Serum acetate levels correlate with disease activity in patients with lupus nephritis

Abstract

INTRODUCTION: Lupus nephritis patients have impaired immune tolerance to self-antigens resulting in immune-mediated kidney injury. It is speculated that gut microbiota or its products are involved in the aetiology or pathogenesis of autoimmune diseases. Bacterial metabolites from the gut can enter the circulation and modulate inflammatory responses. Acetate is a short-chain fatty acid produced by the gut microbiota. We measured serum acetate level and renal expression of its cell surface receptors GPR-41 and GPR-43 in lupus nephritis patients to investigate the potential relationship between the gut microbiota and serological and clinical parameters of disease activity. METHODS: Serum acetate, IL-6, IL-8, MCP-1 and LPS levels were measured in patients with biopsy-proven severe proliferative lupus nephritis, patients with non-lupus glomerular diseases and healthy controls. Renal expression of GPR-41 and GPR-43 was determined by cytochemical staining. RESULTS: Serum acetate level was higher in lupus nephritis patients compared with non-lupus renal disease group (P< 0.05) and healthy subjects (P< 0.01); and in lupus nephritis serum acetate level was higher during disease flare (P=0.04 compared with remission). Furthermore, acetate level in lupus nephritis patients correlated with serum LPS (r=0.34, P< 0.0001), MCP-1 (r=0.21, P< 0.0001), and IL-8 levels (r=0.22, P< 0.0001), and also proteinuria (r=0.29, P< 0.01), but not serum IL-6 level. Renal GPR-41 and GPR-43 expression was markedly increased in active lupus nephritis kidney biopsies, and was predominantly detected in the tubulo-interstitium. CONCLUSIONS: Our data suggest that acetate may contribute to the pathogenesis of lupus nephritis, and may have a role in tubulo-interstitial disease.