Exploring the unseen: Asymptomatic hyperuricemia and its role in the pathogenesis of lupus nephritis, a narrative review

Abstract

Lupus nephritis (LN) is a major cause of morbidity in systemic lupus erythematosus, yet the impact of asymptomatic elevations in serum uric acid (SUA) on its onset and progression remains unclear. This narrative systematic review synthesizes data from observational cohorts, pathology studies, and mechanistic investigations to clarify the role of hyperuricemia in LN. We first describe the high prevalence of elevated SUA among biopsy‐proven LN patients and its consistent association with worse renal function, more severe proteinuria, and higher disease activity indices. We then examine histopathological studies linking hyperuricemia to greater activity and chronicity scores, suggesting that uric acid may exacerbate glomerular and tubulointerstitial injury. Proposed mechanisms include DAMP‐mediated inflammasome activation, endothelial dysfunction, and promotion of fibrotic pathways. Although several reports identify hyperuricemia as a risk factor for chronic kidney disease progression or end‐stage renal disease in LN—particularly in women—results vary by cohort, making its independent prognostic value uncertain. Finally, we review evidence on urate‐lowering therapies in LN, noting that routine treatment is not yet justified in the absence of gout or nephrolithiasis. We conclude that SUA holds promise as a biomarker of LN severity but advocate for prospective trials to determine whether targeted urate reduction can improve renal outcomes.