PATHOPHYSIOLOGY OF THE RENAL ACIDIFICATION DEFECT PRESENT IN THE SYNDROME OF FAMILIAL HYPOMAGNESEMIA-HYPERCALCIURIA

A distal acidification defect is frequently observed in the syndrome o f familial hypomagnesaemia-hypercalciuria and hence this condition can be confused with primary distal renal tubular acidosis (RTA). This st udy demonstrates that in four unrelated patients with familial hypomag nesaemia-hypercalciuria the acidification defect is functionally diffe rent from that present in primary distal RTA. All patients exhibited h ypomagnesaemia, hypermagnesuria, hypercalciuria, hyposthenuria, nephro calcinosis and slight reduction of glomerular filtration rate (GFR). A moderate degree of metabolic acidosis was also present and basal data showed an inappropriately high urine pH (5.7-5.9) and a positive urin e anion gap (Na+K-Cl = 11-28 mmol/l). Stimulation of distal acidificat ion induced a fall in urine pH (4.7-5.6), but ammonium excretion remai ned low despite factoring by GFR (26-46 mu mol/min per 1.73 m(2), 35-5 4 mu mol/100 ml GF). The urine to blood PCO2 gradient also remained lo w after sodium bicarbonate loading (1.3-17.7 mmHg). These results are best explained by both defective ammonia transfer to the deep nephron and impaired hydrogen ion secretion at the level of the medullary coll ecting duct, and probably are secondary effects of the medullary inter stitial nephropathy.