BackgroundDespite increasing recognition of the importance of immune checkpoint inhibitor–associated AKI, data on this complication of immunotherapy are sparse.MethodsWe 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.ResultsLower 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.ConclusionsThis 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.
An 18-year-old man who developed severe HUS due to STEC O121 and was unresponsive to traditional supportive therapies was successfully treated with eculizumab.
The monoclonal gammopathies of renal significance are hematologic disorders defined by monoclonal gammopathymediated kidney damage in patients who do not have systemic lymphoma or multiple myeloma. Diagnosis is usually made by a kidney biopsy showing direct paraprotein-mediated kidney damage on immunofluorescence microscopy. A specific challenge exists in patients with monoclonal gammopathies whose kidney biopsies exhibit patterns of injury without visualization of the monoclonal immunoglobulin. Case reports and case series have been published recently describing monoclonal gammopathy-associated C3 glomerulopathy and monoclonal gammopathy-associated thrombotic microangiopathy, with mechanistic hypotheses including paraprotein-mediated activation of the alternative complement pathway. Here, we evaluate the level of evidence supporting the hypothesis that the monoclonal gammopathy is in the causal pathway of monoclonal gammopathy-associated C3 glomerulopathy and monoclonal gammopathy-associated thrombotic microangiopathy and identify gaps in knowledge required to further support these diagnoses.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.