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


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.
Kakihara
Toshio
T
Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niitata, Japan. shounika@med.niigata-u.ac.jp
Imai
Chihaya
C
Hotta
Hiromitsu
H
Ikarashi
Yukie
Y
Tanaka
Atsushi
A
Uchiyama
Makoto
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology; D008297:Male; D027361:Organic Anion Transporters / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D027361:Organic Anion Transporters; D010130:p-Aminohippuric Acid