N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for Loss of Muscle Mass in Prevalent Hemodialysis Patients

<div><p>Protein-energy wasting (PEW) is common in hemodialysis (HD) patients. A recent study demonstrated that a high level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be associated with PEW in those patients. This prospective study aimed to assess the association of NT-proBNP with body composition and muscle loss. A cohort of prevalent HD patients (n = 238) was examined. Blood samples were obtained at baseline to measure high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin and NT-proBNP. Nutritional status and changes in muscle mass were assessed by subjective global assessment, percentage creatinine generation rate (%CGR), creatinine index (CI) and lean body mass (LBM) estimated by dual-energy X-ray absorptiometry (DXA). The %CGR and CI were calculated five times for one year, and DXA was performed at baseline and one year later. Cardiac function was estimated by ultrasonography at baseline. NT-proBNP was significantly higher in HD patients with PEW. High NT-proBNP was associated with cardiac dysfunction, increased levels of hsCRP and IL-6, and serially decreased levels of the indexes for muscle mass. Multiple regression analysis adjusted with confounders showed that NT-proBNP was an independent predictor for decrease in LBM and serial lower levels of %CGR and CI. In conclusion, the present study demonstrated a novel association between NT-proBNP and muscle loss. NT-proBNP may be an independent biomarker for malnutrition in HD patients, especially in patients with muscles loss, regardless of chronic inflammation, cardiac dysfunction, or overhydration.</p></div

Changes in lean body mass over 12 months (mean ± SEM) between the patients in the higher and middle–lower tertiles of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (a), changes in the percent creatinine generation rate between the patients in the higher and middle–lower tertiles of NT-proBNP (b), changes in creatinine index between the patients in the higher and middle–lower tertiles of NT-proBNP (c).

<p>*** P <0.001 between the higher versus middle–lower tertiles at the time point.</p

Patient characteristics and laboratory data at baseline in all patients and patients grouped according to NT-proBNP tertiles.

<p>Patient characteristics and laboratory data at baseline in all patients and patients grouped according to NT-proBNP tertiles.</p

High fibroblast growth factor 23 levels are associated with decreased ferritin levels and increased intravenous iron doses in hemodialysis patients - Fig 1

<p>Changes in hemoglobin (a), transferrin saturation (TSAT) (b), and ferritin (c) over 6 months among intact fibroblast growth factor 23 (i-FGF23) tertiles: closed circle, higher i-FGF23 tertile; open square, middle i-FGF23 tertile; open circle, lower i-FGF23 tertile.</p

Patients’ characteristics.

<p>Patients’ characteristics.</p

Association of intact fibroblast growth factor 23 levels with doses of intravenous ferrotherapy over 24 weeks.

<p>Association of intact fibroblast growth factor 23 levels with doses of intravenous ferrotherapy over 24 weeks.</p

Laboratory findings at baseline.

<p>Laboratory findings at baseline.</p

Associations among apolipoproteins, oxidized high-density lipoprotein and cardiovascular events in patients on hemodialysis

<div><p>Apolipoproteins are associated with survival among patients on hemodialysis (HD), but these associations might be influenced by dysfunctional (oxidized) high-density lipoprotein (HDL). We assessed associations among apolipoproteins and oxidized HDL, mortality and cardiovascular disease (CVD) events in patients on HD. This prospective observational study examined 412 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, apolipoproteins, oxidized LDL, oxidized HDL, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 at baseline, and HDL-C and hs-CRP were measured 12 months later. Patients were then prospectively followed-up (mean, 40 months) and all-cause mortality and composite CVD events were analyzed. Associations between variables at baseline and clinical outcome were assessed by Cox proportional hazards modeling (n = 412) and Cox hazards modeling with a time-varying covariate with HDL-C and hs-CRP (n = 369). Quartiles of apolipoproteins and oxidized HDL were not associated with all-cause mortality. However, Cox proportional hazards models with quartiles of each variable adjusted for confounders and hs-CRP or IL-6 identified apolipoprotein (apo)B-to-apoA-I ratio (apoB/apoA-I) and oxidized HDL, but not apoA-I or apoA-II, as independent risk factors for composite CVD events. These associations were confirmed by Cox proportional hazards modeling with time-varying covariates for hs-CRP. ApoB/apoA-I was independently associated with composite CVD events in 1-standard deviation (SD) increase-of-variables models adjusted for the confounders, oxidized HDL and hs-CRP. However, these associations disappeared from the model adjusted with IL-6 instead of hs-CRP, and oxidized HDL and IL-6 were independently associated with composite CVD events. Findings resembled those from Cox proportional hazards modeling using time-varying covariates with HDL-C adjusted with IL-6. In conclusion, both oxidized HDL and apoB/apoA-I might be associated with CVD events in patients on prevalent HD, while associations of apoB/apoA-I with CVD events differed between models of apoB/apoA-I quartiles and 1-SD increases, and were influenced by IL-6.</p></div

Patient characteristics.

<p>Patient characteristics.</p

Cox hazard models of events associated with composite cardiovascular disease events.

<p>Cox hazard models of events associated with composite cardiovascular disease events.</p