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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of kidney immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms, and clinicopathologic features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for rechallenge with ICI following AKI episodes. In addition, we explore ICI use in special populations, such as kidney transplant recipients, and propose key areas of focus for future research and clinical investigation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Continuous renal replacement therapy (CRRT) is a dialysis modality used in critically ill patients with acute kidney injury (AKI). Although most dialysate and replacement fluids are dextrose-containing, CRRT-associated hypophosphatemia sometimes warrants the use of phosphorus-containing solutions which are dextrose free. The other less commonly used dextrose-free dialysate solutions are certain formulations of Prismasol and Prismasate. As glucose is a small molecule, which is readily cleared with dialysis, use of these solutions can result in increased caloric loss, net glucose deficit, and shifting of the metabolic pathway towards gluconeogenesis and ketogenesis. Starvation ketosis is usually a benign entity, however when combined with factors such as stress of critical illness, can produce metabolic acidosis which at times can be severe. We describe five patients who developed worsening metabolic acidosis despite adequate clearance from CRRT and were diagnosed with CRRT-associated ketoacidosis. Administration of dextrose-containing fluids or tube feeds promptly resulted in resolution of ketonemia and acidosis. Recognition of this entity is of great importance as the reflexive reaction to increase the prescribed dose of CRRT to improve the acidosis, in fact worsens the problem.

Background: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration., Methods: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days)., Results: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively)., Conclusion: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed., Competing Interests: Competing interests: SG receives research funding from GE Healthcare and BTG International and is President and Founder of the American Society of Onconephrology. CGC has received travel and congress fees support from AstraZeneca, Esteve, NovoNordisk, Boehringer Ingelheim Lilly, Astellas, Otsuka, Novartis, Astellas, and Baxter and has given scientific lectures and participated in advisory boards organized by AstraZeneca, Boehringer Ingelheim Lilly, Mundipharma, and NovoNordisk. DSS participates in the speakers’ bureau at Genentech. FBC is a consultant for ChemoCentryx and Retrophin. AA is supported by the Division of Internal Medicine Immuno-Oncology Toxicity Award Program of the University of Texas MD Anderson Cancer Center. BS is a senior clinical investigator at the Research Foundation Flanders (F.W.O.) (1842919N) and is supported by Stichting tegen Kanker (grant C/2020/1380). AR is a consultant for Otsuka Pharmaceutical, and treasurer of the American Society of Onconephrology. SMH is supported by the Mayo Clinic K2R award. KB receives grant support from Olympia Morata Programme, Foundations Commission of University of Heidelberg, Rheumaliga Baden-Württemberg e.V., AbbVie, and Novartis. KB also serves as a consultant/receives speaker fee/travel reimbursements from AbbVie, BMS, Janssen, MSD, Viatris, Gilead/Galapagos, Lilly, Medac, Mundipharma, Novartis, Pfizer, Roche, and UCB. MES has served on a scientific advisory board for Mallinckrodt. LC serves as a consultant/receives honorarium/travel reimbursements from Pfizer, Bristol Myers Squibb, MSD. The remaining authors have no conflicts of interest or disclosures. MJS reports personal fees from NovoNordisk, Janssen, Mundipharma, AstraZeneca, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare and Boehringer Ingelheim. MJS is a consultant for NovoNordisk, Travere Therapeutics, GE Healthcare, AstraZeneca, and Boehringer. MJS receives grant support form Boehringer Ingelheim, ISCIIII-FEDER and ISCIII-RETICS REDinREN, grant number PI17/00257, PI21/01292, RD16/0009/0030, RICORS RD21/0005/0016, Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, and EIN2020-112338. MJS is elected Editor-in-Chief of Clinical Kidney Journal., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer., Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI., Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI., Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale & Objective: Outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) are not well understood. The goal of this study was to investigate the survival and kidney outcomes of these patients., Study Design: Retrospective cohort study., Setting & Participants: Patients (aged≥18 years) hospitalized with COVID-19 at 13 hospitals in metropolitan New York between March 1, 2020, and April 27, 2020, followed up until hospital discharge., Exposure: AKI., Outcomes: Primary outcome: in-hospital death., Secondary Outcomes: requiring dialysis at discharge, recovery of kidney function., Analytical Approach: Univariable and multivariable time-to-event analysis and logistic regression., Results: Among 9,657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1,000 patient-days. Incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1-3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. Taking those without AKI as the reference group, we observed greater risks for in-hospital death for patients with AKI 1-3 and AKI 3D (HRs of 5.6 [95% CI, 5.0-6.3] and 11.3 [95% CI, 9.6-13.1], respectively). After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI 1-3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI 3D (adjusted HR, 6.4 [95% CI, 5.5-7.6]) compared with those without AKI. Among patients with AKI 1-3 who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI 3D who survived, 30.6% remained on dialysis at discharge, and prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (adjusted OR, 9.3 [95% CI, 2.3-37.8])., Limitations: Observational retrospective study, limited to the NY metropolitan area during the peak of the COVID-19 pandemic., Conclusions: AKI in hospitalized patients with COVID-19 was associated with significant risk for death., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Reports show that AKI is a common complication of severe coronavirus disease 2019 (COVID-19) in hospitalized patients. Studies have also observed proteinuria and microscopic hematuria in such patients. Although a recent autopsy series of patients who died with severe COVID-19 in China found acute tubular necrosis in the kidney, a few patient reports have also described collapsing glomerulopathy in COVID-19., Methods: We evaluated biopsied kidney samples from ten patients at our institution who had COVID-19 and clinical features of AKI, including proteinuria with or without hematuria. We documented clinical features, pathologic findings, and outcomes., Results: Our analysis included ten patients who underwent kidney biopsy (mean age: 65 years); five patients were black, three were Hispanic, and two were white. All patients had proteinuria. Eight patients had severe AKI, necessitating RRT. All biopsy samples showed varying degrees of acute tubular necrosis, and one patient had associated widespread myoglobin casts. In addition, two patients had findings of thrombotic microangiopathy, one had pauci-immune crescentic GN, and another had global as well as segmental glomerulosclerosis with features of healed collapsing glomerulopathy. Interestingly, although the patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RT-PCR, immunohistochemical staining of kidney biopsy samples for SARS-CoV-2 was negative in all ten patients. Also, ultrastructural examination by electron microscopy showed no evidence of viral particles in the biopsy samples., Conclusions: The most common finding in our kidney biopsy samples from ten hospitalized patients with AKI and COVID-19 was acute tubular necrosis. There was no evidence of SARS-CoV-2 in the biopsied kidney tissue., (Copyright © 2020 by the American Society of Nephrology.)

