SAHA Suppresses Peritoneal Fibrosis in Mice

Objective: Long-term peritoneal dialysis causes peritoneal fibrosis in submesothelial areas. However, the mechanism of peritoneal fibrosis is unclear. Epigenetics is the mechanism to induce heritable changes without any changes in DNA sequences. Among epigenetic modifications, histone acetylation leads to the transcriptional activation of genes. Recent studies indicate that histone acetylation is involved in the progression of fibrosis. Therefore, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on the progression of peritoneal fibrosis in mice. Methods: Peritoneal fibrosis was induced by the injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. SAHA, or a dimethylsulfoxide and saline vehicle, was administered subcutaneously every day from the start of the CG injections for 3 weeks. Morphologic peritoneal changes were assessed by Masson’s trichrome staining, and fibrosis-associated factors were assessed by immunohistochemistry. Results: In CG-injected mice, a marked thickening of the submesothelial compact zone was observed. In contrast, the administration of SAHA suppressed the progression of submesothelial thickening and type III collagen accumulation in CG-injected mice. The numbers of fibroblast-specific protein-1?positive cells and α-smooth muscle actin α?positive cells were significantly decreased in the CG + SAHA group compared to that of the CG group. The level of histone acetylation was reduced in the peritoneum of the CG group, whereas it was increased in the CG +SAHA group. Conclusions: Our results indicate that SAHA can suppress peritoneal thickening and fibrosis in mice through up-regulation of histone acetylation. These results suggest that SAHA may have therapeutic potential for treating peritoneal fibrosis

A case of reversible posterior leukoencephalopathy syndrome in a patient on peritoneal dialysis.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently identified clinical and radiologic entity. The characteristic radiologic findings are bilateral gray and white matter edema in the posterior regions of the cerebral hemispheres. The typical clinical syndrome includes headache, confusion, visual symptoms, and seizures. RPLS most often occurs in the setting of hypertensive crisis, preeclampsia, or with cytotoxic immunosuppressive therapy, but many other clinical settings are described, such as cryoglobulinemia, hemolytic uremic syndrome, systemic lupus erythematosus, and use of erythropoietin. A 24-year-old man, diagnosed as having anaphylactoid purpura nephritis at 12 years of age and who started peritoneal dialysis (PD) at 23 years of age, was admitted to our hospital with a seizure and consciousness disturbance. His blood pressure (BP) and body fluid volume had not been controlled well because of poor compliance with medication and PD. T2-weighted magnetic resonance imaging (MRI) revealed high signal intensity changes restricted to the cortex and subcortical white matter of the cerebellum. On the other hand, diffusion-weighted imaging showed an isointense signal. From these findings, he was diagnosed as having RPLS. With appropriate control of BP and volume control by PD and hemodialysis, his symptoms improved, and a follow-up cranial MRI 1 month later was almost normal. To the best of our knowledge, this is the first report of RPLS in an adult PD patient

Significance of subepithelial deposits in patients diagnosed with IgA nephropathy

Subepithelial deposits are observed in rare adult IgA nephropathy (IgAN) cases and are a key diagnostic finding in IgA-dominant infection-related glomerulonephritis (IgA-IRGN). Sometimes, it is difficult to distinguish IgA-IRGN from IgAN without a precise clinical history. We hypothesized that some IgA-IRGN cases might be diagnosed as IgAN with subepithelial deposits (IgAN-SD) and aimed to clarify the significance of subepithelial deposits in patients diagnosed with IgAN. We examined 464 patients diagnosed with IgAN at Nagasaki University Hospital and affiliated hospitals between 1996 and 2013. The differences in clinicopathological findings between IgAN-SD and IgAN with no subepithelial deposits (IgAN-NSD) were investigated.In addition to clinical data and typical IgAN pathological features, we analyzed complement levels, immunoglobulin localization, light chain staining patterns, and intramembranous deposits. There were 214 men and 250 women with a mean age of 38.8 ± 18.3 years. Subepithelial deposition was observed in 51 patients (11%). Compared to patients with IgAN-NSD, those with IgAN-SD had significantly lower mean serum protein (6.4 g/dL vs. 6.7 g/dL; p = 0.02), albumin (3.7 g/dL vs. 3.9 g/dL; p = 0.02), and complement (C3) (94 mg/dL vs. 103 mg/dL; p = 0.02) levels.Diffuse mesangial hypercellularity (M) (65% vs. 45%; p<0.01), endocapillary hypercellularity: (E) (43% vs. 28%; p = 0.03),and IgA staining in the glomerular capillary wall (22% vs. 8%; p<0.01) were more common in patients with IgAN-SD. The incidence of light chain lambda predominance was lower in patients with IgAN-SD (47% vs. 63%; p = 0.03). Hump-shaped subepithelial deposits and intramembranous deposits were observed in nine and 17 patients with IgAN-SD, respectively. Patients with IgAN-SD tended to have the characteristics of IgA-IRGN rather than IgAN-NSD.Since the therapeutic strategies for IgA-IRGN differ from those for IgAN, we should review the clinical history and pay careful attention to the clinical course in cases with atypical findings, such as subepithelial deposits

