BACKGROUND: Both poor residual renal function (RRF) and high fibroblast growth factor 23 (FGF-23) levels are associated with arterial stiffness, left ventricular hypertrophy and increased (cardiovascular) mortality. Whether FGF-23 and RRF are interrelated is unknown.METHODS: We performed a prospective observational cohort study in 35 peritoneal dialysis (PD) patients with evaluation at 1, 6, 12 and 24 months after start of PD. In addition, the role of RRF was assessed in a cross-sectional observational cohort study including 68 prevalent haemodialysis patients.RESULTS: RRF significantly declined over time in PD patients. This decline was parallelled by a significant increase of both serum phosphorus and FGF-23 levels. In the prevalent dialysis cohort, RRF was found to be inversely associated with serum FGF-23 levels, independent of dialysis vintage, dialytic creatinine clearance, estimates of dietary phosphate intake (i.e. normalized protein nitrogen appearance), active vitamin D therapy and serum phosphorus and calcium levels. RRF, serum phosphorus and calcium levels and active vitamin D therapy explain 69% of the variation in FGF-23. The 38 anuric patients had higher FGF-23 levels but similar serum phosphorus levels.CONCLUSIONS: We demonstrate an important association between RRF and FGF-23, independent of classical determinants. This favours the hypothesis that the ailing kidney directly contributes to the raised FGF-23 levels. Whether FGF-23 is associated with poor outcomes independent of RRF, or vice versa, remains to be clarified.