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Abstract: PO0982

Urinary Cubilin Shedding Predicts Progressive Diabetic Nephropathy in Type 1 Diabetes Mellitus

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Ciccia, Eileen Anna, Saint Louis Children's Hospital, Saint Louis, Missouri, United States
  • Costacou, Tina, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Erkan, Elif, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Diabetes mellitus (DM) is the leading cause of end-stage renal disease worldwide. Microalbuminuria(MA) is considered a gold standard to diagnose diabetic nephropathy (DN) however its detection of early kidney damage is questionable. Therefore, there is an emergent need for novel biomarkers to capture early molecular alterations preceding MA . Cubilin is a 460 kd size protein lacking a transmembrane domain and is coexpressed with megalin facilitating albumin endocytosis in proximal tubule epithelial cells. We hypothesize that cubilin trafficking is compromised and is amenable to urinary shedding in DM. We propose that urinary cubilin shedding predicts DN.

Methods

This study assessed urinary IL-8, cubilin, monocyte chemoattractant factor (MCP-1), NGAL and vitamin D binding protein (VDBP) levels by ELISA (normalized for creatinine) across three groups of individuals with type 1 diabetes (T1D): Group 1(n=9) preserved normal kidney function, group 2 (n=10) developed proteinuria (albumin excretion >200microgram/min) and group 3 (n=9) developed progressive DN >40% decline in glomerular filtration rate (GFR) and proteinuria during follow-up of ~10 years. Urine samples for these assessments were obtained from the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort. All patients had normal urine albumin excretion and kidney function.
Duration of diabetes was comparable between groups (13.5 years±1.1). Mann-Whitney U and Kruskal Wallis tests were used to compare groups.

Results

Urinary IL-8 levels were (pg/gr) 229 ± 71, 270 ±146 and 549 ± 41.5 (NS) respectively. Urinary cubilin excretion(pg/gr) was 23±71, 38±9.2 and 47±8.8 (p<0.05). A urinary cubilin excretion >30 pg/mg predicted progressive DN with a 67% sensitivity and 89% specificity and an area under the ROC curve of 0.81(p <0.05). Urinary MCP-1, NGAL and VDBG levels did not significantly differ across the groups.

Conclusion

We demonstrated that urinary cubilin shedding is a reliable biomarker for predicting progressive DN in T1D preceding microalbuminuria. Although not statistically significant urine IL-8 levels were elevated in patients with significant proteinuria and decline in GFR.
The role of urinary cubilin shedding as a biomarker for the diagnosis and treatment of diabetic nephropathy at an early stage should be examined in a larger patient population.