Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes

Abstract

BackgroundImmune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi.MethodsWe conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method.ResultsAmong 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; p<0.001), hypertension (OR 4.3, 95% CI 1.8 to 6.1; p<0.001) and cerebrovascular disease (OR 9.2; 95% CI 2.1 to 40; p<0.001). Baseline sCr, cancer, and ICPi type was not associated with AKI. Use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (OR 2.9; 95% CI 1.5 to 5.7; p=0.002), diuretics (OR 4.3; 95% CI 1.9 to 9.8; p<0.001), and corticosteroid treatment (OR 1.9; 95% CI 1.1 to 3.6; p=0.03) were associated with AKI. In the multivariable analysis, AKI was associated only with other IRAE (OR 2.82; 95% CI 1.45 to 5.48; p=0.002) and hypertension (OR 2.96; 95% CI 1.33 to 6.59; p=0.008). AKI was not associated with increased risk of mortality (HR 1.1; 95% CI: 0.8 to 1.6; p=0.67). ICPi nephrotoxicity was attributed via biopsy or nephrologist assessment in 12 patients (six interstitial nephritis, two membranous nephropathy, two minimal change disease, and two thrombotic microangiopathy). Subsequent doses of ICPi were administered to 12 patients with prior AKI, with one (8.3%) having recurrent AKI.ConclusionAKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.

Biomarkers, Clinical Features, and Rechallenge for Immune Checkpoint Inhibitor Renal Immune-Related Adverse Events

“… 5 Kidney toxicity while on ICI therapy occurs in up to 17% in reported series, but only a fraction is related to ICI, varying from 1% to 5% (depending on the type of ICI or use of combined ICI agents). 10 , 11 , 12 , 13 , 14 , 15 Acute interstitial nephritis (AIN) is the most common histopathological lesion, and depending on the severity of the renal or extra-renal iRAE, further treatment with immunotherapy may be limited. 16 In general, the use of systemic cancer agents is associated with AKI of diverse etiologies, and it is important to understand the likely cause so as to not unnecessarily limit future chemotherapeutic treatment options.…”

Cancer therapy-induced hyponatremia: A case-illustrated review

“…Immune-related toxicities involving the kidneys, the most described being acute interstitial nephritis, occurs in about 2%-4% of patients. [48][49][50][51] ICI have also been associated with electrolytes disturbances, the most frequent being hyponatremia. 52 A meta-analysis of 48 clinical trials of PD-1 inhibitor therapy in different cancer types showed an overall hyponatremia incidence of 1.2% and hyponatremia accounted for more than 53% of Grade 3-5 reported electrolytes abnormalities.…”

Large animal models for translational research in acute kidney injury

“…However, CTLA-4 Ig does not significantly affect human Th1 cells in renal graft tissue [ 74 ]. Moreover, immunotherapy with CTLA-4 antibodies causes AKI in some cancer patients [ 75 , 76 ].…”