A survey of environmental sustainability in Japanese dialysis facilities.

BACKGROUND: Dialysis practice has a particularly high environmental impact, including responsible for carbon emissions and climate change. Insufficient research has been conducted on environmental sustainability activities in dialysis therapy in Japan. METHODS: We conducted an online Green Survey comprising 30 question items based on a previously conducted survey in Australia. Between August and September 2023, this was sent to members of the Japanese Association of Dialysis Physicians, including hospital and clinic physicians, working across 885 dialysis facilities in Japan. RESULTS: In total, 255 (29%) facilities responded to the survey. More than half of the facilities (n = 157; 61.6%) responded that they did not have a strategy, policy, or action plan for environmental sustainability. In four-fifths of the facilities (n = 208; 81.6%), no "green team" or committee had been formed to promote environmental protection. By contrast, most of the surveyed facilities had emergency strategies for natural disasters, such as covering for patient visits and staff commuting during extreme weather conditions (n = 169; 66.3%), water shortages (n = 159; 62.4%), and power outages (n = 188; 73.7%). CONCLUSIONS: Following the UK, Australia and New Zealand, and Portugal, this is the fourth Green Survey to be conducted, and the first on environmental sustainability among kidney health-care providers in Japan. The results indicated that daily activities for environmental protection are still lacking at many facilities, even though the management of dialysis treatment during a natural disaster is well conducted.

Effect of proactive combination therapy with peritoneal dialysis and hemodialysis on technique survival and mortality.

PURPOSE: Clinically relevant evidence for the timing of starting combination therapy with peritoneal dialysis and hemodialysis remains scarce. We retrospectively examined whether combination therapy during the induction phase of dialysis prolongs peritoneal dialysis duration. METHODS: This retrospective study includes 160 patients who underwent combination therapy from 20 dialysis facilities. Four groups were categorized: combination at peritoneal dialysis induction (n = 12, Proactive combination group), and combination following peritoneal dialysis durations of < 2 years (n = 65), 2-5 years (n = 70), or > 5 years (n = 13). Differences in technique survival of dialysis, mortality, and hospitalization due to cardiovascular events in the groups were observed. RESULTS: The Proactive combination group had the longer mean duration of combination therapy (3.18 years) comparing to that of combination therapy following peritoneal dialysis (1.45 years), but total peritoneal dialysis duration was shorter than in control groups (4.02 years). Of the 160 cases in the entire cohort, there were 8 deaths, 18 ischemic heart disease hospitalizations, and 18 stroke hospitalizations. The Proactive group had lower crude mortality rate (0/12 cases, 0.0%) and crude hospitalization rate for ischemic heart disease (1/11, 8.3%) than the other groups. However, this cohort study did not have enough statistical power to adjust for patients' background, and we were unable to fully examine the differences in such clinical outcomes by the timing of initiation of combination therapy. CONCLUSION: Use of combination therapy in the induction phase might prolong the duration of combination therapy, but is not necessarily effective for prolonging peritoneal dialysis technique survival.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Sustainability of peritoneal dialysis and renal function with proactive combination therapy.

Most combined peritoneal dialysis and hemodialysis therapies are used to compensate for the lack of dialysis volume and efficiency in pre-started peritoneal dialysis patients. The aim was to determine the effects on both peritoneal dialysis and residual renal function when proactively combined therapy is started at dialysis induction. This report was based on observation of 10 patients who initiated dialysis therapy with a combination of peritoneal and hemodialysis at induction, and the control group consisted of 24 patients with peritoneal monotherapy in a single dialysis center. The technical survival of peritoneal dialysis therapy and urinary volume and creatinine clearance as residual renal function were assessed. Technical survival of peritoneal dialysis during the 5-year observation period was much better in patients who started with proactive combination therapy than with peritoneal dialysis monotherapy. Between induction and 24 months later, median urinary volume (interquartile value) changed from 1500 (1100-1583) to 800 (545-1875) mL/day and from 1600 (1300-2150) to 1480 (115-1885) mL/day for peritoneal alone and for combination therapy, respectively. Creatinine clearance values changed from 7.0 (6.0-8.7) to 2.0 (1.0-3.0) mL/min for peritoneal alone and from 6.0 (4.0-7.3) to 3.0 (0.5-4.0) mL/min for combination therapy. Though some possible confounding factors, including selection bias, cannot be ruled out, this investigation suggests the benefit of proactive combination dialysis therapy on the sustainability of peritoneal dialysis and residual renal function.

Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis.

Therapeutic options with immunosuppressive agents for glomerular diseases have widened with refinements to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines from 2012 to 2021. However, international guidelines do not necessarily match the reality in each country. Expensive therapies such as rituximab and calcineurin inhibitors are sometimes inaccessible to patients with refractory nephrotic syndrome due to cost or regulations. Under the Japanese medical insurance system, rituximab is accessible but still limited to steroid-dependent patients who developed idiopathic nephrotic syndrome in childhood. Based on international KDIGO guidelines and other national guidelines, possible applications of immunosuppressive agents for nephrotic syndrome are comprehensively examined in this review. While rituximab has become the mainstay of immunosuppressive therapy for nephrotic syndrome, clinical trials have indicated that options such as cyclophosphamide, calcineurin inhibitors, and mycophenolate mofetil would be preferable. Given the rising number of patients with nephrotic syndrome worldwide, KDIGO guidelines mention the need for further consideration of cost-effectiveness. If the new option of rituximab is to be the first choice in combination with steroids for nephrotic syndrome, its cost-effectiveness should also be verified. Among the few studies examining the cost-effectiveness of treatments for nephrotic syndrome, administration of rituximab to young adults has been shown to be cost-beneficial, at least in Japan. However, further large-scale studies involving multiple facilities are needed to verify such findings. Network meta-analyses have concluded that the efficacy of rituximab remains controversial and confirmation through high-quality studies of large cohorts is needed. To this end, the mechanisms of action underlying immunosuppressive agents, both old and new, need to be understood and experience must be accumulated to evaluate possible effects and side effects.

Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice.

Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcεRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1-/-) mice developed more severe hypothermia, a higher mortality rate and a greater incidence of diarrhea than did wild-type (WT) mice in an oral ovalbumin (OVA)-induced food allergy model. MC-deficient Mas-TRECK mice, which had been reconstituted with either WT or Milr1-/- bone marrow-derived cultured MCs, did not develop hypothermia in this food allergy model. On the other hand, depletion of basophils by injection of anti-CD200R3 antibody rescued Milr1-/- mice from lethal hypothermia but not from diarrhea. In vitro analyses demonstrated that Allergin-1 inhibits IgE-dependent activation of both human and mouse basophils. Thus, Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis.

Literature review of allograft adenovirus nephritis and a case presenting as mass lesions in a transplanted kidney without symptoms of urinary tract infection or acute kidney injury.

Adenovirus (AdV) infection is a common complication in bone marrow/hematopoietic stem cell transplant and solid organ transplant recipients. AdV infection usually presents as hemorrhagic cystitis, but sometimes it can progress to acute kidney injury showing AdV nephritis (AdVN). We present the case of a 52-year-old Japanese female who had received a living kidney transplantation (KT) from her husband. At 21 months post-KT, the patient presented with a fever, but no renal dysfunction and no abnormal urine findings. A contrast-enhanced computed tomography (CT) scan revealed a few mass lesions with hypoperfusion in the transplanted kidney. An enhanced CT-guided biopsy targeting one of these lesions revealed a necrotizing tubulointerstitial nephritis suggesting AdVN. The polymerase chain reaction tests for ADV were negative in a urine sample but positive in the sera and the frozen kidney biopsy samples. AdVN can manifest as an unusual pattern of acute lobar nephritis/acute focal bacterial nephritis-like localization without symptoms of acute kidney injury or urinary tract infection. Enhanced CT can provide clues for clinical diagnosis.

Estimating the prevalence of definitive chronic kidney disease in the Japanese general population.

BACKGROUND: Most data on chronic kidney disease (CKD) prevalence has been based on single measurements of renal function and proteinuria. The aim was to determine the prevalence of CKD diagnosed by chronic proteinuria and/or reduced eGFR in a recent year in Japan. METHODS: In the main study, using a population-based cohort in Japan, the overall prevalence of CKD, defined as persistent positive proteinuria and/or eGFR < 60 ml/min/1.73 m2, was determined. Of 2,849,557 persons, 763,104 had data for eGFR and proteinuria in both 2014 and 2015. For estimating number of CKD cases in Japanese adults, a regional cohort data with age ranging 22-87 years (N = 22,037) was further applied to the analysis. RESULTS: Definitive CKD was present in 2.3-23.0% of men and 1.7-17.1% of women age from 40 to 74 years in the main cohort. The estimated prevalence of reduced eGFR and/or proteinuria in the baseline year alone was 15.7% in men and 13.6% in women; the prevalence of definitive CKD was 10.9% in men and 9.2% in women. The number of CKD cases based on a single-year test in Japanese adults over 20 years of age increased from 13.3 million to 14.8 million between 2005 and 2015. CONCLUSIONS: Recent changes in prevalence of CKD seem to be mainly caused by an increase in Japan's elderly population. Although past reports may lead to overdiagnosis of CKD by a single-year test, the estimated number of definitive CKD was 10.2 million in 2015.

