Sodium Bicarbonate Loading Limits Tubular Cast Formation Independent of Glomerular Injury and Proteinuria in Dahl Salt-Sensitive Rats
Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.
Ray, Sarah C.; Patel, Bansari; Irsik, Debra L.; Sun, Jingping; Ocasio, Hiram; Crislip, Gene R.; Jin, Chunhua H.; Chen, Jian Kang; Baban, Babak; Polichnowski, Aaron J.; and O’Connor, Paul M.. 2018. Sodium Bicarbonate Loading Limits Tubular Cast Formation Independent of Glomerular Injury and Proteinuria in Dahl Salt-Sensitive Rats. Clinical Science. Vol.132(11). 1179-1197. https://doi.org/10.1042/CS20171630 PMID: 29650676 ISSN: 0143-5221