Characteristics of neutralizing antibody titers of the SARS-CoV-2 vaccine in maintenance hemodialysis patients.

AIMS: Hemodialysis patients have high COVID-19 severity and mortality rates. For this high-risk group of hemodialysis patients with SARS-CoV-2 infection, early SARS-CoV-2 vaccination is recommended to prevent infection and severe disease. Thus far, few reports have evaluated COVID-19 antibody titers in hemodialysis patients. In this study, we investigated the time course of antibody titers acquired by vaccination in patients on dialysis. MATERIALS AND METHODS: The anti-SARS-CoV-2 spike protein S1 IgG (anti-SP-IgG) antibody titers were compared between 33 outpatient maintenance hemodialysis patients and 32 age- and sex-matched healthy subjects. Antibody tests were performed at five time points: 6 months after the 2nd vaccination, immediately before the 3rd vaccination (8 months after the 2nd vaccination), and 2 weeks, 1 month, and 3 months after the 3rd vaccination. RESULTS: The dialysis patient group had significantly lower values of anti-SP-IgG antibody titers than the control group 6 months after the 2nd vaccination (433.7 ± 36.24 vs. 650.2 (427.2 - 759.4) (AU/mL), p = 0.006) and immediately before the 3rd vaccination (219.3 (129.4 - 423.4) vs. 443.3 (267.1 - 600.4) (AU/mL), p = 0.034), but no significant differences were observed after the 3rd vaccination (19,000.0 (11,000.0 - 3,6000.0) vs. 23,500.0 (20,250.0 - 29,000.0) (AU/mL), p = 0.538). CONCLUSION: This study confirmed that patients undergoing hemodialysis were proven to have acquired sufficient antibody titers after the vaccination.

Characteristics of Month-by-Month Blood Pressure Variability in Patients on Hemodialysis.

INTRODUCTION: Poor prognosis in hemodialysis (HD) patients is due to the increased prevalence of cardiovascular diseases among them. We previously reported that higher visit-by-visit blood pressure variability is associated with increased cardiovascular mortality in HD patients. This present study aimed to investigate the characteristics of month-by-month blood pressure variability (MMBPV) in these patients. METHODS: A total of 324 maintenance HD patients, who could be followed up for 60 months, were recruited. We used standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM) in pre- and post-dialysis systolic blood pressure (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) as an index of MMBPV. We investigated (1) the reproducibility of MMBPV, (2) relationship between these values and background factors, and (3) association between these values and mortality. RESULTS: MMBPV (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) showed significant reproducibility (intraclass correlation, 0.483 [p < 0.001], 0.553 [p < 0.001], 0.450 [p < 0.001], 0.518 [p < 0.001], 0.456 [p < 0.001], and 0.522 [p < 0.001], respectively). High pre-VIM was associated with high interdialytic weight gain and poor nutritional status. High post-VIM was associated with glucose intolerance, high interdialytic weight gain, and poor nutritional status and associated with high rate of cardiovascular deaths independent of other factors (hazard ratio: 1.104, 95% confidence interval: 1.011-1.207, p = 0.028). CONCLUSION: These data suggested that pre- and post-VIM in HD patients are reproducible and associated with various background factors, and especially post-VIM is independently correlated with cardiovascular mortality. Further studies are necessary to confirm the mechanism of increased post-VIM and clarify whether reducing post-VIM can improve the prognosis of HD patients.

Impact of Abdominal Fat Distribution on Mortality and Its Changes Over Time in Patients Undergoing Hemodialysis: A Prospective Cohort Study.

