TY - JOUR
T1 - Kidney phosphate wasting predicts poor outcome in polycystic kidney disease
AU - Xue, Laixi
AU - Geurts, Frank
AU - Meijer, Esther
AU - DiPAK Consortium
AU - de Borst, Martin H
AU - Gansevoort, Ron T
AU - Zietse, Robert
AU - Hoorn, Ewout J
AU - Salih, Mahdi
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.
PY - 2024/7/1
Y1 - 2024/7/1
N2 - Background. Patients with autosomal dominant polycystic kidney disease (ADPKD) have disproportionately high levels of fibroblast growth factor 23 (FGF-23) for their chronic kidney disease stage, however only a subgroup develops kidney phosphate wasting. We assessed factors associated with phosphate wasting and hypothesize that it identifies patients with more severe disease and predicts disease progression. Methods. We included 604 patients with ADPKD from a multicenter prospective observational cohort (DIPAK; Developing Intervention Strategies to Halt Progression of Autosomal Dominant Polycystic Kidney Disease) in four university medical centers in the Netherlands. We measured parathyroid hormone (PTH) and total plasma FGF-23 levels, and calculated the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) with <0.8 mmol/L defined as kidney phosphate wasting. We analysed the association of TmP/GFR with estimated GFR (eGFR) decline over time and the risk for a composite kidney outcome (≥30% eGFR decline, kidney failure or kidney replacement therapy). Results. In our cohort (age 48 ± 12 years, 39% male, eGFR 63 ± 28 mL/min/1.73 m
2), 59% of patients had phosphate wasting. Male sex [coefficient -0.2, 95% confidence interval (CI) -0.2; -0.1], eGFR (0.002, 95% CI 0.001; 0.004), FGF-23 (0.1, 95% CI 0.03; 0.2), PTH (-0.2, 95% CI -0.3; -0.06) and copeptin (-0.08, 95% CI -0.1; -0.08) were associated with TmP/GFR. Corrected for PTH, FGF-23 and eGFR, every 0.1 mmol/L decrease in TmP/GFR was associated with a greater eGFR decline of 0.2 mL/min/1.73 m
2/year (95% CI 0.01; 0.3) and an increased hazard ratio of 1.09 (95% CI 1.01; 1.18) of the composite kidney outcome. Conclusion. Our study shows that in patients with ADPKD, phosphate wasting is prevalent and associated with more rapid disease progression. Phosphate wasting may be a consequence of early proximal tubular dysfunction and insufficient suppression of PTH.
AB - Background. Patients with autosomal dominant polycystic kidney disease (ADPKD) have disproportionately high levels of fibroblast growth factor 23 (FGF-23) for their chronic kidney disease stage, however only a subgroup develops kidney phosphate wasting. We assessed factors associated with phosphate wasting and hypothesize that it identifies patients with more severe disease and predicts disease progression. Methods. We included 604 patients with ADPKD from a multicenter prospective observational cohort (DIPAK; Developing Intervention Strategies to Halt Progression of Autosomal Dominant Polycystic Kidney Disease) in four university medical centers in the Netherlands. We measured parathyroid hormone (PTH) and total plasma FGF-23 levels, and calculated the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) with <0.8 mmol/L defined as kidney phosphate wasting. We analysed the association of TmP/GFR with estimated GFR (eGFR) decline over time and the risk for a composite kidney outcome (≥30% eGFR decline, kidney failure or kidney replacement therapy). Results. In our cohort (age 48 ± 12 years, 39% male, eGFR 63 ± 28 mL/min/1.73 m
2), 59% of patients had phosphate wasting. Male sex [coefficient -0.2, 95% confidence interval (CI) -0.2; -0.1], eGFR (0.002, 95% CI 0.001; 0.004), FGF-23 (0.1, 95% CI 0.03; 0.2), PTH (-0.2, 95% CI -0.3; -0.06) and copeptin (-0.08, 95% CI -0.1; -0.08) were associated with TmP/GFR. Corrected for PTH, FGF-23 and eGFR, every 0.1 mmol/L decrease in TmP/GFR was associated with a greater eGFR decline of 0.2 mL/min/1.73 m
2/year (95% CI 0.01; 0.3) and an increased hazard ratio of 1.09 (95% CI 1.01; 1.18) of the composite kidney outcome. Conclusion. Our study shows that in patients with ADPKD, phosphate wasting is prevalent and associated with more rapid disease progression. Phosphate wasting may be a consequence of early proximal tubular dysfunction and insufficient suppression of PTH.
UR - https://www.scopus.com/pages/publications/85197238779
U2 - 10.1093/ndt/gfad247
DO - 10.1093/ndt/gfad247
M3 - Article
C2 - 37985930
SN - 0931-0509
VL - 39
SP - 1105
EP - 1114
JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
IS - 7
M1 - gfad247
ER -