Impaired tubular excretory function as a late renal side effect of chemotherapy in children

Purpose: Renal drug excretion is variously influenced by nephrotoxic drugs. This study was designed to evaluate renal function as a late renal side effects in children receiving combination chemotherapy for malignancy. Patients and Methods: Follow-up studies of 30 newly diagnosed patients were performed a median of 12 months after completion of chemotherapy. The glomerular filtration rate (GFR) was measured using sodium thiosulfate. The following were also assessed: urinary high-molecular-weight fraction (urinary albumin/urinary creatinine ratio); para-aminohippurate (PAH) clearance; urinary low-molecular-weight fraction (urinary beta2-microglobulin/urinary creatinine ratio); and routine serum and urinary parameters. Results: Serum and urinary electrolytes were normal in most patients. GFR was low in four patients (13%). Urinary high-molecular-weight fraction was elevated in two patients. Urinary low-molecular-weight fraction was elevated in one patient. PAH clearance was below the referenced normal value in 73% of the patients. Conclusions: This report demonstrates decreased PAH clearance as a late renal side effect of chemotherapy and suggests disturbed function of the organic anion transport system. The unexpected high serum concentration of drugs excreted through the organic anion transport system may induce severe side effects. Elucidation of the mechanism and clinical relevance of decreased PAH clearance is warranted.