Background: Apelin, a newly discovered adipocytokine, is produced by white adipose tissue and is also expressed in the kidney and heart. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. Cardiovascular disease is a major contributor to the mortality and morbidity in patients with chronic renal failure. The aim of this study was to assess associations between apelin, coronary artery disease (CAD) and echocardiographic parameters in hemodialyzed patients. Patients and Methods: We investigated plasma apelin levels (using commercially available kits) in 81 nondiabetic, clinically stable hemodialyzed patients (38 females, 43 males) with and without CAD. Results: Patients with CAD were significantly older, with significantly increased left ventricular internal end-diastolic dimension (LVIDd), left ventricular internal end-systolic dimension (LVISd), right ventricle (RV), left atrium (LA), interventricular septum in diastole, left ventricle posterior wall in diastole (LVPW), aorta, pulmonary artery, significantly lower ejection fraction and apelin than patients without CAD. We observed statistically significant correlations between apelin and echocardiographic parameters: LVIDd, LVISd, RV, LA, right atrium, LVPW, aorta, and serum lipids: cholesterol, LDL, triglycerides. In multiple logistic regression analysis, the only associate of apelin was LVIDd. Conclusions: Apelin level was significantly lower in dialyzed patients with CAD and it was associated with cardiac function. Apelin might be involved in the pathophysiology of cardiovascular disease in chronic renal failure. Since apelin is an inotrope in normal and failing hearts, this finding may have clinical implications for future use of apelin as a novel inotropic agent also for patients with uremic cardiomyopathy.

Our preliminary results suggest that renalase, probably due to the sympathetic nervous system hyperactivity, could be associated with hypertension and cardiovascular complications, including stroke in hemodialyzed patients. However, further studies are needed to establish the possible role of renalase in these complications. Renalase is "a new postulated therapeutic target."

Background. The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods. FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400–600 µg/L) or lower (100–200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results. The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions. These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD.

Elevated resistin related to markers of inflammation may represent a novel link between inflammation and adipocytokines in HD patients. Impaired renal function and inflammation are responsible for elevated resistin in HD patients.

Neutrophil gelatinase-associated lipocalin (NGAL) has recently been proved useful in the quantitation of chronic kidney disease. A cross-sectional study was performed to assess NGAL in serum, urine and ultrafiltrate in relation to the type of renal replacement therapy and NGAL correlations with renal function and markers of inflammation. Methods: NGAL, hsCRP, TNFα, and IL-6 were measured using commercially available kits in 200 patients on hemodialysis (HD), 17 on hemodiafiltration (HDF). Results: Patients on HDF had lower serum NGAL than those on HD. In hemodialyzed patients with residual renal function, serum NGAL was significantly lower than in anuric patients. NGAL was significantly higher in patients dialyzed on modified cellulose dialyzers versus polysulphone dialyzers. NGAL correlated with age, residual renal function, hsCRP, IL-6, TNF-α, time on HD, ferritin, TSAT, creatinine, urea, urea reduction ratio, and Kt/V in hemodialyzed patients. In multiple regression analysis, residual renal function and hsCRP were predictors of NGAL in hemodialyzed patients. NGAL correlated with hsCRP and creatinine in HDF patients. Conclusions: Residual renal function seems to play a pivotal role in NGAL levels in dialyzed patients. Low-grade inflammation, more pronounced in anuric patients may also contribute to elevated NGAL. Removal of NGAL with ultrafiltrate may also partially explain its lower concentration after dialysis.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) binds small, iron-carrying molecules – siderophores. On the other hand, hepcidin is a small defensin-like peptide produced by hepatocytes, modulated in response to anaemia, hypoxia, or inflammation. We tested the hypothesis that NGAL may be related to hepcidin, not only to iron metabolism, in 182 prevalent haemodialysed patients. Methods: Iron status (iron, total iron-binding capacity, ferritin, total saturation of transferrin, TSAT), complete blood count, creatinine, albumin, serum lipids were assessed using standard laboratory methods. Soluble receptor of transferrin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, prohepcidin, hepcidin and NGAL were measured in serum using commercially available kits. Results: Serum NGAL, prohepcidin, hepcidin levels were significantly higher in haemodialysed patients over healthy volunteers (579.11 ± 213.95 vs. 78.43 ± 32.21 ng/ml, p < 0.001, 320.54 ± 182.65 vs. 98.65 ± 34.32 ng/ml, p < 0.01, 155.30 ± 94.05 vs. 23.65 ± 12.76 ng/ml, p < 0.001, respectively). Serum NGAL correlated strongly with residual renal function (r = –0.54, p < 0.001), Kt/V (r = 0.41, p < 0.001), hepcidin (r = –0.28, p < 0.01), serum creatinine (r = 0.63, p < 0.001), iron (r = 0.25, p < 0.01), TSAT (r = 0.30, p < 0.001), ferritin (r = 0.33, p < 0.001), hsCRP (r = 0.32, p < 0.001). In multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in haemodialysed patients. Conclusions: NGAL is highly induced in dialysed patients. NGAL could reflect both kidney function and iron metabolism. Taking into account the antimicrobial properties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure.