Effectiveness of music therapy for alleviating pain during haemodialysis access cannulation for patients undergoing haemodialysis: a multi-facility, single-blind, randomised controlled trial

Background: Repeated pain during haemodialysis access cannulations is a serious problem for haemodialysis patients even when prescribed oral or topical analgesics. Although some studies have observed the efficacy of music therapy for improving pain and anxiety, its effectiveness during haemodialysis access cannulations during dialysis is uncertain. The purpose of this study is to investigate the effects of music therapy for pain when cannulating haemodialysis access for haemodialysis patients. Methods: A prospective, multi-facility, single-blind, crossover, randomised controlled trial will be implemented. The intervention includes listening to Mozart, along with a white noise control condition. One hundred twenty haemodialysis patients will be enrolled across five facilities. Patients will be randomly allocated to either an Early-sequence group or a Later-sequence group. The Early-sequence group will receive cannulation while listening to Mozart\u27s Sonata for two pianos in D major (K.448) during the second week (Music period) and white noise during the fourth week (White noise period). The Later-sequence group will receive cannulation along with white noise first, followed by Mozart. All patients will also undergo cannulation during a no-sound period (wearing only headphones) during the first and third week (No-sound period). The music or no-music protocol will begin 8 min prior to the cannulating procedure, and participants will finish listening after starting haemodialysis during each period. The primary outcomes that will be assessed include the Visual Analogue Scale (VAS) score for pain during cannulation, and secondary outcomes are blood pressure, heart rate, VAS anxiety score, State-Trait Anxiety Inventory score, and salivary amylase activity. The operators who are in charge of haemodialysis access cannulation will be blind to the listening condition and VAS report. Discussion: The proposed study has several methodological benefits. First, using white noise is a suitable control condition for addressing the role of sound in pain management. Additionally, using a crossover design with repeated measurements can help control individual differences between participants, which should better distinguish between- and within-participant variability. Overall, music therapy is a safe and inexpensive intervention that does not have the problematic side effects typically associated with pharmacological treatment. If effective, music therapy can be easily implemented for reducing pain and anxiety during cannulation. Trial registration: This trial was prospectively registered to UMIN Clinical Trials Registry on 1 July 2018 (UMIN 000032850)

Importance of feeding status evaluation in older patients undergoing hemodialysis

Older hospitalized patients undergoing hemodialysis are increasingly experiencing malnutrition caused by dysphagia. However, only a few studies have focused on this problem. We used the Kuchikara Taberu Balance Chart (KTBC) to evaluate the patients’ feeding status and examined its association with their nutritional status and prognosis. This study included elderly patients undergoing hemodialysis who were hospitalized at Nagasaki Renal Center for > 3 days between June 2021 and February 2022. In total, 82 inpatients were included [mean age, 73.4 ± 10.0 years; men, 57.3%; median dialysis vintage, 79.0 months (interquartile range, 37.3–164.8)]. We classified patients with lower than the median KTBC score (57 points) as being at risk for dysphagia; 37 patients (45.1%) were at risk for dysphagia. Spearman’s rank correlation coefficient (ρ) elucidated that the KTBC total score was significantly associated with each nutritional indicator [serum albumin level (ρ = 0.505, p < 0.001); geriatric nutritional risk index (ρ = 0.600, p < 0.001); and nutritional risk index (ρ = -0.566, p < 0.001)]. The KTBC score was also closely associated with the body mass index (ρ = 0.228, p = 0.04). Patients with a lower KTBC score showed poor prognosis (log-rank test: p = 0.001), and age- and sex-adjusted Cox proportional analysis showed that the KTBC score was associated with life prognosis (hazard ratio, 0.90; 95% confidential interval, 0.86–0.94; p < 0.001). Therefore, we concluded that the patients at risk of dysphagia, identified using the KTBC score, were malnourished and had a poor prognosis. Hence, the evaluation of dysphagia using the KTBC is encouraged to prevent malnutrition in vulnerable older patients undergoing hemodialysis

The impact of muscle mass loss and deteriorating physical function on prognosis in patients receiving hemodialysis

