EARLY DIETARY-PROTEIN RESTRICTION SLOWS DISEASE PROGRESSION AND LENGTHENS SURVIVAL IN MICE WITH POLYCYSTIC KIDNEY-DISEASE

The objective of these studies was to examine the effects of early die tary protein restriction on disease progression and survival in the DB A/2FG-pcy (pcy) mouse model of polycystic kidney disease. Male pcy mic e of 70 days of age were fed either a normal protein (NP, 25% casein) or a low-protein (LP, 6% casein) diet for 105 days. At the end of the dietary treatment, kidney weight, kidney weight relative to body weigh t, and kidney water contents were almost 50% lower, and relative renal phospholipid and triglyceride contents were almost 50% higher, in mic e fed the LP diet, indicating a marked reduction in the progression of cystic disease. Morphometric analyses also revealed a lower total and percent cyst area in kidneys derived from mice on the LP compared wit h the NP diet. There were no significant differences in final body wei ght, urine volume and osmolality, GFR, proteinuria, or plasma levels o f protein and urea between these two groups. In a second study, it was found that all mice fed an NP diet from 70 days of age onward had die d by 310 days of age, compared with a 42% survival rate in LP-fed mice at this age. Overall, the mean lifespan for pcy mice on the LP diet w as 24% longer than that for those mice on the NP diet(310 +/- 20 versu s 251 +/- 16 days; P < 0.01). These studies demonstrate that the intro duction of a diet that has a reduced level of protein, yet one that pr ovides adequate amounts of protein to prevent any signs of dietary def iciency, is effective in slowing down the progression of polycystic ki dney disease in pcy mice. More important, in the long term, survival i n pcy mice can be significantly improved by mice being fed the LP diet . Thus, early dietary protein reduction initiated in pcy mice before t he manifestation of clinical symptoms of disease results in the attenu ation of polycystic kidney disease progression.