Cisplatin-induced renal toxicity in elderly people

Abstract

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m²) are needed.

Keywords: acute kidney injury; aging; cisplatin; renal toxicity; risk factors.

Figure 1.

Risk factors for, and the pharmacokinetics of cisplatin-induced renal toxicity in, elderly patients. Renal hypoperfusion, a high incidence of CKD, high initial and cumulative doses, multiple comorbidities (such as hypertension, diabetes, and ischemic heart disease), and drug types (ACEI/ARB, NSAIDS, diuretic, and antibiotic) are risk factors for cisplatin-induced renal toxicity in elderly patients. Compared with young patients, elderly patients have high plasma levels of ultrafilterable cisplatin, and a lower clearance of total and ultrafilterable cisplatin at a dose of 50 mg/m² or more. ACEI/ARB, angiotensin-converting enzyme inhibitor and angiotensin receptor blocker; CKD, chronic kidney disease; NSAIDS, non-steroidal anti-inflammatory drugs.