Sulfate homeostasis, NaSi-1 cotransporter, and SAT-1 exchanger expression in chronic renal failure in rats

Background. It is known that hypersulfatemia, like hyperphosphatemia, occur s in chronic renal failure (CRF). The aim of this study was to assess the e ffects of CRF on sulfate homeostasis and on sodium sulfate cotransport (NaS i-1) and sulfate/ oxalate-bicarbonate exchanger (Sat-1) expression in the k idney. In addition, sulfate homeostasis was compared with phosphate homeost asis. Methods. Experimental studies were performed in adult male rats at three an d six weeks after 80% subtotal nephrectomy (Nx) or sham-operation (8) (N = 9 per group). Transporter protein and mRNA expressions were measured by Wes tern blot and RNase protection assay (RPA), respectively. Results were quantitated by densitometric scanning (Western) and electronic autoradiography (RPA), and were expressed in densitometric units (DUs: Wes tern) and cpm (RPA). Results. Creatinine clearance was lower in Nx-3 compar ed with S-3 rats (0.23 vs. 0.51 mL/min/100 g body weight, P < 0.001) and wa s further impaired in Nx-6 rats (0.15 vs. 0.48, P < 0.001). Sulfatemia was significantly higher in Nx-3 rats (1.08 vs. 0.84 mmol/L, P < 0.05) and furt her increased in Nx-6 rats (1.42 vs. 0.90 mmol/L, P < 0.01). Fractional sul fate excretion (FESO4) was increased by twofold in Nx-3 and Nx-6 rats compa red with corresponding S rats. Phosphatemia did not differ between Nx-3 rat s and controls, but was increased in Nx-6 rats (P < 0.01). Total amounts of both NaSi-1 and Sat-1 proteins were significantly decreased in both Nx-3 a nd Nx-6 rats when compared with controls. However, NaSi-1 protein and mRNA densities did not significantly change in Nx-3 rats, but were significantly increased in Nx-6 rats when compared with controls (4.8 vs. 3.7 DU/<mu>g p rotein, P < 0.05, and 7.1 vs. 2.8 cpm/<mu>g RNA, P < 0.01, respectively, fo r protein and mRNA). In contrast to NaSi-1, Sat-1 protein density was signi ficantly decreased both in Nx-3 (2.9 vs. 3.6 DU/<mu>g protein, P < 0.05) an d Nx-6 rats (2.4 vs. 3.4 DU/<mu>g protein, P < 0.05), and Sat-1 mRNA densit y significantly decreased in Nx-6 rats (10.7 vs. 14.7 cpm/<mu>g RNA, P < 0. 05). Na-PO4 cotransporter (NaPi-2) protein total abundance and density were decreased at three and six weeks in Nx rats. Conclusions. These results demonstrate that both NaSi-1 and Sat-1 total pro tein abundances are decreased in CRF, which may contribute to the increase in fractional sulfate excretion. Strikingly, NaSi-1 density was not decreas ed in CRF three weeks after Nx, and furthermore, increased six weeks after Nx, in contrast to NaPi-2 density, which was decreased at both times. The s ignificance of this difference remains to be determined, but may explain wh y hypersulfatemia occurs earlier than hyperphosphatemia in CRF.