OBJECTIVE: Measures of fat distribution and visceral fat accumulation maintain a direct association with mortality in the general population. However, among patients undergoing hemodialysis (HD), there are few reports of this association. This study aimed to investigate the impact of computed tomography (CT)-measured abdominal fat levels, including the visceral fat area (VFA) and subcutaneous fat area (SFA), on all-cause mortality in patients undergoing HD and investigate whether there are sex-specific particularities regarding the associations between the abovementioned parameters. METHODS: A total of 258 participants were selected from the population of patients undergoing stable HD. The baseline characteristics were collected by records and interviews. The following variables were assessed at baseline and every year: body mass index, abdominal circumference, VFA, and SFA. Abdominal circumference and body fat distribution were assessed at the level of the umbilicus via CT. All CT scans were performed on a nondialysis day with the subject in a supine position. The primary end point was the 5-year all-cause mortality. RESULTS: This prospective cohort study revealed that age, cardiothoracic ratio, %VFA (VFA/[VFA + SFA]), and albumin were independent predictors of death via multivariable analyses. Regarding the %VFA, its area under the curve (0.599), which did not suffice to predict mortality, was higher than that of VFA, SFA, and body mass index. Also, the effect was recognized mainly in male patients. The %VFA of patients who survived for 60 months increased over time. CONCLUSION: These data suggest that patients (especially men) with a high VFA-to-abdominal fat ratio have a high risk of death. Thus, more attention should be paid to such patients.

Case report of a Japanese patient with chronic renal failure who developed SARS-CoV-2 in a hospital cluster during treatment for acute respiratory failure: An autopsy report.

This article reports a clinical and histopathological perspective which noted not only COVID-19 pneumonia but also exacerbation of chronic renal failure potentially caused by thrombus in the kidney, possibly COVID-19-related lesions. The accumulation of autopsy cases will elucidate the pathogenesis of COVID-19 and aid in the development of effective therapeutics.

Serum soluble (pro)renin receptor level as a prognostic factor in patients undergoing maintenance hemodialysis.

The (pro)renin receptor [(P)RR)] is a multifunctional protein that is cleaved to generate the soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. The serum s(P)RR level is associated with arteriosclerosis, independent of other risk factors, in patients undergoing hemodialysis (HD). This study was conducted to investigate whether the s(P)RR level was associated with new-onset cardiovascular events or malignant diseases and poor prognosis in patients undergoing HD. Overall, 258 patients [70 (61-76) years, 146 males] undergoing maintenance HD were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new-onset cardiovascular events/ malignant diseases and mortality during the follow-up period using Cox proportional hazard analyses. The cumulative incidence of new-onset cardiovascular events (P = 0.009) and deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001-1.083, P = 0.046). The serum s(P)RR level was associated with cardiovascular events and mortality, thus qualifying as a biomarker for identifying patients requiring intensive care.

Association between serum soluble (pro)renin receptor level and worsening of cardiac function in hemodialysis patients: A prospective observational study.

The (pro)renin receptor ((P)RR) is cleaved to generate soluble (P)RR (s(P)RR), which reflects the status of the tissue renin-angiotensin system. Hemodialysis (HD) patients have a poor prognosis due to the increased prevalence of cardiovascular diseases. The present study aimed to investigate whether serum s(P)RR level is associated with the worsening of cardiac function in HD patients. A total of 258 maintenance HD patients were recruited and serum s(P)RR concentration was measured. Background factors in patients who survived (S group) and patients who died (D group) during the 12-month follow-up period and relationships between serum s(P)RR level and changes in cardiac function during the follow-up period in the S group were investigated. The median serum s(P)RR value at baseline was 29.8 ng/ml. Twenty-four patients died during the follow-up period. Cardiothoracic ratio, human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), and E over e-prime were significantly higher in the D group. In the S group, changes in hANP or BNP were significantly greater in the higher serum s(P)RR group than in the lower serum s(P)RR group. High serum s(P)RR level was significantly correlated with changes in BNP, independent of other factors. High serum s(P)RR level was associated with increases in BNP, independent of other risk factors, suggesting that an increased expression of (P)RR may be associated with a progression of heart failure in HD patients and that serum s(P)RR concentration could be used as a biomarker for selecting patients requiring intensive care.

Characteristics of visit-to-visit blood pressure variability in hemodialysis patients.