Ratio of serum creatinine to cystatin C is related to leg strength in predialysis CKD patients.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) patients have lower levels of physical function. Especially, leg strength is important for daily living and preventing falls. However, physical function screenings are difficult to perform at clinical sites. To find clinically useful method to evaluate physical function in predialysis CKD patients, we tried to evaluate the relationship between the ratio of serum creatinine to serum cystatin C (Cre/CysC), and knee extensor muscle strength/body weight (KEMS) which reflects their leg strength. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We recruited 147 outpatients with CKD (87 men; mean age, 61.6 ± 9.8 years; mean eGFRcreat, 40.7 ± 12.9 mL/min/1.73m2) in this cross-sectional study. KEMS was assessed using a wire strain gauge dynamometer. Skeletal muscle mass and body fat mass were assessed by bioelectrical impedance analysis. RESULTS: The mean value of Cre/CysC was 1.01 ± 0.18. The mean value of KEMS was 1.60 ± 0.47 Nm/kg. In multivariate linear regression analysis, skeletal muscle mass (p < 0.01), body fat mass (p < 0.01), hemoglobin (p = 0.01), and Cre/CysC (p < 0.01) was independently related to KEMS. The correlation between Cre/CysC and KEMS is stronger in high quantile of Cre/CysC. CONCLUSIONS: In predialysis CKD patients, KEMS showed lower as CKD stage advanced. Cre/CysC is significantly related to KEMS independently. Cre/CysC may be an alternative marker for leg strength in CKD patients and even more valuable to utilize in cases with high Cre/CysC.

Weight loss reduces the incidence of dipstick proteinuria: a cohort study from the Japanese general population.

BACKGROUND: Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the incidence of proteinuria in the general population is still unclear. METHODS: The study cohort was based on a general population of 9,33,490 from 40 to 74 years of age who had undergone annual specific health checkups. The subjects who were finally included were the 2,74,598 people for whom all the data necessary for this study were available. The incidence of proteinuria in this study was defined as negative proteinuria at the primary and secondary survey years, and newly developed proteinuria during subsequent follow-up years. RESULTS: Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI < 18.5 kg/m2) and normal weight (18.5-24.9 kg/m2) groups, the obese group (≥ 25.0 kg/m2) with rapidly decreased weight had a lower incidence compared to those with stable weight. In the obese population, a rapid decline of BMI (- 1 to - 5 kg/m2 per year) was associated with a reduced risk (hazard ratio [95% confidence interval]; 0.89 [0.80-0.98], P = 0.02) of proteinuria. CONCLUSIONS: Weight reduction can lead to a risk reduction of 11% in the incidence of proteinuria in obese Japanese adults. This is the first study to report the effects of weight reduction on the early phase of chronic kidney disease in obesity relevant to the characteristics of the Japanese general population. The present findings might have a role in renal health promotion in Japan.

Comparison of annual eGFR decline among primary kidney diseases in patients with CKD G3b-5: results from a REACH-J CKD cohort study.

BACKGROUND: Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. METHODS: Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). RESULTS: Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, - 2.96 ± 0.13; PKD, - 2.82 ± 0.17; and others, - 1.95 ± 0.05, p < 0.01). The declines were faster with higher CKD stages. In DKD patients, the eGFR decline was significantly faster in CKDG5 than CKDG4 (- 4.10 ± 0.18 vs - 2.76 ± 0.20, p < 0.01), while these declines in PKD patients were similar. The eGFR declines in PKD patients were significantly faster than DKD patients in CKDG4 (- 2.92 ± 0.23 vs - 2.76 ± 0.20, p < 0.01) and in CKDA2 (- 3.36 ± 0.35 vs - 1.40 ± 0.26, p < 0.01). CONCLUSION: Our study revealed the disease-specific annual eGFR declines by CKD stages and the level of proteinuria. Comparing to the other kidney diseases, the declines in PKD patients were getting faster from early stages of CKD. These results suggest the importance of CKD managements in PKD patients from the early stages.

