Abstract: FR-PO997
Urine and Blood Biomarkers Correlate with Rate of eGFR Decline in Alport Syndrome
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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
| Biomarker | Correlation | FDR 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 | -0.30 | 0.002 |
| CO2 | 0.28 | 0.002 |
| LDL Cholesterol | -0.29 | 0.002 |
| Total Protein | 0.28 | 0.002 |
| Total Cholesterol | -0.27 | 0.005 |
| Albumin | 0.25 | 0.008 |
| Chloride | -0.25 | 0.008 |
| Cystatin c | -0.24 | 0.012 |
Funding
- Commercial Support – Regulus Therapeutics