Intravenous iron affects serum levels of intact fibroblast growth factor-23 (iFGF23) and its cleavage product c-terminal FGF23 (cFGF23) in iron-deficient people with normal renal function. We hypothesized that intravenous iron modulates iFGF23 and cFGF23 in haemodialysis patients differently according to the type of iron used. Prevalent, stable haemodialysis patients requiring protocol-based intravenous iron therapy were randomized to a single 200 mg dose of either ferric carboxymaltose (FCM) or iron sucrose (IS). The primary outcome was change in iFGF23 and cFGF23 from pre-infusion to Day 2 post-infusion. Serum hepcidin, ferritin and phosphate were also measured. Pair-wise comparisons utilised the Wilcoxon rank sum test; linear mixed models with an interaction term for treatment and time evaluated between-group effects. Forty-two participants completed the study. In those randomized to FCM (n = 22), median (interquartile range) values pre-infusion and Day 2, respectively, were 843 pg/mL (313–1922) and 576 pg/mL (356–1296, p = 0.05) for iFGF23, 704RU/mL (475–1204) and 813RU/mL (267–1156, p = 0.04) for cFGF23, and 1.53 mmol/L (1.14–1.71) and 1.37 (1.05–1.67, p = 0.03) for phosphate. These parameters did not change following IS. Both serum ferritin (p < 0.001) and hepcidin (p < 0.001) increased in both groups, and the increase in hepcidin was greater in the FCM group (p = 0.03 for between-group difference). Contrary to iron-deficient people with normal renal function, haemodialysis patients given protocol-driven intravenous FCM demonstrated a fall in iFGF23 and a rise in cFGF23, changes not evident with IS. This suggests a differential effect of intravenous iron treatment according to both formulation and renal function. Australian and New Zealand Clinical Trials Register ACTRN12614000548639 . Registered 22 May 2014 (retrospectively registered).

Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2–4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2–4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD.

B-type natriuretic peptide (BNP) concentration predicts outcome in patients undergoing dialysis. Because survival and cardiovascular risk change across the CKD continuum, serial changes in BNP were compared in patients at different CKD stages and after kidney transplantation. Patients with CKD stages 3 and 4 (CKD 3-4), dialysis patients, and kidney transplant recipients (KTRs) from one center had two measurements of BNP taken a median of 161 days apart in 2003-2004 and were followed until July 2012. Both BNP-32 (Triage BNP; Biosite Diagnostics) and NT-BNP-76 (proBNP; Roche Diagnostics) were assayed. The interaction between change in log-transformed BNP concentration over time and patient group was tested by fitting regression models on panel data with random effects. Survival after the second measurement was compared by tertile of change in BNP. Patients with CKD 3-4 (n=48), dialysis patients (n=102), and KTRs (n=73) were followed for a median of 5.7, 4.8, and 5.9 years, respectively. The interaction between patient group and BNP measurements over time was significant for NT-BNP-76 (P<0.001) and BNP-32 (P<0.01). Median NT-BNP-76 increased in dialysis patients and those with CKD 3-4 from 3850 pg/ml (interquartile range [IQR], 1776-12,323 pg/ml) to 18,830 pg/ml (IQR, 6114-61,009 pg/ml; P<0.001) and from 698 pg/ml (IQR, 283-2922 pg/ml) to 2529 pg/ml (IQR, 347-9277 pg/ml; P=0.002), respectively. Change was not significant for KTRs or comparisons made with BNP-32. Survival rate was significantly lower for patients with the highest tertile of change in NT-BNP-76 among patients with CKD 3-4 (P=0.02), but not in the dialysis or KTR groups. In 11 patients who received a kidney transplant during the study, median NT-BNP-76 decreased from 9607 pg/ml (IQR, 2292-31,282 pg/ml) to 457 pg/ml (IQR, 203-863 pg/ml) after transplant (P<0.01). The temporal trajectory of BNP differs between dialysis patients and those with CKD 3-4 and KTRs. This has important implications for the development of BNP-guided management strategies in CKD.