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Background:The COVID-19 pandemic is challenging healthcare systems worldwide and has placed hospitals and healthcare providers (HCPs) at the center of a global crisis. Disruptions to hospital priorities, and limitations placed on the mobility of societies, have contributed to changes in the way HCPs and patients view and access dialysis for kidney failure, including which dialysis modality is preferred. Summary:This article explores the dialysis experience within the COVID-19 pandemic environment in the Asia Pacific region and presents evidence that peritoneal dialysis (PD) provides benefits to patients, HCPs, and health systems. As the number of people infected with COVID-19 has increased, the advantages of PD as a dialysis modality for limiting the spread of COVID-19 infection has been recognized. Key Message:The utility of PD has been demonstrated during the COVID-19 pandemic; thus, ensuring that the usage of PD is maintained and increased in a post-pandemic future is key. Such a scenario could enhance our ability to care for patients without interruption in circumstances of unforeseen obstacles and supports the ability of healthcare systems and patients to overcome barriers to dialysis access.

Recent evidence has suggested that the innate immune response may play a role in the development of eosinophilic airway inflammation. We previously reported that uric acid (UA) and adenosine triphosphate (ATP), two important damage-associated molecular pattern molecules (DAMPs), activate eosinophil functions, suggesting that these molecules may be involved in the development of eosinophilic airway inflammation. The objective of this study was to measure the concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP).

Eosinophilic esophagitis (EoE) is related to allergic diseases such as bronchial asthma (BA), atopic dermatitis, and allergic rhinitis. The aim of this study was to examine the eosinophil infiltration in the upper gastrointestinal (GI) tract in patients with BA using esophagogastroduodenoscopy.

Eosinophils play important roles in the development of asthma exacerbation. Viral infection is a major cause of asthma exacerbation, and the expression of IFN-γ-inducible protein of 10 kDa (IP-10) and cysteinyl leukotrienes (cysLTs) is up-regulated in virus-induced asthma. As β2-adrenergic agonists, such as formoterol or salbutamol, are used to treat asthma exacerbation, we examined whether formoterol or salbutamol could modify eosinophil functions such as adhesiveness, particularly those activated by cysLTs or IP-10.

Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood.

Introduction Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD). Over the past decade in Japan, a multidisciplinary approach has been adopted to minimize the incidence and improve outcomes of EPS. This strategy includes planned PD discontinuation for high-risk patients and the introduction of biocompatible solutions. This study examined the current clinical status of EPS in representative PD centers in Japan.Design, setting, participants and measurements Patients (n= 1,338) from 55 PD centers in Japan who were using neutral-pH solutions from the initiation of therapy (mean age, 62 years; median PD duration, 32 months; concomitant use of icodextrin, 35.2%; PD and hemodialysis combination therapy, 12.2%) were assessed every 6 months to ascertain the reasons for PD discontinuation and the development of EPS development. Outcomes were also recorded. The study period was from November 2008 to March 2012.Results There were 727 patients who discontinued PD, including 163 deaths. Among all causes of PD withdrawal except for death, planned PD discontinuation to avoid EPS was utilized in 58 cases (7.1% in total). The strategy was increasingly utilized in proportion to the duration of PD: 0.5% for patients undergoing PD for < 3 years, 0.6% for patients undergoing PD for 5 years, 14.7% for patients undergoing PD for 8 years, and 35.5% for patients undergoing PD for > 8 years. Fourteen patients developed EPS (three cases after PD), which corresponded with an overall incidence of 1.0%. The incidence according to the duration of PD was 0.3% for PD < 3 years, 0.6% for PD = 5 years, 2.3% for PD = 8 years, and 1.2% for PD > 8 years. In terms of therapy, 11 patients were treated with prednisolone (PSL), and surgical enterolysis was utilized in two cases. Complete remission of abdominal symptoms was achieved in twelve patients (85.7%), and three died due to EPS (mortality rate of 21.4%).Conclusions Use of the multidisciplinary approach described above reduces the risk of the development of EPS according to PD duration. In cases of de novoEPS cases in Japan, this strategy can also attenuate the clinical course of the condition.

