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.

Potassium homeostasis in chronic diabetes mellitus.

Potassium homeostasis was evaluated in 13 patients with diabetes mellitus. In eight, plasma renin activity was low; plasma aldosterone concentration was decreased in all; seven had a history of spontaneous hyperkalemia. After administration of glucose orally, there were paradoxical increases in serum potassium levels in seven patients. After potassium loading, maximal values and increments of serum potassium were higher and fractional potassium excretion was lower in the diabetic than in the control subjects, although the differences were not statistically significant. Abnormalities of potassium homeostasis in diabetes are probably related to insulin and mineralocorticoid deficiency. Diabetic patients with hypoaldosteronism have the potential for severe hyperkalemia should renal or extrarenal mechanisms for potassium homeostasis be challenged by severe acidosis be challenged by severe acidosis, diminished renal function, marked hyperglycemia, or administration of potassium salts or potassium-sparing diuretics.

Hyporeninemia and hypoaldosteronism in diabetes mellitus.

The changes in plasma renin activity (PRA) and plasma aldosterone concentration (PA) in response to postural stimuli were evaluated in 12 patients with stable diabetes mellitus and in five volunteers. Seven diabetic patients had hyperkalemia, and several had renal insufficiency and neurological complications. Five diabetics and had normal serum potassium concentration, a mean creatinine clearance within the normal range, and few complications. PRA and PA were measured in these patients and in the control subjects, all of whom were receiving a diet containing 10 mEq of sodium and 50 mEq of potassium while they were in a supine position, after they were tilted to a 90 degrees position, and after upright posture for two hours. The results indicate that impaired responsiveness of PRA and PA may occur in patients with complicated and those with uncomplicated diabetes and may be responsible in part for a relatively high prevalence of hyperkalemia especially in those diabetic patients with reduced renal function.

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.

The effect of dexamethasone on urinary acidification.

Although it is well recognized that mineralocorticoids enhance renal acid excretion, the effect of glucocorticoids on renal acidification is unclear. Oral administration of dexamethasone to six healthy volunteers for 1 week at a daily dose of 4.5 mg was associated with mild respiratory alkalosis and a small but statistically significant increase in baseline urine pH. However, neither the ability to lower urine pH nor to excrete titratable acid and ammonium after NH4Cl acid-loading was altered. Administration of a single intravenous dose of dexamethasone sodium phosphate (7.5 mg) was associated with a significant rise in urine pH and potassium excretion and decreased titratable acid, ammonium , and phosphorus excretion in the absence of changes in blood acid-base status, creatinine clearance, or urine flow.

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.