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, 241.5 and 223.3 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.

Cisplatin-induced mitochondrial dysfunction is associated with impaired cognitive function in rats

“…Oxidative stress is involved in the pathogenesis of CDDP-induced dose-limiting toxicities, including nephrotoxicity [30], ototoxicity [31], and peripheral neuropathy [32]. We examined oxidative stress production in hippocampal neurons and NSCs following CDDP treatment (Fig.…”

Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: CON

“…However, investigation into these cases suggests other reasons for ATN on kidney biopsy. As an example, two of five patients underwent prior platinum therapy which is nephrotoxic and known to cause ATN (20,21). Further, the majority of these patients had more cardiovascular risk factors and marked histologic vascular lesions on kidney biopsy (13).…”

Edaravone-Loaded Mesoscale Nanoparticles Treat Cisplatin-Induced Acute Kidney Injury

“…AKI can result from a variety of insults including volume depletion, septicemia, hypotension, and commonly used drugs including antibiotics and chemotherapeutic agents.Cisplatin is a widely used chemotherapy in the treatment of a variety of cancers including ovarian, head and neck, bladder, testicular, and lung, among others 6,7 . A significant side effect of cisplatin therapy is the occurrence of AKI in approximately 33% of patients 8,9 . Indeed, it has been reported that about 20% of all AKI incidences are caused by cisplatin 7,10 .…”

“…Indeed, it has been reported that about 20% of all AKI incidences are caused by cisplatin 7,10 . The development of AKI in these patients can result in the interruption of chemotherapy or a change to less effective chemotherapies 8,9 . There is therefore a critical need to develop novel strategies to prevent or treat AKI induced by cisplatin.…”