Muscle mass loss and worsening physical function are crucial issues in patients receiving hemodialysis (HD). However, few studies have investigated the association between temporal changes in muscle mass and physical function in a large number of HD patients. We examined 286 patients receiving HD (males, 58%; age, 66.8 ± 13.0 years) at a single center, and calculated the percent changes in psoas muscle mass index (%PMI) using computed tomography over two screenings, once per year (July 2011–June 2013). Physical function was evaluated using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (range 0–4). The observation period was from July 2012 to June 2021. The median %PMI was -9.5%, and those with the lowest quartile of %PMI (< −20.5%) showed a significantly poor prognosis compared with other patients (p < 0.001). Multivariable logistic regression analysis revealed that these patients tended to have decreased physical function (ECOG-PS 2–4) [odds ratio (OR): 2.46, p < 0.001] and albumin levels (OR: 0.22, p = 0.007). Multiple-factor-adjusted Cox regression analyses showed that %PMI (hazard ratio: 0.99, p = 0.004) and each ECOG-PS stage (1–4 vs. 0) (p < 0.01) were associated with mortality. Augmenting physical activities in daily life and serum albumin levels should be considered to maintain muscle mass and improve the prognosis of patients receiving HD

Evaluation of a renal risk score for Japanese patients with ANCA-associated glomerulonephritis in a multi-center cohort study

Background: In patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, prediction of renal survival should guide the choice of therapy, but a prediction of the histological classification has inconsistencies.Objectives: To evaluate the usefulness of renal risk score (RRS) for Japanese patients with ANCA-associated glomerulonephritis (AAGN) and compare the prediction for end-stage renal disease (ESRD) between RRS and the histological classification.Methods: We retrospectively analyzed 96 patients with AAGN who underwent a renal biopsy. Renal survival was categorized by RRS, and the histological classification was assessed separately. We compared the predictive values for RRS and the histological classification.Results: The median observational period was 37.5 (interquartile range [IQR] 21.5–77.0) months. The median RRS point at the time of renal biopsy was 2 (IQR 0–7.8), and the patients were categorized into low- (n = 29), medium- (n = 43), and high-risk groups (n = 24) using RRS. As expected, the renal prognosis was the worst in the “high-risk” group and the best in the “low-risk” group. In the histological classification, the survival deteriorated progressively from “focal” (best) to “mixed,” “crescentic,” and “sclerotic” (worst) classes, different from the order in the original proposal for this system. Multivariable Cox regression analysis revealed that RRS was independently associated with ESRD. The difference in prediction for renal survival between RRS and the histological classification was not significant using area under receiver-operatingcharacteristic curves.Conclusion: We evaluated the usefulness of RRS in Japanese patients with AAGN and found it a stable predictor of renal survival in such patients

Association between the psoas muscle index and hospitalization for pneumonia in patients undergoing hemodialysis

Background: Although muscle mass loss and pneumonia are common and crucial issues in hemodialysis (HD) patients, few reports have focused on their association, which remains unclear. This study assessed the association between skeletal muscle mass and the incidence of pneumonia in HD patients using the psoas muscle index (PMI).Methods: This retrospective study included 330 patients on HD who were treated at a single center between July 2011 and June 2012. The observation period was between July 2011 and June 2021. Demographic, clinical, and HD data were collected, and the associations between PMI and hospitalization due to bacterial pneumonia were evaluated using Cox proportional hazards models adjusted for patients’ background data. Additionally, the correlation between patient characteristics and PMI was evaluated using multivariable linear regression.Results: Among 330 patients (mean age, 67.3 ± 13.3; 56.7% male; median dialysis vintage 58 months, (interquartile range [IQR] 23–124), 79 were hospitalized for pneumonia during the observation period (median observation period was 4.5 years [IQR 2.0–9.1]). The multivariable Cox proportional analysis, which was adjusted for age, sex, dialysis vintage, diabetes mellitus, and stroke history and considered death as a competing risk, indicated that decreased PMI/(standard deviation) was closely associated with the development of pneumonia (hazard ratio: 0.67, 95% confidence interval: 0.47–0.95, p = 0.03).Conclusions: Skeletal muscle mass was associated with the development of pneumonia in patients on HD and could be a useful marker for the risk of pneumonia

A case of a chronic expanding hematoma in a hemodialysis patient

A 70-year-old woman undergoing chronic maintenance hemodialysis had felt a mass in her left hip 4 years prior. As the mass gradually expanded, magnetic resonance imaging (MRI) was performed. The MRI findings showed mosaic patterns with various signal intensities inside the mass and a low-signal band at its periphery. Because of the slow expansion of the mass over a course of at least 4 years and its characteristic MRI findings, the patient was diagnosed with a chronic expanding hematoma (CEH), a comparatively rare type of hematoma. To our knowledge, this is the first report of a CEH occurring in a hemodialysis patient in the English literature

Association between serum calcium levels and prognosis, hematoma volume, and onset of cerebral hemorrhage in patients undergoing hemodialysis

Background: High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient\u27s prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage. Methods: This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis. Results: Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43-4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50-10.4; P = 0.005)had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07-2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23-1.59; P < 0.001). Conclusions: Although the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient\u27s calcium level