⋄ Background Although the effects of angiotensin type 1 receptor blocker (ARB) have been studied, little is known about ARBs in hypertensive patients undergoing dialysis. In the present study, we evaluated the effect of an ARB, olmesartan medoxomil (CS866), on the progression of peritoneal fibrosis in peritoneal dialysis by examining its effect in a model of peritoneal fibrosis in hypertensive rats.⋄ Materials and Methods We allocated40 male Wistar rats with 2-kidney, 1-clip renovascular hypertension (2K1C-RVH) to 4 groups (each n =10) that were dialyzed using various solutions for 42 days as follows: Dialysis solution was injected every day for 42 days.⋄ Results Treatment with CS866 and amlodipine induced a significant reduction of blood pressure in 2K1C-RVH rats. In rats treated with pH 3.5 dialysis solution, necropsy findings revealed features identical to those of encapsulating peritoneal sclerosis (EPS). The typical appearance was multiple surfaces covered with granulation tissue or fibrosic tissue or both. Multiple adhesions were present. Microscopic findings revealed that acidic dialysis solution induced peritoneal fibrosis and loss of mesothelium. Treatment with CS866 prevented the progression of peritoneal fibrosis and adhesions. However amlodipine did not improve the progression of peritoneal fibrosis and peritoneal adhesions. In CS866-treated rats, no signs of EPS were present.⋄ Conclusions Long-term intraperitoneal exposure to acidic dialysis solution produced features typical of EPS. Acidic dialysis solution induces activation of the peritoneal renin– angiotensin system and progression of peritoneal fibrosis. For the peritoneum undergoing peritoneal dialysis, ARB protects against progression of peritoneal fibrosis and peritoneal adhesions.

We developed a new data collection system named i-converter that could transmit data to a website via cellular phone. Using the system, we compared the effects of two calcium channel blockers on the home blood pressure.

Over recent decades, rapid progress in information and telecommunications technology has led to the application of these technologies in the medical field. In 1999, we reported on a telemedicine system (version 1.0) that used an automated peritoneal dialysis machine to collect data on patients with end-stage renal disease. After 2002, we focused on using cellular telephones in a new telemedicine system (version 2.0) to monitor patient data at home, including blood pressure (BP), heart rate, body weight, urine volume, and blood glucose. By 2003, we had developed a fully automatic system called I-converter (version 3.0) to collect data from a fully automatic device and send it via cellular telephone. After the fully automatic device measures a patient's BP, I-converter sends the data directly to the main server in our central data center. That server is directly connected to Web site by application service provider (ASP) technology. Recently, to make the system simpler, we developed a new version called D-converter (version 4.0). The telephone used in this new system is a Personal Handy-phone System (PHS). The PHS has several advantages: high-speed data transmission, low power output, little electromagnetic interference with medical devices, and easy locating of patients. The D-converter system uses a small computer and a PHS card called a Dopa card.Our telemedicine systems monitor continuous ambulatory peritoneal dialysis (CAPD) patients at home. For elderly and handicapped patients, these systems are very advantageous because they reduce visits to the outpatient clinic. In addition, data can be monitored at the patient's home in real time. The present paper reports our recent advances in telemedicine systems for CAPD patients.

Experiments were performed to characterize renal hemodynamics in Thy-1 nephritic rats. A monoclonal antibody against Thy-1 was intravenously injected to induce mesangiolysis in rats, and 2 days later renal hemodynamic responses to variations in blood pressure were determined. In the first series of experiments, autoregulation of renal plasma flow (RPF) or glomerular filtration rate (GFR) was impaired in nephritic rats. In response to a reduction in blood pressure (98 ± 2 to 80 ± 1 mmHg), both RPF (4.17 ± 0.63 to 3.20 ± 0.45 ml·min−1·g kidney wt−1, P< 0.05, n= 6) and GFR (0.88 ± 0.05 to 0.75 ± 0.06 ml·min−1·g kidney wt−1, P< 0.05) were decreased in nephritic rats. Intravenous administration of furosemide and 30% albumin, both of which inhibit tubuloglomerular feedback, diminished renal autoregulation in control but not nephritic rats. In the second studies, the infusion of 5′-nucleotidase, an enzyme expressed on mesangial cells, into a renal artery ameliorated the magnitude of autoregulatory decrements in GFR in nephritic rats (−16 ± 5 to −6 ± 2%, P< 0.05, n= 6), but this enzyme failed to alter renal autoregulation in control rats. In the third studies, the effects of indomethacin were examined in nephritic rats. Inhibition of prostaglandin synthesis reduced RPF (4.07 ± 0.30 to 1.54 ± 0.22 ml·min−1·g kidney wt−1, P< 0.05, n= 5) and GFR (1.03 ± 0.18 to 0.69 ± 0.13 ml·min−1·g kidney wt−1, P< 0.05) in nephritic rats. However, cyclooxygenase inhibition failed to restore renal autoregulation in nephritic rats. Our results indicate that renal autoregulation is impaired in Thy-1 nephritis. Furthermore, the present data provide evidence that prostanoids contribute to maintain renal circulation in nephritic rats. Finally, our findings suggest that mesangial cells and/or 5′-nucleotidase plays an important role in mediating renal autoregulation.

