Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and

Chimeric antigen receptor (CAR) T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies. Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are recognized toxicities of CAR-T, whereas kidney injury remains less well recognized. The objective of the present study was to identify the incidence of acute kidney injury (AKI) after CAR-T cell therapy, potential risk factors, and recovery of kidney function. We performed a retrospective review of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T therapy between February 2018 and February 2019 at our institution. Serum creatinine values before CAR-T therapy through day 100 were used to assess AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5-to <2-fold of baseline; grade 2, 2-to <3-fold of baseline; grade 3, 3-fold of baseline. CRS and ICANS were graded using the consensus criteria of the American Society of Transplantation and Cellular Therapy. The overall incidence of CRS was 78.3% (95% confidence interval [CI], 66% to 90.5%), of whom 13% (95% CI, 3.3% to 22.8%) developed grade 3-4 CRS, whereas the overall incidence of ICANS was lower at 45.7% (95% CI, 3.1% to 60.3%). The cumulative incidence of any grade AKI by day 100 was 30% (95% CI, 16.9% to 43.9%), with a grade 1 AKI incidence of 21.7% (95% CI, 9.7% to 33.8%) and a grade 2-3 AKI incidence of 8.7% (95% CI, .4% to 17%). No patients developed severe AKI necessitating renal replacement therapy. Patients with previous autologous or allogeneic stem cell transplantation, those requiring intensive care unit level care and with grade 3-4 CRS had a higher incidence of AKI. Most patients recovered, with kidney function returning to baseline within 30 days. We conclude that with early recognition and management of CAR-T complications, the incidence of AKI is low, the severity of injury is mild, and most patients recover kidney function within 30 days.

Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020. With a median follow-up of 8.5 years, the median overall survival from renal transplantation was 8.6 years and was significantly longer in patients with complete and very good partial hematologic responses (CR + VGPR) compared to less than VGPR (9 versus 6.8 years; HR: 1.5, P = 0.04 [95% CI: 1–2.1]) at renal transplantation. Median graft survival was 7.8 years and was better in the CR + VGPR group (8.3 vs 5.7 years, HR: 1.4, P = 0.05 [95% CI: 1–2]). The frequency and time to amyloid recurrence in the graft was also lower (16% vs 37%, p = 0.01) and longer (median time not achieved vs 10 years, p = 0.001) in the CR + VGPR group. Comparing CR vs. VGPR there was no difference in overall or graft survival. Although 69 patients (29%) experienced hematologic relapse, treatment effectively prevented graft loss in the majority (87%). Renal transplantation in selected AL amyloidosis patients is associated with extended overall and renal graft survival. Patients with hematologic CR or VGPR have the most favorable outcomes, and these patients should be considered for renal transplantation.

Background and objectives Acute kidney injury (AKI) is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of non-relapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft-versus-host disease (GVHD) regimens. To date, GVHD and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre/post-hematopoietic transplant risk factors in a large recent cohort. Design, setting, participants, and measurements We performed a single-center retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014-2017. We defined AKI and CKD based on KDIGO criteria and estimated GFR using CKD-EPI equation. We assessed AKI pre/post-hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using Chi-squared test. AKI was treated as a time-dependent variable in relation to non-relapse mortality. Results Incidence of AKI by day-100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced intensity conditioning carried higher AKI risk compared to myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and CNI nephrotoxicity. Kidney replacement therapy was initiated in 21/616 (3%) of whom 9/21 (43%) recovered and 5/21 (24%) survived to hospital discharge. T-cell depleted transplants, higher baseline albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73/345) of patients after 12 months. Non-relapse mortality was higher in those with AKI (HR 2.77, 95% CI: 1.8-4.27). Conclusions AKI post-hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to CNIs. T cell depleted hematopoietic cell transplants and higher albumin had lower risk of AKI. Forty-three percent of patients requiring KRT recovered kidney function. Prospective studies are needed to further assess modification of these risk factors.