KIDNEY TOXICITY OF IMMUNE CHECKPOINT INHIBITORS IN ONCOLOGY PATIENTS: AN ONCONEPHROLOGY PERSPECTIVE FROM A MULTI-ETHNIC COHORT IN SOUTHEAST ASIA

Introduction:

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy by boosting the immune system's ability to target cancer cells. Despite their efficacy, ICIs can cause immune-related adverse events, including kidney toxicity. With the increasing use of ICIs, the role of onconephrology is becoming more critical, yet data on this topic are scarce among multi-ethnic cohorts in Southeast Asia. Hence, this study aims to evaluate the incidence and risk factors of kidney toxicity and survival in oncology patients receiving ICI therapy. It also examines nephrology referral practices for those with significant kidney toxicity.

Methods:

A retrospective cohort study was done at a tertiary teaching centre in Malaysia on oncology patients treated with ICIs between January 2016 and December 2023. Patients aged ≥18 years with baseline kidney function data and a minimum follow-up of three months post-ICI therapy were included. Clinical data, including kidney function parameters at baseline and at 3, 6, and 12 months post-ICI initiation, were extracted from electronic medical records. Significant kidney toxicity was defined as worsening kidney function (≥30% decline in eGFR), worsening proteinuria (an increase in KDIGO 2012 CKD Albuminuria category), or significant electrolyte disorders (e.g., hyponatremia <130 mmol/L, hypernatremia >150 mmol/L, hypokalemia <3 mmol/L, hyperkalemia >6 mmol/L). Statistical analyses included descriptive statistics, Kaplan-Meier survival analysis, and multivariate logistic regression.

Results:

A total of 322 patients were included (median age 60.1 years; 39.8% female; 79.5% Chinese). Of these, 5.3% had preexisting chronic kidney disease (eGFR <60 mL/min/1.73 m²), and 9.3% were active smokers. Concomitant chemotherapy and targeted therapy were used in 62.4% and 40.1% of patients, respectively. The most common cancer type was lung cancer (29.5%), followed by liver cancer (19.9%), with 75.2% of patients having stage 4 cancer. Pembrolizumab was the most common ICI (51.9%), followed by atezolizumab (22%), and nivolumab (18.6%). Significant kidney toxicity occurred in 45% of patients: 9.9% experienced worsening kidney function, 33.7% developed worsening proteinuria, and 16.1% had electrolyte disorders post-ICI therapy, with hyponatremia being the most common electrolyte imbalance. Figure 1 depicts the proportions of patients with overlapping kidney toxicities. There were no significant differences in kidney toxicity or patient survival among different ICIs. Multivariate logistic regression analysis showed that concomitant use of chemotherapy significantly increased the risk of kidney toxicity (adjusted OR: 3.53, p = 0.018). 25% of patients with significant kidney toxicity were referred for nephrology consultation. None of the patients underwent kidney biopsy or immunology tests for kidney toxicity evaluation.

Conclusions:

These findings contribute to the growing body of evidence underscoring the significant incidence of kidney toxicity in oncology patients receiving ICI therapy. Nephrology referral and investigation patterns highlight potential gaps in clinical management. This study calls for vigilant monitoring and enhanced multidisciplinary collaboration, including early nephrology involvement, to optimize care. Future research should aim to develop predictive models and guidelines to improve management strategies in onconephrology.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.