Significance Statement: Kidney toxicity from use of immune checkpoint inhibitors is being recognized as an increasingly frequent complication of treatment. However, existing data on immune checkpoint inhibitor–associated AKI have been limited to small, mostly single-center studies. In this multicenter study of 138 patients with immune checkpoint inhibitor–associated AKI and 276 controls, the authors characterize the clinical features of this complication and identify risk factors associated with its development, clinicopathologic features, and determinants of kidney recovery after an episode. Failure to achieve kidney recovery was associated with worse overall survival, and a minority (23%) of patients who were retreated with immune checkpoint inhibitors had a recurrence of AKI. The study provides insights into immune checkpoint inhibitor–associated AKI, although further study is needed to inform the care of affected patients. Background: Despite increasing recognition of the importance of immune checkpoint inhibitor–associated AKI, data on this complication of immunotherapy are sparse. Methods: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor–associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. Results: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor–associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6–37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis–causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis–causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor–associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. Conclusions: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor–associated AKI.

The aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors. We conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579. A total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95–3.64] and 1.67 (95% CI 0.89–3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57–11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40–84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5–3.0%) and 1.0% (95% CI 0.6–1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2–26.0%). Treatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring.

Background: Telenephrology has become an important health care delivery modality during the COVID-19 pandemic. However, little is known about patient perspectives on the quality of care provided via telenephrology compared to face-to-face visits. We aimed to use objective data to study patients’ perspectives on outpatient nephrology care received via telenephrology (phone and video) versus face-to-face visits. Methods: We retrospectively studied adults who received care in the outpatient Nephrology & Hypertension division at Mayo Clinic, Rochester, from March to July 2020. We used a standardized survey methodology to evaluate patient satisfaction. The primary outcome was the percent of patients who responded with a score of good (4) or very good (5) on a 5-point Likert scale on survey questions that asked their perspectives on access to their nephrologist, relationship with care provider, their opinions on the telenephrology technology, and their overall assessment of the care received. Wilcoxon rank sum tests and chi-square tests were used as appropriate to compare telenephrology versus face-to-face visits. Results: 3,486 of the patient encounters were face-to-face, 808 phone and 317 video visits. 443 patients responded to satisfaction surveys, and 21% of these had telenephrology encounters. Established patients made up 79.6% of telenephrology visits and 60.9% of face-to-face visits. There was no significant difference in patient perceived access to health care, satisfaction with their care provider, or overall quality of care between patients cared for via telenephrology versus face-to-face. Patient satisfaction was also equally high. Conclusions: Patient satisfaction was equally high amongst those patients seen face-to-face or via telenephrology.

Background: Peptide receptor radionuclide therapy with ¹⁷⁷Lu-dotatate is a novel therapy for metastatic neuroendocrine cancers. It undergoes reabsorption at the proximal tubule; after the breakdown of the peptide fragment, ¹⁷⁷Lu is retained and continues its decay process exposing the nephron to continuous low dose radiation. Pivotal NETTER-1 trial did not include patients with eGFR <50 and so its effects in CKD patients is not known. Methods: We performed a retrospective chart review of all consecutive adult patients that received ¹⁷⁷Lu-dotatate over 1 year at Mayo Clinic, Rochester. We analyzed renal and hematological laboratory data obtained prior to each of four treatment cycles and at 3- and 6-month post completion of all treatment. We defined CKD as eGFR <60 ml/min and AKI as creatinine increase of ⩾0.3 from baseline by AKIN criteria. Results: Overall 86 patients were included in the study with 39 (45%) with known CKD. About three patients had CKD, four with eGFR of 20–30 ml/min. About 4 (4.6%) patients had AKI and the predominant cause being hypotension. Among the CKD patients the average eGFR improved after the first cycle of PRRT therapy from baseline of 49 (13) to 53.5 (17) ml/min ( p = 0.01) with no significant decline of renal function noted at 3- and 6-months post treatment follow up. Rate of thrombocytopenia and leukopenia were significantly more in the CKD patients starting even after single treatment. No drug dose correlation was noted. Conclusion: Patients with CKD are at a higher risk of hematological toxicity especially with thrombocytopenia and require close monitoring and ongoing dose adjustment. Ongoing safety studies to assess the long-term impact of ¹⁷⁷Lu-dotatate on the kidney are needed.

Peptide receptor radionuclide therapy (PRRT) has transformed the management of neuroendocrine tumors and other malignancies by enabling targeted radiation delivery while minimizing systemic toxicity. However, incidental renal radiation exposure presents a significant risk of radiation nephropathy, and this risk varies based on the unique characteristics of the radionuclide and its decay phenomenon as well as the peptide being utilized. This review explores the historical development of PRRT, the physics of radionuclide therapy as necessary for a practicing nephrologist, and key mechanisms of radiation-related kidney injury. We detail renal handling of radionuclides, dose thresholds and pathological features of PRRT-induced nephropathy. Furthermore, we discuss both current and prospective strategies to reduce renal toxicity—such as amino acid infusions, receptor saturation, cleavable linkers and emerging protective agents. Special considerations for PRRT in patients with chronic kidney disease and those on dialysis are highlighted. As PRRT applications expand, multidisciplinary collaboration is essential to optimize renal safety.