Nephrotoxicity of Cancer Treatment in Children

Roderick Skinner

Disclosures

Pediatr Health. 2010;4(5):519-538. 

In This Article

Carboplatin

The use of carboplatin as an adjunct or alternative to cisplatin in several adult and pediatric solid tumors (e.g., brain tumors, neuroblastoma and germ-cell tumors) has increased in the last 20 years in view of emerging evidence for its efficacy and lower nephrotoxic potential.[108] Preclinical and early clinical studies in adults suggested that carboplatin causes much less renal damage than cisplatin.[109,110] Carboplatin nephrotoxicity (Box 5), similar to that seen after cisplatin, may occur in children, but it is less frequent, usually milder and often reversible.

Frequency

The incidence of glomerular impairment has ranged from 0 to 15–25% and that of hypomagnesemia from 0 to 10%.[3,72,111–114]

Clinical Features

Glomerular impairment is generally absent[6] or mild with a small reduction in GFR,[112] but rare cases of ARF, sometimes reversible, have been described in adults.[115–117] ARF and occasionally CRF have been reported in children treated with high-dose carboplatin.[118,119] Tubular damage leading to hypomagnesemia may occur[110] but is often reversible.[120] Reversible natriuria and hyponatremia have been described.[121] Chronic subclinical tubular damage, manifest by increased urine RBP and RTE excretion, is reported.[120] Clinical sequelae of carboplatin nephrotoxicity in children are rare and usually fully reversible, except for hypomagnesemia[70] and, rarely, CRF.[118,122]

Natural History

Although carboplatin may occur acutely or develop after completion of treatment, a longitudinal very long-term study of 24 children followed-up for 10 years after completion of carboplatin therapy found no evidence of recovery or deterioration of nephrotoxicity.[70]

Risk Factors

Adult studies have not revealed clear relationships between individual or cumulative carboplatin dose, age or sex, and nephrotoxicity.[115,117] However, pediatric studies have found that the frequency and severity of chronic hypomagnesemia appears to be correlated with cumulative carboplatin dose,[70,120] whilst both long-term glomerular toxicity (reduced GFR) and hypomagnesemia were more common in older children.[70] It is likely that other potentially nephrotoxic chemotherapy may increase carboplatin-induced renal damage since glomerular clearance is the major route of carboplatin excretion. Patients with pre-existing renal impairment may be more susceptible to carboplatin nephrotoxicity,[110] whilst carboplatin-induced ARF has been reported in adults who have previously received cisplatin,[115,116] and prior ifosfamide or concomitant melphalan have been associated with carboplatin-induced ARF in children.[118,119]

Pathogenesis

Histopathological lesions suggesting interstitial nephritis have been described in two women with nephrotoxicity after intraperitoneal carboplatin, one of whom also had 'toxic' tubular changes on electron microscopy,[116] but the route of carboplatin administration in these cases may mean that the histological findings are not truly representative of carboplatin nephrotoxicity. It is usually assumed that cisplatin and carboplatin share the same nephrotoxic mechanism, but that the greater frequency and severity of cisplatin toxicity results from formation of increased amounts of a putative nephrotoxic metabolite due to the increased lability of the chloride ligands of cisplatin compared with the cyclobutane dicarboxylate group of carboplatin.[123]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....