Naofumi Ikeda

Effect of Angiotensin Receptor Blockers on Cardiovascular Events in Patients Undergoing Hemodialysis: An Open-Label Randomized Controlled Trial

BACKGROUND Cardiovascular disease is the leading cause of mortality in patients with kidney failure treated with hemodialysis (HD). Although angiotensin receptor blockers (ARBs) reduce cardiovascular disease (CVD) events in patients with diabetes and chronic kidney disease, their effect in patients with kidney failure on HD therapy is not known. STUDY DESIGN Open-labeled randomized trial. SETTING & PARTICIPANTS Patients aged 30 to 80 years receiving HD 2 to 3 times weekly for 1 to 5 years at 5 university-affiliated dialysis centers. INTERVENTIONS Treatment with ARBs (valsartan, candesartan, and losartan) versus without ARBs after stratification by sex, age, systolic blood pressure, and diabetes. OUTCOMES The primary end point is the development of fatal and nonfatal CVD events, defined as the composite of CVD death, myocardial infarction, stroke, congestive heart failure, coronary artery bypass grafting, or percutaneous coronary intervention. The secondary end point is all-cause death. RESULTS 366 subjects initially were randomly assigned to an ARB or no ARB (control), but after a run-in phase, 180 were retained in each group. Mean age was 60 years, 59% were men, 51% had diabetes, and mean predialysis systolic blood pressure was 154 mm Hg. There were 93 fatal or nonfatal CVD events (52%); 34 (19%) in the ARB group and 59 (33%) in the non-ARB group. After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002). There were 63 deaths (35%); 25 (14%) in the ARB group and 38 (21%) in the non-ARB group. After adjustment, all-cause mortality differed between the 2 groups (hazard ratio, 0.64; 95% confidence interval, 0.39 to 1.06; P = 0.1). LIMITATIONS Because of the small sample size of this trial, the large effect may be a spurious finding. Use of an open-label design and 3 different agents in the ARB group might have influenced results. CONCLUSION Use of an ARB may be effective in reducing nonfatal CVD events in patients undergoing long-term HD. A larger study is required to confirm these results.

Telmisartan Lowers Home Blood Pressure and Improves Insulin Resistance Without Correlation Between Their Changes

Telmisartan is an angiotensin type 1 receptor blocker (ARB), which also partially activates liganding peroxisome proliferator-activated receptor gamma. However, the relationship between the effects of telmisartan on hemodynamics and metabolism has not sufficiently been elucidated in clinical settings. We examined the long-term effects of telmisartan on hemodynamics including home blood pressure (BP) and on insulin resistance representing as homeostasis model assessment (HOMA-R). Twenty-seven hypertensive patients were consecutively enrolled at our outpatient department. At entry, all of the participants were previously prescribed another ARB for more than 3 months and then the former ARB were replaced by telmisartan. Hemodynamic and metabolic parameters were measured before treatment and at points 1 and 3 months after treatment with telmisartan. Telmisartan significantly lowered home systolic blood pressure (SBP) and diastolic blood pressure (DBP) (DBP) and improved HOMA-R during the treatment period. However, the changes in home SBP and DBP were not correlated with that of HOMA-R. In conclusion, telmisartan lowers home BP and improves insulin resistance without correlation between their changes.

An atypical pattern of Epstein-Barr virus infection in a case with idiopathic tubulointerstitial nephritis

Recently, Epstein-Barr virus (EBV) received attention because a latent form of its infection in renal proximal tubular epithelial cells was found to cause idiopathic, chronic tubulointerstitial nephritis. In this report, we describe the case of a patient with a replicative form of EBV infection, chronic active EBV infection (CAEBV), who developed acute tubulointerstitial nephritis and minimal change nephrotic syndrome. A renal biopsy revealed papillary infoldings of atypical tubular epithelium and adjacent dense infiltration of lymphocytes. Using in situ polymerase chain reaction methods, we detected the EBV genome in some of the infiltrating lymphocytes, but not in the tubular epithelial cells. EBV-infected T cells are thought to activate other educated T cells, as well as secrete an unrestricted variety of cytokines, thus playing a pivotal role in CAEBV and its end organ disease. Therefore, in our case, the CAEBV activated, educated T cells may have followed the EBV-infected lymphocytes as they infiltrated into the peritubular interstitium, and promoted focal tubular epithelial atypia and minimal change nephrotic syndrome. The long-term observation of such patients is important because CAEBV may progress into lymphoproliferative diseases.