Experiments were performed to characterize renal hemodynamics in Thy-1 nephritic rats. A monoclonal antibody against Thy-1 was intravenously injected to induce mesangiolysis in rats, and 2 days later renal hemodynamic responses to variations in blood pressure were determined. In the first series of experiments, autoregulation of renal plasma flow (RPF) or glomerular filtration rate (GFR) was impaired in nephritic rats. In response to a reduction in blood pressure (98 ± 2 to 80 ± 1 mmHg), both RPF (4.17 ± 0.63 to 3.20 ± 0.45 ml·min–1·g kidney wt–1, P < 0.05, n = 6) and GFR (0.88 ± 0.05 to 0.75 ± 0.06 ml·min–1·g kidney wt–1, P < 0.05) were decreased in nephritic rats. Intravenous administration of furosemide and 30% albumin, both of which inhibit tubuloglomerular feedback, diminished renal autoregulation in control but not nephritic rats. In the second studies, the infusion of 5'-nucleotidase, an enzyme expressed on mesangial cells, into a renal artery ameliorated the magnitude of autoregulatory decrements in GFR in nephritic rats (–16 ± 5 to –6 ± 2%, P < 0.05, n = 6), but this enzyme failed to alter renal autoregulation in control rats. In the third studies, the effects of indomethacin were examined in nephritic rats. Inhibition of prostaglandin synthesis reduced RPF (4.07 ± 0.30 to 1.54 ± 0.22 ml·min–1·g kidney wt–1, P < 0.05, n = 5) and GFR (1.03 ± 0.18 to 0.69 ± 0.13 ml·min–1·g kidney wt–1, P < 0.05) in nephritic rats. However, cyclooxygenase inhibition failed to restore renal autoregulation in nephritic rats. Our results indicate that renal autoregulation is impaired in Thy-1 nephritis. Furthermore, the present data provide evidence that prostanoids contribute to maintain renal circulation in nephritic rats. Finally, our findings suggest that mesangial cells and/or 5'-nucleotidase plays an important role in mediating renal autoregulation.

Technique failure resulting in transfer to hemodialysis (HD) remains one of the most important challenges in long-term peritoneal dialysis (PD). In general, the proportion of patients transferring from PD to HD is much greater than the proportion transferring from HD to PD. However, technique failure rates differ considerably between and within countries.The question arises as to how technique failure rates in Japan compare with those in other countries. To address this issue, we reviewed the literature and our experience of 139 incident continuous ambulatory peritoneal dialysis (CAPD) patients from January 1995 to December 1999.Based on our review, we estimate that the 5-year technique survival rate in Japanese CAPD patients is approximately 70%, and that technique failure rate is around 7% per year. This rate is significantly lower than that in many other countries. The most common reasons for technique failure in Japan are peritoneal membrane failure, ultrafiltration loss, and inadequate dialysis. Another factor contributing to the low technique failure rate in Japan is an extremely low peritonitis rate. This may be related to good sanitation and excellent PD training programs. Peritoneal membrane failure continues to be the major challenge for long-term technique survival on PD in Japan.

Encapsulating peritoneal sclerosis (EPS) is recognized as a serious complication of continuous peritoneal dialysis. A preliminary diagnosis of EPS is usually based on clinical signs and symptoms, which commonly include abdominal pain, nausea, vomiting, anorexia, abdominal fullness, an abdominal mass, bowel obstruction, and radiologic findings, including abdominal roentgenogram, contrast studies, ultrasound studies, and computed tomography. The diagnosis is confirmed by laparoscopy or laparotomy showing the characteristic gross thickening of the peritoneum enclosing some or all of the small intestine in a cocoon of opaque tissue.A variety of therapeutic approaches to EPS have been reported. This review discusses medical treatment of EPS and includes an overview of the clinical features and diagnostic aspects of the condition.

This comprehensive update on the management of encapsulating peritoneal sclerosis incorporates insights gained from recently published findings and the accumulated experience of the authors. Aspects covered include diagnosis, risk factors and predictive markers, treatment, and prevention, including criteria for withdrawal from peritoneal dialysis.