Visit-to-visit blood pressure variability (VVBPV) is an independent risk factor for cardiovascular morbidity and mortality in the general population. Hemodialysis (HD) patients have a poor prognosis due to an increased prevalence of cardiovascular disease. Intradialytic hypotension is associated with excess mortality, but whether VVBPV influences mortality is still unclear in HD patients. The present study aimed to investigate the characteristics of VVBPV in these patients. A total of 324 maintenance HD patients, who could be followed for 60 months, were recruited. We used variation independent of the mean (VIM) in pre-dialysis systolic blood pressure (pre-VIM-SBP) as an index of VVBPV. We investigated (1) the reproducibility of pre-VIM-SBP, (2) the relationship between pre-VIM-SBP and background factors, and (3) the association between pre-VIM-SBP and mortality. Pre-VIM-SBP showed significant reproducibility [intraclass correlation, 0.45 (P < 0.001)]. Higher pre-VIM-SBP was associated with less physical activity and worse left ventricular diastolic function. Higher pre-VIM-SBP was associated with a higher rate of cardiovascular deaths independent of other factors. These data suggest that VVBPV in HD patients is reproducible and associated with various background factors. VVBPV is independently correlated with cardiovascular mortality (hazard ratio: 1.166, 95% confidence interval: 1.030-1.320, P = 0.015). Further studies are necessary to confirm the mechanism of increased VVBPV and to clarify whether reducing VVBPV will improve the prognosis for HD patients.

Investigation of small intestinal lesions in dialysis patients using capsule endoscopy.

INTRODUCTION: Although gastrointestinal hemorrhage is an important complication for dialysis patients, the details of many points remain unclear with regard to small intestinal lesions. METHODS: Capsule endoscopy was performed in fecal occult blood-positive dialysis (n =16) and non-dialysis (n = 20) patients after upper and lower gastrointestinal endoscopies failed to reveal hemorrhagic lesions. FINDINGS: Erosive lesions were observed in 50.0% (8/16) and 25.0% (5/20) of the dialysis and non-dialysis groups, respectively. Vascular lesions were observed in 62.5% (10/16) and 25.0% (5/20), respectively. Vascular lesions were observed at a significantly higher rate in the dialysis patients (P = 0.041), but no significant difference was noted in erosive lesions (P = 0.188). Of patients taking proton pump inhibitor (PPI), Non-Steroidal Anti-Inflammatory Drugs, and antiplatelet drugs, only oral PPI administration was associated with vascular lesions (P = 0.02). DISCUSSION: In dialysis patients, vascular lesions are the most common among small intestinal lesions, suggesting that they may have caused previously unexplained gastrointestinal hemorrhage in dialysis patients. It was also suggested that the frequent use of PPI may be a cause of small intestinal lesions.

Effects of L- and N-Type Ca Channel Blocker Cilnidipine on Changes in Heart Rate and QT Interval During Dialysis.

BACKGROUND/AIMS: Hemodialysis patients have poor prognosis due to increased prevalence of cardiovascular diseases. Treatment to suppress increases in sympathetic nerve activity and QT prolongation may have the potential to reduce the occurrence of these events. The L/N-type Calcium (Ca) channel blocker cilnidipine has unique inhibitory action to inhibit sympathetic nerve activity and in a canine model ameliorates QT prolongation. In this study, we investigated whether cilnidipine has inhibitory effects on heart rate, an index of sympathetic nerve activity, and QT prolongation in patients undergoing dialysis. METHODS: An L-type Ca channel blocker amlodipine was administered for 4 weeks followed by cilnidipine treatment for 4 weeks. On the last day of each period, heart rate and corrected QT interval were estimated and compared between the two periods. RESULTS: Cilnidipine showed greater suppression of heart rate during dialysis than did amlodipine. The corrected QT interval in one dialysis session was significantly increased, and 3 of 17 patients showed prominent QT prolongation during administration of amlodipine but not cilnidipine. CONCLUSION: These data suggested that cilnidipine may inhibit increases in heart rate and QT interval. Cilnidipine may have beneficial effects in reducing cardiovascular events, resulting from increased sympathetic nerve activity and lethal arrhythmias in hemodialysis patients.

Correlation of lanthanum dosage with lanthanum deposition in the gastroduodenal mucosa of dialysis patients.

Lanthanum (La) deposition has been observed in gastrointestinal mucosa of dialysis patients treated with La carbonate to treat hyperphosphatemia in the 6 years since its authorization in Japan. We investigated gastrointestinal biopsies from 112 dialysis patients, and found 15 cases of histiocytic aggregation with crystalloids and one case of duodenitis with histiocyte aggregation without crystalloids in the 30 patients treated with La carbonate. No histiocytic lesions were observed in the 82 patients without La carbonate administration. So far in total 70 cases of La deposition in the alimentary tract have been reported, including our 16 cases. Neither clinical nor histological findings other than histiocytic aggregation were specific in the patients with La deposition. We also compared the groups with and without La deposition, revealing that the daily and total doses of La carbonate showed statistically significant correlations with La deposition. However the causality with their histologic features, e.g. intestinal metaplasia and degree of inflammation, were inconclusive between the two groups. Although no critical symptoms have been reported, it is necessary to accumulate more cases to clarify the mechanism of La deposition, because dialysis patients must take phosphate buffers for a long period.

