Abstract: SA-PO0576
Uric Acid Microcrystal Injury as a Driver of CKD and PKD
Session Information
- Cystic Kidney Diseases: Clinical Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Holznecht, Nickolas J., University of California Santa Barbara, Santa Barbara, California, United States
- Strubl, Sebastian, Universitat zu Koln, Cologne, NRW, Germany
- Torres, Jacob A., University of California Santa Barbara, Santa Barbara, California, United States
- Schimmel, Margaret, University of California Santa Barbara, Santa Barbara, California, United States
- Messing, Melina, University of California Santa Barbara, Santa Barbara, California, United States
- Arjune, Sita, Universitat zu Koln, Cologne, NRW, Germany
- Glaser, Jason R., La Isla Network, Washington, District of Columbia, United States
- Leiva, Ricardo A., La Isla Network, Washington, District of Columbia, United States
- Brown, Jared, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Roncal-Jimenez, Carlos Alberto, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Johnson, Richard J., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Grundmann, Franziska, Universitat zu Koln, Cologne, NRW, Germany
- Mueller, Roman-Ulrich, Universitat zu Koln, Cologne, NRW, Germany
- Weimbs, Thomas, University of California Santa Barbara, Santa Barbara, California, United States
Background
CKD affects over 10% of the global population and 14% in the US, mainly due to T2D. While historically driven by hypertension and hyperglycemia, CKD now more often advances due to repeated acute renal insults (AKI). A key risk factor for CKD and repeated AKI is the Western diet, high in sugar and ultra-processed foods (UPFs), contributing to hyperuricemia. The increased uric acid (UA) needs to be excreted via the kidneys, but in the presence of of low urine pH, UA crystals can form in renal tubules. We previously found that calcium oxalated crystals trigger an inflammatory process characterized by tubule dilation. We find here that tubular UA micro-crystals trigger a similar response, worsen CKD progression, and trigger new cyst growth in ADPKD.
Methods
We analyzed clinical data from two ADPKD studies (NCT02497521, NCT04680780), excluding patients on tolvaptan. We assessed eGFR slopes, UA levels, urine pH, and neutrophil-to-lymphocyte ratios (NLR), using regression models and the Marshal lithogenic risk equation. Data from Nicaraguan sugarcane workers with AKI vs controls were also analyzed.
Results
Sugarcane workers had elevated urinary UA, crystalluria, and IL-8/IL-12 levels, with strongly increased NLR and pyuria. AKI cases showed abundant UA crystals, low urine pH, and high neutrophil activity. In ADPKD, the Marshal lithogenic risk score for UA – relying on serum UA and urinary pH - was a significant predictor of kidney decline irrespective of initial eGFR, . In a trial of ketogenic therapy for ADPKD, persistent ketosis (BHB ≥0.8 mmol/L) reduced NLR, supporting an anti-inflammatory role for BHB in ameliorating PKD progression.
Conclusion
UA in combination with acidic urine triggers tubular microcrystal formation leading to a neutrophil inflammatory response that causes AKI and drives CKD and ADPKD progression. Reducing UA formation, and urine alkalization with citrate may be disease-modifying in CKD and ADPKD. NLR or pyuria may serve as biomarkers of progression.