Background:Both residual renal function and blood pressure (BP) control contribute to patient survival in patients receiving continuous ambulatory peritoneal dialysis (CAPD). It is unknown whether antihypertensive drugs affect residual renal function in addition to BP reduction. Methods:We examined the effects of an angiotensin II receptor blocker, valsartan, on residual renal function and total clearance (renal and peritoneal) in 34 Japanese CAPD patients from 3 months to 2 years after the start of dialysis therapy. Patients were randomly assigned to valsartan (n = 18; age, 63.5 ± 3.7 years; 11 men, 7 women) or a control group (n = 16; age, 63.5 ± 3.3 years; 10 men, 6 women). Conventional antihypertensive treatment was continued in all patients to achieve the target BP in both groups of 130/80 mm Hg or less, measured at home. Results:BP reduction was similar in the valsartan and control groups. Valsartan significantly slowed the progressive decline in both residual renal function (3.2 ± 0.3 to 4.3 ± 0.7 mL/min/1.73 m2) and total clearance (42.1 ± 3.2 to 48.3 ± 4.8 L/wk/1.73 m2) by dialysis in CAPD patients compared with controls (5.9 ± 0.5 to 2.8 ± 0.4 mL/min/1.73 m2; 47.1 ± 4.8 to 31.4 ± 5.2 L/wk/1.73 m2). Conclusion:This study shows that in patients with hypertension starting CAPD therapy, valsartan slows the decline in residual renal function and contributes to maintenance of weekly creatinine clearance and Kt/V (fraction per dialysis), which are the major factors contributing to the mortality and morbidity of CAPD patients. This effect appears to be mostly a result of maintaining residual renal function.

Background The present study used the newly developed personal dialysis capacity (PDC) peritoneal function test to investigate differences in individual peritoneal membrane transport function and nutritional status in non diabetic (non DM) and diabetic (DM) patients on continuous ambulatory peritoneal dialysis (CAPD).Patients and Methods To clarify the differences in peritoneal function that determine plasma protein levels, we carried out PDC tests in non DM and DM patients. Between May 1995 and May 1999, in multicenter study in Japan, we carried out 232 PDC tests on 232 non DM patients and 47 PDC tests on 47 DM patients who had been on CAPD for 1 – 210 months.Results Plasma levels of total protein and albumin in DM patients were significantly lower than those in non DM patients (total protein: 6.5 ± 0.1 g/dL non DM vs. 5.9 ± 0.1 g/dL DM, p< 0.0001; albumin: 3.5 ± 0.1 g/dL non DM vs. 2.9 ± 0.1 g/dL DM, p< 0.0001). The mean membrane area in the DM group was significantly larger than that in the non DM group (21943 ± 608 cm/1.73 m2non DM vs. 26 304 ± 1699 cm/1.73 m2DM, p= 0.0076). The mean plasma loss through the large pores in the DM group was significantly greater than that in the non DM group (0.095 ± 0.004 mL/min/1.73 m2non DM vs. 0.119 ± 0.008 mL/min/1.73 m2DM, p= 0.0113). Protein loss into dialysate in DM patients was significantly greater than that in non DM patients. We observed a significant correlation between total protein or albumin and plasma loss from dialysis solution in non DM and DM patients on CAPD.Conclusions The study demonstrated that peritoneal function, including peritoneal membrane transport and peritoneal permeability to protein was significantly higher in DM patients than in non DM patients. Hypoproteinemia in DM patients might be associated with high permeability of peritoneal membrane in CAPD.

Background:We evaluated differences in individual peritoneal membrane transport function and nutritional status in patients with diabetes mellitus (DM) and nondiabetic (non-DM) patients on continuous ambulatory peritoneal dialysis (CAPD). Methods:We used a newly developed peritoneal function test, personal dialysis capacity, in 88 patients (44 DM and 44 non-DM) on CAPD for 1 to 210 months. Sex, age, past history of peritonitis, and duration of CAPD were matched in DM and non-DM patients. Results:Serum albumin (mean ± SEM) was lower in DM compared with non-DM patients: 3.0 ± 0.1 g/dL (30 ± 1 g/L) versus 3.5 ± 0.1 g/dL (35 ± 1 g/L), P< 0.001. Peritoneal area and dialysis protein loss were greater in DM versus non-DM patients. In multiple linear regression analysis, the only independent predictor of serum albumin in patients with DM was dialysis protein loss. In contrast, age, past history of peritonitis, duration of CAPD, caloric intake, protein nitrogen appearance and protein catabolic rate, and residual renal function did not correlate with serum albumin in DM patients. In non-DM patients, age, duration of CAPD, and past history of peritonitis, but not dialysis protein loss, were independent predictors of serum albumin. There was a significant correlation in DM patients, but not in non-DM CAPD patients, between dialysis protein loss and urinary excretion of protein (r= 0.866, P= 0.0005). Conclusion:In this multicenter study, peritoneal membrane transport and peritoneal protein permeability were significantly higher in DM than in non-DM patients. Hypoproteinemia in DM patients is attributable to the high permeability of the peritoneal membrane undergoing CAPD. Am J Kidney Dis40:1045-1054. © 2002 by the National Kidney Foundation, Inc.

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.

