EFFECT OF AGE ON FUROSEMIDE-INDUCED NEPHROCALCINOSIS IN THE RAT

Furosemide (F)-induced nephrocalcinosis (NC) has been traditionally de scribed in low birth weight premature infants. To investigate the role of age on F-induced nephrocalcinosis we studied 24 Sprague-Dawley mal e rats grouped by age and F therapy vs. control as follows: A (4-week- old control), B (4-week-old + F), C (6-week-old control), D (6-week-ol d + F), E (10-week-old control), F(10-week-old + F). The rats were pla ced in metabolic cages for measurement of urine output, food and water intake. At day 14 they were anesthetized, exsanguinated and their kid neys harvested. Renal calcium deposition was assessed using NC score ( scale 0-4) and quantitative calcium analysis in the contralateral kidn ey. Treated animals gained less weight and had higher urine output and fluid intake than the age-matched controls demonstrating the diuretic effect of furosemide. Control groups A, C, and E scored 0 histologica lly compared with B 2.75 +/- 0.50, D 2.00 +/- 0.58, and F 3.00 +/- 0.8 2 (p < 0.05 in all three paired groups). Kidney calcium content (mu g/ g dry weight) in B was 2,815.68 +/- 1,553.77 vs. A 202.58 +/- 32.02 (p = 0.04); D 1,574.05 +/- 540.21 vs. C 212.22 +/- 30.91 (p = 0.02); F 2 ,591.40 +/- 1,269.80 vs. E 210.38 +/- 26.79 (p = 0.02). There was no d ifference in the magnitude of NC among the three treated groups themse lves. To determine the possible effect of age on timing of onset of NC additional 30 4-week-old and 30 10-week-old rats were studied. All 60 rats received furosemide, Six rats from each group were sacrificed on days 1, 3, 5, 7 and 11. In both groups, significant calcifications we re seen already on day 3 and maximum calcification noted between days 3 and 5. We conclude that in this model the development of NC occurs w ithin a few days of furosemide administration and that this phenomenon is not age dependent but rather reflects a property of the loop diure tic itself.