Ogborn M R, Sareen S
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
J Am Soc Nephrol. 1995 Dec;6(6):1649-54. doi: 10.1681/ASN.V661649.
Polycystic kidney disease is the most common potentially lethal single- gene inherited disease in man. There is no specific therapy. Previous studies in the pcy mouse model of polycystic kidney disease have shown amelioration of cystic change by reduction in dietary protein intake. The Han:SPRD-cy rat is a model of autosomal dominant polycystic kidney disease that closely resembles human disease in its histology and clinical course. We compared the morphometric assessment of cystic change and standard laboratory measures of renal function in heterozygous Han: SPRD-cy rats that received isocaloric diets containing either 8% or 20% protein as casein. This level of dietary protein restriction was associated with a significant reduction of mean body weight in the 8% protein group (358 g) compared with 20% protein (490 g; P = 0.027). Mean renal volume, adjusted for the difference in body weight, was significantly lower in the 8% protein group (6.2 mL/kg) compared with the 20% protein group (11.6 mL/kg; P = 0.016). The major component in this reduction was a reduction in total cyst volume to a mean 0.47 mL in the 8% protein group from 2.68 mL in the 20% protein group (P < 0.0001). All 8% protein diet animals survived to 6 months of age, but 3 of 11 20% protein diet animals died between 5 and 6 months of age. Mean serum creatinine and urea levels were significantly lower in the 8% protein group (118 mmol/L and 15.6 mmol/L) compared with the 20% protein group (272 mmol/L, P = 0.0033, and 81.5 mmol/L, P = 0.0002, respectively). Dietary protein restriction is a potent method for modifying the course of polycystic kidney disease in the Han:SPRD-cy/+ rat. These findings emphasize the potential for diet to alter the physiology of the renal tubulointerstitium.
多囊肾病是人类最常见的潜在致死性单基因遗传病。目前尚无特效疗法。此前在多囊肾病的pcy小鼠模型中的研究表明，减少饮食中的蛋白质摄入量可改善囊性病变。Han:SPRD-cy大鼠是常染色体显性多囊肾病的模型，其组织学和临床病程与人类疾病极为相似。我们比较了接受含8%或20%酪蛋白等热量饮食的杂合子Han:SPRD-cy大鼠的囊性病变形态学评估和肾功能的标准实验室指标。与20%蛋白质组（490克；P = 0.027）相比，8%蛋白质组（358克）的这种饮食蛋白质限制水平与平均体重显著降低有关。根据体重差异进行调整后，8%蛋白质组的平均肾体积（6.2毫升/千克）显著低于20%蛋白质组（11.6毫升/千克；P = 0.016）。这种减少的主要成分是总囊肿体积从20%蛋白质组的2.68毫升减少到8%蛋白质组的平均0.47毫升（P < 0.0001）。所有8%蛋白质饮食的动物均存活至6月龄，但11只20%蛋白质饮食的动物中有3只在5至6月龄之间死亡。与20%蛋白质组（分别为272毫摩尔/升，P = 0.0033，和81.5毫摩尔/升，P = 0.0002）相比，8%蛋白质组的平均血清肌酐和尿素水平显著较低（分别为118毫摩尔/升和15.6毫摩尔/升）。饮食蛋白质限制是改变Han:SPRD-cy/+大鼠多囊肾病病程的有效方法。这些发现强调了饮食改变肾小管间质生理学的潜力。
