Clinical Features and Outcomes of Immune Checkpoint Inhibitor–Associated AKI: A Multicenter Study

Abstract

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.

Immune Checkpoint Inhibitor Nephrotoxicity: Update 2020

“…Finally, the latency period between ICPI initiation and AKI is often longer than observed with other more commonly reported irAEs, with dermatitis usually occurring within 4 weeks of treatment (4,30,31) and colitis within 6 weeks (32). In our multicenter study, the median time from ICPI initiation to AKI onset was 14 weeks (interquartile range, 6-47 weeks), and many patients presented much later (21).…”

“…In contrast, the Kidney Disease: Improving Global Outcomes Work Group (KDIGO) consensus criteria define AKI according to relative changes in SCr (Table 2) (19). Even among studies that use the KDIGO criteria to define ICPI-AKI, some define ICPI-AKI as any stage (20), whereas others include only stage 2 or higher (21). Thus, there is a need for harmonization of definitions of ICPI-AKI across studies (discussed further below).…”

“…present with sterile pyuria or subnephrotic-range proteinuria (Table 3) (15,16,28), similar to patients with ATIN from other causes (29), but neither finding is sufficiently sensitive or specific to confirm or rule out ICPI-AKI. Eosinophilia is found only in a minority of patients (15,16,21), but may be helpful when present. Finally, the latency period between ICPI initiation and AKI is often longer than observed with other more commonly reported irAEs, with dermatitis usually occurring within 4 weeks of treatment (4,30,31) and colitis within 6 weeks (32).…”

“…In our multicenter study of 138 patients with ICPI-AKI, which included 276 unmatched control patients who received ICPIs contemporaneously but did not develop AKI, we identified three independent risk factors for development of ICPI-AKI: concomitant use of PPIs, combination treatment with anti-CTLA-4 and anti-PD-1/PD-L1 agents, and lower baseline eGFR (Figure 1) (21). Smaller studies have also implicated PPI use as a risk factor for ICPI-AKI (15,16,20), and PPI use is associated with an increased risk of ATIN in the general population (33).…”

Nebenwirkungen neuer onkologischer Immuntherapien

“…Die Formen renaler Beteiligung durch gesteigerte Autoimmunität bei Checkpoint-Inhibition wurden in den letzten 5 Jahren zunehmend gut beschrieben [19,20]. Aktuell liegen zwei gleichermaßen rezente wie lesenswerte Studien zum Thema vor -die eine von Anker et al, erschienen in der Januarausgabe von Der Nephrologe [21,22]. Auf letztere Arbeit möchten wir ausdrücklich zum Nachschlagen der Details bezüglich Diagnostik und Therapie verweisen [21].…”