Truncal Adiposity Influences High-Density Lipoprotein Cholesterol Levels and Cardiovascular Events in Hemodialysis Patients.

OBJECTIVE: Adiposity influences lipid metabolism and atherosclerotic cardiovascular disease (CVD) in the general population. The aim of the present study was to assess the association between fat mass (FM) and lipid metabolism and CVD events among patients on hemodialysis (HD). METHODS: This prospective observational study examined 240 patients on prevalent HD. Blood samples were obtained before dialysis at baseline to measure lipids, high-sensitivity C-reactive protein (hs-CRP), interleukin-6, and adiponectin. Lipids and hs-CRP were measured every 3 months for 12 months. FM was estimated by dual energy x-ray absorptiometric scan at baseline and 12 months later. Patients were then prospectively followed up for 36 months after the 1-year measurement period, and composite CVD events were estimated. RESULTS: Truncal FM was positively correlated with body mass index, hs-CRP, interleukin-6, total cholesterol, low-density lipoprotein-C, triglyceride, and negatively correlated with high-density lipoprotein (HDL)-C and adiponectin at baseline. HDL-C levels were repeatedly decreased, and triglyceride and non-HDL-C were serially increased in the patient group with truncal FM > 7,000 g at both baseline and 12 months (large truncal FM group) compared with the other groups. Cox proportional hazards models adjusted for confounders showed composite CVD events occurred significantly in patients with large truncal FM and continuous low HDL-C levels. CONCLUSIONS: Truncal adiposity influences lipid metabolism in patients on HD, and the prevalence of CVD events may be increased in those patients with high fat and lipid abnormalities, especially continuously low HDL-C levels.

Fasting for 3 days during the suckling-weaning transient period in male rats induces metabolic abnormalities in the liver and is associated with impaired glucose tolerance in adulthood.

PURPOSE: Recent studies suggest that nutritional status during developmental periods is associated with subsequent development of metabolic abnormalities. In this study, we examined whether malnutrition by fasting for 3 days during the suckling-weaning transient period induces subsequent development of metabolic abnormalities in rats. METHODS: Male Sprague-Dawley rats were fasted for 3 days during the suckling-weaning transient period. They are subsequently fed a high-fat, high-sucrose (HF) or low-fat, high-starch (LF) diet for 14 weeks from 17 weeks of age, and the liver and blood samples were collected for measuring mRNA and protein levels of metabolic genes and blood concentrations of glucose and insulin, respectively. RESULTS: Fasting for 3 days during the suckling-weaning transient period induced impaired glucose tolerance in rats fed the LF diet in adulthood. Liver triglycerides in rats fed the HF diet in adulthood increased to 140 % in rats fasted for 3 days during the suckling-weaning transient period compared with those non-fasted. Furthermore, liver expression of FBP1 and ACCα genes in adult rats fed the LF diet increased to 125 and 145 %, respectively, in rats fasted for 3 days during the suckling-weaning transient period compared to non-fasted rats. PEPCK1 protein expression levels in rats fed the LF diet were higher in rats fasted for 3 days during the suckling-weaning transient period than in non-fasted rats. CONCLUSION: Fasting for 3 days in rats during the suckling-weaning transient period enhances metabolic abnormalities in animals fed a HF or LF diet in adulthood by confounding metabolism of lipid and sugar in the liver.

Combination Therapy of Denosumab and Calcitriol for a Renal Transplant Recipient with Severe Bone Loss due to Therapy-Resistant Hyperparathyroidism.

