Bicarbonate therapy has no effect on renal T‐cell infiltration or blood pressure but markedly reduces tubular casts/fibrosis and is associated with an M1 to M2 polarization in Dahl salt‐sensitive rats

Abstract

Immune cell infiltration into the kidney has been suggested to occur in response to renal injury but may also contribute to the development of hypertension in the Dahl salt‐sensitive (SS) rat model, initiating a feed‐forward cascade of progressive hypertension, hypertension induced kidney injury, and immune cell infiltration. Experimentally, it has been difficult to separate these factors, given the normally close relationship between blood pressure and renal injury in this model. We have recently reported that HCO3− supplementation limits the development of tubular casts and fibrosis in the kidneys of high salt fed Dahl SS rats, independent of lowering systemic arterial pressure. Therefore, in the current study we leveraged this phenotype to better delineate the roles of hypertension and renal tubular injury/fibrosis on the renal immune cell profile.11 week old Dahl SS rats were either treated with vehicle (0.1M NaCl; n=5) or NaHCO3−(0.1M; n=5) in drinking water for the length of the study. At the beginning of the study, rats were maintained on a 0.4% NaCl diet (Dyets AIN76A) for 4 days before being switched to an 8% NaCl diet for 14 days. On day 14 of 8% NaCl feeding, rats were anesthetized, arterial blood gas measurements taken and both arterial blood and the left kidney excised for flow cytometry analysis. Data are presented in the table below.Results and ConclusionsBicarbonate treatment markedly reduced tubular injury and fibrosis accompanied with significantly higher levels of M2 macrophages and a significantly lower levels of M1 macrophages, without altering renal T‐cell infiltration or blood pressure. Thus, our data for the first time suggest that the potential therapeutic effect of bicarbonate treatment might be mediated by induction of a phenotypic change of pro‐inflammatory M1 macrophage to tissue reparative M2 macrophage in Dahl salt‐sensitive ratsSupport or Funding InformationThis work was supported by NIH NIDDK grant 5R01DK099548 KIDNEY CD3+ CD4+(% CD3) CD44+(% CD3) CD69+ (% CD3) FOXP3+ (% CD3) M1 M2 Vehicle (n=5) 1.44±0.23 55.2±1.6 59±2 0.6±0.1 1.1±0.2 0.30±0.03 0.16±0.04 Bicarbonate (n=5) 1.44±0.39 51.4±3.1 52±3 0.8±0.2 1.8±0.4 0.14±0.02 0.3±0.03 p (t‐test) 0.4 0.3 0.08 0.44 0.17 0.004** 0.03* BLOOD Vehicle (n=4) 54±1.2 55±1.9 19±2.2 1.2±0.3 2.5±0.3 Bicarbonate (n=5) 57.4±2 52.6±1.4 14.2±1.9 0.9±0.3 4.4±0.5 p (t‐test) 0.22 0.33 0.14 0.45 0.02*