Objective Encapsulating peritoneal sclerosis (EPS), in which all or part of the intestine is enveloped in a fibrous ball resembling a cocoon, is a serious complication of peritoneal dialysis (PD). The aim of the present study was to investigate whether pH-neutral or acidic dialysis solutions induce peritoneal fibrosis.Design We divided 18 male Wistar–Kyoto (WKY) rats into three groups and dialyzed them with various solutions as follows: group I, 10 mL acidic dialysis solution (pH 3.8, containing 1.35% glucose), n= 6; group II, 10 mL pH 5.0 dialysis solution, n= 6; and group III, 10 mL neutral dialysis solution (pH 7.0), n= 6. Peritoneal catheters were inserted, and dialysis solution was injected every day for 40 days. At the end of the experiment, a peritoneal equilibration test (PET) was performed. Expression of mRNA of aquaporins 1 and 4 (AQP-1 and AQP-4) in the peritoneum were studied by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR).Results In rats treated with pH 3.8 dialysis solution, necropsy findings revealed features identical to those of EPS. The typical appearance was of granulation tissue or fibrotic tissue (or both) covering multiple surfaces. Multiple adhesions were present. In microscopic examinations, peritoneal fibrosis and loss of mesothelium were found. In rats treated with pH 7.0 dialysis solution, no signs of EPS were seen. In rats treated with pH 5.0 dialysis solution, milder changes (subserosal thickening and partial adhesion of the peritonea) were observed. The mRNA of AQP-1 and AQP-4 were expressed in the peritonea of the rats. The expression of the AQPs was significantly suppressed in rats treated with pH 3.8 dialysis solution.Conclusions In rats, long-term intraperitoneal injection of acidic dialysis solution produced features typical of EPS in humans. Newly developed neutral dialysis solutions protected the against the development of EPS during peritoneal dialysis in rats.

We report the use of thoracoscopic pericardiectomy to treat two elderly patients with massive pericardial effusion caused by uremic pericarditis. A 79-year-old man, admitted to our hospital complaining of dyspnea, was diagnosed with end-stage renal failure and began maintenance hemodialysis. Although intensive hemodialysis was performed, the patient could not remain on hemodialysis because of severe hypotension during the procedure. Echocardiography revealed massive pericardial effusion and severe hypokinesis of the left ventricular wall. Pericardiocentesis was performed first, without success, followed by thoracoscopic pericardiectomy under general anesthesia. One month after the pericardiectomy, episodes of hypotension during hemodialysis improved, and dyspnea diminished. Echocardiography showed no pericardial effusion and improvement of left ventricular wall motion. Pericarditis is a fatal complication in patients with end-stage renal failure and patients on maintenance hemodialysis. The second patient received the same procedure with a similar improvement of clinical symptoms. These cases suggest that thoracoscopic pericardiectomy is a safe and effective treatment of pericardial effusion caused by uremic pericarditis in elderly patients on hemodialysis.

Background:Sepsis and septic shock are still major causes of morbidity and mortality in spite of the availability of powerful and broadly active antibiotics. Methods:A prospective, open and randomized trial of the effect of immobilized polymyxin fibers (PMX-F) on the survival of patients with sepsis throughout a follow-up period of 28 days or until discharge, if earlier, was carried out. Ninety-eight patients were included who met at least 4 of the criteria for systemic inflammatory response syndrome due to infection. The patients were classified into three groups based on their Acute Physiology and Chronic Health Evaluation (APACHE) II score. Results:The overall survival rate was significantly improved by using PMX-F compared to the control group (41 vs. 11%) (p = 0.002). In patients with an APACHE II score less than 20, treatment with PMX-F was shown to improve outcome (65 vs. 19%) (p = 0.01). In cases of more severe sepsis with an APACHE II score of 20–29, PMX-F still maintained efficacy in improving outcome (40 vs. 11%) (p = 0.04). However, PMX-F treatment did not improve the survival rate in patients with an APACHE II score of greater than 30 (survival rate 7 vs. 0%) (p = 0.59). Conclusion:From these results, it is concluded that treatment with PMX-F in patients with sepsis is effective and prolongs the survival rate when applied at an early stage of sepsis. However, in severe sepsis, this therapy does not improve the survival rate.

