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Background/Aims: In this study, we investigated the severity and frequency of uremic pruritus and itch-associated insomnia in patients with end-stage renal disease (ESRD) or chronic kidney disease (CKD). Methods: This questionnaire-based study included outpatients with ESRD or CKD who were attending Tokorozawa Renal Clinic in Saitama Prefecture or Musashi Ranzan Hospital and were stable on treatment. The questionnaire was completed by patients on hemodialysis (HD) before a dialysis session and by patients on peritoneal dialysis (PD) or conservative treatment at the time of an outpatient hospital visit. Results: Itching was reported by 61.6% of patients on HD, 61.5% on PD, and 43.2% on conservative CKD management. There was no statistically significant difference in the severity or frequency of itch according to whether patients were on HD for ESRD, PD for ESRD, or receiving conservative treatment for CKD. However, insomnia was significantly more common in the PD group than in the HD and conservative CKD groups. Conclusion: Better skin management is needed for itch in patients with ESRD or CKD. Moisturizing and lifestyle factors are important. Topical or oral medications may also be used. Nalfurafine, a κ receptor agonist, is now available in Japan for the treatment of uremic pruritus in these patients. [ABSTRACT FROM AUTHOR]

Background: Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year.Methods: This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch.Results: Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation.Conclusions: Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems. [ABSTRACT FROM AUTHOR]

Background: Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid κ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year. Methods: This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 μg/day) in 211 hemodialysis patients with a treatment-resistant itch. Results: Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation. Conclusions: Nalfurafine hydrochloride, orally administered at 5 μg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In women, the role of estrogen in the interrelationship between the progression of kidney and cardiac diseases is not fully understood. The present study attempted to elucidate the relationship between the process of cardiac remodeling and nephrosclerosis in ovariectomized Dahl salt-sensitive (DSS) rats with myocardial infarction (MI). Methods: 60 DSS rats with MI produced by ligation of the left coronary artery were divided into 5 groups as follows: group 1: MI rats without ovariectomy (OVX); group 2: MI rats with OVX; group 3: MI and OVX rats with estradiol (E) (17β-estradiol 15 mg/pellet/90 days subcutaneous pellet) supplementation; group 4: MI rats with OVX administered an angiotensin receptor antagonist (ARB), olmesartan, (2.5 mg/kg b.w. per day), and group 5: MI and OVX rats with E supplementation and administration of ARB in combination. Two weeks after ligation of the left coronary artery, OVX was carried out; this marked the start of the experiment. Body weight, systolic blood pressure (SBP), and urinary protein excretion were measured every 2 weeks for 12 weeks. Transthoracic echocardiogram was performed under anesthesia at 12 weeks. Blood samples for measurement of plasma renin activity, angiotensin (Ang) II, and aldosterone were obtained. At the end of the study, the heart and the kidney tissues were collected for light microscopic examination and evaluations of the expression of mRNA of angiotensin-converting enzyme and endothelial nitric oxide synthase (ecNOS). Results: SBP in female DSS rats with MI and with or without OVX transiently increased at week 4 and then gradually decreased toward the end of the study. Administration of ARB reduced SBP significantly (p < 0.05) in rats with OVX independently of E supplementation. OVX significantly (p < 0.05) increased and E supplementation further increased (p < 0.01) urinary protein excretion. E supplementation plus ARB administration significantly decreased urinary protein excretion. OVX increased activity in renin-angiotensin-aldosterone system (RAS) and both E and ARB supplementation suppressed RAS (p < 0.05). Expression of ecNOS was decreased in the rats with OVX and this was reversed by E supplementation in the heart but not in the kidneys, although combined administration with ARB reversed it in the kidney (p < 0.01). Transthoracic echocardiogram showed decreased ejection fraction by OVX and it was reversed by E supplementation and administration of ARB. Pathological changes of the kidney showed that E supplementation produced thrombotic microangiopathic lesions in the glomeruli. These changes were reversed by concomitant administration of ARB. Conclusion: Although estrogen appears to protect the development of cardiac remodeling and heart failure, it promotes microangiopathy in the kidney due to thrombosis. Concomitant administration of estrogen and ARB might be effective for protection of the heart and the kidney in OVX DSS rats with CHF. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: Icodextrin reduces glucose absorption from the peritoneal dialysate. We conducted this prospective, open-labeled, multicenter study to determine the effects of icodextrin on glycemic and lipid parameters in diabetic patients undergoing continuous ambulatory peritoneal dialysis (PD) or automated PD.Methods: Patients were recruited from 15 institutions in Japan, and a total of 51 patients (15 women and 36 men, mean age: 59 +/- 10 years, median duration of PD: 13 months) were enrolled. The patients were administered an overnight or daytime dwell of 1.5 or 2.0 l of 7.5% icodextrin-containing solution. At baseline and 3, 6, 9 and 12 months after the start of icodextrin, nonfasting blood was drawn for measurement of glycated hemoglobin (HbA1C) and serum lipids.Results: During icodextrin treatment, there was no change in overall HbA1C levels compared to baseline values; however, for those with baseline HbA1C > or =6.5% (n = 22), significant decreases in HbA1C were observed. Mean total/LDL cholesterol and triglycerides were decreased significantly during icodextrin treatment, with greater decreases for patients with baseline total cholesterol > or =220 mg/dl, LDL cholesterol > or =120 mg/dl or triglycerides > or =150 mg/dl. HDL cholesterol did not differ at any time point; however, values for patients with baseline HDL cholesterol <40 mg/dl tended to increase with marginal significance.Conclusions: In the current study, switching from glucose-containing dialysis solution to icodextrin resulted in improved lipid profiles and possibly a favorable metabolic profile, particularly in patients with poor glycemic control. These hypotheses remain to be proven in controlled clinical trials. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the frequency of heparin/platelet factor (PF) 4 complex antibodies in 305 uremic patients treated with chronic intermittent hemodialysis using unfractionated heparin or low-molecular-weight heparin for 3 months. Heparin-induced thrombocytopenia (HIT) antibodies were detected by ELISA in 7 patients (2.3%) who had no history of HIT. Two patients abruptly developed HIT associated with the formation of clots in the extracorporeal circuit after they were found to be carrying HIT antibodies. These patients were suspected to have a similar trigger: an increased dose of recombinant human erythropoietin (rHuEPO). The drug might induce parallel changes in hematocrit (Ht) levels and platelet counts until the onset of HIT. After the onset of HIT, a parallel phenomenon between Ht and platelet counts was not found because of the thrombocytopenia due to HIT. Although HIT onset has been reported during the initial phase of dialysis sessions, there have been few reports on the onset of HIT in uremic patients on dialysis with long-term heparin anticoagulation. In this study, HIT was observed in 2 uremic patients on chronic dialysis with intermittent use of heparin. In some patients on chronic intermittent dialysis carrying HIT antibodies, HIT may occur following rHuEPO treatment. The presence of HIT should be borne in mind in chronic dialysis patients carrying HIT antibodies for 3 months or more. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]