Anti-CTLA4 Antibody–Induced Lupus Nephritis

Fadel, Fouad; Karoui, Khalil El; Knebelmann, Bertrand

doi:10.1056/nejmc0904283

Cited by 287 publications

(189 citation statements)

References 3 publications

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“…Cell-mediated immune response leading to inflammatory cell infiltrates with and without granulomas has been reported [15,16]. Cases of acute interstitial nephritis (AIN) in the initial trials, arising 2-12 weeks post drug administration have been reported and one of them demonstrated granulomas [12,17,18,19,20,21,22]. The largest series of biopsy-proven cases of AKI was reported by Cortazar et al [12].…”

Section: Introductionmentioning

confidence: 99%

“…Pathology revealed AIN in most cases with varying degrees of foot process effacement. In addition, cases of nephrotic syndrome [7,19] in the form of minimal change disease and membranous nephropathy have been reported. Out of a total of 13 cases that were noted to have renal injury associated with ipilimumab, there was no specific gender predilection noted (online suppl.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo

Karam²,

Uppal³

et al. 2017

Am J Nephrol

11,140

256

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Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo

Karam²,

Uppal³

et al. 2017

Am J Nephrol

11,140

256

View full text Add to dashboard Cite

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“…The first presumes to involve cell-mediated immunity since biopsies have demonstrated the presence of severe inflammatory cell infiltrates with or without granuloma formation [90]. The second mechanism may be related to autoimmunity since circulating antidsDNA antibodies and glomerular IgG, C3, and C1q deposits, similar to lupus nephritis, have been reported in patients with nephrotic syndrome following ipilimumab therapy [91]. However, it is unclear if these autoantibodies contribute to the pathogenesis or are formed as a possible protective mechanism against ongoing organ damage.…”

Section: Mechanismmentioning

confidence: 98%

Renal Toxicities of Targeted Therapies

et al. 2015

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With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

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“…There have been a number of case reports of rare toxicities that have an autoimmune basis in patients treated with ipilimumab such as lupus nephritis [45], inflammatory enteric neuropathy, Tolsosa-Hunt syndrome, acquired haemophilia A, autoimmune polymyositis and myocardial fibrosis [43,46].…”

Section: Rare Toxicitiesmentioning

confidence: 99%