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Kidney Week

Abstract: FR-PO997

Urine and Blood Biomarkers Correlate with Rate of eGFR Decline in Alport Syndrome

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Rheault, Michelle N., University of Minnesota, Minneapolis, Minnesota, United States
  • Gross, Oliver, University Medicine Goettingen, Goettingen, Germany
  • Knebelmann, Bertrand, Necker Hopsital, Paris, France
  • Simon, James F., Cleveland Clinic, Cleveland, Ohio, United States
  • Guner, Jale, Regulus Therapeutics, San Diego, California, United States
  • Deeg, Mark, Regulus Therapeutics, San Diego, California, United States
  • Kashtan, Clifford E., University of Minnesota, Minneapolis, Minnesota, United States
Background

Alport syndrome (AS) is a genetic condition leading to progressive glomerular disease and hearing loss in many affected individuals. This natural history study was performed to identify novel predictors of kidney function decline in patients with AS in order to populate future clinical trials with individuals at greatest risk of progressive kidney disease.

Methods

ATHENA (NCT02136862) was a non-interventional, global, multicenter study enrolling patients with CKD due to AS. Urine and plasma renal biomarkers and estimated GFR (eGFR) were assessed at baseline and every 12 weeks thereafter for up to 2 years. Pearson correlations of the GFR slope (provided at least 3 time points) with each baseline biomarker were derived. Statistical significance was based on FDR adjusted p-value <0.02.

Results

165 individuals were enrolled (33.9% male, 64.8% X-linked, age mean 44.8 years, 83% white). Baseline mean eGFR was 63.9 (SD 21.6) ml/min/1.73m2 and 24 urine protein was 1844mg (SD 2608). The median slope of eGFR was -2.35 ml/min/year. Higher serum albumin, protein, and CO2 correlated with a less negative slope of decline in eGFR. Higher urine albumin/cr ratio, urine protein/cr ratio, chloride, cholesterol, LDL cholesterol, and NGAL correlated with a more negative slope of decline in eGFR.

Conclusion

A number of urine and blood biomarkers correlate with short term rate of decline in eGFR in patients with AS. Multivariable models to predict slope of GFR decline using demographic and baseline biomarker data are in progress.

Correlation between baseline biomarker and slope of GFR
BiomarkerCorrelationFDR p-value
U Alb/Cr ratio-0.40<0.001
U Microalb/Cr ratio-0.36<0.001
U Prot/Cr ratio-0.35<0.001
NGAL-0.300.002
CO20.280.002
LDL Cholesterol-0.290.002
Total Protein0.280.002
Total Cholesterol-0.270.005
Albumin0.250.008
Chloride-0.250.008
Cystatin c-0.240.012

Funding

  • Commercial Support