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Abstract: TH-PO383

Urinary Citrate Is Associated With Kidney Outcomes in Early Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic

Authors

  • Xue, Laixi, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Rocha, Daniel Ribeiro da, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Sousa, Hiago Murilo, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Matos, Ana, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Salih, Mahdi, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
  • Heilberg, Ita Pfeferman, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
Background

Patients with autosomal dominant polycystic kidney disease (ADPKD) are prone to develop hypocitraturia at early stages of disease, predisposing them to calcium microcrystal formation. Recent animal studies demonstrated that microcrystal lodging in the tubules initiate cyst formation and growth. Therefore, we hypothesize that patients with ADPKD and lower urinary citrate levels are at increased risk of rapid disease progression.

Methods

We included patients with ADPKD in which urinary citrate levels were measured between 2002-2021 at our outpatient clinic at the Universidade Federal de São Paulo, Brazil. We collected baseline urine metabolic profiling, ultrasound-based total kidney volumes (TKV) and eGFR values at baseline and follow-up. We used linear mixed models to evaluate the association of urine citrate excretion with eGFR slope and Kaplan-Meier and Cox-regression models to assess the risk rate to a kidney outcome (eGFR decline >40%, kidney failure or kidney replacement therapy).

Results

From a total of 736 screened patients, 95 met our inclusion criteria. Patients were 33± 14 years, 66% were females, with a relatively preserved kidney function (eGFR of 91± 29 mL/min/1.73m2). Median follow-up was 11 years (IQR 5-15y). Lower citrate levels were associated with male sex, larger TKV and lower eGFR (p<0.05 for all). The urine citrate/creatinine ratio (uCit/Cr) correlated with eGFR and TKV (R2= 0.17 and 0.22, P< 0.001 for both). Patients with the lowest tertile of uCit/Cr (T1) had an eGFR decline of 3.7, compared to 3.3 (T2) and 2.3 ml/min/1.73m2/year (T3) (p=0.04 for T1 vs. T3). Median kidney survival time was lower in patients with lower levels of uCit/Cr (9 vs. 18 years for T1 vs. T3, p= 0.002). Adjusted for age, sex and baseline eGFR, each log unit decrease in uCit/Cr was associated with a 5-fold higher risk for a kidney outcome.

Conclusion

Low urinary citrate excretion is associated with a more rapid eGFR decline and worse kidney survival in patients with ADPKD, independent of other disease determinants. Our findings suggest urinary citrate may add to current prognostic markers of disease progression in ADPKD.