Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73 m². During a median follow-up of 2.9 yr, 453 (41%) patients died from any cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progressively higher risk for death, adjusted for confounders (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08] for the second through fourth quartiles, respectively). In addition, compared with the lowest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated risk for cardiovascular events and initiation of chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-cause mortality, cardiovascular events, and initiation of chronic dialysis.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases.

Longitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49–0.89), cardiac events (HR, 0.71; 95% CI, 0.53–0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34–0.62) in time-dependent analyses. No significant associations of 1,25(OH)₂D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13–2.18), cardiac events (HR, 1.49; 95% CI, 1.06–2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07–2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.