High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent's disease

Abstract

High citrate diet preserved renal function and delayed progression of renal disease in ClC-5 knockout mice even in the apparent absence of stone formation. We conclude from this that long-term control of hypercalciuria is an important factor in preventing renal failure in these mice.

Hypothesis

“…An accurate diagnosis could prevent needless exposure to potentially hazardous cytotoxic medications in some patients. Furthermore, Cebotaru et al (24) fed high-citrate diets to ClC-5 knockout mice (a murine model of Dent disease) and significantly delayed progression of renal disease. If these findings translate to human patients, then making the appropriate diagnosis could be important.…”

Clinical utility gene card for: Dent disease (Dent-1 and Dent-2)

“…Potential medical interventions include high fluid intake, thiazide diuretics 18 and potassium citrate supplementation. 19 Animal studies suggest a positive effect of citrate suppletion in a Clcn5 knockout mouse model (on kidney function and calcium deposits). 19 Human data have documented a decrease in hypercalciuria with thiazide diuretics, 18 yet at the expense of hypokalemia in some patients.…”

“…19 Animal studies suggest a positive effect of citrate suppletion in a Clcn5 knockout mouse model (on kidney function and calcium deposits). 19 Human data have documented a decrease in hypercalciuria with thiazide diuretics, 18 yet at the expense of hypokalemia in some patients. The long-term efficacy on the progression of renal failure has not been studied, however.…”

A Patient with Nephrotic-Range Proteinuria and Focal Global Glomerulosclerosis

“…Treatment of rickets with vitamin D also requires close monitoring because it may increase hypercalciuria. Studies in ClC-5 knockout mice suggest that a high citrate diet helps to control the hypercalciuria and delays renal disease progression even in the absence of stone formation (62). Therefore, treatment with a citrate buffer can be attempted.…”