Sodium thiosulfate attenuates high phosphorous induced vascular calcification in rats with 5/6 nephrectomy

Objective To observe the expression of Klotho and Na+/Pi cotransporter in high phosphorous-induced rats with 5/6 nephrectomy and its relationship with vascular calcification, as well as to investigate the effect of early intervention by sodium thiosulfate (STS) on the progression of vascular calcification. Methods Either 5/6 nephrectomy (n=21) or sham operation (n=14) was conducted on 35 Sprague Dawley rats, who were then fed with high phosphorus (HP) diet or normal phosphorus (NP) diet for 16 weeks respectively. The rats were divided into 5 groups as follows: (1) remnant kidney rats receiving HP diet (NHP, n=7), (2) remnant kidney rats receiving NP diet (NNP, n=7), (3) sham operation rats receiving NP diet (SNP, n=7), (4) sham operation rats receiving HP diet (SHP, n=7), (5) remnant kidney rats receiving HP diet with STS (THP, n=7). The treatment group was given STS intraperitoneally three times a week for 16 weeks. At the end of the 16th week, rats tail artery blood pressures were tested, serum creatinine (Scr), calcium (Ca2+), phosphorus (P3+), FGF23, iPTH and urine protein were examined. Throacic aorta and kidney were then removed. Vascular calcification was confirmed by Von kossa staining. Klotho and Pit-1 expression in aortas were determined by immunohistochemistry. Renal lesion was determined by PASM-Masson staining. Renal Klotho and NaPi-2a mRNA were determined by real time RT-PCR. Results After 16 weeks, Scr, P3+, FGF23, iPTH, uric protein and blood pressure were significantly higher in NHP than those in SNP rats (all P＜0.05). PASM-Masson staining revealed typical renal pathology of chronic renal failure in NHP group. With the treatment of STS, THP rats showed significant decrease in Scr, P3+, FGF23, iPTH, uric protein and blood pressure by comparison with NHP group (all P＜0.05). Significant vascular calcification was found in NHP group while NNP and SHP group occasionally had vascular calcification; THP group had marked alleviation of vascular calcification. The aorta and renal expression of Klotho decreased remarkably while expression of Pit-1 and NaPi-2a increased significantly in NHP compared with SNP group (all P＜0.05). Accordingly, the aorta and renal expression of Klotho increased and Pit-1 and NaPi-2a decreased significantly in THP compared with NHP group (P＜0.05). Conclusions The early intervention of sodium thiosulfate might regulate Klotho and Na+/Pi cotransporter expression in both aorth and kidney, decreasing serum phosphate, delaying progression of vascular calcification and improving renal function.