HYPERPARATHYROIDISM SECONDARY TO RENAL-INSUFFICIENCY - PATHOPHYSIOLOGY, CLINICORADIOLOGICAL ASPECTS AND TREATMENT

Stimulation of PTH secretion and synthesis in chronic renal failure involves direct and indirect factors. The indirect ones are those contributing to a decrease of plasma ionized calcium concentration which stimulates the release of PTH (I) primarily the negative calcium balance due to the iatrogenic reduction of dietary calcium intake associated with an inadequate synthesis of calcitriol, this latter being explained by a reduction in the nephronic mass, the phosphate retention, the acidosis and the retention of uremic toxins (2) more accessorily, the physicochemical dysequilibrium induced by the late occuring hyperphosphatemia. The factors acting directly on the parathyroid gland stimulating synthesis of prepro PTH at its transcription level: not only hypocalcitriolemia but also hypocalcemia and hyperphosphatemia. The clinicoradiological manifestations appear late, mostly only after the patient has been put on dialysis. The most precocious sign is the subperiosteal resorption assessed on the hand Xrays. Therefore diagnosis of hyperparathyroidism relies mainly on the measurement of plasma concentration of intact PTH. In dialysis patients the optimal range corresponding to the best bone histology is between 1 an 3 times the upper limit of normal. No such data exist for predialysis patients. Medical treatment of hyperparathyroidism should primarily be preventive, probably in predialysis lipin patient as soon as plasma intact PTH is greater than the normal upper limit. This treatment is based primarily on the prevention of phosphate retention, of negative calcium balance and acidosis by the use of oral alkaline salts of calcium given with the meals in association with appropriate dietary protein and phosphate restriction. Native vitamin D depletion should also be prevented but use of 1 alpha OH vitamin D3 metabolites in controversial : it is reasonable to administer them only when plasma intent PTH is above 3-7 the normal upper limit and when plasma phosphate is below 1.2 in predialysis patients below 1.5 mmol/l in dialysis patients and plasma calcium remains below 2.3 mmol/l in spite of CaCO3 administration. This situation is encountered in less than 50% of the dialysis patients and rarely in predialysis patients. In dialysis patients the calcium concentration in the dialysate should be chosen in relation to the dose of oral calcium and the use of 1 alpha OH vitamin D3. The superiority of the intermittent (oral or intravenous) over the daily oral administration is not yet clinically proven. The surgical parathyroidectomy is indicated when hypercalcemia and/or hyperphosphatemia occur under medical treatment, whereas the intact PTH levels remain very high (> 500 pg/ml). Necrotic ulcerations of the extremities in relation to calciphylaxis is an urgent PTX indication. At the latter exception, PTX should be performed only after exclusion or treatment of aluminium overload by deforoxamine.