Cebotaru Valeriu, Kaul Sadhana, Devuyst Olivier, Cai Hui, Racusen Lorraine, Guggino William B, Guggino Sandra E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kidney Int. 2005 Aug;68(2):642-52. doi: 10.1111/j.1523-1755.2005.00442.x.
Dent's disease, an X-linked renal tubular disorder, is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. Dent's disease results from mutations of the voltage-gated chloride channel CLC-5.
We studied the effect of zero and high citrate diet on renal function of ClC-5 knockout mice and wild-type mice. The mice were placed in metabolic cages from which the urine was collected. Mice were sacrificed to obtain serum and tissues for analysis.
ClC-5 knockout mice fed zero or high citrate diet had significantly increased urinary calcium excretion compared with wild-type mice fed the same diets. Nine-month-old ClC-5 knockout mice on a zero citrate diet had significantly decreased glomerular filtration rate (GFR), whereas 9-month-old ClC-5 knockout mice on a high citrate diet had normal renal function. ClC-5 knockout mice fed a zero citrate diet had significantly increased tubular atrophy, interstitial fibrosis, cystic changes, and nephrocalcinosis compared to ClC-5 knockout mice fed a high citrate diet. Transforming growth factor-beta1 (TGF-beta1) was significantly increased in 9-month-old ClC-5 knockout mice on zero citrate diet compared to 9-month-old wild-type mice on the same diet.
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.
丹特病是一种X连锁肾小管疾病，其特征为低分子量蛋白尿、高钙尿症、肾钙质沉着、肾结石和进行性肾衰竭。丹特病由电压门控氯离子通道CLC-5的突变引起。
我们研究了零柠檬酸盐饮食和高柠檬酸盐饮食对ClC-5基因敲除小鼠和野生型小鼠肾功能的影响。将小鼠置于代谢笼中收集尿液。处死小鼠以获取血清和组织进行分析。
与喂食相同饮食的野生型小鼠相比，喂食零柠檬酸盐饮食或高柠檬酸盐饮食的ClC-5基因敲除小鼠尿钙排泄显著增加。喂食零柠檬酸盐饮食的9月龄ClC-5基因敲除小鼠肾小球滤过率（GFR）显著降低，而喂食高柠檬酸盐饮食的9月龄ClC-5基因敲除小鼠肾功能正常。与喂食高柠檬酸盐饮食的ClC-5基因敲除小鼠相比，喂食零柠檬酸盐饮食的ClC-5基因敲除小鼠肾小管萎缩、间质纤维化、囊性改变和肾钙质沉着显著增加。与喂食相同饮食的9月龄野生型小鼠相比，喂食零柠檬酸盐饮食的9月龄ClC-5基因敲除小鼠中转化生长因子-β1（TGF-β1）显著增加。
高柠檬酸盐饮食可保留ClC-5基因敲除小鼠的肾功能并延缓肾病进展，即使在明显无结石形成的情况下也是如此。我们据此得出结论，长期控制高钙尿症是预防这些小鼠肾衰竭的一个重要因素。
