The effect of active vitamin D administration on muscle mass in hemodialysis patients.

BACKGROUND: Muscle wasting is common and insidious in end-stage renal disease (ESRD). Loss of muscle quantity and quality reduces quality of life and increases mortality in ESRD patients. Additionally, secondary hyperparathyroidism (SHPT) causes muscle atrophy. Meanwhile, vitamin D, which is used for SHPT treatment, plays an essential role in muscle growth. OBJECTIVES: We prospectively investigated the effect of active vitamin D administration on muscle mass. METHODS: We measured muscle mass based on bioelectrical impedance analysis in 68 hemodialysis patients. Patients were divided into a control group (without active vitamin D administration) and a VitD group (with active vitamin D administration). We compared muscle mass at the beginning of treatment and 1 year later. We also investigated health-related quality of life (HR-QOL) using the Medical Outcome Study Short Form-36 (SF-36). RESULTS: The VitD group experienced a significant increase in the amount of change in total muscle mass and muscle mass percentage in men (p = 0.025) but not in women (p = 0.945). By multivariable logistic regression analysis, active vitamin D administration was independently associated with increased muscle mass percentage in men only. In the SF-36, the physical functioning (PF) scores were significantly decreased at the end of the study in the patients without active vitamin D treatment, especially in women. CONCLUSION: Our results suggested that active vitamin D treatment was associated with increased muscle mass in men, and it might have a favorable effect on maintaining PF in HR-QOL in hemodialysis patients.

A case of acute kidney injury with marked hyperuricemia during mizoribine administration.

A 52-year-old woman was diagnosed with Blau syndrome and rheumatoid arthritis and was treated with prednisolone and methotrexate. Joint pain and skin ulcers were poorly controlled; therefore, mizoribine (MZ; 150 mg/day) was administered once daily from March 2011. In early July 2011, the patient was hospitalized because of acute kidney injury (AKI) and acute pancreatitis. We reasoned that AKI resulted from hyperuricemia during MZ administration because serum concentrations of uric acid (31.6 mg/dL) and MZ (trough level, 5.14 µg/mL) were markedly elevated on admission. MZ should be administered with caution because of the risk of marked hyperuricemia leading to AKI.

Identification of a novel mutation and prevalence study for fabry disease in Japanese dialysis patients.

Fabry disease--a genetic disorder characterized by the accumulation of globotriaosylceramide in cell lysosomes resulting from an X-linked deficiency of α-galactosidase A activity--presents with multiorgan manifestations, including progressive renal disease. Recently, its prevalence has been reported to be higher in hemodialysis (HD) patients than in the general population. We, therefore, examined patients on maintenance dialysis living in the Nagasaki Prefecture, Japan, to clarify the prevalence of Fabry disease. We screened 933 patients on maintenance dialysis, who were residents of Nagasaki Prefecture in Japan, for α-galactosidase A activity using a dried blood spot on filter paper. Patients with low α-galactosidase A activity were clinically assessed; subsequently, genetic analysis of the α-Galactosidase A gene (MIM:30064) was performed in these patients. Of the 933 patients, 55 had low α-galactosidase A activity; of these, one male and two females had α-Galactosidase A mutations. The prevalence of Fabry disease was thus 0.32%, which was similar to that reported previously. However, one mutation was newly identified, while the E66Q mutation observed in two patients was as previously identified. These two patients with the E66Q mutation were excluded because of the possibility of polymorphism; the prevalence of Fabry disease in the HD population was finally calculated to be 0.11%. The prevalence of Fabry disease in patients on maintenance dialysis living in Nagasaki Prefecture was 0.32%. Dried blood spot screening was considered as a simple and effective method for screening patients on maintenance dialysis for Fabry disease.

Serum pro-hepcidin level and iron homeostasis in Japanese dialysis patients with erythropoietin (EPO)-resistant anemia.

BACKGROUND: Resistance to EPO therapy in hemodialysis (HD) patients is ascribed to inflammation and iron deficiency. Hepcidin, an antimicrobial peptide, is a key regulator of iron metabolism and synthesis of hepcidin is regulated by iron status and inflammation. The role of hepcidin in the pathogenesis of EPO-resistant anemia was assessed through measurement of serum pro-hepcidin in HD patients. MATERIAL/METHODS: Serum pro-hepcidin was measured by ELISA in 57 HD patients, who were divided into three groups: Group I (n=19) had EPO-resistance anemia, based on serum ferritin of > or =100 ng/ml and EPO dose (9,000 IU/week maximum dose for 6 months); Group II (n=19) had iron-deficiency anemia, based on serum ferritin of <100 ng/ml and/or <20% transferrin iron saturation (TSAT); and Group III (n=19) had no iron deficiency and anemia. Nineteen age- and sex-matched healthy volunteers were enrolled as controls (Group IV). RESULTS: Serum pro-hepcidin was significantly lower in Group II than in other groups. In Group I, serum pro-hepcidin did not differ significantly from controls. Serum levels of ferritin, hs-CRP and IL-6 were higher in Group I than in other groups, and serum sTfR was higher in Groups I and II than in controls. CONCLUSIONS: In EPO resistant anemia, multiple factors, including iron and inflammation related conditions, are likely to affect the level of hepcidin and this may explain the lack of elevated serum hepcidin in this condition.

Plasma concentrations of adrenomedullin and ghrelin in hemodialysis patients with sustained and episodic hypotension.

Sustained and/or episodic hypotension during hemodialysis (HD) is an important clinical issue. Plasma adrenomedullin (AM) is increased in HD patients with sustained hypotension, but little is known about its implications for episodic hypotension. Ghrelin may also contribute to the pathophysiology of hypotension in HD patients. We evaluated plasma levels of AM and total ghrelin in sustained hypotensive (SH; n = 23), episodic hypotensive (EH; n = 30) and normotensive (NT; n = 23) HD patients. In the EH group, the relationship between low blood pressure during HD and circulating levels of AM and ghrelin was also evaluated. Plasma levels of AM were significantly higher in SH (34.3 +/- 8.3 fmol/ml, p<0.01) than in NT patients (27.6 +/- 5.2 fmol/ml), but not in EH patients (30.8 +/- 6.1 fmol/ml). There was no significant difference of plasma total ghrelin in SH (548.1 +/- 426.5 fmol/ml) and in EH patients (544.6 +/- 174.3 fmol/ml), compared with NT patients (400.0 +/- 219.7 fmol/ml). On the other hand, in EH patients, the "suppressed blood pressure ratio" during HD significantly correlated with plasma AM (r = 0.77, p<0.001) and with total ghrelin levels (r = 0.44, p<0.05). Our results suggest that ghrelin, as well as AM, may play an important role as vasodilator local hormones and regulation of blood pressure during HD, especially the occurrence of EH. Further studies are necessary to clarify the implication of these hormones in the control of hypotension during HD.