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Renal adaptation to gentamicin-induced mineral loss Lee CT; Chen HC; Ng HY; Lai LW; Lien YHAm J Nephrol 2012[]; 35 (3): 279-86BACKGROUND: Gentamicin, a well-known nephrotoxic drug, affects calcium and magnesium homeostasis. Although gentamicin induces urinary calcium and magnesium wasting immediately, it rarely causes significant hypocalcemia or hypomagnesemia clinically. METHODS: We conducted an animal study to investigate the renal adaptation in calcium and magnesium handling after gentamicin treatment and effects on the expression of calcium and magnesium transport molecules in distal tubule. Gentamicin (40 mg/kg) was injected daily in male Sprague-Dawley rats (220-250 g) for up to 7 days. RESULTS: This treatment did not affect serum creatinine, calcium, or magnesium levels. Gentamicin induced significant hypercalciuria (14-fold) and hypermagnesiuria (10-fold) in 6 h, which was associated with upregulation of TRPV5 (175 +/- 3%), TRPV6 (170 +/- 4%), TRPM6 (156 +/- 4%) and calbindin-D28k (174 +/- 3%; all p < 0.05 vs. control). This gene upregulation was maintained with daily injection of gentamicin for 7 days. The gentamicin-induced urinary calcium loss was reduced by 80% at days 3 and 7, while magnesium loss was reduced by 52 and 57% at days 3 and 7, respectively. On the other hand, urinary loss of potassium became worse on day 7 (2-fold), and phosphorus loss worse from day 3 to day 7 (3-fold). CONCLUSION: There is a rapid adaptation to gentamicin-induced hypercalciuria and hypermagnesiuria. The upregulation of distal tubule transport molecules, TRPV5, TRPV6, TRPM6 and calbindin-D28k occurs within 6 h of gentamicin treatment. This renal adaptation prevents further mineral loss due to gentamicin treatment.|Animals[MESH]|Anti-Bacterial Agents/*pharmacology/toxicity[MESH]|Calbindin 1[MESH]|Calbindins[MESH]|Calcium Channels/drug effects/metabolism[MESH]|Calcium/blood/*metabolism/urine[MESH]|Gentamicins/*pharmacology/toxicity[MESH]|Hypercalciuria/*chemically induced[MESH]|Kidney Tubules, Distal/drug effects/*metabolism[MESH]|Magnesium/blood/*metabolism/urine[MESH]|Male[MESH]|Rats[MESH]|Rats, Sprague-Dawley[MESH]|S100 Calcium Binding Protein G/drug effects/metabolism[MESH]|TRPV Cation Channels/drug effects/metabolism[MESH] |