Tubulointerstitial change is a common histopathologic feature of acute and chronic glomerular diseases and is more closely correlated than glomerular damage with renal function and subsequent outcome. Monocyte infiltration is presumed to be initiated by chemoattractants and has a pivotal role in tubulointerstitial changes. Osteopontin (OPN) is a candidate as such a chemoattractant and has been shown to recruit monocytes into the interstitium of animal models of renal diseases. In this study, we investigated OPN expression by immunostaining and its correlation with clinical and histopathologic parameters in patients with immunoglobulin A (IgA) nephropathy, diffuse proliferative lupus nephritis (DPLN), and myeloperoxidase–antineutrophil cytoplasmic autoantibody–associated microscopic polyangiitis (MMP). Twenty patients with IgA nephropathy, 12 patients with DPLN, and 14 patients with MMP were studied. OPN expression, which was constitutively observed on the apical membrane of distal tubules, was upregulated in the cytoplasm of proximal and distal tubular epithelium parallel to the degree of interstitial mononuclear cell infiltration in patients with IgA nephropathy, as well as those with DPLN. CD68+monocyte infiltration significantly correlated with the degree of OPN expression in the tubular epithelium. Conversely, there was no apparent induction of OPN in the proximal and distal tubular epithelium of patients with MMP despite remarkable monocyte infiltration. In conclusion, these data suggest that inducible expression of OPN in the tubular epithelium seems to be associated with interstitial monocyte infiltration and subsequent tubulointerstitial changes in some forms of human renal diseases.

Abstract: Plasma exchange (PE) has been one of the most powerful treatments for patients with myasthenia gravis (MG) since Pinching et al. reported its clinical usefulness in 1976, despite the need for supplemental human plasma. However, new apheresis techniques, e.g., plasma adsorption (PA) and double filtration plasmapheresis (DFPP), which do not need human plasma, were developed and have been introduced for clinical use in MG. We compared the effects of these plasma purification therapies in patients with MG and found that DFPP improved such subjective symptoms as chest compression and general fatigue better than PA while both of them could decrease the serum level of acetylcholine receptor (AChR) antibodies and relieve objective muscle weakness to a similar degree. It may be that DFPP can remove some circulating pathogenic factors other than AChR antibodies more efficiently than PA.—

Abstract: We tried to compare the efficacy of plasma exchange (PE) with that of intravenous immunoglobulin (IVIG) in patients with postinfectious polyneuritis (Guil‐lain‐Barre syndrome [GBS] and cranial neuritis). Fifteen patients with postinfectious polyneuritis were divided into 2 groups. The IVIG group included 5 cases of GBS and 2 cases of postinfectious cranial neuritis (ophthalmoplegic type). The PE group included 5 cases of GBS and 3 cases of postinfectious cranial neuritis (ophthalmoplegic type). The changes and incidences of improvement of muscle strength scores (MSSs) and ocular movement scores (OMSs) were evaluated before treatment and 1, 2, 3, and 4 weeks after treatment. No significant differences between the IVIG and PE groups were found in the MSSs or OMSs at any time after treatment. These data suggested that PE and IVIG had equivalent efficacy. In the IVIG group, the proportion of suppressor‐inducer T cells significantly increased (p ≤ 0.01) (before versus after treatment), and the proportion of suppressor‐effector cells also increased but not significantly (before versus after treatment). In the PE group, the percentage of suppressor‐inducer T cells significantly decreased (p ≤ 0.05) (before versus after treatment) while the proportion of suppressor/ cytotoxic T cells significantly increased (p ≤ 0.05) (before versus after treatment). The percentage of suppressor‐effector T cells also increased (before versus after treatment) but not significantly.

1. The effects of l-arginine on systemic and renal haemodynamics were investigated in conscious dogs. l-Arginine was administered intravenously at doses of 15 and 75 μmol min−1 kg−1 for 20 min. 2. Mean arterial blood pressure, heart rate and cardiac output were not changed significantly by l-arginine infusion. However, l-arginine infusion induced a significant elevation of renal blood flow from 50 ± 3 to 94 ± 12 ml/min (means ± sem, P < 0.01). 3. Simultaneous infusion of NG-monomethyl-l-arginine (0.5 μmol min−1 kg−1) significantly inhibited the increase in renal blood flow produced by l-arginine (15 μmol min−1 kg−1) without significant changes in mean arterial blood pressure or heart rate. 4. Pretreatment with atropine completely inhibited the l-arginine-induced increase in renal blood flow, whereas pretreatment with indomethacin attenuated it (63 ± 4 versus 82 ± 10 ml/min, P < 0.05). 5. A continuous infusion of l-arginine increased renal blood flow in the intact kidney (55 ± 3 versus 85 ± 9 ml/min, P < 0.05), but not in the contralateral denervated kidney (58 ± 3 versus 56 ± 4 ml/min, P > 0.05). 6. These results suggest that intravenously administered l-arginine produces an elevation of renal blood flow, which may be mediated by facilitation of endogenous acetylcholine-induced release of endothelium-derived relaxing factor and vasodilatory prostaglandins.

The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p<0.05), ACTH (by 85%, p<0.05), AVP (by 89%, p<0.05), and ANH (by 36%, p<0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p<0.05). Cortisol did not change significantly. Infusion of 1 pmol·kg−1·min−1of angiotensin II produced an elevation of aldosterone (by 186%, p<0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.

