Journal of the American Society of Nephrology : JASN
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Anti-CD8 Monoclonal Antibody Therapy Is Effective in the Prevention and Treatment of Experimental Autoimmune Glomerulonephritis
Journal of the American Society of Nephrology : JASN - Tập 13 Số 2 - Trang 359-369 - 2002
Insights into the Abnormalities of Chronic Renal Disease Attributed to Malnutrition
Journal of the American Society of Nephrology : JASN - Tập 13 Số suppl_1 - Trang S22-S27 - 2002
Clinical Features and Outcomes of Immune Checkpoint Inhibitor–Associated AKI: A Multicenter Study
Significance Statement
Kidney 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.
Background
Despite increasing recognition of the importance of immune checkpoint inhibitor–associated AKI, data on this complication of immunotherapy are sparse.
Methods
We 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.
Results
Lower 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.
Conclusions
This 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.
Journal of the American Society of Nephrology : JASN - Tập 31 Số 2 - Trang 435-446 - 2020
Absence of vacuolar H(+)-ATPase pump in the collecting duct of a patient with hypokalemic distal renal tubular acidosis and Sjögren's syndrome.
Journal of the American Society of Nephrology : JASN - Tập 6 Số 2 - Trang 295-301 - 1995
Protein Degradation by the Ubiquitin–Proteasome Pathway in Normal and Disease States
Journal of the American Society of Nephrology : JASN - Tập 17 Số 7 - Trang 1807-1819 - 2006
De Novo Uroplakin IIIa Heterozygous Mutations Cause Human Renal Adysplasia Leading to Severe Kidney Failure
Journal of the American Society of Nephrology : JASN - Tập 16 Số 7 - Trang 2141-2149 - 2005
Blockade of Vascular Endothelial Growth Factor Signaling Ameliorates Diabetic Albuminuria in Mice
Journal of the American Society of Nephrology : JASN - Tập 17 Số 11 - Trang 3093-3104 - 2006
Resolved
Journal of the American Society of Nephrology : JASN - Tập 18 Số 9 - Trang 2432-2438 - 2007
A possible molecular basis of natriuresis during ischemic-reperfusion injury in the kidney.
Journal of the American Society of Nephrology : JASN - Tập 9 Số 4 - Trang 605-613 - 1998
ELABELA and an ELABELA Fragment Protect against AKI 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.
Journal of the American Society of Nephrology : JASN - Tập 28 Số 9 - Trang 2694-2707 - 2017
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