Cardiac valve calcification in patients on maintenance dialysis. The role of malnutrition-inflammation syndrome, adiposity andcomponents of sarcopenia. A cross-sectional study.

BACKGROUND & AIMS: Cardiac valve calcification (CVC) is a predictor of cardiovascular disease and all-cause mortality in end stage kidney disease (ESKD) patients. Several risk factors are related to CVC in patients with ESKD including traditional ones as well as inflammation, bone mineral disease and malnutrition. Adiposity is associated with dyslipidemia and proinflammatory activity which could predispose for CVC. Sarcopenia or dynapenia is a state common in patients with ESKD. This study aimed to investigate the relationship of adiposity, sarcopenia and malnutrition-inflammation markers with CVC in patients on maintenance hemodialysis. METHODS: CVC in aortic (AVC), mitral valves (MVC) and systolic and diastolic dysfunction (DD) were assessed by using two-dimensional echocardiography. Nutritional, adiposity and anthropometric assessments were made using several indices respectively. Creatinine index and muscle strength measurements were also performed. Biochemical parameters such as total proteins, albumin, calcium, phosphate, plasma lipoproteins, C-Reactive Protein and parathyroid hormone were also measured. RESULTS: Adiposity, nutritional, and sarcopenia parameters did not show any difference between patients with or without CVC. Age ≥ 65 years [PR: 1.47 p = 0.012], DD [PR: 2.31, p = 0.005], high CRP/albumin ratio [PR: 1.46, p = 0.01], mid arm circumference (MAC) < 26 cm [PR: 1.37, p = 0.03] were associated with increased prevalence of AVC, while DD [PR: 1.97 p = 0.02], high CRP/albumin ratio [PR: 1.56, p = 0.02], and MAC < 26 cm [PR: 1.52, p = 0.01], showed positive correlation with MVC. Age ≥ 65 years [PR: 1.33, p = 0.028], DD [PR: 1.72, p = 0.01], high CRP/albumin ratio [PR: 1.53, p = 0.003], and MAC < 26 cm [PR: 1.4, p = 0.006], related to greater prevalence of calcification at any valve. CONCLUSIONS: Ageing, diastolic dysfunction, MAC and increased CRP/albumin ratio were powerful predictors of CVC in patients on hemodialysis.

Creatinine index as a predictive marker of sarcopenia in patients under hemodialysis.

PURPOSE: Sarcopenia is a clinical condition that comprises declined skeletal muscle (SM) mass and SM strength, and is a risk factor for physical disability, impaired quality of life, and advanced morbidity and mortality in patients on hemodialysis (HD). The existing difficulty in evaluating SM mass and consequently of sarcopenia, with affordable and practical methods in clinical practice, is well established. The purpose of this study is to examine the creatinine index (CrI), a surrogate of SM mass, as a potential predictive marker of sarcopenia. METHODS: In this cross-sectional study, we included 130 patients on HD with a mean age of 66.17 ± 12.47 years. SM mass and SM strength were evaluated with CrI and hand grip strength, respectively. Anthropometric, adiposity, nutritional, and biochemical assessments were also performed. Partial correlation and multivariate regression analyses were applied to investigate the association between CrI and SM strength. RESULTS: Correlation analysis showed that mid-arm circumference, calf circumference, Geriatric nutritional index, and albumin-to-total protein ratio were positively associated with SM strength. Multivariate model indicated that CrI (ß = 2.05, p < 0.001) and dialysis duration (ß =- 0.53, p = 0.001) were independently related to SM strength. The significant positive correlation between CrI and SM strength remained unaffected even after adjusting for potential confounders. CONCLUSIONS: Creatinine Index was significantly associated with SM strength highlighting its value as a new emerging practical in clinical setting sarcopenia predictive marker in HD patients.

Assessment of serum bioactive hepcidin-25, soluble transferrin receptor and their ratio in predialysis patients: Correlation with the response to intravenous ferric carboxymaltose.

BACKGROUND: No reliable biomarker exists to predict responsiveness to intravenous (IV) iron (Fe) in iron deficient patients with CKD. We aimed to investigate the clinical value of bioactive Hepcidin-25 and soluble Transferrin Receptor (sTfR) levels in predialysis patients. PATIENTS AND METHODS: In this prospective study 78 stable stage III-IV CKD predialysis patients with (responders) (40 patients) and without (non-responders) (38 patients) adequate erythropoiesis after IV administration of ferric-carboxymaltose (FCM). Patients were divided in two groups according to their response to IV administration of ferric-carboxymaltose (FCM). Along with measurements of common hematologic and blood chemistry parameters, determinations of sTfR and bioactive Hepcidin-25 were performed. RESULTS: Hepcidin-25 levels were lower in the responders (p=0.025), while sTfR and sTfR/Hepcidin-25 ratio were higher (p<0.01 and p=0.002 respectively). Diagnostic efficacy indicated cut off point of 1.49 for Hepcidin-25 had sensitivity 84% and specificity 48%, while cut off point of 1.21 for sTfR/Hepcidin-25 ratio had sensitivity 82% and specificity 52% to predict correctly response to iron supplementation therapy. Furthermore, log sTfR/Hepcidin-25 correlated negatively with hs-CRP (p=0.005) and IL-6 (p<0.04) in non-responders, while such correlations were not found in responders (p>0.05). CONCLUSIONS: These results suggest that lower Hepcidin-25, as well as higher sTfR and sTfR/Hepcidin-25 ratio were significant predictors of favorable hemoglobin response within a month after IV administration of FCM in patients with CKD. Further experiments and clinical studies in other groups of patients are needed to better elucidate the role of Hepcidin-25 and sTfR/Hepcidin-25 ratio as predictors of response to intravenous iron administration.

Spironolactone improves endothelial and cardiac autonomic function in non heart failure hemodialysis patients.

OBJECTIVES: Hemodialysis patients have a cardiovascular mortality rate of 20-40 times that of the general population. Aldosterone inhibition by spironolactone has exerted beneficial, prognostically significant cardiovascular effects in patients with heart failure maintained on hemodialysis or peritoneal dialysis. Our aim was to investigate spironolactone's effect in non heart failure hemodialysis patients. METHODS: Fourteen stable chronic hemodialysis patients (nine men), 59.5 ±â€Š3.1 years of age were evaluated in a sequential, fixed-dose, placebo-controlled study. Heart failure was diagnosed on the basis of signs and symptoms of heart failure or left ventricular ejection fraction less than 50%. Following an initial 4-month period of placebo administration after each dialysis, patients received spironolactone (25 mg thrice weekly after dialysis) for the next 4 months. Data were recorded at baseline, at the end of placebo administration, and at the end of spironolactone treatment and included endothelial function by forearm reactive hyperemia during venous occlusion plethysmography, cardiac autonomic status by heart rate variability in the time and frequency domain, blood pressure response, and echocardiographic and laboratory data. RESULTS: Placebo induced no changes in the aforementioned parameters. Following spironolactone, salutary effects were observed in the extent and duration of reactive hyperemia (P < 0.05 for both), as well as in heart rate variability (P < 0.05) and blood pressure control (P < 0.05). No changes occurred in echocardiographically derived left ventricular dimensions or mass. CONCLUSION: Low-dose spironolactone therapy in clinically stable non heart failure hemodialysis patients is associated with favorable effects on cardiovascular parameters known to adversely affect survival, such as endothelial dysfunction and heart rate variability. Spironolactone treatment might benefit long-term cardiovascular outcome of such patients.