MP539FGF23 CLEARANCE IN PERITONEAL DIALYSIS

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INTRODUCTION AND AIMS:Introduction - Fibroblast growth factor (FGF23) plays an important role in mineral bone metabolism and maintaining phosphate haemostasis. It is one of the strongest independent prognostic factors predicting outcome. Aim -The aim of this study was to understand the effect of residual renal function and treatment with peritoneal dialysis (PD) on the clearances of FGF23. The variability of FGF23 over time was also examined. METHODS: Adult patients with end-stage renal disease (ESRD) on peritoneal dialysis and no planned change in modality of renal replacement therapy (RRT) over a 9 month period were included. FGF23 and phosphate levels were measured from plasma and 24-hour collections of urine and dialysate at 0 (start), 3, 6 and 9 months (end of the study). Serial dilutions (plasma) and concentrations (dialysate) of FGF23 was performed as necessary and measured in duplicate using second-generation C-terminal assays (Immutopics Inc., San Clemente, CA, USA). FGF23 clearance was calculated. RESULTS: A total of 19 patients were identified at the start (11 females, 8 males). The average age was 59.2 years (range 26.7-84.3), with mean RRT and PD vintage of 4.0 and 2.8 years respectively. Primary renal diagnoses were grouped into diabetes (n=3), familial nephropathies (n=2), glomerular disease (n=6), systemic disease (n=4), tubulointerstitial disease (n=3) and unknown (n = 1). Plasma phosphate concentration ranged from 0.76 to 2.91 mmol/l (mean ± SD, 1.76 ± 0.46, n = 60) and was normally distributed over 9 months. FGF23 levels were positively skewed and further analyses were performed using log-transformed values. Median plasma, urinary and dialysate FGF23 were 8219.2 RU/ml (IQR 2749.2 - 21390.0, n = 61), 5738.0 RU/ml, (IQR 1498.4 - 12019.6, n = 25) and 522.8 RU/ml, (IQR 252.4 - 995.1, n = 26) respectively. Across all time periods there were 58 measurements of both FGF23 and phosphate taken at the same time. There was a significantly positive correlation of plasma FGF23 with serum phosphate (r = 0.52, p< 0.001), urinary FGF23 (r = 0.68, p < 0.001) and dialysate FGF23 (r = 0.89, p <0.001). The strong correlation of urinary FGF23 clearance (ml/min/1.73m2) to total FGF23 clearance (r = 0.84, p < 0.001) and a moderately negative, non-significant correlation to dialysate FGF23 clearance (r = - 0.34, p = 0.13) suggests that residual renal function is an important determinant of FGF23 clearances. Dialysate FGF23 clearance had a moderate, non-significant correlation to total FGF23 clearance (r = 0.22, p = 0.34). In 9 patients with four repeated measures the within subject means and variation were rank ordered for individual patients to calculate intraclass correlation coefficient (ICC). A high ICC indicates greater stability over time in repeated measures as most of the variability is due to between subject variability. ICC for FGF23 was 0.90 while for phosphate this was 0.63. CONCLUSIONS: FGF23 is significantly raised in patients with ESRD on PD and is associated with hyperphosphatemia. Residual renal function is an important determinant of FGF23 clearance. FGF23 may be an additional reliable marker with more stability over time to study disordered phosphate metabolism.

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