Synergistic deterioration of prognosis associated with decreased grip strength and hyporesponse to erythropoiesis-stimulating agents in patients undergoing hemodialysis.

INTRODUCTION: We examined the combined effect of erythropoietin (EPO) hyporesponsiveness and low handgrip strength (HGS) on the prognosis of patients undergoing hemodialysis (HD). METHODS: We recruited patients with chronic kidney disease (CKD) Stage 5, who were undergoing HD at our dialysis clinic between January 2015 and March 2015 (n = 182). Patients of ≥20 years of age and who had been undergoing HD for ≧3 months at enrollment were eligible for inclusion. Seven patients treated with epoetin-ß pegol were excluded. First, the erythropoietin resistance index (ERI) and HGS were measured. The patients were stratified by the ERI of 9.44 (U/kg/week/g/dL), and by the HGS of 28 kg for men and 18 kg for women. We then observed death and cardiovascular disease (CVD), composite endpoint (deaths or CVD) for a median of 2 years. RESULTS: A total of 175 patients (male, n = 122; female, n = 53; age, 34-92 years) were included in the analysis. During the observation period of 24 months, 57 events (14 deaths and 43 CVD) were observed. High ERI and low HGS were associated with a high incidence of endpoints compared to low ERI and high HGS. Among the four groups classified by ERI and HGS values, the highest risk group was the high ERI/low HGS group (HR: 4.20 95% CI 2.12-8.33). CONCLUSIONS: EPO hyporesponsiveness combined with low HGS were found to be significant predictors of a poor outcome, and the synergistic effects of the two factors had stronger predictive ability than either single factor.

Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study.

BACKGROUND: Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients. METHODS: Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient's self-report during the one-year period. RESULTS: Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22-4.52], P < 0.05). Receiver operating characteristic curves were constructed to determine the optimal cutoffs of quadriceps muscle thickness, thigh circumference, and handgrip strength that best predicted fall injury (quadriceps muscle thickness, 3.37 cm and 3.54 cm in men and women; thigh circumference, 44.6 cm and 37.2 cm in men and women; and handgrip strength, 23.3 kg and 16.5 kg in men and women). Using these cutoff values, the areas under the curve were 0.662 (95% CI, 0.576-0.738), 0.625 (95% CI, 0.545-0.699), and 0.701 (95% CI, 0.617-0.774), for quadriceps muscle thickness, thigh circumference, and handgrip strength, respectively. Quadriceps muscle thickness was a more precise predictor of fall injury than thigh circumference and had similar diagnostic performance as handgrip strength tests in dialysis patients. CONCLUSIONS: Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.

Association of gait speed and grip strength with risk of cardiovascular events in patients on haemodialysis: a prospective study.

BACKGROUND: Gait speed (GS) and handgrip strength (HGS), both factors associated with frailty and sarcopenia, are reportedly associated with CV events in the general population. However, little is known about the impact of these factors on the outcome of patients on dialysis. This study aimed to evaluate whether evaluation of GS and HGS could be associated the onset of fatal/non-fatal cardiovascular (CV) events in patients on haemodialysis (HD). METHODS: One-hundred-eighty-two patients with end-stage renal disease (ESRD) undergoing HD at four dialysis clinics in April 2015 provided written informed consent to participate in the study. We excluded patients who had physical disability, were unable to walk without help, or had recently experienced CV events. Usual GS over a 4-m walk and HGS were measured at baseline, and 173 patients (men, 124; women, 49) were divided into sex-specific quartiles according to GS and HGS and were followed-up for fatal/non-fatal CV events for a median of 2 years. We examined the association of GS and HGS with CV events and determined cut-off values using Cox regression analysis adjusted for age, sex, HD duration, history of CVD, and diabetes. RESULTS: During the follow-up period, 46 CV events occurred. Both physical performance factors were significantly associated with CV events. Low GS (< 0.82 m/s for men and 0.81 m/s for women) and weak HGS (< 29.0 kg for men and 19.7 kg for women) were associated with CV events. For low vs. high GS, the hazard ratio (HR) for CV events was 2.29 [95% confidence interval (CI): 1.20-4.33; P = 0.01], and for low vs. high HGS, the HR was 2.15 [95% CI: 1.00-5.04; P < 0.05]. These HRs remained significant after adjusting for confounding factors, such as sex, age, dialysis vintage, history of CV disease, and diabetes. CONCLUSIONS: Slow GS and weak HGS in patients on HD were suggested to be independent predictors of fatal/non-fatal CV events.

Correction: Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients.

[This corrects the article DOI: 10.1371/journal.pone.0201662.].

Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients.

