Long-Term Renal Outcomes after Cisplatin Treatment

Abstract

Background and objectives: Nephrotoxicity remains the dose-limiting side effect of cisplatin, an effective chemotherapeutic agent with applications across diverse tumor types. This study presents data on renal outcomes across multiple tumor types in 821 adults. We report on incidence of AKI, initial and long-term changes in eGFR after cisplatin, and relationships between cumulative dose, initial eGFR, age, sex, and long-term renal function.

Design, setting, participants, & measurements: This was a retrospective study of adult patients treated with cisplatin from January 1, 2000 to September 21, 2011 who had survived ≥5 years after initial dose. The Modification of Diet in Renal Disease equation was used to calculate eGFR. AKI was defined as an increase from the baseline creatinine of >25% within 30 days after the first cycle of cisplatin. Chi-squared tests were done to evaluate the relationships between categorical or ordinal variables; ANOVAs or t tests were used to evaluate continuous or categorical variables. Changes in eGFR over time were evaluated in a growth curve model.

Results: Mean follow-up was 6 years (25th and 75th percentiles, 4 and 9 years). AKI occurred in 31.5% of patients, with a median initial decline in eGFR of 10 ml/min per 1.73 m(2) (25th and 75th percentiles, -41.5 and -23.3 ml/min per 1.73 m(2)). At any time point after the first cycle of cisplatin, <3% of patients progressed to eGFR<29 ml/min per 1.73 m(2), and none were known to be on dialysis. Age was associated with a higher risk for AKI after cisplatin. Compared with age <25 years old, the odds ratios for AKI versus no AKI are 1.22 for >26-44 years old (95% confidence interval [95% CI], 0.60 to 2.4), 1.54 for >45-65 years old (95% CI, 0.78 to 3), and 2.96 for >66 years old (95% CI, 1.4 to 6.1). The lowest dose categories of cisplatin (≤100 and 101-250 mg/m(2)) are associated with increases in eGFR (P=0.06 and P=0.02, respectively) compared with the highest dose category (>701 mg/m(2)).

Conclusions: This is the largest study of adult patients with cancer who received cisplatin for treatment across multiple tumor types. Most patients experience small but permanent declines in eGFR, but none progressed to ESRD requiring hemodialysis.

Keywords: Acute Kidney Injury; Follow-Up Studies; Humans; chronic kidney failure; cisplatin; cisplatin nephrotoxicity; creatinine; glomerular filtration rate; nephrotoxicity; renal dialysis.

Figure 1.

Box plot (10th and 90th percentiles) of change in median eGFR (milliliters per minute per 1.73 m²) from baseline to year 12. Time points and numbers of total patients with a serum creatinine (SCr) at each time point are shown. Time points are in years. BL, baseline; Last Cis, at completion of the first cycle of cisplatin.

Figure 2.

Percentages of patients within each stage of CKD at baseline, completion of cisplatin, year 1, and year 5. CKD stage (eGFR): CKD stage 1 (≥90 ml/min per 1.73 m²), CKD stage 2 (≥60–89 ml/min per 1.73 m²), CKD stage 3 (≥30–59 ml/min per 1.73 m²), and <29 ml/min per 1.73 m².

Figure 3.

For patients with a SCr at baseline and at completion of cisplatin and for those with a SCr at Year 1 and Year 5, fewer than 6% progressed to a GFR <29 ml/min per 1.73 m². Changes in individual patient’s CKD stage over time: from baseline to the completion of cisplatin (left panel) and from year 1 to year 5 (right panel). SCr, serum creatinine.