Effects of dietary sodium content on cysts formation in ARPKD

Polycystic kidney diseases (PKD) are a group of nephropathies marked with the formation of fluid-filled cysts along the nephron. Generally, patients with PKD are advised to restrict their dietary sodium intake to 100 mmol/day or less, as it is expected to reduce blood pressure and albuminuria. Here we hypothesize that general manipulation with sodium content in the diet can alter cyst formation. To test this, PCK rats were fed a normal (0.4%; NS), high salt (4%; HS), and sodiumdeficient (0.01%; SD) NaCl diets for 8 weeks (starting at 6 weeks of age). Immunohistochemistry, Western blotting, GFR measurements in conscious animals, and routine molecular biology approaches were applied to evaluate effects of various diets. Both HS and SD diets resulted in a dramatic increase in the cyst formation: 43.6% and 39.8% of whole kidney areas were cystic, compared to 28.5% in the NS group. However, the development of cysts was different between HS and SD diet fed groups. HS diet provoked cyst enlargement in a manner seen in NS group; in contrast, SD diet caused an extensive growth of small cysts in the cortical area, and increased hypertrophy of the renal tissue (2 kidney to body weight ratio was 15.9 ± 0.7 in animals fed a SD diet vs 11.5 ± 0.9 and 13.7 ± 0.8 mg/g in NS and HS groups). Additionally, SD diet-fed PCK rats exhibited reduced body weight (324 ± 11 compared to 517 ± 6 and 496 ± 5 g in NS and HS groups). Urinary output was significantly higher in the HS animals compared to both SD and NS groups; interestingly, we found no difference in food intake. There was no change in urinary creatinine over the course of diet challenge in either group; urinary chloride and sodium excretion were elevated in HS fed animals compared to NS and SD groups, as expected. GFR levels were assessed in conscious unrestrained animals after an injection of FITC-conjugated inulin and were found to be 0.40 ± 0.05, 0.65 ± 0.03, and 0.98 ± 0.11 uL/min/100g of body weight in SD, NS and HS fed rats, respectively. Plasma electrolytes (K+, Na+, Cl-, and Ca2+) were significantly lower in PCK rats fed SD diet, but not different between NS and HS groups. Consistent with other data, BUN was almost 130 mg/dL in the SD group compared to \u3c 20 mg/dL in NS and HS animals, indicative of renal failure in the SD fed rats. Western blotting and immunohistochemistry demonstrated a prominent decrease in the expression of the alpha and beta ENaC subunits in the SD fed group compared to the NS and HS groups. These data are consistent with our earlier studies where we reported that lower ENaC activity can contribute to cyst development in ARPKD; however the exact mechanism remains to be revealed in the future studies. In summary, both HS and SD diets significantly increased cystic area in PCK rats, although cyst formation and its effects on kidney function are different between these groups