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Abstract: FR-PO920

Urinary Epidermal Growth Factor Is a Distal Tubule Marker for Kidney Health in the General Population

Session Information

Category: CKD (Non-Dialysis)

  • 2201 CKD (Non-Dialysis): Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Geurts, Frank, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • van der Burgh, Anna C., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Fenton, Robert A., Aarhus Universitet, Aarhus, Midtjylland, Denmark
  • Chaker, Layal, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
Background

Kidney health is usually assessed by glomerular rather than tubular markers. In the kidney EGF is exclusively expressed in the distal tubule. In patients with chronic kidney disease (CKD) urinary epidermal growth factor (uEGF) correlates with interstitial fibrosis and tubular atrophy and predicts kidney failure. Here, we hypothesize that uEGF is a distal tubule marker of kidney health in the general population.

Methods

To assess uEGF as tubular marker, it was initially measured before and three months after kidney donation (n = 19). Tubule segment-specific proteins were also quantified in urinary extracellular vesicles (uEV) using immunoblot. Next, uEGF was measured in the Rotterdam Study (n = 2382), a population-based cohort with long-term follow-up (median 13.0 years). The association between uEGF excretion and estimated glomerular filtration rate (eGFR, median of 7 eGFRs available) was assessed using multivariable linear regression. Furthermore, multivariable Cox regression analysis was used to analyze kidney outcomes (eGFR < 60 or 45 ml/min/1.73m2, 40% loss of eGFR). eGFR, albumin creatinine ratio (ACR), age, sex, body mass index, hypertension, diabetes, smoking status, history of cardiovascular disease and total cholesterol were used as covariates. uEGF was measured in 24 h urine (kidney donors) or spot urines (general population, normalized to creatinine, uEGF/cr).

Results

Kidney donation decreased eGFR from 91 to 58 ml/min/1.73m2 (36% reduction, 95%CI 31–42%), while uEGF excretion reduced from 28 to 14 μg/day (51% reduction, 95%CI 46–58%). In uEVs, proximal tubule markers increased while distal tubule proteins remained unchanged. In the population-based cohort, uEGF/cr correlated with baseline eGFR (β 0.02, 95%CI 0.02–0.03) and ACR (β -0.09, 95%CI -0.15– -0.03). uEGF/cr was inversely associated with incident eGFR < 60 ml/min/1.73m2 (HR 0.85, 95%CI 0.76–0.95). Similar results were obtained using an outcome of two consecutive eGFR measurements < 60 ml/min/1.73m2 (HR 0.81, 95%CI 0.69–0.94), eGFR < 45 ml/min/1.73m2 (HR 0.84, 95%CI 0.69–1.02) and 40% loss of eGFR (HR 0.83, 95%CI 0.7–0.98).

Conclusion

Urinary EGF is a distal tubule marker that is not affected by glomerular hyperfiltration and proximal tubule hypertrophy. In the general population, uEGF/cr is associated with incident CKD independent of eGFR and ACR.