Renal acidification in sickle cell trait.

Nine sickle cell trait and nine control subjects underwent six-hour ammonium chloride acid loading. Maximal urine osmolality and renal hemodynamics were studied separately. Base line arterial pH, carbon dioxide pressure (Pco2), and [HCO3] were normal and comparable in the two groups. After ammonium chloride loading, urine pH decreased to 5.3 or less in all, and maximal excretion of ammonium and titratable and net acid was comparable as was urine minus blood Pco2 after bicarbonate loading. The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4, sickling, or adverse effects. Control and sickle cell trait subjects had comparable renal hemodynamics but maximal urine osmolality was lower in sickle-cell trait subjects. Adults with sickle cell trait have diminished renal concentrating ability and normal renal acidification and hemodynamics.

Effect of alterations of sodium intake in patients with hyporeninemic hypoaldosteronism.

The effect of changes of sodium intake on serum and urinary electrolytes, plasma renin activity (PRA) and plasma aldosterone concentration (PA) was studied in five hyperkalemic patients with the syndrome of hyporeninemic hypoaldosteronism (SHH). The patients were evaluated during 8 days on a 10-mEq sodium and 50-mEq potassium diet plus furosemide, followed by 8 days on a 150-mEq sodium and 50-mEq potassium diet. After sodium depletion, both PRA and PA were substantially higher than after a previous 4-day period of simple dietary sodium restriction and an increase in serum potassium concentration occurred in only one subject. Administration of a normal sodium intake induced small increases in serum chloride in all five subjects and a decrease in bicarbonate concentration in one patient. It is concluded that, at least in some patients with SHH, PRA and PA are volume-responsive and that considerable alterations of sodium intake have relatively little influence on serum electrolyte concentrations.

Renal acidifying ability in subjects with recurrent stone formation.

To determine the incidence of an acidification defect in men in whom calcium stones form and its relationship to parathyroid function 120 such patients were given an acute dosage of 0.1 gm. per kg. oral ammonium chloride and circulating immunoreactive parathyroid hormone was determined. The subjects were divided into 2 groups, according to normal or high parathormone levels. Group 1 consisted of 46 men in whom immunoreactive parathyroid hormone was less than or equal to 60 mulEq. per ml. and group 2 consisted of 74 men with immunoreactive parathyroid hormone greater than 60 mulEq. per ml. Of 8 men in whom the urine failed to acidify to less than a pH of 5.3, 3 were from group 1 and 5 were from group 2. None of the patients had an active urinary tract infection. There was no difference in minimal urine pH among the patients in whom the urine acidified normally regardless of immunoreactive parathyroid hormone. The incidence of abnormal acidification in our population was 6% and all of these patients had the incomplete form of renal tubular acidosis. These findings have important therapeutic implications.

Renal acidification in sickle-cell disease.

Renal acidification was evaluated in patients with sickle-cell disease (HvSS) with both oral NH4CI and NaHC03 and the results were compared to those of subjects with sickle-cell trait (HbAS) and controls. The pH of arterial blood was normal in HbSS subjects but their PC02 and [HC03] were lower than those of controls. In response to NH4CI, six of 20 HbSS subjects had an abnormal minimal urine pH (greater than 5.3) and the entire HbSS group had a higher mean value than did either controls or HbAS subjects. Since none of the six HbSS subjects had evidence of proximal tubular abnormalities, it was concluded that they exhibited the syndrome of incomplete distal renal tubular acidosis. Only one of the six HbSS volunteers with an abnormal response to NH4CI and two of seven with a normal response increased their urinary PC02 normally after bicarbonate loading. PAH clearance was significantly higher and inulin clearance tended to be higher in HbSS subjects than in either controls or HbAS subjects. Maximal concentrating ability was decreased in both sickle-cell groups but more so in HbSS. No adverse effects occurred and no appearance or increase in per cent of sickled cells resulted from short-duration NH4CI acid-loading. No differences were found either in the clinical characterstics or in hematological, renal, and acid-base variables between the HbSS subjects with and without a normal response to acid-loading. The mechanism for the observed renal acidification abnormality remains unknown.