NaCl Intake Promotes Greater Fluid Retention and Blood Pressure Increases than NaHCO 3 in Rats with Chronic Kidney Disease

Abstract

Several small clinical trials have shown that oral sodium bicarbonate (NaHCO3) can slow kidney disease progression, and NaHCO3 use is now common in chronic kidney disease (CKD) patients. One potential adverse effect of NaHCO3 use in CKD patients is the increased dietary sodium, which may worsen fluid retention and hypertension, potentially driving cardiovascular disease. It remains unclear however whether the anion coupled with sodium is important in mediating volume retention and blood pressure (BP) increases in this setting. Additionally, the effects of NaHCO3 loading on fluid retention and blood pressure compared to sodium chloride (NaCl) have not been rigorously investigated in CKD. We hypothesized that NaCl loading promotes greater volume retention and increases blood pressure to a greater degree than equimolar NaHCO3 across a range of renal mass reduction in rats. We utilized 11, 10-week-old male Sprague Dawley rats that underwent either 2/3 (n=6) or 5/6 nephrectomy (n=5). Following 4 weeks of recovery, animals were allocated to treatment groups based on renal mass reduction and placed in metabolic cages. Rats were then placed on either 0.1M NaCl (n=5) or 0.1M NaHCO3 (n=6) drinking water. Urine output, fluid and food ingestion were determined daily. Urine sodium (Na+) content was measured by flame photometry. BP was measured in separate group with telemetry. Following initiation of treatment, there was a significant increase in urinary Na+ in rats given NaCl (0.89 ± 0.06 mmol vs 5.06 ± 0.14 mmol; paired t-test, p<0.0001). Similarly, rats given NaHCO3 also exhibited a significant increase in urinary Na+ excretion (1.10 ± 0.06 mmol vs 3.13 ± 0.15 mmol; paired t-test, p<0.0001). However, there was no significant difference in Na+ retention observed between NaCl (1.8 ± 0.41 mmol) and NaHCO3 (1.2 ± 0.51 mmol) treated groups (unpaired t-test, p=0.38). No relationship between Na+ retention and degree of renal mass reduction was observed. Interestingly, rats given NaCl tended to have greater volume retention compared to NaHCO3, but this did not reach statistical significance (delta -11.1 ± 2.9 mL vs -4.35 ± 8.5 mL; unpaired t-test, p=0.12). Consistent with greater fluid retention in NaCl treated animals, we found that 0.1M NaCl resulted in greater increases in mean arterial pressure over 7 weeks in 2/3 nephrectomy rats compared to 0.1M NaHCO3 (RM Two-Way ANOVA, PRxGroup=0.0021, PTime<0.0001, PInteraction=0.0266, PSubjects=<0.0001; n=6/6). We conclude NaHCO3 promotes volume retention in CKD, however volume retention may be greater with NaCl than NaHCO3. Further, NaCl increases blood pressure to a greater degree than NaHCO3 in remnant kidney rats despite similar Na+ retention. As NaHCO3 loading may not promote volume retention to the same degree as NaCl, NaHCO3 loading may limit the risk of adverse cardiovascular effects associated with Na+ loading when given as NaHCO3 in patients with CKD.