Abstract 535: Chronic High Sodium Diet Attenuates The Development Of Renal Injury And Inflammation In Murine Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent renal disease, a consequence of increased and abnormal survival of B and T lymphocytes. Recent evidence suggests that dietary salt may be an important environmental factor that promotes certain autoimmune diseases by stimulating pro-inflammatory T lymphocyte differentiation. Therefore, we hypothesized that a long-term high salt diet would accelerate the progression of renal disease during SLE. In order to test this, an established experimental model of SLE (female NZBWF1 mice) was fed a standard (0.4% NaCl) or high salt (4% NaCl) diet starting at 10 weeks of age. Sodium intake (in meq/day) was measured three times throughout the study and was significantly greater in high salt fed animals at 16 weeks of age (2.9±0.6 vs. 0.5±0.06 , p=0.01), 23 weeks (4.8±0.8 vs. 0.6±0.06, p=0.004) and 29 weeks (5.7±0.6 vs. 0.6±0.05, p=0.0007). Urinary albumin was monitored monthly until 30 weeks then weekly by dipstick assay as a marker of renal injury until 34 weeks of age, at which time catheters were implanted into the carotid arteries for measurement of mean arterial pressure (MAP). Mice were then euthanized and kidneys collected. Renal cortex enriched mRNA was analyzed by qRT-PCR for inflammatory markers, and renal medullary enriched mRNA was analyzed for expression of serum glucocorticoid kinase 1 (SGK1), a salt-sensing kinase. Counter to our hypothesis, 75% (9/12) of animals on a normal diet developed albuminuria (≥ 100 mg/dL), whereas 17% (2/12) of the high salt fed animals developed albuminuria (p=0.0002). MAP was not different between groups (132±4 mmHg 0.4% NaCl vs. 144±8 mmHg 4% NaCl), nor was renal medullary expression of SGK1 mRNA (0.25±0.03 vs. 0.20±0.04). However, renal cortical interleukin-2 (IL-2), a cytokine important for T cell differentiation, expression was significantly lower in high salt fed animals (0.31±0.03 vs. 1.16±0.34, p=0.03). These data suggest that a long-term high salt diet may protect against the renal injury associated with SLE, possibly through alterations in IL-2 mediated T cell differentiation, without a significant effect on MAP. Furthermore, the data advance our overall understanding of how dietary salt may impact different autoimmune disorders.
Author Disclosures: H.J. Broome: None. M.J. Ryan: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; AHA GIA.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2014 by American Heart Association, Inc.