Primary hepatic leiomyosarcoma in a patient with autosomal dominant polycystic kidney disease.

Primary hepatic leiomyosarcoma is an extremely rare tumor. The diagnosis is difficult, and its etiologic factors have not been clarified. A 63-year-old woman with numerous cysts in her kidneys and liver was diagnosed with autosomal dominant polycystic kidney disease (ADPKD). Several members of her family also had ADPKD. She underwent treatment with tolvaptan to inhibit cyst growth and slow the decline in kidney function. Eight months after the start of the therapy, she was hospitalized with fatigue and fever of unknown origin. Diagnostic imaging showed a very large hepatic tumor, and histologic examination of a fine-needle biopsy specimen revealed the tumor to be malignant. Differentiation between carcinoma and sarcoma was difficult based on the histological findings. The tumor was thought to be excisable; therefore, hepatic resection was attempted. At the time of surgery, as the tumor had grown larger than when imaged, complete resection was impossible. However, a part of the tumor was resected. Histopathological and immunohistological examinations of the surgical specimen confirmed a primary hepatic leiomyosarcoma. Whether the tumor was associated with the presence of ADPKD remains unclear, however, this is the first report of the combination of these two diseases in a patient.

Serum Soluble (Pro)Renin Receptor Levels in Maintenance Hemodialysis Patients.

The (pro)renin receptor [(P)RR] is cleaved by furin to generate soluble (P)RR [s(P)RR], which reflects the status of the tissue renin-angiotensin system. Hemodialysis patients have advanced atherosclerosis. The aim of this study was to investigate the relationships between serum s(P)RR levels and background factors, including indices of atherosclerosis, in hemodialysis patients. Serum s(P)RR levels were measured in hemodialysis patients and clearance of s(P)RR through the membrane of the dialyzer was examined. Furthermore, relationships between serum s(P)RR levels and background factors were assessed. Serum s(P)RR levels were significantly higher in hemodialysis patients (30.4 ± 6.1 ng/ml, n = 258) than those in subjects with normal renal function (21.4 ± 6.2 ng/ml, n = 39, P < 0.0001). Clearance of s(P)RR and creatinine were 56.9 ± 33.5 and 147.6 ± 9.50 ml/min, respectively. Serum s(P)RR levels were significantly higher in those with ankle-brachial index (ABI) of < 0.9, an indicator of severe atherosclerosis, than those with ABI of ≥ 0.9 (32.2 ± 5.9 and 30.1 ± 6.2 ng/ml, respectively, P < 0.05). An association between low ABI and high serum s(P)RR levels was observed even after correction for age, history of smoking, HbA1c, and LDL-C. Serum s(P)RR levels were significantly higher in hemodialysis patients when compared with subjects with normal renal function, although s(P)RR is dialyzed to some extent, but to a lesser extent than creatinine. High serum s(P)RR levels may be associated with atherosclerosis independent of other risk factors, suggesting that serum s(P)RR could be used as a marker for atherosclerotic conditions in hemodialysis patients.

Effects of nocturnal oxygen therapy on heart function in SDB patients undergoing dialysis.

There is a close relationship between sleep disordered breathing (SDB) and heart failure. We performed home oxygen therapy (HOT) in patients with SAS undergoing dialysis, and investigated its effects on the heart function. The subjects were 10 SDB patients on dialysis. On retiring at night, oxygen was transnasally administered at 1.0 L/min. The human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), total protein, Alb, cholesterol and phosphorus levels were measured before the start of oxygen therapy and after 6 weeks. The mean SpO2 increased from 93.5% [91.5, 97.0] to 96.3% [94.8, 97.4] (median [interquartile range]) (p = 0.015). The hANP (p = 0.0039), BNP (p = 0.0098) and serum Alb (p = 0.015) levels significantly improved. There were no significant changes in the cholesterol, phosphorus or total protein levels. These results suggest that nocturnal oxygen therapy improves indices of heart failure, contributing to the prevention and treatment of heart failure in dialysis patients with SDB.

[Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis with acute pancreatitis: a case report].

We report here a case of a 64-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis who developed acute pancreatitis. The patient was admitted to our hospital because of abnormal urinalysis findings, edema, and progressive renal failure. Laboratory studies showed a high white blood cell count (11,570/µL), anemia (hemoglobin 7.8 g/dL), and elevated serum creatinine (2.36 mg/dL) and C-reactive protein (12.20 mg/dL) levels. Furthermore, the MPO-ANCA titer was very high (1,625 U/mL, normal range < 10 U/mL). Histopathological findings of the renal biopsy were consistent with microscopic polyangiitis. Accordingly, we diagnosed MPO-ANCA-associated glomerulonephritis. On the day after the renal biopsy, the patient complained of low back pain. Computed tomography (CT) revealed postbiopsy hemorrhage. Thereafter, the patient's symptoms and laboratory studies gradually worsened. A repeat CT performed a few days later revealed no changes in the perirenal hematoma; however, an enlarged pancreas head was incidentally observed. There was no obvious cause of acute pancreatitis, and MPO-ANCA-associated vasculitis, although rare, was suspected as the cause. We initiated prednisolone pulse therapy for vasculitis along with the administration of nafamostat mesilate and ulinastatin for acute pancreatitis. Subsequently, the levels of pancreatic enzymes gradually increased, but several days later, abdominal magnetic resonance imaging showed improvement in the pancreas head. The pancreatitis gradually resolved over time. Acute pancreatitis occurring concurrently with MPO-ANCA-associated glomerulonephritis is extremely rare. To our knowledge, only a few such cases have been reported and have suggested that steroid therapy may play a role in triggering pancreatic involvement. In our case, however, an enlarged pancreas head was observed before steroid therapy was initiated. Therefore, we consider our case to be very rare.

Accumulation of visceral fat in maintenance hemodialysis patients.

BACKGROUND: In hemodialysis (HD) patients, obesity has been recognized as a serious risk factor for mortality and morbidity for cardiovascular diseases. In addition, abnormalities of lipid profiles exist in these patients. METHODS: In patients undergoing maintenance HD, incidences of abnormality of lipid profiles and visceral obesity determined by computed tomography scans were compared. In addition, the relationship between visceral fat area (VFA) and brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, or carotid intima-media thickness (IMT), an index of atherosis, was examined. RESULTS: The incidence of high VFA (27.0%) was significantly greater than that of high body mass index (BMI) (9.7%), high low-density-lipoprotein cholesterol (LDL-C) (4.8%), and high triglyceride (12.7%). In patients with diabetes mellitus (DM), waist circumference and VFA showed a significant positive relationship with baPWV. baPWV was significantly higher in patients with high VFA and DM than in patients with low VFA without DM, those with high VFA without DM, and those with low VFA and DM. Carotid IMT was significantly greater in patients with high VFA and DM than in those with low VFA without DM and those with low VFA and DM. CONCLUSIONS: The incidence of high VFA was much greater than that of high BMI, high LDL-C, or high triglyceride. Visceral fat accumulation may be related to both arterial stiffness and atherosis in diabetic patients on maintenance HD.

MRSA tricuspid valve infective endocarditis with multiple embolic lung abscesses treated by combination therapy of vancomycin, rifampicin, and sulfamethoxazole/trimethoprim.

A 26-year-old pregnant woman who was an intravenous drug user (IDU) was admitted to our hospital for the treatment of tricuspid valve infective endocarditis (IE) and lung abscesses due to methicillin-resistant Staphylococcus aureus (MRSA). We started to treat her with vancomycin (VCM) alone and then in combination with rifampicin (RFP), but her condition did not improve. Then we added sulfamethoxazole/trimethoprim (SMZ/TMP) to VCM and RFP. After that, she improved rapidly. In Japan, there are very few reports about tricuspid valve IE caused by MRSA in IDUs. This case suggests that the combination of VCM, RFP, and SMZ/TMP may be effective for the treatment of severe MRSA infections.