Abstract: TH-PO438
Changes in Tubular Biomarkers with Dietary Intervention and Metformin in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Session Information
- Genetic Diseases: Cystic - Therapeutic Investigations and Prognosis
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- You, Zhiying, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Steele, Cortney, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Gitomer, Berenice Y., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Chonchol, Michel, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Nowak, Kristen L., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Background
Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in progression of ADPKD. We evaluated changes in tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury.
Methods
66 participants (26M/40F) with ADPKD and estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 who participated in either a 12-month metformin clinical trial (n=22 metformin [max dose 2,000 mg/d]; n=23 placebo) or 12-month dietary weight loss study (n=10 daily caloric restriction [DCR; 34% restriction]; n=11 intermittent fasting [IMF]; 3x/wk) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline levels with change in height-adjusted total kidney volume (htTKV) and eGFR, with covariate adjustment, was also assessed.
Results
Mean+s.d. age was 48±8 years, eGFR was 71±16 ml/min/1.73m2, and baseline BMI was 30.5±5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Tubular biomarkers were not associated with change in eGFR or htTKV over one year, after adjustments for demographics, group assignment, and clinical characteristics (Table).
Conclusion
In this cohort of patients with ADPKD, tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression.
| Tubular Biomarker (log-adjusted) | Adjusted association with change in htTKV (B-estimate [95% CI]) | Adjusted association with change in eGFR (B-estimate [95% CI]) |
| KIM-1 | 4.3 (-1.1, 9.6) | 2.1 (-6.4, 10.6) |
| FABP4 | 0.52 (-3.2, 4.3) | -2.3 (-7.5, 2.9) |
| IL-18 | 0.14 (-7.4, 7.8) | -7.5 (-17.0, 2.0) |
| MCP-1 | 2.7 (-4.5, 9.8) | -3.5 (-38.5, 21.5) |
| NGAL | 1.2 (-2.4, 4.8) | -1.3 (-6.2, 3.6) |
| Clusterin | 2.6 (-4.1, 9.2) | 1.7 (-4.7, 8.1) |
| YKL-40 | -0.36 (-3.3, 2.6) | -0.10 (-4.3, 4.1) |
Funding
- NIDDK Support