Effects of pre- and postnatal cysteamine exposure on renal function and structure in rats

The safety of cysteamine after renal transplantation and during pregnancy are important issues to children with cystinosis because these children often require renal transplants and the girls with cystinosis are in better health and thus more likely to become pregnant. Recent reports of adverse effects on the developing fetus after treatment of the pregnant rat with cysteamine have raised concerns about the safety of cysteamine during human pregnancy. We studied the long term consequences of exposure to cysteamine during periods of maturation for the kidneys. In the first study, cysteamine was given to pregnant rats on days 6.5-18.5 post conception in oral doses of 0, 37.5, 75, 100 and 150 mg/kg/day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5-19.5 post-conception in oral doses of 0, 37.5, 50 and 75 mg/kg/day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4-21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, the creatinine clearance, free water clearance, osmolar clearance and fractional excretion of Na, K and P were similar between the control and cysteamine treated animals on day 35. These findings suggest that cysteamine therapy is not likely to affect renal development in the human and that it may be safe to re-institute cysteamine therapy soon after kidney transplantation.