Purpose of Review: Acute kidney injury (AKI) in the setting of hematopoietic stem cell transplantation (HSCT) is common in pediatric and adult patients. The incidence ranges from 12 to 66%, and development of AKI in the posttransplant course is independently associated with higher mortality., Recent Findings: Patients who undergo HSCT have many risk factors for developing AKI, including sepsis, use of nephrotoxic medications, graft versus host disease (GVHD), and veno-occlusive disease (VOD). In addition, engraftment syndrome/cytokine storm, transplant-associated thrombotic microangiopathy (TA-TMA), and less common infections with specific renal manifestations, such as BK and adenovirus nephritis, may lead to kidney injury. There has been significant advancement in the understanding of TA-TMA in particular, especially the role of the complement system in its pathophysiology. The role of early dialysis has been explored in the pediatric population, but not well studied in adult HSCT recipients SUMMARY: This review provides an update on the risk factors, causes, and treatment approaches to HSCT-associated AKI.

Acute kidney injury (AKI) after surgery or intervention is an important complication that may impact mortality, morbidity, and health care costs. Endovascular procedures are now performed routinely for a variety of pathologies that were traditionally treated with open surgery because randomized trials comparing endovascular and open surgery have shown at least equally good results and reduced complication and hospitalization rates with endovascular techniques. However, endovascular procedures have been associated with an increased risk for postoperative AKI, predominantly owing to contrast nephrotoxicity. Over the years, endovascular techniques have progressively been applied for the treatment of complex cardiovascular pathologies, and in recent years, nephrologists have increasingly encountered patients who developed AKI after endovascular aneurysm repair or transcatheter aortic valve replacement. These 2 procedures typically involve high-risk patients who have several established AKI risk factors prior to intervention. Several studies have investigated the incidence, risk factors, and natural course of AKI after endovascular aneurysm repair and transcatheter aortic valve replacement. This review summarizes current data on incidence, risk factors, pathophysiology, prognostic implications, and treatment of AKI associated with endovascular aneurysm replacement and transcatheter aortic valve replacement., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers., Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important., (© 2017 S. Karger AG, Basel.)

Pomalidomide is an analog of thalidomide with immunomodulatory, anti-angiogenic, and anti-neoplastic activity indicated for the treatment of multiple myeloma refractory to at least two prior therapies. The incidence for renal failure was <5% in a single phase II study of pomalidomide and dexamethasone in patients with multiple myeloma that failed both lenalidomide and bortezomib therapy. We report a case suggesting crystal nephropathy as the mechanism for acute kidney injury in pomalidomide and fluoroquinolone use., (© The Author(s) 2015.)

Carfilzomib is a second-generation epoxyketone proteasome inhibitor that is approved for treatment of relapsed and refractory multiple myeloma. Phase 2 trials have reported that 25% of treated patients have renal adverse effects. Pre-renal/vasoconstriction-related insult from this chemotherapy agent has been documented. We describe a case of a 78-year-old man with refractory multiple myeloma with acute kidney injury associated with carfilzomib treatment. We show that use of N-acetyl-l-cysteine in our patient partially mitigated the renal injury upon re-challenge. This case report hypothesizes that acute renal injury from carfilzomib is caused by vasoconstriction of the renal vessels, which may be prevented by N-acetyl-l-cysteine., (© The Author(s) 2014.)