Denosumab (DMAb), a complete human type monoclonal antibody directed against the receptor activator of nuclear factor-κB ligand, has gained attention as a novel treatment for osteoporosis. However, its efficacy in patients with chronic kidney disease (CKD) remains unclear. We describe a 64-year-old man with severe bone loss and persistent secondary hyperparathyroidism (SHPT) after renal transplantation, whose condition failed to respond to conventional pharmacologic or surgical interventions. He underwent parathyroidectomy with left forearm autograft of crushed tiny parathyroid gland (PTG) particles. However, the autografted PTGs became swollen and caused persistent SHPT in spite of two additional parathyroidectomies of the left forearm. A single subcutaneous administration of DMAb induced hypocalcemia, which was corrected by calcium supplementation and high-dose calcitriol. Eventually, combination therapy with DMAb and calcitriol led to a decline in the patient's elevated serum parathyroid hormone levels, normalization of laboratory markers of bone metabolism, and improvement in bone mineral density in a short period of time. To the best of our knowledge, this is the first case report of severe bone loss with persistent SHPT in a renal transplant recipient effectively treated with the combination therapy of DMAb and vitamin D (VD). Although DMAb itself exerts no direct effects on PTGs, the DMAb treatment improved the patient's bone loss. In addition, administration of DMAb allowed for high-dose VD therapy which ultimately controlled SHPT and prevented DMAb-induced hypocalcemia. Therefore, this combination therapy might be a reasonable therapeutic strategy to reverse severe bone loss due to therapy-resistant SHPT in patients with CKD.

Membranous glomerulonephropathy in a patient with bullous pemphigoid.

Bullous pemphigoid (BP) is a common autoimmune blistering disease that can be complicated by autoimmune disorders. We describe a patient with BP who developed membranous glomerulonephropathy (MN). Proteinuria decreased during the clinical course as anti-BP180 antibody titers decreased. This finding suggested an association between the pathogenesis of these two diseases in terms of immunological disorders.

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

A recent study demonstrated the association between inflammation, iron metabolism and fibroblast growth factor (FGF) 23. The present clinical study aimed to assess associations between anemia, iron metabolism and FGF23 in hemodialysis (HD) patients. This prospective observational study examined a cohort of prevalent HD patients (n = 282). Blood samples were obtained before dialysis sessions to measure baseline levels of hemoglobin (Hb), transferrin saturation (TSAT), ferritin, albumin-adjusted calcium (Ca), phosphate (P), intact (i)-PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact (i)-FGF23, high sensitive (hs)-CRP, and interleukin-6. After the baseline measurement, study patients were followed-up for 6 months. Biochemical measurements were subsequently performed at 1 (Hb), 2 (TSAT and ferritin) or 3 (Ca, P and hs-CRP) month intervals. Doses of ESAs and intravenous iron supplementation during the study period were recorded. i-FGF23 was positively correlated with Ca, P, i-PTH and inversely correlated with TSAT and ferritin. However, levels of Hb and hs-CRP and doses of ESAs during the study period did not differ among the i-FGF23 tertiles, with levels of ferritin and TSAT in the higher i-FGF23 tertile being consistently lower than in the middle to lower i-FGF23 tertiles. Multivariate repeated measures analysis indicated that the higher i-FGF23 tertile was independently associated with repeated measurements of ferritin, but not of TSAT. Doses of intravenous iron supplementation were significantly increased in the higher i-FGF23 tertile in multivariate models. In conclusion, high i-FGF23 levels may be associated with prolongation of low levels of ferritin, resulting in increased usages of iron supplementation in HD patients.

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

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.

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

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.

Light-Chain Deposition Disease Successfully Treated with Bortezomib in an Elderly Patient: A Case Report and Review of the Literature.

We herein report the case of an elderly patient with light-chain deposition disease (LCDD) successfully treated with bortezomib. An 83-year-old woman was admitted because of nephrotic syndrome. She was diagnosed to have monoclonal gammopathy of undetermined significance (IgG-κ type) and LCDD, on the basis of serum and urinary immunoelectrophoresis and renal biopsy. She responded to a modified regimen of bortezomib-based chemotherapy with disappearance of proteinuria without any adverse effects. According to a literature review of 16 cases, including the present case, bortezomib-based chemotherapy appears to be a convincing strategy for the treatment of LCDD even in elderly patients.