End-stage renal disease (ESRD) contributes to the increasing prevalence of herpes zoster

Sir, Varicella-zoster virus (VZV) causes two clinically distinct diseases: varicella (chickenpox) and herpes zoster (HZ; shingles). The lifetime cumulative incidence is ∼10–20% of the population [1]. The incidence rates progressively increase with age, presumably owing to decline in the VZV-specific cell-mediated immunity [2]. Age is the most important risk factor for the development of HZ; however, immunocompromised patients such as transplant recipients, patients receiving selective immunomodulatory therapy and HIV-infected patients have an increased risk of VZV reactivation [3,4]. Further, immunosuppressed individuals with HZ exhibit a significantly higher rate of complications (e.g. dissemination of the disease and ocular involvement) [5]. Patients who have end-stage renal disease (ESRD) with uraemia exhibit an impaired host immune response. The reported immunological abnormalities in ESRD patients include decreased phagocytic function of granulocytes and monocytes/macrophages, defective antigen presentation by monocytes/macrophages, reduced antibody production by B lymphocytes and impaired T-cell-mediated immunity [6]. Physicians working in dialysis facilities generally presume that ESRD contributes to the increase in the prevalence of HZ. Despite this presumption, the morbidity of HZ in ESRD has not been previously reported. This retrospective study includes information on all septuagenarian patients who visited the outpatient clinic of the nephrology division and dialysis centre affiliated to our university. A total of 220 patients were followed up for at least 3 years within the last 3.5 years. Of these 220 patients, 45 were excluded from this study because they exhibited one or more already identified risk factors for HZ (e.g. corticosteroid and/or immunomodulatory therapies, carcinomas and autoimmune disorders). Potential patients were identified by searching the diagnostic and billing codes of hospital records. If HZ was confirmed in a patient, the medical records were reviewed to verify that the case of HZ was indeed a new one. Our results revealed that the incidence of HZ increased with the progression in the stages of chronic kidney disease (CKD) (Table ​(Table1,1, Figure ​Figure1).1). In fact, the incidence rate of HZ was 84.8 per 1000 person-years in our outpatients undergoing haemodialysis or continuous ambulatory peritoneal dialysis. However, in patients with CKD stage 1, 2 or 3, the incidence rate (8.2 per 1000 person-years) was as low as that in septuagenarian HZ patients without kidney disease [5]. Diabetic nephropathy is the most important cause of ESRD that requires renal replacement therapy. Diabetes as well as CKD is a risk factor for some infectious diseases because these conditions result in a compromised immune system. However, the incidence of HZ and diabetes was not found to be significantly related as determined by the examinations performed in our hospital followed by analysis with the chi-square test. Table 1 The number of patients per group and their gender, classified according to their CKD stage Fig. 1 The graph shows the incidence (%) of HZ in patients classified by chronic kidney disease (CKD) stage. We concluded that ESRD, which requires renal replacement therapy, may contribute to the increased prevalence of HZ. Conflict of interest statement. None declared.

Clinical Effects of the New Phosphorus Binder, Bixalomer in Hemodialysis Patients Switched From Sevelamer Hydrochloride

It has been reported that sevelamer hydrochloride, which is often used as a polymer phosphorus (P) binder for managing serum P concentration in dialysis patients, causes gastrointestinal adverse effects such as constipation, etc. The reason for this is thought to be that sevelamer hydrochloride has high water absorption, causing it to absorb water and swell in the gastrointestinal tract. In June 2012, the new polymer P binder bixalomer was launched in Japan. Since bixalomer has low swelling due to water absorption, it can be expected to alleviate adverse effects in the gastrointestinal system. In our study, for 21 cases of maintenance hemodialysis patients undergoing treatment with sevelamer hydrochloride at our hospital, the P binder was switched from sevelamer hydrochloride to the same dosage of bixalomer, and the concentrations of serum P, corrected calcium (Ca) and whole parathyroid hormone (PTH) before and one month after the switch were compared. In addition, gastrointestinal symptoms (acid reflux, abdominal pain, indigestion, diarrhea and constipation) were evaluated before and after the switch using a questionnaire based on the Japanese version of the Gastrointestinal Symptom Rating Scale (GSRS). By switching to bixalomer, serum P concentration was significantly reduced (P = 0.024), but there were no significant changes observed for serum corrected Ca and whole PTH. Furthermore, there were no significant changes observed for all five of the evaluation items of the GSRS, before and after the switch. These results suggest that although bixalomer can more potently reduce the serum P concentration than sevelamer hydrochloride, there were no significant differences in the effects of both P binders on the gastrointestinal symptoms.

