vitamin-d-2 and Acidosis

Metabolic acidosis is an important acid-base disturbance in humans. It is characterised by a primary decrease in body bicarbonate stores and is known to induce multiple endocrine and metabolic alterations. Metabolic acidosis induces nitrogen wasting and, in humans, depresses protein metabolism. The acidosis-induced alterations in various endocrine systems include decreases in IGF-1 levels due to peripheral growth hormone insensitivity, a mild form of primary hypothyroidism and hyperglucocorticoidism. Metabolic acidosis induces a negative calcium balance (resorption from bone) with hypercalciuria and a propensity to develop kidney stones. Metabolic acidosis also results in hypophosphataemia due to renal phosphate wasting. Negative calcium balance and phosphate depletion combine to induce a metabolic bone disease that exhibits features of both osteoporosis and osteomalacia. In humans at least, 1,25-(OH)2 vitamin D levels increase, probably through phosphate depletion-induced stimulation of 1-alpha hydroxylase. The production rate of 1,25-(OH)2 vitamin D is thus stimulated, and parathyroid hormone decreases secondarily. There is experimental evidence to support the notion that even mild degrees of acidosis, such as that occurring by ingestion of a high animal protein diet, induces some of these metabolic and endocrine effects. The possible role of diet-induced acid loads in nephrolithiasis, age-related loss of lean body mass and osteoporosis is discussed.

Topics: Acidosis; Diet; Endocrine Glands; Ergocalciferols; Growth Hormone; Humans; Nitrogen; Parathyroid Hormone; Proteins

Studies in rats with renal ablation indicate that anemia lessens, whereas its vigorous correction with recombinant human erythropoietin (r-HuEPO) worsens systemic and glomerular hypertension, factors known to promote progression of chronic renal failure (CRF). However, in human studies, use of r-HuEPO in predialysis patients has not been associated with worsening renal function, provided blood pressure control is achieved. Histological evidence of bone disease is common in early renal failure, and deficits in calcitriol synthesis seem to be an important factor in the pathogenesis of secondary hyperparathyroidism (HPTH) in early CRF. Reports to data, on the use of low dose active vitamin D metabolites in predialysis patients, indicate either a reversible decline or no decline in renal function. Adynamic bone disease, however, may ensure during such therapy if excessive reductions in serum intact parathyroid hormone concentrations occur. Recent data suggest that chronic metabolic acidosis decreases albumin synthesis, increases muscle proteolysis, and induces negative nitrogen balance in patients with CRF. Despite these experimental data, the clinical relevance of correction of metabolic acidosis in end-stage renal disease (ESRD) is still not defined. Even though therapy of metabolic acidosis in the adult patient with CRF remains conjectural at this time, reports indicate that its correction might lead to healing of osteomalacia and osteopenia, and possibly may decrease protein degradation and improve growth in children with CRF.

Topics: Acidosis; Adult; Anemia; Animals; Calcitriol; Calcium Compounds; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Erythropoietin; Humans; Kidney Failure, Chronic; Rats; Recombinant Proteins; Renal Dialysis

Topics: Acidosis; Acidosis, Renal Tubular; Adolescent; Age Determination by Skeleton; Alkaline Phosphatase; Blood; Bone Resorption; Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Cystoscopy; Dwarfism; Ergocalciferols; Humans; Hydronephrosis; Kidney Papillary Necrosis; Kidney Tubules; Pathology; Phosphates; Rickets; Schistosomiasis; Tuberculosis; Tuberculosis, Miliary