Altered expression of Na transporters NHE-3, NaPi-II, Na-K-ATPase, BSC-1, and TSC in CRF rat kidneys

In chronic renal failure (CRF), reduction in renal mass leads to an increas e in the filtration rates of the remaining nephrons and increased excretion of sodium per nephron. To address the mechanisms involved in the increased sodium excretion, we determined the total kidney levels and the densities per nephron of the major renal NaCl transporters in rats with experimental CRF. Two weeks after 5/6 nephrectomy (reducing the total number of nephrons to similar to 24 +/- 8%), the rats were azotemic and displayed increased N a excretion. Semiquantitative immunoblotting revealed significant reduction in the total kidney levels of the proximal tubule Na transporters NHE-3 (4 8% of control), NaPi-II (13%), and Na-K-ATPase (30%). However, the densitie s per nephron of NHE-3, NaPi-II, and Na-K-ATPase were not significantly alt ered in remnant kidneys, despite the extensive hypertrophy of remaining nep hrons. Immunocytochemistry confirmed the reduction in NHE-3 and Na-K-ATPase labeling densities in the proximal tubule. In contrast, there was no signi ficant reduction in the total kidney levels of the thick ascending limb and distal convoluted tubule NaCl transporters BSC-1 and TSC, respectively. Th is corresponded to a 3.6 and 2.5-fold increase in densities per nephron, re spectively (confirmed by immunocytochemistry). In conclusion, in this rat C RF model: 1) increased fractional sodium excretion is associated with alter ed expression of proximal tubule Na transporter expression (NHE-3, NaPi-II, and Na-K-ATPase), consistent with glomerulotubular imbalance in the face o f increased single-nephron glomerular filtration rate; and 2) compensatory increases in BSC-1 and TSC expression per nephron occur in distal segments.