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.
Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. It remains an important and effective therapy in many forms of cancer today. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Although it is best known for DNA damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic reticulum and mitochondria. It also activates apoptotic pathways and inflicts cellular damage via oxidative stress and inflammation. One of its dose limiting toxicities is its effects on the kidney. This includes acute kidney injury as well as tubular injury resulting in electrolyte wasting. Extensive research has found that cisplatin entry into a cell is facilitated by a number of cellular transporters including human copper transport protein 1 (Ctr1) and the organic cation transporter 2 (OCT2) which are expressed on renal tubular cells. The interactions between the mechanisms of cytotoxicity and cellular transport play an important role in the nephrotoxicity. Better understanding of these interactions could one day help devise better renoprotection that would not reduce its anti-tumor effects.
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.
Based on the findings of our meta-analysis, shiftwork status may play an important role in HTN, as there is a significant association between rotating shift work and HTN. However, there is no significant association between night shift status and risk of HTN.
Introduction: Kidney transplant (Ktx) recipients are excluded from clinical trials of immune checkpoint inhibitors. The aim of this systematic review was to assess the safety of immune checkpoint inhibitors among Ktx patients. Methods: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2019. We included studies that reported outcomes of Ktx recipients who received immune checkpoint inhibitors for cancer treatment. Outcomes of interest were allograft rejection and/or allograft failure. Results: Twenty-seven articles with a total of 44 Ktx patients treated with immune checkpoint inhibitor were identified. Of 44 Ktx patients, 18 were reported to have acute rejection. Median time from immune checkpoint inhibitors to acute rejection diagnosis was 24 (interquartile range, 10-60) days. Reported types of acute allograft rejection were cellular rejection (33%), mixed cellular and antibody-mediated rejection (17%), and unspecified type (50%). Fifteen (83%) had allograft failure and 8 (44%) died. Three patients had a partial remission (17%), 1 patient achieved cancer response (6%), and 5 patients had stable disease (28%). Conclusion: The findings of our study raise awareness of the increased risk for acute allograft rejection/ failure following immune checkpoint inhibitors for cancer treatment among Ktx patients, in particular with programmed cell death 1 (PD-1) inhibitors. Future large-scale clinical studies are required to appraise the pathogenesis and plan optimal balanced therapy that helps sustain graft tolerance.
Introduction Immune checkpoint inhibitors (ICIs) are effective in treating several cancers; however, acute kidney injury (AKI) can occur as part as an immune-related adverse event (iRAE). Biomarkers at the time of AKI diagnosis may help determine whether they are ICI- related and guide therapeutic strategies. Methods In this retrospective study, we reviewed patients with cancer treated with ICI therapy between 2014 and 2020 who developed AKI (defined as a ≥1.5-fold increase in serum creatinine [SCr]) that was attributed to ICI (ICI-AKI) and compared them with an adjudicated non–ICI-AKI group. Clinical and laboratory features, including SCr, serum C-reactive protein (CRP), and urine retinol binding protein/urine creatinine (uRBP/Cr) levels at AKI event were evaluated. Results There were 37 patients with ICI-AKI and 13 non–ICI-AKI referents in the cohort for analysis. At time of AKI, SCr, CRP, and uRBP/Cr were significantly higher in the ICI-AKI compared with the non–ICI-AKI patients (median [interquartile range (IQR)] SCr 2.0 [1.7, 2.9] vs. 1.5 [1.3, 1.6] mg/dl, serum CRP 54.0 [33.7, 90.0] vs. 3.5 [3.0, 7.9] mg/l, and uRBP/Cr 1927 [1174, 46,522] vs. 233 [127, 989] μg/g Cr, respectively, P < 0.05 for all). Compared with the referent group, time from ICI initiation to AKI was shorter in the ICI-AKI patients. Among the ICI-AKI group, complete renal recovery occurred in 39% of patients by 3 months; rechallenge occurred in 16 (43%) of patients, of whom 3 (19%) had recurrence of AKI. Conclusion Our findings suggest that serum CRP and uRBP/Cr may help to differentiate AKI due to ICI from other causes.
Background The objective of this case cohort study was to describe our experience in the care of patients with immune checkpoint inhibitor-related acute interstitial nephritis (ICI-AIN) including rechallenge. Methods A descriptive case series of patients that received an ICI and had an AKI (defined as a $1.5-fold increase in serum creatinine) as an immune-related adverse event (irAE), with biopsy-proven or clinically suspected ICI-AIN from January 1, 2014 to December 1, 2018 at Mayo Clinic, Rochester. We studied details regarding diagnosis, clinical course, management, and outcomes of rechallenge of immunotherapy. Complete response (CR) was defined as return of kidney function back to baseline or ,0.3 mg/dl above baseline creatinine; partial response (PR) was defined as creatinine .0.3 mg/dl from baseline, but less than twofold above the baseline by the end of steroid course. Results A total of 14 cases of biopsy-proven (35%) or clinically suspected (65%) ICI-AIN was identified. All patients had their ICI withheld and 12 patients received steroids. Steroid regimens were highly variable. The starting equivalent dose of prednisone was higher in those that had a CR versus a PR (median 0.77 mg/kg versus 0.66 mg/kg). Proton pump inhibitors (PPIs) were used in 11 patients and were stopped in eight (73%) patients at the time of the AKI event. A CR was seen in five (63%) of the eight patients who discontinued PPIs. Rechallenge was attempted in four of the 14 patients: three were successful with no recurrence of AKI, but one patient had recurrent AKI and fatal pneumonitis. Conclusions Careful review, withholding ICI and concomitant known AIN-inducing medications, along with prompt initial steroid management were the key in complete renal kidney recovery. A kidney biopsy should be strongly considered. Rechallenge of immunotherapy after a kidney irAE, although challenging, is possible and would need careful evaluation on an individual basis.
The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN. The level of free light chain (FLC) in the blood and urine is directly associated with the risk of developing LCCN. Recovery of renal function is related to the speed and degree of the serum FLC reduction. Recently, two randomized trials using high cutoff dialyzer for the removal of serum FLC produced different results in terms of renal recovery. FLC plays a key role in the development and resolution of LCCN. Future therapies will aim to rapidly reduce its concentration or interrupt its interaction with Tamm-Horsfall protein.
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.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.