Pathogenesis of hypertension in Cushing’s syndrome has remained controversial. A 56-year-old Japanese man with Cushing’s syndrome due to adrenal carcinoma has been followed up for more than 6years. During the followup period, left adrenalectomy and hemi-hepatectomy due to metastatic lesion were performed. Blood pressure, serum Cortisol, and urinary excretion of 17-OHCS, as well as other routine biochemicals, have been measured periodically. These data revealed that there is a marked correlation between the levels of blood pressure and serum Cortisol or urinary excretion of 17-OHCS. This finding suggests that Cortisol production by tumor is a determinant factor in hypertension in Cushing’s syndrome.

1. The effects of endothelin on systemic and renal haemodynamics and plasma concentrations of neuroendocrine hormones including plasma renin activity, aldosterone, adrenocorticotropic hormone, Cortisol, catecholamines and arginine vasopressin were investigated in 18 conscious dogs. 2. Bolus injection of 4 pmol of endothelin/kg did not cause any significant changes in haemodynamics. Mean arterial pressure was elevated by both doses of 40 pmol/kg [91 ± 2 to 99 ± 2 mmHg (12.1 ± 0.3 to 13.2 ± 0.3 kPa), P < 0.05] or 200 pmol/kg [93 ± 2 to 107 ± 3 mmHg (12.4 ± 0.3 to 14.3± 0.4 kPa), P < 0.01], the latter dose increasing cardiac output (14%, P < 0.05) and heart rate (9%, P < 0.05), and the former reducing these parameters (14% and 8%, P < 0.05, respectively). 3. In contrast with the various changes in systemic haemodynamics, renal blood flow transiently increased immediately after bolus injection in a dose-dependent manner (28%, P < 0.05, 50%, P < 0.01 and 110%, P < 0.01 with 4, 40 and 200 pmol of endothelin/kg, respectively). This transient elevation of renal blood flow was followed by a gradual decrease (16%, P < 0.05; 31%, P < 0.01 and 36%, P < 0.01) at 10 min. 4. All neurohormones were elevated in a dose-dependent manner. 5. Among these hormones, arginine vasopressin and plasma renin activity reached a peak level at 5 min (from 2.21 ± 0.45 to 6.37 ± 0.60 pmol/l, P < 0.01, and from 0.65 ± 0.08 to 1.09 ± 0.10 pmol of angiotensin 1 h−1 ml−1P < 0.01, respectively) after bolus injection of 200 pmol of endothelin/kg, whereas adrenocorticotropic hormone and Cortisol reached a peak level at 15 min (from 6.0 ± 0.7 to 18.2 ± 1.5 pmol/l, P < 0.01, and from 4.4 ± 0.9 to 16.5 ± 2.7 × 10−2 μmol/l, P < 0.01, respectively). 6. These results suggest that endothelin is a potent vasoconstrictive peptide in vivo with a marked effect on the renal vascular system, and that it induces elevation of vasoactive hormones directly and/or through central effects.

1. We have investigated the effects of the non-renin-mediated actions of angiotensin converting enzyme inhibitors on the progression of chronic renal failure accelerated by hypertension. For this purpose, we studied the effects of captopril (a thiol-containing angiotensin converting enzyme inhibitor), enalapril (an angiotensin converting enzyme inhibitor without a thiol group) and cysteine (a thiol-containing amino acid which has no angiotensin converting enzyme-inhibitory action) in adriamycin-treated rats with deoxycorticosterone acetate-salt hypertension, in which the renin-angiotensin system was suppressed. 2. There were no significant differences in blood pressure between these groups and the control group [adriamycin-treated group with deoxycorticosterone acetate-salt loading, 206 ± 7 mmHg (27.4 ± 0.9 kPa) at week 10]. 3. Massive proteinuria occurred in all groups. At the end of the experiment (at week 10), urinary protein excretion was significantly reduced in the captopril and cysteine groups compared with the control group. No manifest improvements appeared in the enalapril group. 4. Levels of serum creatinine and blood urea nitrogen increased progressively. At week 10, the increases in the serum levels of creatinine were less in the captopril (87 ± 16 mmol/l) and cysteine (80 ± 19 mmol/l) groups than in the control group (124 ± 27 mmol/l) (P < 0.01). No marked differences were found between the control and enalapril groups. 5. Captopril and cysteine caused more than a threefold reduction in the focal glomerulosclerosis score when compared with that in the control group, but enalapril did not decrease the score. The extent of tubulo-interstitial change was parallel with the focal glomerulosclerosis score. 6. We conclude that the thiol group is possibly involved in the mechanism of the beneficial effects of some angiotensin converting enzyme inhibitors on the progression of chronic renal failure exacerbated by hypertension.

The aim of this study was to investigate the role of depressor systems in glucorticoid-induced hypertension.

