Whether phosphate itself has nephrotoxicity in patients with chronic kidney disease (CKD) is controversial, although phosphate excretion into urine may cause tubular damage in rat models. To evaluate actual phosphate load on each nephron, we examined the association between 24-h urinary phosphorus excretion per creatinine clearance (24-h U-P/CCr), a newly proposed index that is a surrogate for nephron load, and CKD progression in patients with CKD.
We conducted a single-center, retrospective cohort study. To avoid potential confounders for protein intake, only patients on our educational program for CKD with a fixed diet regimen and aged 20 years or older were included. The observation period was 3 years. Primary outcomes were CKD progression defined as a composite of end-stage kidney disease (ESKD) or 50 % reduction of estimated glomerular filtration rate. Patients were stratified by quartiles of 24-h U-P/CCr levels as Quartiles 1–4. The association was examined in three models: unadjusted (Model 1), adjusted for risk factors for CKD progression (Model 2), and factors that affect renal phosphate handling (Model 3).
A total of 191 patients met the eligibility criteria. Patients with higher 24-h U-P/CCr showed a higher risk for the composite outcomes. The hazard ratios [95 % confidence interval] for 24-h U-P/CCr levels in Quartile 2, 3, and 4, respectively, versus Quartile 1 were 2.56 (1.15–6.24), 7.53 (3.63–17.62), and 12.17 (5.82–28.64) in Model 1; 1.66 (0.63–4.97), 3.57 (1.25–11.71), and 5.34 (1.41–22.32) in Model 2; and 3.07 (0.97–11.85), 7.52 (2.13–32.69), and 7.89 (1.74–44.33) in Model 3.
Our study showed that higher phosphorus excretion per creatinine clearance was associated with CKD progression.||