SERUM NEPHRIN AS AN EARLY BIOMARKER OF DIABETIC KIDNEY DISEASE IN CHILDREN WITH TYPE 1 DIABETES MELLITUS

Abstract

Background. Diabetic kidney disease (DKD) is one of the most important microvascular complications of type 1 diabetes mellitus (T1DM). Conventional markers, including albuminuria, serum creatinine and estimated glomerular filtration rate (eGFR), may not adequately reflect the earliest structural changes in the glomerular filtration barrier. Nephrin is a key transmembrane protein of the podocyte slit diaphragm and is essential for maintaining glomerular filtration barrier integrity. Previous studies have demonstrated that nephrin loss may occur before clinically detectable albuminuria, suggesting its potential role as an early marker of podocyte injury [1–3].

Objective. To evaluate the diagnostic and prognostic significance of serum nephrin for the early detection of renal injury in children with T1DM at the normoalbuminuric stage.

Materials and Methods. The study included 80 children with T1DM at the normoalbuminuric stage. Clinical and laboratory assessment included serum creatinine, urea, eGFR and urinary albumin excretion. Serum nephrin concentration was measured by enzyme-linked immunosorbent assay (ELISA). Patients with elevated nephrin levels were prospectively followed for three years to assess subsequent changes in renal function and the development of microalbuminuria.

Results. Mean serum nephrin concentration in children with T1DM was 0.65 ± 0.06 ng/mL, compared with 0.018 ± 0.08 ng/mL in the control group (p<0.001). Elevated serum nephrin was detected in 26 of 80 patients (32.5%), with a mean concentration of 1.13 ± 0.10 ng/mL among nephrin-positive patients.

During three years of prospective observation, patients with elevated nephrin demonstrated progressive deterioration of renal parameters. Mean eGFR decreased from 82.7 ± 1.78 mL/min/1.73 m² at baseline to 73.1 ± 1.98 mL/min/1.73 m² after one year, 65.4 ± 2.11 mL/min/1.73 m² after two years and 58.2 ± 2.36 mL/min/1.73 m² after three years (p<0.001).

The development of microalbuminuria showed a parallel progressive pattern. Microalbuminuria was detected in approximately 38% of patients after one year, around 60% after two years, and in more than 80% by the end of the third year.

Conclusion. Elevated serum nephrin may indicate early podocyte injury in children with T1DM even at the normoalbuminuric stage. Its association with subsequent eGFR decline and development of microalbuminuria suggests that nephrin may have value as an early biomarker for identifying patients at increased risk of progression to diabetic kidney disease..