NaCl Intake Promotes Greater Increases in Blood Pressure Than NaHCO3 in Rats with Chronic Kidney Disease

Abstract

Sodium bicarbonate (NaHCO3) is used in patients with chronic kidney disease (CKD) to treat metabolic acidosis and slow CKD progression. One potential adverse effect of NaHCO3 use in patients with CKD is the increase in dietary sodium (Na+) intake, which may worsen both fluid retention and hypertension in this already vulnerable population. Previous data, however, indicate that anions other than Cl‐ coupled to Na+ may not lead to increases in volume retention and blood pressure. These data raise the possibility that ingestion of NaHCO3 in patients with CKD may be relatively benign. The effects of NaHCO3 loading on fluid retention and blood pressure, however, have not been directly investigated in a model of CKD.We hypothesized that NaHCO3 loading promotes similar levels of Na+ retention and hypertension as NaCl loading in a rat model of CKD. We utilized 21, 12‐week‐old male Sprague Dawley rats that underwent sham (n=6), 2/3 (n=7), or 5/6 nephrectomy (n=8, Nx). In order to limit intra‐animal variability, we utilized a crossover study design. After 4 weeks of recovery from surgery, rats were matched by renal mass reduction and assigned to one of two groups. One group was started on a 0.1M NaHCO3 (n=11) drinking water solution while the other was started on 0.1M NaCl (n=10) in the drinking water for 2 weeks before a wash‐out (tap water for 2 weeks). The first group was then started on 0.1M NaCl while the other received 0.1M NaHCO3 for 2 weeks. Rats were maintained in metabolic cages during the initiation of treatments to allow for daily measurements of urine output, fluid, and food ingestion. Urine Na+ content was measured by atomic absorption spectrometry. Mean arterial pressure was measured in separate group with telemetry over 2 weeks of treatment with NaHCO3 or NaCl.Following the initiation of treatment, there was a significantly greater increase in urinary Na+following NaCl treatment (1.18 ± 0.09 mmol vs 5.74 ± 0.39 mmol) compared to NaHCO3 treatment (1.23 ± 0.06 mmol vs 4.82 ± 0.40 mmol; Two‐Way ANOVA, PRx=0.006). However, there was no significant difference in total retained Na+ following NaCl (2.03 ± 0.73 mmol) and NaHCO3 treatment (2.19 ± 0.62 mmol; unpaired t‐test, P=0.87). There was also no significant difference in Na+ retention between the different levels of Nx after the initiation of NaCl (Two‐Way ANOVA, PLevelofNx=0.50) and NaHCO3 treatments (Two‐Way ANOVA, PLevelofNx=0.53).Despite a similar amount of Na+ retention, we found that 0.1M NaCl resulted in greater increases in mean arterial pressure over 2 weeks in 5/6 Nx rats compared to 0.1M NaHCO3 (RM Two‐Way ANOVA, PInteraction=0.02, PSubjects<0.0001; n=4/5). The change in mean arterial pressure from baseline was greater in 5/6 Nx rats treated with NaCl (40.5 ± 5.6 mmHg) compared to NaHCO3 (20.9 ± 0.82 mmHg; unpaired t‐test, P=0.03).We conclude NaHCO3 supplementation promotes Na+ and fluid retention and increases in blood pressure in rats with CKD, however, blood pressure responses are less than that observed with NaCl. Our data indicate that NaHCO3 loading in patients with CKD is unlikely to be benign. As NaHCO3 loading can promote increases in blood pressure, caution is warranted with chronic NaHCO3 use in patients with CKD.