The relative importance of urinary pH and urinary content of citrate, magnesium and calcium in the production of nephro calcinosis by diet and acetazolamide in the rat.

1. The association of varying levels of urinary pH, urinary citrate and urinary calcium and magnesium excretion rates with kidney citrate, calcium and magnesium concentrations in experimental nephrocalcinosis was examined in twenty-four rats in a 3 x 2 multifactorial experiment with four replicates. All rats received the same synthetic diet for 6 weeks before being killed in the seventh week. In addition the rats received calcium supplements as calcium chloride (diet A), calcium carbonate (diet B), or as an equal mixture of calcium chloride and carbonate (diet N), the content of calcium being kept constant at 6.3 mg per g of diet for all rats. Half of the rats also received 2.5 mg of acetazolamide per g of diet. 2. Diet A produced a systemic acidosis and the most acid urinary pH. Diet B plus acetazolamide produced a more severe systemic acidosis and the most alkaline urinary pH. Urinary magnesium, citrate and calcium excretion rates were generally reduced below normal. Urinary excretion of magnesium and calcium were significantly higher in those rats on diet A than in those on diet By while urinary citrate excretion was highest in the latter. Acetazolamide caused a further increase in urinary calcium excretion but a decrease in urinary magnesium and citrate excretions. 3. Acetazolamide significantly reduced plasma calcium but elevated plasma magnesium. The changes produced in plasma and urinary calcium and magnesium in the present study were consistent with an action through systemic acidosis for calcium and through urinary pH for magnesium, both being effected at a tubular site. 4. Variation in diet alone as well as acetazolamide administration were significantly associated with variation in the degree of nephrocalcinosis (P < 0.05 and P < 0.005 respectively). Acetazolamide increased nephrocalcinosis by a factor of at least 10. Analysis of covariance showed that acetazolamide was no longer associated with significant nephrocalcinosis when its effects on urinary pH and magnesium were