Abstract 860

Erythrocytes in Hb SC disease have increased density because of the presence of both Hb S and Hb C. In adults with Hb SC disease, treatment with HU was associated with reduced hemolysis and improved cell hydration. The early functional reversibility of the urinary concentrating defect is ultimately lost in sickle cell disease. We hypothesized that HU, through its effects on cell density, will reduce the polymerization tendancy of Hb S and improve the ability of young patients with Hb SC disease to concentrate urine.

Eight children with Hb SC disease, ages 10 to 17 years (mean age 11 years), were treated with 15mg/kg of HU daily for a mean of 10.6 months (6 - 14mos.). Urine osmolality was measured by freezing point depression. Non-steroidal anti-inflammatory drugs and aspirin were discontinued for at least 1 week. To measure maximal urine concentrating ability, subjects fasted overnight and discarded their first morning voided urine. Following the collection of the next spontaneously voided urine, 0.08mcg/kg of Desmopression Acetate (dDAVP) was given subcutaneously. Urine voided at 2 and 4 hours after dDAVP administration was collected. No patient had an overnight urine concentration greater that 545 milliosmoles (mean 445 mOsm; normal 800 - 1000 mOsm). Pretreatment maximum urine concentrations were 528±31 mOsms. Seven of 8 patients did not significantly increase their urine concentration after dDAVP. In no patient did HU appear to increase the maximal urine concentrating ability beyond that of pretreatment value. The mean 4 hr post dDAVP urine concentration was 537±34 mOsm after 6 months treatment and appeared to fall by 9 to 12 months. MCV and reticulocyte MCV increased and MCHC fell. There was no change in hemoglobin concentration, PCV or reticulocyte counts. Two patients increased their concentration of Hb F during treatment with HU, 6.3% to 15% Hb F after 2 - 3 months of treatment and 1% to about 6% after 5 - 6 months of treatment. There were no complications of treatment.

Treatment with HU was associated with nearly uniform increases in MCV and reduced MCHC but did not increase their ability to concentrate urine. The ability to concentrate urine was permanently compromised despite the effects of HU on the Hb SC disease erythrocyte. HU may have to be started at a very young age to prevent irreversible renal medullary injury in sickle cell disease.