Nature of the Renal Concentrating Defect in Sickle Cell Disease*

Abstract

Summary. Free water reabsorption (TCeiO) measured during 10% mannitol diuresis and subsequently during 3% saline diuresis was compared in patients with sickle cell anemia and in normal subjects. During mannitol infusion, TCHSO progressively rose with increasing osmolar clearance (Cosm) and reached a maximal level in both groups studied. During hypertonic saline diuresis, TCH0o progressively rose in the normal subjects and exceeded the maximal levels attained during mannitol diuresis, with no evidence of a maximal TCH,0 level appearing. In contrast, none of the saline curves significantly exceeded the mannitol curves in the sickle cell patients but tended to parallel the mannitol curves at comparable rates of solute clearance.Since TCH,0 is an index of both solute (sodium) transport from the loop of Henle and solute accumulation in the hypertonic medullary interstitium, tubular sodium handling was examined in both sickle cell patients and control subjects alike. No difference in the tubular transport of sodium could be demonstrated either under conditions of sodium loading or under conditions in which the tubular sodium load was low (water diuresis).These data support the conclusion that the defect in urinary concentration in sickle cell patients is caused by a limitation in maintaining a high concentration of solute in the medullary interstitium, thus limiting the rate of TcH,0 from the collecting duct.

Urine concentrating ability in infants with sickle cell disease: Baseline data from the phase III trial of hydroxyurea (BABY HUG)

“…That 20 percent of our infants had dilute urines in spite of our attempt to have parents withhold fluid indicates the limitation of our methodology to fully assess concentrating function. Although even older sickle cell patients with a concentrating defect maintain free-water clearance and thus the ability to dilute urine if fluid-loaded [13,14], it was not anticipated that any fluid restricted subjects would have osmolalities below that of serum. We speculate that some parents may have aggressively hydrated their children just prior to commencing the period of deprivation, resulting in dilute urine.…”

Dysnatremias in Patients With Kidney Disease

“…Further evidence is provided by observations made in kidney diseases that affect the medulla out of proportion to a decrement in overall kidney function. Thus, in patients with sickle cell disease, 28 polycystic disease, 29 and medullary cystic disease, 30 a concentrating defect is evident with only modest decrements in kidney function.…”

Urinary Concentration and Dilution after Unilateral Nephrectomy in the Rat

“…The seemingly paradoxical combination of impaired Urnax. and normal free water reabsorption during solute diuresis is thought to occur in other conditions as well, including hyperthyroidism (Cutler, Glatte & Dowling, 1963, sickle cell nephropathy (Witten & Younes, 1960;Hatch, Culbertson & Diggs, 1967) and cirrhosis (Jick, Kamm, Snyder, Morrison & Chalmers, 1964), and was produced experimentally by papillectomy in the rat (Lief, Sullivan & Goldberg, 1969;Martinez-Maldonado, Eknoyan & Suki, 1972). Whereas free water reabsorption is maximal during high rates of solute clearance, Urnax.…”