Lubiprostone, a novel laxative, might improve hyperphosphatemia without water dilution

BackgroundHemodialysis patients often develop constipation due to dietary restriction and the use of phosphate and/or potassium binders. Lubiprostone is a novel laxative that promotes defecation by activating the chloride ion channel 2 (ClC-2) in the gastrointestinal tract. While lubiprostone has been reported to be useful in bowel control of dialysis patients, no studies have examined changes in electrolyte levels following administration of lubiprostone.MethodsWe prospectively compared stool frequency and electrolyte levels before and after treatment with lubiprostone in 28 hemodialysis patients treated with the drug for at least 3 months in our hospital.ResultsMean ± standard deviation of stool frequency was significantly increased from 1.8 ± 1.3 times/week before treatment to 4.3 ± 1.8 times/week at Month 1, 4.9 ± 1.9 times/week at Month 2, and 4.5±1.5 times/week at Month 3 (p < 0.001, p < 0.001, and p < 0.001, respectively). With regard to electrolyte levels, only serum inorganic phosphorus (IP) level was significantly decreased, from 4.7 ± 1.5 mg/dL at baseline to 4.5 ± 1.6 mg/dL at Month 1, 4.0 ± 1.3 mg/dL at Month 2, and 3.8 ± 1.1 mg/dL at Month 3 (p = 0.123, p < 0.001, and p < 0.001, respectively). Lubiprostone not only improved bowel control, but also decreased serum IP levels in hemodialysis patients.ConclusionsLubiprostone may improve prognosis of hemodialysis patients through bowel control and a decrease in serum IP.

Infected Aneurysm after Endoscopic Submucosal Dissection

A 79-year-old man on hemodialysis was hospitalized for further investigation. Early gastric cancer was diagnosed by gastrointestinal endoscopy and endoscopic submucosal dissection (ESD) was performed. Fever and abdominal pain thereafter developed, and a severe inflammatory response was observed on a blood test. Contrast computed tomography (CT) showed ulcer-like projections and soft tissue surrounding the aorta, from the celiac to left renal artery. An infected aneurysm was diagnosed. Although infected aneurysms developing after laparoscopic cholecystectomy or biopsy of contiguous esophageal duplication cyst have been reported, those developing after ESD have not. When fever and abdominal pain develop after ESD, an infected aneurysm should be considered and contrast CT performed.

A case of histopathologically confirmed infective endocarditis with no vegetations observed during preoperative diagnosis

An 81-year-old woman on maintenance hemodialysis (HD) was admitted to the hospital with fever and repeated positive blood cultures for coagulase-negative staphylococci. The patient had a history of aortic valve replacement for aortic valve stenosis (AS). Although one major criterion and two minor criteria from the Duke criteria were met and therefore infective endocarditis (IE) was suspected for this case, no definitive diagnosis was made. Vegetations were not observed on the transesophageal echocardiography, but AS was prominent. The patient was refractory to antibiotic therapy using vancomycin, and blood cultures did not convert to negative. To treat the suspected IE and AS, aortic valve replacement was performed. Although vegetations were not observed in the resected valve, gram-positive cocci were found in clusters, and a histopathological diagnosis of IE was made. The postoperative blood culture converted from positive to negative, and the patient was subsequently discharged from the hospital. While relative risk of IE is high in HD patients, a definitive diagnosis of IE may be difficult due to calcification of the valve and valve replacement. In HD patients with bacteremia, suspicion of IE should be aggressively pursued if other sources of infections are negative, and if the patient is refractory to medical treatment, surgical treatment may be necessary.

A Case of Neurosarcoidosis-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone Diagnosed with Neuroendoscopy

We treated a patient with neurosarcoidosis, which caused the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in whom diagnosis was performed using neuroendoscopy. The patient was a 56-year-old female who was hospitalized for hyponatremia and diagnosed with SIADH based on a detailed examination. During the course, she developed impaired consciousness due to acute hydrocephalus, which improved after ventricular drainage. Head magnetic resonance imaging (MRI) confirmed nodular lesions at the floor of the third ventricle and the cerebral aqueduct. Neuroendoscopic biopsy led to the diagnosis of neurosarcoidosis. Her hyponatremia improved after steroid therapy. Neurosarcoidosis can cause SIADH, and complication of hydrocephalus may lead to a poor prognosis. Neuroendoscopy appears to be effective for the diagnosis of neurosarcoidosis with hydrocephalus and helps in deciding the treatment modality.