Abstract: FR-PO376

Increased Sodium Chloride Cotransporter Expression in a Rat Remnant Kidney Model

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Sakuya, Ito, Kurume University School of Medicine, Kurume, Fukuoka, Japan
  • Kaida, Yusuke, Kurume University School of Medicine, Kurume, Fukuoka, Japan
  • Nakayama, Yosuke, Division of Nephrology,Department of Medicine,Kurume University, Kurume, Fukuoka, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Fukami, Kei, Kurume University School of Medicine, Kurume, Japan
Background

Antihypertensive therapies such as renin-angiotensin system (RAS) inhibitor and diuretics are the promising therapeutic strategy for inhibiting the progression of chronic kidney disease (CKD). The salt-sensitive hypertension is associated with the progression of CKD through the activation of the sodium chloride cotransporter (NCC). However, changes in the expression of NCC in the distal tubule of the different CKD stages are unknown. Thus, we investigated the blood pressure and the expression of NCC in the distal tubule of rats with mild to severe renal failure induced by nephrectomy(Nx).

Methods

Sprague Dawley (SD) rats were randomly allocated into the control and CKD groups. We assigned the Nx rats to three groups by the several degrees of kidney resection: sham (n=4), mild CKD (n=3), moderate CKD (n=4), severe CKD (n=3). The Nx and sham-operated rats were sacrificed at 4 weeks after operation. We examined the blood pressure, renal function, and urinary albumin excretion in rats with remnant kidney. Further, we explored the expression of NCC in renal tubule of the remnant kidneys by western blotting and immunostaining.

Results

Systolic blood pressure was significantly higher in the moderate and severe CKD rats compared with those in the sham-operated rats at 4 weeks after operation (148.3±17.9, 149.3±19.7 vs 114.8±12.8 mmHg; P<0.05, respectively). However, there was no difference of blood pressure between the mild CKD and the sham-operated rats (119.2±29.2 vs 114.8±12.8 mmHg; P=0.79). Serum blood urea nitrogen (BUN) and creatinine (Cr) levels, and urinary albumin excretion were significantly increased in all stages of CKD rats at 4 weeks after operation. The expression of total NCC were gradually up-regulated with the progression of CKD in the remnant kidney model.

Conclusion

In this study, increased NCC protein expression was observed in the remnant kidney model, which might induce the salt-sensitive hypertension in CKD. Therefore, the thiazide diuretics might be useful for controlling blood pressure in CKD patients. Further studies are needed to clarify the precise mechanisms of the increased NCC and its therapeutic strategy in CKD patients with hypertension.