JASN publishes highly competitive original manuscripts, brief reviews, and special articles in areas of basic and clinical science relevant to the broad discipline of nephrology. Subject matter appropriate for JASN includes, but is not restricted to: cell biology; developmental biology; genetics; cell and transport physiology; hemodynamics and vascular regulation; immunology and pathology; pathophysiology of renal disease and progression; mineral metabolism and bone disease; clinical nephrology, epidemiology, and outcomes; dialysis; and transplantation. The editors encourage only the submission of meritorious research that will communicate important advances in the field of nephrology.
Frank B. Cortazar, Zoé A. Kibbelaar, Ilya Glezerman, Ala Abudayyeh, Omar Mamlouk, Shveta S. Motwani, Naoka Murakami, Sandra M. Herrmann, Sandhya Manohar, Anushree C. Shirali, Abhijat Kitchlu, Shayan Shirazian, Amer Assal, Anitha Vijayan, Amanda D Renaghan, David I. Ortiz-Melo, Sunil Rangarajan, A. Bilal Malik, Jonathan J. Hogan, Alex Dinh, Daniel Sanghoon Shin, Kristen A. Marrone, Zain Mithani, Douglas B. Johnson, Afrooz Hosseini, Deekchha Uprety, Shreyak Sharma, Shruti Gupta, Kerry L. Reynolds, Meghan E. Sise, David E. Leaf
Significance StatementKidney 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.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.
Dagan Jenkins, Maria Bitner‐Glindzicz, Sue Malcolm, Chih‐Chi Andrew Hu, Jennifer Allison, Paul J.D. Winyard, Ambrose Gullett, David F. Thomas, Rachel Belk, Sally Feather, Tung‐Tien Sun, Adrian S. Woolf
Hong Chen, Lin Wang, Wenjun Wang, Cheng Cheng, Yu Zhang, Yu Zhou, Cong‐Yi Wang, Xiaoping Miao, Jiao Wang, Chao Wang, Jianshuang Li, Ling Zheng, Kun Huang
Renal ischemia-reperfusion (I/R) injury is the most common cause of AKI, which associates with high mortality and has no effective therapy. ELABELA (ELA) is a newly identified 32-residue hormone peptide highly expressed in adult kidney. To investigate whether ELA has protective effects on renal I/R injury, we administered the mature peptide (ELA32) or the 11-residue furin-cleaved fragment (ELA11) to hypoxia-reperfusion (H/R)–injured or adriamycin-treated renal tubular cells in vitro. ELA32 and ELA11 significantly inhibited the elevation of the DNA damage response, apoptosis, and inflammation in H/R-injured renal tubular cells and suppressed adriamycin-induced DNA damage response. Similarly, overexpression of ELA32 or ELA11 significantly inhibited H/R-induced cell death, DNA damage response, and inflammation. Notably, treatment of mice with ELA32 or ELA11 but not an ELA11 mutant with a cysteine to alanine substitution at the N terminus (AE11C) inhibited I/R injury-induced renal fibrosis, inflammation, apoptosis, and the DNA damage response and markedly reduced the renal tubular lesions and renal dysfunction. Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI.
Chỉ số ảnh hưởng
Các tạp chí khác
Tạp chí Khoa học Tự nhiên Đại học Quốc gia Thành phố Hồ Chí Minh
Tạp chí Khoa học Kiểm sát
Tạp chí Khoa học Kiến trúc và Xây dựng
Tạp chí Nghiên cứu Khoa học và phát triển Trường Đại học Thành Đô
Tạp chí Khoa học - Công nghệ trong lĩnh vực An toàn thông tin
Tạp chí Phát triển Khoa học và Công nghệ Đại học Quốc gia Thành phố Hồ Chí Minh