Kidney Week

Abstract: TH-PO382

Kidney Phosphate Wasting Predicts Worse Outcomes in Patients With Polycystic Kidney Disease

Session Information

• Genetic Diseases of the Kidneys: Cystic - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1101 Genetic Diseases of the Kidneys: Cystic

Authors

• Xue, Laixi, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Laixi Xue,

• Meijer, Esther, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Esther Meijer,

• De Borst, Martin H., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Martin H. De Borst,

• Gansevoort, Ron T., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Ron T. Gansevoort,

• Zietse, Robert, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Robert Zietse,

• Hoorn, Ewout J., Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Ewout J. Hoorn,

• Salih, Mahdi, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands

Mahdi Salih,

Group or Team Name

• on behalf of the DIPAK Consortium

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited chronic kidney disease (CKD) which often leads to kidney failure. Patients with ADPKD have disproportionately high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23) for their CKD-stage, but only a subgroup seems to develop kidney phosphate wasting. Because phosphate wasting is considered a marker for tubular dysfunction, we hypothesize it is associated with worse kidney outcomes in ADPKD patients.

Methods

We included 670 patients with ADPKD from the DIPAK observational cohort with serial measurements of kidney function (eGFR) and MRI-based total kidney volume (TKV). We measured baseline serum c-terminal FGF23 levels and calculated the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) using the Bijvoet formula. We defined a TmP/GFR <0.8 mmol/L as kidney phosphate wasting. We used linear mixed models and Cox regression models to study the association of TmP/GFR ratios with eGFR decline over time and the hazard ratios for composite kidney outcome (≥ 40% estimated GFR decline, incident of kidney failure or kidney replacement therapy).

Results

Phosphate excretion was measured in 604 patients (age 48± 12 years, 39% male, eGFR 63±28 mL/min/1.73m²). Mean TmP/GFR was 0.76± 0.23 mmol/L and mean FGF23 was 121± 74 RU/mL. Kidney phosphate wasting was observed in 357 (59%) patients. Male gender, eGFR and FGF23 were independently associated with TmP/GFR (P<0.05 for all). During follow-up of 3 years, 145 kidney outcomes were observed. After adjusting for risk factors for kidney function decline (including gender, genotype and TKV), every 0.1 mmol/L decrease in TmP/GFR was associated with a steeper eGFR decline of 0.15 ml/min/1.73m²/year (p=0.01) and 1.17 times higher risk of the kidney outcome (95% CI 1.04 to 1.31, p=0.007). FGF23 or hypophosphatemia were not associated with the composite kidney outcome.

Conclusion

In patients with ADPKD, phosphate wasting is highly prevalent and is independently associated with an increased risk for disease progression. This effect was not mediated by FGF23 or serum phosphate levels. Our results suggest that TmP/GFR adds to the current prognostic models for ADPKD.