INTROduCTION Iron metabolism has been studied for many years. New substances involved in iron metabolism continue to be described. Functional iron deficiency (FID) is characterized by the presence of adequate iron stores (as defined by standard criteria) but insufficient iron mobilization required for erythropoiesis during administration of erythropoiesis-stimulating agents. ObjECTIvEs The aim of the study was to evaluate new parameters of iron metabolism and the prevalence of FID as well as to assess potential correlations in patients on hemodialysis (HD). PATIENTs ANd mEThOds The study included 98 patients on maintenance HD. Standard laboratory methods were used to measure the iron status, complete blood count, creatinine, calcium, phosphorus, albumin, intact parathyroid hormone, and lipids. Commercially available kits were used to measure high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor-α, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF15), bone morphogenetic protein (BMP6), hemojuvelin, and hepcidin. REsuLTs FID was present in 23% of the patients on HD and was associated with significantly higher serum ferritin, IL-6, hsCRP, hepcidin, and NT-proBNP levels. There were no significant differences in BMP6 and GDF15 levels between patients with and without FID. Patients on HD had increased prevalence of hypertension, diabetes, and left ventricular hypertrophy and required slightly, but insignificantly, higher erythropoietin doses. Predictors of FID included serum iron levels and residual renal function. CONCLusIONs FID is present in a substantial proportion of patients on HD, who thus should be screened for reversible causes of inflammation. New parameters in iron metabolism do not seem to be related to FID in patients on HD.

Hepcidin is a small defensin-like peptide, the production of which by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Kidneys are involved in not only the synthesis of hepcidin, but they also may be involved in its elimination. A cross-sectional study was performed to assess prohepcidin and hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to type of renal replacement therapy and prohepcidin and hepcidin correlations with renal function, iron status, and markers of inflammation. Methods. Prohepcidin and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using commercially available kits in 102 patients on hemodialyses, 17 on hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers. Results. In hemodialyzed and peritoneally dialyzed patients with residual renal function, serum prohepcidin (264.21 ± 95.84 vs. 341.84 ± 90.45 ng/mL, p < 0.01; 142.76 ± 57.87 vs. 238.42 ± 84.32 ng/mL, p < 0.01, respectively) and hepcidin (178.89 ± 89.87 vs. 295.76 ± 129.65 ng/mL, p < 0.01; 108.43 ± 75.49 vs. 186.53 ± 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in anuric patients. In peritoneal effluent, prohepcidin level was significantly higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis, residual renal function, ferritin, and hsCRP were predictors of hepcidin in hemodialyzed patients, while residual renal function and ferritin were predictors of hepcidin in peritoneally dialyzed patients. Conclusions. Residual renal function seems to play a pivotal role in hepcidin levels in dialyzed patients. In addition, the presence of low-grade inflammation, more pronounced in anuric patients, and functional iron deficiency may also contribute to the elevated hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may partially explain its lower concentration in peritoneal dialysis and hemodiafiltration.