Abstract: TH-PO918
Determinants of Urinary C-Megalin Among a Large Diabetes Cohort: Albuminuria, Reduced Kidney Function, and Demographic Factors
Session Information
- Diabetic Kidney Disease: Biomarkers, Pathogenesis
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Kurita, Noriaki, Fukushima Medical University, Fukushima, Japan
- Hayashino, Yasuaki, Tenri Hospital, Nara, Japan
Background
Urinary c-megalin is a multi-ligand receptor shed from proximal tubule cells. It is expected as a biomarker for early kidney injury associated with diabetic kidney disease (DKD) among diabetes. The aim of this study was to examine the determinants of urinary c-megalin values.
Methods
This single-center cross-sectional study included 1491 Japanese patients with diabetes (including 104 type 1 and 1387 type 2 diabetes). The outcome was urinary c-megalin measured by enzyme-linked immunosorbent assay and expressed as both urinary creatinine (Cr)-corrected value (unit: pM/gCr) and non-corrected value (unit: fM/L). The candidate predictors were: age, type 1 diabetes, hemoglobin, hemoglobin A1c, antihypertensives, estimated glomerular filtration rate (eGFR: ≥130, >90-<130 [ref.], >60-≤90, >30-≤60, ≤30 mL/min/1.73m2), and urine albumin Cr ratio (uACR: <10 [ref.], ≥10-<30, ≥30-<300 [i.e., microalbuminuria], ≥300 mg/gCr [i.e., macroalbuminuria]). The two-part model was fit to estimate the marginal effects of the predictors as urinary c-megalin values of both units have zero-inflated heavily skewed distributions.
Results
Cr-corrected c-megalin showed higher values associated with both microalbuminuria and macroalbuminuria (difference: 0.06 and 0.31 pM/gCr), whereas aging (≥65-<75 yr and ≥75 yr compared to <55 yr) was also associated with higher c-megalin values (Figure1). Uncorrected c-megalin showed higher values associated with macroalbuminuria (difference: 132 fM/L), eGFR >30-≤60, and ≤30 mL/min/1.73m2 (difference: 62 and 134 fM/L). For both units, higher c-megalin values were associated with male sex and lower hemoglobin values.
Conclusion
Uncorrected c-megalin was independently associated with reduced kidney function and macroalbuminuria, both of which were included in a current concept of DKD. However, for both units, careful interpretation would be required as anemia and sex affect both units and especially, aging affects Cr-corrected values.
Marginal effects of predictors on urinary c-megalin values expressed as Cr-corrected (left panel) and uncorrected values (right panel). Error bars indicate 95% confidence intervals.