Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates.

The contention that cyclosporin A (CyA) nephrotoxicity may be due to renal afferent arteriolar constriction was inferred from rat studies showing CyA to increase renal vascular resistance, to reduce glomerular filtration rate (GFR) and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle (Vprox), and to increase proximal fractional reabsorption. In order to test whether the mechanism of human CyA nephrotoxicity is similar to its rat analogue, and whether CyA treatment causes prolonged renal malfunction after drug withdrawal, renal function was investigated with clearance techniques including lithium clearance (CLi) as a measure of Vprox. The subjects were patients (n = 11) with previously normal renal function, given CyA in the treatment of ocular manifestation of extrarenal disease, or bone-marrow transplant recipients. Nine out of these eleven patients were investigated before and during CyA treatment: GFR (P less than 0.05) and Vprox (P less than 0.005) decreased while proximal fractional reabsorption increased (P less than 0.01). In six patients investigated before CyA was given, and re-examined a mean of 273 days (range 84-384 days) after CyA withdrawal, CLi was reduced (P less than 0.05) while mean GFR was not significantly lowered (0.5 greater than P greater than 0.2). In one of these six patients GFR was reduced to a subnormal value of 26 ml min-1 (1.73 m2 body surface)-1. In conclusion, human and rat CyA nephrotoxicity have the same pattern of renal functional deterioration. Cyclosporin A nephrotoxicity was evident in patients investigated a mean of 9 months after CyA withdrawal.

Diagnosis and treatment of neuroblastoma using 131I-meta-iodobenzylguanidine.

Neuroblastoma is a lethal and not uncommon tumor in childhood. Early detection and display of the spread of the tumor is highly desirable for proper treatment. Nine children suspected of having neuroblastoma were examined by 131I-meta-iodobenzylguanidine (131I-MIBG) scintigraphy. In two recent studies 123I-meta-iodobenzylguanidine (123I-MIBG) was used. A primary adrenal neuroblastoma was correctly identified in 3 cases. In 2 patients additional tumor sites were found. In one patient, who was in complete remission, no pathological accumulation of 131I-MIBG was found. 131I-MIBG scintigraphies were also normal in 4 patients with other types of tumor. In one girl with a large adrenal neuroblastoma high uptake of 131I-MIBG was observed. She received two therapy doses of 131I-MIBG (1300-2800 MBq) with curative intention giving a total absorbed dose in the tumor of approximately 90 Gy. In spite of high retention of radioactivity in the tumor, regression did not appear, but her general condition was improved. In the present study images of superior quality were obtained by 123I-MIBG scintigraphy. It is concluded that scintigraphy with 131I- or 123I-MIBG should be used for primary visualization and control of neuroblastomas.