Sickle Cell Disease and Kidney Injury: Circulating Uromodulin Allows Early Tissue Specific Diagnosis and Monitoring of Treatment

Sickle cell nephropathy (SCN) is a major determinant of morbidity and mortality in sickle cell disease (SCD), yet early injury remains difficult to recognize with conventional laboratory markers alone. Creatinine-based assessment is problematic in SCD because low muscle mass, increased tubular secretion, and glomerular hyperfiltration may keep serum creatinine (SCr) deceptively low even in the presence of evolving nephropathy. Cystatin C (Cys-C) is useful but can still remain within reference range in early disease, while albuminuria reflects predominantly glomerular injury and may miss an earlier phase of tubular damage. Serum uromodulin (sUmod), a circulating form of the kidney-specific glycoprotein produced by the epithelial cells of the thick ascending limb of Henle's loop, may therefore provide a tissue-specific marker of tubular integrity and an opportunity to detect SCN before conventional filtration markers become abnormal [1-8].