Fibroblast Growth Factor 21 (FGF-21) in Peritoneal Dialysis Patients: Natural History and Metabolic Implications

Abstract

BackgroundHuman fibroblast growth factor 21 (FGF-21) is an endocrine liver hormone that stimulates adipocyte glucose uptake independently of insulin, suppresses hepatic glucose production and is involved in the regulation of body fat. Peritoneal dialysis (PD) patients suffer potential interference with FGF-21 status with as yet unknown repercussions.ObjectivesThe aim of this study was to define the natural history of FGF-21 in PD patients, to analyze its relationship with glucose homeostasis parameters and to study the influence of residual renal function and peritoneal functional parameters on FGF-21 levels and their variation over time.MethodsWe studied 48 patients with uremia undergoing PD. Plasma samples were routinely obtained from each patient at baseline and at 1, 2 and 3 years after starting PD therapy.ResultsPlasma FGF-21 levels substantially increased over the first year and were maintained at high levels during the remainder of the study period (253 pg/ml (59; 685) at baseline; 582 pg/ml (60.5–949) at first year and 647 pg/ml (120.5–1116.6) at third year) (p<0.01). We found a positive correlation between time on dialysis and FGF-21 levels (p<0.001), and also, those patients with residual renal function (RRF) had significantly lower levels of FGF-21 than those without RRF (ρ -0.484, p<0.05). Lastly, there was also a significant association between FGF-21 levels and peritoneal protein losses (PPL), independent of the time on dialysis (ρ 0.410, p<0.05).ConclusionOur study shows that FGF-21 plasma levels in incident PD patients significantly increase during the first 3 years. This increment is dependent on or is associated with RRF and PPL (higher levels in patients with lower RRF and higher PPL). FGF-21 might be an important endocrine agent in PD patients and could act as hormonal signaling to maintain glucose homeostasis and prevent potential insulin resistance. These preliminary results suggest that FGF-21 might play a protective role as against the development of insulin resistance over time in patients undergoing a continuous glucose load.

Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease

“…In a study with CKD patients and healthy controls, plasma FGF21 levels were significantly increased with the development of early- to end-stage CKD and were independently associated with the renal function [ 10 ]. In ESRD patients receiving peritoneal dialysis, the circulating FGF-21 levels were also inversely correlated with the residual renal function [ 13 ]. The present study also showed that plasma FGF21 levels in end-stage CKD patients are about 10-fold higher than those in normal subjects and about 4.5-fold higher than those in early-stage CKD patients [ 10 ].…”

“…In addition, the circulating FGF21 level increases progressively from the early to end stages of chronic kidney disease (CKD) and is associated with the renal function [ 10 , 11 ]. Indeed, end-stage renal disease (ESRD) patients receiving dialysis showed 8- to 15-fold higher circulating FGF21 levels than normal subjects [ 9 , 12 ], and circulating FGF-21 levels were inversely correlated with the residual renal function in peritoneal dialysis patients [ 13 ]. Furthermore, the FGF21 level is an independent biomarker of rapid CKD progression in patients at early stages of diabetic nephropathy [ 14 , 15 ].…”

Fibroblast growth factor 21 in chronic kidney disease

“…Highest levels appear to be present in hemodialysis, diabetic and male patients [2, 15]. Patients on peritoneal dialysis (PD), despite the glucose supply from the dialysis solution, have lower circulating FGF21 levels than patients on hemodialysis, possibly due to the better residual renal function in these patients [44, 45]. But whether peritoneal dialysis is able to clear circulating FGF21 is still unknown.…”

“…However, these correlations seem to depend on the diabetic state and CKD stage. Similarly, FGF21 serum levels correlate positively with inflammatory markers such as IL-6, hrCRP, β-microglobulin and fibrinogen [2, 3, 15, 44, 45, 103–105]. …”

“…Over 3 years, with annual measurement of serum FGF21, there was progressive elevation with dialysis vintage, a negative correlation with residual renal function, and a positive correlation with peritoneal protein loss. However, no correlation was observed between serum FGF21 levels and parameters related to glucose metabolism such as HOMA-IR, fasting glycemia and insulin levels [45]. Despite the very high serum FGF21 levels in hemodialysis patients, serial FGF21 measurements over a period of 8 h in 12 nondiabetic HD patients showed that the increment to meal intake or glucose/insulin infusion remains preserved even though in a lower extent than in control patients [46].…”