than those observed for enteric hyperoxaluria, if the offending agent is identified and removed.

SummaryNew-onset diabetes after transplantation (NODAT) is increasing in frequency and creates many challenges directly impacting the patient and graft survival. Most transplant programs offer a fixed-dose prednisone taper schedule for the prevention of acute rejection following kidney transplantation. In this study, we investigated the incidence of NODAT in new kidney transplant recipients.MethodsThis was a retrospective, single-center study assessing rates of NODAT according to age, ethnicity, body weight, BMI, rejection, and prednisone dosing among kidney transplant recipients.ResultsAmong non-diabetic consecutive kidney transplant recipients (n = 261) from 1/2014 to 12/2018, a total of 47 (18%) kidney transplant recipients developed NODAT. After adjusting for common NODAT risk factors, analysis of the population indicated that age, and corticosteroid dose in the Asian American population [adjusted for lower body weight, BMI] significantly increased the risk of NODAT. In multi-variance analysis, despite receiving lower standard doses of protocol corticosteroid daily, when adjusted for actual body weight (mg/kg/day) Asian American recipients had high incidence of NODAT compared to other ethnicity. Asian American received higher doses or corticosteroids (prednisone) than non-Asian Americans (0.14 mg/kg vs. 0.11 mg/kg) (p = 0.008). The overall incidence of rejection was not higher among those who developed NODAT (p = 0.55)ConclusionThis is the first study to explore the relationship between corticosteroid dose and diabetes in Asian Americans. Asian Americans had higher rates of NODAT and received higher doses of weight-based corticosteroids. There is a possible iatrogenic, pharmacogenomic, and addressable etiology to NODAT in this population.

Approximately 6% of deceased kidney donors (DKDs) are diabetic; their kidneys may be associated with worse allograft survival, but published studies suggest that recipient diabetes status has a greater impact on mortality and survival. Since biopsy findings are the most common reason for organ discard, we sought to understand histologic and clinical factors that influence graft survival in patients who receive a kidney from a diabetic DKD. We retrospectively reviewed our institutional experience from 2005 to 2019, and re-evaluated pre-implantation and earliest post-transplant biopsies. Histologic findings were compared against a control cohort of non-diabetic DKD. Of 829 adult DKD transplants, 37 (4.5%) came from diabetic donors. There was no significant difference in diabetic vs. non-diabetic DKD graft survival for all-comers; however, when stratified by duration of donor diabetes, donor diabetes ≥6 years was associated with graft failure. In 25 patients with post-transplant biopsies available, diabetic DKD allografts had significantly greater non-glomerular chronic injury than non-diabetic DKD allografts. Moderate arteriolar hyalinosis (in 24%), moderate tubular atrophy and interstitial fibrosis (IFTA, in 36%), and diabetic glomerulopathy (in 24%) on early post-transplant biopsy were associated with allograft failure. Pre-implantation frozen section discrepancies were more common in long-standing donor diabetes, and arteriolar hyalinosis and IFTA scores on frozen accurately prognosticated graft loss. There was no morphologic improvement in lesions of diabetic nephropathy on short-term follow-up. In conclusion, donor diabetes ≥6 years, and histologic findings on frozen section and early post-transplant biopsy are associated with diabetic DKD allograft loss.

Introduction: Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on human leukocyte antigens (HLAs). Materials and Methods: Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from 2 North American and 1 European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. The prevalence of HLAs was compared to external healthy controls of European ancestry (n = 15,740). Graft survival was assessed by the Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses. Results: Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR = 1.68, p = 0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR = 0.46, p < 0.001) and HLA-DQ6 (32% vs. 45%, OR = 0.59, p = 0.003); however, the frequency of these HLAs were similar in recurrent versus nonrecurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living-unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival. Conclusion: Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLAs associated with IgAN in the native kidney and HLA matching in recipients of deceased or living-unrelated transplants are not.

Cytomegalovirus (CMV) is a major cause of infection-related morbidity and mortality in kidney transplantation. The most significant risk for developing CMV infection after transplant depends upon donor (D) and recipient (R) CMV serostatus. In 2012, our Organ Procurement Organization (OPO) began a novel pretransplant CMV prevention strategy via matching deceased kidney donors and recipients by CMV serostatus. Prior to the matching protocol, our distribution of seropositive and seronegative donors and recipients was similar to the United States at large. After the matching protocol, high-risk D+R- were reduced from 18.5% to 2.9%, whereas low-risk D-R- were increased from 13.5% to 24%. There was no adverse effect on transplant rates and no differential effect on waiting times for R+ vs R- after the protocol was implemented. This protocol could be implemented on a regional or national level to optimize low and high-risk CMV seroprofiles and potentially improve CMV-related outcomes in kidney transplantation.