Abstract
Few studies have linked high levels of plasma C-terminal fibroblast growth factor 23 (FGF23) with poor clinical outcomes in patients on maintenance haemodialysis (MHD), while the association between intact FGF 23 and mortality in this group of patients remains inconclusive. Therefore, the aim of this study was to evaluate the association between plasma levels of intact FGF 23 and mortality in dialysis patients. A 3.3 year prospective multicenter study involving patients undergoing dialysis at three dialysis centers in Johannesburg was undertaken between the periods of October 2014 and December 2017. The association between the quartiles of FGF-23 and mortality was assessed using the Cox proportional hazard model. The fully adjusted model; adjusted for Age, gender, calcium, phosphate, parathyroid hormone, FGF23, bone specific alkaline phosphatase, dialysis modality, diabetic status, CKD-MBD medications. FGF23 was categorized based on 25, 50 and 75 percentiles. PTH was categorized based on KDIGO recommendations. The study comprised 165 chronic dialysis patients (111 blacks, 54 whites) with a mean age of 46.6 ±14.2 years. During a three year follow up period, there were 46 deaths (1.03 per 100 person- years). The median plasma FGF 23 was 382 pg/ml (interquartile range [IQR], 145-2977). In adjusted multivariable analyses, there was a non-statistically significant increase in the risk of mortality with higher quartiles of FGF 23 levels : the adjusted hazard ratios(HR) for the second, third and fourth quartiles were HR 3.08 (95% CI, 0.98-9.72; P=0.06), HR 2.41 (95% CI, 0.66-9.03; P=0.19), and HR 2.15 (95% CI, 0.26-7.58; P= 0.24 respectively. In comparison to normal levels of calcium (2.11-2.37 mmol/l), serum albumin corrected calcium levels of 2.38-2.5 mmol [HR 3.00 (95% CI, 1.08-8.38); P=0.04] and > 2.50 mmol [HR 5.93 (95% CI, 1.84-19.02); P=0.003] were independently associated with increased risk of death. Likewise, patients with intact parathyroid hormone > 600 pg/ml had a 3.5 fold higher risk of death (HR 3.51, 95% CI, 1.23-9.97; P=0.02). These findings persisted on time -dependent analyses. Table 1Hazard ratios of all-cause mortalityVariableUnadjusted Hazard ratio (95 %CI)P valueAdjusted Hazard ratio (95 %CI)P valueCalcium< 1.801.45(0.49-4.27)0.501.08(0.20-5.35)0.931.80-2.100.50(0.15-1.69)0.270.99(0.26-3.80)0.182.11-2.371.00(ref)1.00(ref)2.38-2.502.21(1.05-4.60)0.043.00(1.08-8.38)0.04>2.502.94(1.17-7.40)0.025.93(1.84-19.02)0.003PTH<651.18(0.31-4.47)0.801.45(0.25-8.46)0.68)>=65-<1301.03(0.22-4.87)0.970.95(0.17-5.29)0.96>=130-<=6001.00(ref)1.00*ref)>6002.23(1.03-4.85)0.043.51(1.23-9.97)0.02FGF23<1481.00 (ref)1.00(ref)148-3821.80(0.76-4.23)0.183.08(0.98-9.72)0.06383-29771.49(0.63-3.48)0.362.41(0.66-7.58)0.19> 29771.28(0.52-3.15)0.602.15(0.61-7.58)0.24 Open table in a new tab Higher levels of intact FGF 23 appear not to be independently associated with all-cause mortality in our dialysis patients, while hypercalcaemia and severe hyperparathyroidism were found to be independent predictors of mortality in this cohort of patients.
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