To determine whether the central nervous system has a pressor or a depressor role in glucocorticoid-induced hypertension.

The effects of low-dose endothelin on systemic haemodynamics and vasoactive hormones were examined in conscious dogs. In addition, we examined the effects of endothelin on pressor responses to noradrenaline and angiotensin II and the baroreflex regulation of heart rate in conscious dogs. Continuous infusion of 40 fmol/kg per min endothelin for 40min induced a mild but significant reduction in mean arterial pressure from 89.1 ± 1.7 to 82.7 ± 2.0mmHg (P<0.05), associated with decreases in total peripheral resistance 20 min later. A 400 fmol/kg per min dose of endothelin, on the other hand, induced a gradual elevation of mean arterial pressure from 89.2 ± 2.3 to 96.8 ± 2.0 mmHg (P<0.05), associated with increases in total peripheral resistance over 30 min. The 40fmol/kg per min dose of endothelin infusion induced a significant reduction in plasma arginine vasopressin (AVP; P<0.05) and elevations of plasma atrial natriuretic peptide (ANP; P<0.05), plasma prostaglandin E2(PGE2; P<0.05) and plasma 6-keto-prostaglandin F1α(6-keto-PGF1α; P<0.05). The 400 fmol/kg per min dose produced elevations of AVP, ANP, PGE2and 6-keto-PGF1α(P<0.05). Pressor responses to noradrenaline and angiotensin II were significantly attenuated during continuous infusion of 40 fmol/kg per min endothelin, whereas 400 fmol/kg per min endothelin did not induce any significant changes compared with the control. Furthermore, baroreflex sensitivity was attenuated with 40 fmol/kg per min endothelin but did not show any significant changes at 400 fmol/kg per min. These data demonstrate that low-dose endothelin has effects on haemodynamics and hormonal responses which are the opposite of those of the pharmacological dose employed, suggesting that the earlier hypothesized physiological role of endothelin has now been challenged.

Purpose We wanted to clarify, in a large population, the reasons that peritoneal dialysis (PD) was interrupted and to propose appropriate strategies that might prolong the use of PD as a renal replacement therapy.Patients and Methods We enrolled 5 391 patients from 439 centers into the study. Each center used a worksheet to report details about patients who either transferred to hemodialysis (HD) or died on continuous ambulatory peritoneal dialysis (CAPD) over a 6-month period from 1 April 2000, to 30 September 2000.Results We collected 252 drop-out cases from 141 centers. Of the 252 cases, 170 (67.5%) involved transfer to HD, and 82 (32.5%) involved death while on PD. Primary renal diseases were chronic nephritis (CN: 51.6%), diabetic nephropathy (DM: 26.6%), nephrosclerosis (4%), and unspecified or other condition (15.8%). Mean duration on PD in drop-out cases was 4.47 years. The age of patients at transfer to HD was younger (53.7 years) than the age of patients at death on PD (65.2 years). Patients with CN remained on PD significantly longer than did patients with DM (5 years vs 2.4 years). The three main reasons for PD discontinuation were overhydration because of ultrafiltration failure (UFF) or poor compliance with salt and fluid restrictions (34.1%); peritonitis (30.1%); and preference of the physician, patient, or family (6.5%). The proportional share represented by those three major reasons varied with the number of years since PD initiation (from 1 year to more than 8 years). Patients who had been on PD for a longer time were more likely to drop out because of UFF and less likely to drop out because of peritonitis. The three major causes of death on CAPD were cerebrovascular accident (22%), ischemic heart disease (14.6%), and sudden death (9.8%).Conclusion Approximately 10% of patients drop out from PD programs annually in Japan. To prolong PD treatment, new solutions that better preserve peritoneal function need to be developed, and patients and caregivers alike need to receive intensive education in preventing and treating peritonitis.

Two patients on continuous ambulatory peritoneal dialysis (CAPD) developed right massive hydrothorax and were diagnosed as having pleuroperitoneal communication. Thoracoscopic surgery and pleurodesis were performed. It showed that one was caused by multiple flaws in the diaphragm and that the other was attributable to multiple blebs in the diaphragmatic dome. After the procedure, both of them had no recurrence of hydrothorax and underwent CAPD safely. We recommend thoracoscopic surgery and pleurodesis as the first choice of therapeutic methods for pleuroperitoneal communication.

Home blood pressure (BP) is not only more associated with prognosis than clinic BP, but also more stable and reproducible. Patient's marked home BP, however, is not always correct. We conducted some home BP trials using telemedicine mediated precise home BP monitoring via cellphone. The aim is to elucidate the effectiveness of the combination of telmisartan (TEL) and low-dose hydrochlorothiazide (HCTZ) on home BP monitored by our telemedicine system.