Bone and mineral metabolism and chronic alcohol abuse.

Studies of bone and mineral metabolism were made in 22 patients with chronic alcohol abuse and varying degrees of liver damage. None of the patients had clinical evidence of metabolic bone disease, but quantitative bone histology showed that six had osteoporosis, three osteomalacia, and two osteoporosis and osteomalacia combined. Trabecular bone volume (TBV) tended to be reduced in relation to age, and there was histological evidence of reduced bone formation particularly among the patients with osteoporosis. Multivariate analysis of the relevant variables showed that the major determinants of age-adjusted trabecular bone volume were the serum concentration of albumin and the dietary calcium. The presence of osteoporosis was related to the state of liver function and the type of alcohol habitually consumed, and was a particular feature of patients with severe liver disease and those who only drank spirits. Six patients (five with osteoporosis) had biochemical evidence of hyperparathyroidism, but none showed histological evidence of increased bone resorption or of osteitis fibrosa. In four patients the development of hyperparathyroidism was probably related to underlying magnesium deficiency. Serum calcidiol tended to be reduced and was directly related to the state of liver function; four patients had reduced or low normal serum concentrations of calcitriol. In only three patients could the development of osteomalacia be related to vitamin D deficiency; in two patients the cause of the osteomalacia was obscure. Significant changes in bone structure and mass appear to be common among heavy drinkers even in the absence of clinical metabolic bone disease. These skeletal abnormalities are likely to be relevant to the increased fracture risk associated with heavy drinking.

Captopril for refractory hypertension in patients with impaired renal function.

The use of captopril in 19 patients with renal parenchymal disease and refractory hypertension was studied for a mean period of 12 months. There was a significant reduction in the systolic and diastolic blood pressures, with a reduction in the mean arterial pressure of 29 mmHg. The mean maintenance dose of captopril was 142 mg daily in three divided doses. All but one of the patients required a diuretic for satisfactory blood pressure control and 3 patients were also given a beta-blocker. In all patients a simplification of the previous therapeutic regimen was achieved. A significant rise in serum creatinine was noted in 2 patients, one of whom had to be withdrawn from the study. Despite the presence of renal functional impairment, proteinuria did not occur de novo nor did established proteinuria increase. Leukopenia was noted in any of the patients in this group.

Effects of diuretics on the renal handling of magnesium.

Diuretic-induced magnesium losses may contribute significantly to magnesium deficiency. Loop diuretics especially cause major losses of urinary magnesium. Our initial experiments in saline-loaded rats indicated that frusemide greatly increased magnesium excretion, while bendrofluazide caused no significant change and triamterene actually decreased magnesium excretion. Therefore, not all diuretics are magnesium-wasting. There is evidence that the potassium-sparing diuretic amiloride may also exert magnesium-sparing properties. In saline-loaded rats, the magnesium-sparing effect of amiloride was demonstrated when the drug was administered either alone or in combination with frusemide. Renal clearance studies in rats indicated that the magnesium-sparing effect of amiloride was a direct renal action and not secondary to possible extrarenal actions. A dose-response relationship has been established for the effect of amiloride in reducing fractional excretion of magnesium and potassium during frusemide diuresis in rats. Congestive heart failure patients being treated with frusemide were found to be both potassium- and magnesium-deficient, as indicated by reduced lymphocyte concentrations of potassium and magnesium. In these patients, amiloride reduced urinary magnesium and potassium, increased plasma magnesium and potassium, and also increased lymphocyte magnesium and potassium. The effects of amiloride most likely involve enhanced reabsorption of magnesium, but further studies are required to establish the precise mechanism(s) involved in the drug's magnesium-sparing properties.

The effect of diuretics on lymphocyte magnesium and potassium.

Lymphocytes have advantages over other tissues, such as erythrocytes and muscle, for assessing intracellular magnesium and potassium. During experimental magnesium deficiency in rats, the magnitude of the magnesium loss from lymphocytes was similar to that of cardiac and skeletal muscle. During experimental potassium deficiency, cardiac muscle retained potassium more effectively than skeletal muscle. The magnitude of the potassium loss from lymphocytes was of similar magnitude to that of cardiac muscle. Chronic congestive heart failure patients being treated with the loop-blocking diuretic, furosemide, were found to have significantly reduced lymphocyte magnesium (p less than 0.05) and potassium (p less than 0.01) compared to values obtained in 20 control subjects. The effects of acute administration of the potassium-sparing diuretic, amiloride, were investigated in 10 congestive heart failure patients. Each patient was studied over a 6-day period comprising a 3-day control period involving furosemide administration, followed immediately by a 3-day test period when amiloride (10 mg twice daily) was added to the therapeutic regimen. Amiloride reduced urinary potassium and magnesium, and increased both plasma and lymphocyte potassium and magnesium. Under these conditions, amiloride exerted magnesium-sparing actions in addition to its well-established potassium-sparing actions. The magnesium-sparing actions may be beneficial in that many experimental studies have shown that magnesium is required for maintenance and restoration of cell potassium.

Renal clearance of pancreatic and salivary amylase relative to creatinine in patients with chronic renal insufficiency.

Pancreatic and salivary amylase/creatinine clearance ratios in patients with various degrees of renal impairment were compared with those obtained for control subjects. In chronic renal insufficiency (mean GFR 30 ml/min +/- 15 SD; n = 13) the clearance ratios for pancreatic (mean 3.5 +/- 1.85 SD) and salivary (mean 2.3 +/- 1.3 SD) amylase were significantly higher (P less than 0.05) than those in controls. Corresponding control values (n = 26) were 2.64 +/- 0.86 (pancreatic) and 1.64 +/- 0.95 (salivary). Three patients showed values above the normal limit. In the diabetic group (mean GFR 41 ml/min +/- 22 SD; n = 10) salivary amylase/creatinine clearance ratios (mean 2.36 +/- 1.55 SD) were significantly higher than in controls (P less than 0.05). Three patients showed raised values. Pancreatic amylase clearance was raised in only one of these patients. Three patients with terminal disease (mean GFR 10 ml/min) showed markedly raised (two- to threefold) clearance ratios for both salivary and pancreatic amylase. Of a total of 26 patients, eight had increased total amylase/creatinine clearance ratios. Pancreatic amylase/creatinine clearance was increased in seven patients, while nine patients showed raised salivary amylase/creatinine ratios. Patients with raised clearance ratios did not have clinical evidence of pancreatitis. We suggest that, in the presence of impaired renal function, a high amylase/creatinine clearance ratio need not be indicative of pancreatic disease.