BACKGROUND: While iron deficiency (ID) is a frequent cause of anemia in hemodialysis patients, the clinical impact of ID without anemic level of hemoglobin remains unclear. As such, this study was designed to clarify the manifestations of ID itself in subjects on hemodialysis. METHODS: Maintenance hemodialysis patients achieving target hemoglobin levels (≥ 10.0g/dL) under treatment in our clinic were stratified for comparison from three perspectives: ID (transferrin saturation [TSAT] < 20% or ferritin < 100ng/mL) vs non-ID, level of TSAT (< or ≥ 20%), and level of serum ferritin concentration (< or ≥ 100ng/mL). The severity of frequent symptoms was determined by a self-rating symptom score questionnaire, and the rate of those with severe manifestations was calculated for each symptom. Significant difference was examined between groups; univariate and adjusted multivariate odds ratios and 95% confidence intervals were obtained by logistic regression. RESULTS: Among 154 subjects selected for analysis, the ratio of severe arthralgia and fatigue was significantly higher in the ID group (n = 94) compared to the non-ID group (n = 60), in both univariate and adjusted multivariate analyses. Moreover, in multivariate analysis, low TSAT was significantly associated with exacerbation of pain during vascular access puncture and intradialytic leg cramps, while low serum ferritin concentration was related to significant increase in severe arthralgia, fatigue, intradialytic headache and leg cramps. CONCLUSIONS: ID was identified as a risk factor regarding severity of several symptoms even without low hemoglobin level among chronic hemodialysis patients, and supplementation of iron was considered efficacious for improving critical symptoms affecting those undergoing maintenance dialysis.

Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes.

Recent studies have highlighted the renoprotective effect of sirtuin1 (SIRT1), a deacetylase that contributes to cellular regulation. However, the pathophysiologic role of SIRT1 in podocytes remains unclear. Here, we investigated the function of SIRT1 in podocytes. We first established podocyte-specific Sirt1 knockout (SIRT1(pod-/-)) mice. We then induced glomerular disease by nephrotoxic serum injection. The increase in urinary albumin excretion and BUN and the severity of glomerular injury were all significantly greater in SIRT1(pod-/-) mice than in wild-type mice. Western blot analysis and immunofluorescence showed a significant decrease in podocyte-specific proteins in SIRT1(pod-/-) mice, and electron microscopy showed marked exacerbation of podocyte injury, including actin cytoskeleton derangement in SIRT1(pod-/-) mice compared with wild-type mice. Protamine sulfate-induced podocyte injury was also exacerbated by podocyte-specific SIRT1 deficiency. In vitro, actin cytoskeleton derangement in H2O2-treated podocytes became prominent when the cells were pretreated with SIRT1 inhibitors. Conversely, this H2O2-induced derangement was ameliorated by SIRT1 activation. Furthermore, SIRT1 activation deacetylated the actin-binding and -polymerizing protein cortactin in the nucleus and facilitated deacetylated cortactin localization in the cytoplasm. Cortactin knockdown or inhibition of the nuclear export of cortactin induced actin cytoskeleton derangement and dissociation of cortactin from F-actin, suggesting the necessity of cytoplasmic cortactin for maintenance of the actin cytoskeleton. Taken together, these findings indicate that SIRT1 protects podocytes and prevents glomerular injury by deacetylating cortactin and thereby, maintaining actin cytoskeleton integrity.

[Case of acute primary HIV infection with menigoencephalitis demonstrating high signal intensity of the bilateral globus pallidus in T2-weighted MRI].

A slightly obtunded 59-year-old man admitted for headache and consciousness disturbance after two weeks of fever, sore throat, and general malaise. His cerebrospinal fluid showed a slight increase in the white cell count and protein content. T2-weighted MRI demonstrated high signal intensity of the bilateral globus pallidus. Cerebrospinal fluid culture was negative for fungi and bacteria, including mycobacterium tuberculosis. Negative results for PCR and ELISA made herpes simplex virus encephalitis unlikely. We treated him empirically with aciclovir and cefpirome, conducting further tests because a HIV serological test was positive on admission. HIV RNA was 2.9 x 10(5) copies/ml in the blood. Western blot analysis demonstrated positive bands at gp160, p24, p55, and p68, but negative at gp120, p52, gp41, p40, p34, and p18. These results yielded a definitive diagnosis of acute primary HIV infection presenting as meningoencephalitis. His clinical condition improved over the next few days. Repeated MRI showed a new lesion in the pons on T2-weighted images. No MRI abnormality has reported previously in acute primary HIV infection with meningoencephalitis. High signal intensity in the bilateral globus pallidus and the pons in patients with meningoencephalitis may thus be a useful indicator for acute primary HIV infection.