Analysis of clinical characteristics of 50 patients with renal immune-related adverse events induced by immune checkpoint inhibitors:a real-world observational study
XUE Zhuo-rui
TENG Fei
HU Rong-rong
AI San-xi
SHI Xiao-xiao
WANG Xiang
SI Xiao-yan
WANG Han-ping
YING Hong-yan
XU Yan
YE Wei
FAN Xiao-hong
LI Xue-mei
ZHENG Ke
Abstract：Objective To analyze the clinical chara-cteristics of immune-related adverse events(irAEs)affecting the kidneys of patients treated with immune checkpoint inhibitors(ICIs)in real-world practice.Methods Clinical data of 50 patients with renal irAEs treated at Peking Union Medical College Hospital between 2018 and 2024 were retrospectively analyzed.The tumor-related features,clinical manifestations and grading of renal irAEs,treatment regimens and therapeutic effects,related risk factors,and prognosis were analyzed.Results Of the 50 patients,46 were diagnosed with ICI-associated tubulointerstitial nephritis(ICI-TIN)and 4 with ICI-associated glomerulonephritis(ICI-GN).The median time to irAE onset was 93 days after ICI initiation,with a median baseline estimated glomerulor filtration rate(eGFR)of 49.9 mL/(min·1.73 m2)at diagnosis.Renal irAEs were predominantly grade 2-3 AKI(68.00％,34/50).There existed positive autoantibodies(ANA 38.71％,12/31),anti-SSA and anti-SSB(3.45％,1/29),ANCA(4.35％,1/23),and anti-GBM(8.00％,2/25);all became negative after immunosuppression.No complement reduction was observed in the detection(34/34),while elevated IL-6(47.37％,9/19)and TNF-α(90.48％,19/21)were noted.ICI-GN patients had higher grade of AKI than ICI-TIN(P＜0.05).Among 27 cases with biopsy,23 showed TIN and 4 GN[2 proliferative,2 non-proliferative;75.00％(3/4)coexisted with TIN].Among the 50 patients,38 received steroids treatment(median prednisone 50.0 mg/day for 71 days),with a 62.00％renal recovery rate.No kidney in patients diagnosed with proliferative GN recovered.ICIs were discontinued in 47 patients,and 7 rechallenged without recurrent irAEs.Univariate analysis showed that older age and larger dose of steroids were related to poor renal outcomes(OR 1.122,95％CI 1.013-1.243,P＜0.05).The irAE-AKI grade,combination with ICI-GN,renal recovery,and initiation of steroid use showed no significant association with tumor prognosis or patient survival.Domestic ICIs were used in 28 patients and imported ICIs in 22 patients,which had no statistical difference in combined medication,type of renal irAEs,time of disease onset,creatine level at disease onset or peak value of creatine(all P＞0.05).Cox regression analysis showed that there was no relationship between domestic or imported ICIs and tumor prognosis or patient survival.Conclusion Renal irAEs due to domestic or imported ICIs share similar clinical manifestations and prognosis.TIN predominates in renal irAEs,but GN results in worse injury.Most renal irAEs can be recovered after ICI withdrawal and immunosuppression,except proliferative GN.Multiple positive autoimmune antibodies may exist in renal irAEs.Older age and larger starting dose of steroids impair renal recovery.while immunosuppression does not affect the overall survival of patients.ICI origin(domestic/imported)does not influence survival prognosis.
Keywords：immune checkpoint inhibitorsimmune-related kidney injuryrenal biopsyrisk factortreatmentprognosis
Publication Date：2025-06-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：11( 522-532 )