The utility of 99mTc-DMSA and Tc99m-EC scintigraphy for early diagnosis of ifosfamide induced nephrotoxicity

A serious undesired effect of certain cytostatics is their nephrotoxicity. In this study, we investigated the toxic effects of ifosfamide and cisplatin by clinical and biochemical parameters in relation to Tc-99m-dimercaptosuccinic acid (Tc-99m-DMSA) and (TcN)-N-99m, N-ethylenedicysteine (EC) renal scintigraphy. The indicators were urinary beta (2)-microglobulin levels, tubular resorption of phosphate, urinary protein and glucose excretion, glomerular filtration rate, urinary pH and osmolarity. Thirteen paediatric patients (seven boys and six girls), aged 2-16 years, were investigated. Five patients received only cisplatin, six patients were treated with ifosfamide and cisplatin and two with ifosfamide and carboplatin for various malignancies. All except three patients had normal DMSA uptake (median, 19; range, 16-29%) prior to chemotherapy. The reduction in DMSA uptake was unilateral due to tumour invasion in those three patients. Following chemotherapy, DMSA uptake showed reduction in five patients with or without clinical nephrotoxicity. The observed pattern was decreased renal uptake and elevated bladder activity. Three patients with decreased DMSA uptake had normal tubular maximum phosphate reabsorpsion, which suggested subclinical injury. Decrease in DMSA uptake and tubular phosphate reabsorption (-ITR) was detected simultaneously in two patients. No abnormalities were seen on Tc-99m-EC scintigraphy to suggest nephrotoxicity in our investigation. However, Tc-99m-EC clearly demonstrated a reduction in split renal function in children with tumour invasion. In summary, we found that ifosfamide induced tubular injury can be detected with Tc-99m-DMSA scintigraphy before chemotherapy associated nephrotoxicity is observed by laboratory measurements. Our results also imply that, although a tubular agent, renal scintigraphy performed with Tc-99m-EC is not able to detect subclinical injury or predict the outcome during treatment. ((C) 2001 Lippincott Williams & Wilkins).