Uromodulin as a Biomarker in Lupus Nephritis

Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) and remains a major cause of chronic kidney disease and end-stage renal disease, particularly among young adults.

Early diagnosis and accurate assessment of disease activity are essential to optimize treatment and improve long- term renal outcomes. Renal biopsy remains the gold standard for the diagnosis and classification of lupus nephritis, providing valuable information regarding histopathological activity and chronicity indices that guide therapeutic decisions. However, renal biopsy is an invasive procedure associated with potential complications and cannot be performed repeatedly for disease monitoring. Consequently, there is growing interest in identifying reliable non-invasive biomarkers that accurately reflect renal inflammation and chronic damage. Uromodulin, also known as Tamm-Horsfall protein, is the most abundant protein produced by the epithelial cells of the thick ascending limb of the loop of Henle. Experimental and clinical studies suggest that serum uromodulin is closely related to renal tubular integrity and overall nephron mass. Reduced serum uromodulin levels have been associated with impaired renal function and progressive kidney diseases. Although serum uromodulin has emerged as a promising biomarker in various chronic kidney disorders, its role in lupus nephritis remains insufficiently investigated. Determining whether serum uromodulin correlates with renal histopathological activity and chronicity indices may provide a valuable non-invasive tool for assessing disease severity and monitoring renal involvement.

Inclusion criteria

• • Group I: 30 patients with different classes of Lupus Nephritis. These cases are biopsy proven

LN. Histological diagnosis of LN is according to the revised International Society of

Nephrology/ Renal Pathology Society (ISN/RPS) classification and modified National Institute of Health (NIH) activity and chronicity indices (Bajema et al 2018) .

• Biopsy-proven lupus nephritis at the time of uromodulin blood sampling.
• Group II: 10 patients with active SLE without renal involvement and with SLEDAI score ≥6
• Group III: 10 patients with non-active SLE with SLEDAI score <6
• Group IV: 30 patients with primary forms of non-lupus Glomerulonephritis
• Group V: 10 healthy control subjects
• All cases are adults ≥18 years.
• Diagnosis of systemic lupus erythematosus according to the 2019 EULAR/ACR Classification

Criteria (Ref).Exclusion Criteria:

• • .Pregnancy or lactation

• AKI secondary to pre renal OR post renal cause (from clinical history and imaging).
• End-stage renal disease requiring dialysis
• Active infection or sepsis
• Active malignancy (either under treatment or within 5 years of successful treatment)
• History of renal transplantation
• Heart failure with NYHA III and IV
• Hhistory of other autoimmune diseases or diabetes mellitus