Physical functioning in patients with chronic kidney disease stage G3b-5 in Japan: The reach-J CKD cohort study.

AIM: Chronic kidney disease (CKD) is an important public health problem. Recently, CKD has been found to be associated with poor physical functioning in community-dwelling elderly individuals. However, the physical functioning of non-dialysis (ND) patients with advanced CKD treated by nephrologists is unknown. METHODS: Patients with ND-CKD stage G3b-5 who participated in a nationwide Reach-J CKD cohort study were included in this study. Physical functioning and physical activity were assessed by the Katz Index, Lawton-Body instrumental activities of daily living (IADL) scale, and Rapid Assessment of Physical Activity questionnaire of the international CKD Outcomes and Practice Patterns Study (CKDopps) questionnaires. Dichotomies between good and poor physical functioning and physical activity scores were explored. RESULTS: Among 1628 patients, 84.3% had good physical functioning. Poor physical functioning was more common with older age (p < .001), higher CKD stage (p < .05), and comorbid conditions such as diabetes (p < .001), cardiovascular disease (p < .05), cerebrovascular disease (p < .001), and cancer (non-skin) (p < .05). Forty percent of the patients were inactive. Physical inactivity was more common with older age (p < .001) and higher CKD stage (p < .001). CONCLUSION: A minority, but sizeable proportion of patients with advanced CKD treated by nephrologists in Japan have some disability in ADLs/IADLs. Nephrologists need to routinely assess the physical functioning and physical activity of patients with advanced CKD to provide individualized guidance and comprehensive support to these patients for their daily life.

Preserved peritoneal function by short-term two-day peritoneal rest in hemodialysis combination therapy patients.

Several reports have demonstrated that peritoneal rest (PR) is considered to preserve the peritoneal function in peritoneal dialysis (PD) patients. However, there has been no report that examines the peritoneal permeability before and after a short-term PR of two days. We examined the effect of the two-day PR on peritoneal permeability. We observed and compared the daily PD ultrafiltration changes in the four PD and hemodialysis (HD) combination patients from the start of dialysis therapy throughout the total observation period of each case. Next, 6 months after the initiation of dialysis therapy we performed a set of peritoneal equilibrium tests (PET) before and after the 2-day PR. D/P creatinine, daily urine volume, daily ultrafiltration volume in PD, weekly residual renal creatinine clearance, and weekly PD creatinine clearance were measured. The daily PD ultrafiltration volume increased significantly after the 2-day PR, and gradually decreased over the last four days throughout the observation period in each patient. In the PET results, D/P creatinine in all patients decreased after the short-term PR, and accordingly the peritoneal ultrafiltration volume increased. However, urine volume, residual renal creatinine clearance, and peritoneal creatinine clearance did not change. The peritoneal permeability clearly decreased after the short-term PR. The repeated improvement in the PD ultrafiltration volume after the short-term PR implies that the peritoneal permeability alteration might be due to a reversible functional change in the initial dialysis period. These results suggest that a short-term PR may preserve the peritoneal function.

Biologicals targeting T helper cell subset differentiating cytokines are effective in the treatment of murine anti-myeloperoxidase glomerulonephritis.

Anti-myeloperoxidase nephritogenic autoimmunity induces severe glomerulonephritis. To assess the therapeutic potential of monoclonal antibodies targeting T helper (Th) subset differentiation determining cytokines, we studied a murine model of anti-myeloperoxidase glomerulonephritis. The temporal participation of T helper subsets was determined by quantitating gene expression of CD4+ T-cells isolated from nephritic kidneys and cytokine production by lymphocytes from nodes draining myeloperoxidase immunization sites. Th17 cytokines (IL-17A and IL-6) rose rapidly but declined as autoimmunity matured when Th1 cytokines (IL-12 and TNF) predominated. Therefore, T helper subset participation in anti-myeloperoxidase autoimmunity is biphasic, with Th17 early and Th1 late. To confirm the functional relevance of this biphasic pattern, we compared systemic anti-myeloperoxidase autoimmunity in wild type, Th17 deficient and Th1 deficient mice. Early, Th1 deficient mice developed similar autoimmunity and glomerulonephritis to wild type mice. However, Th17 deficient mice had significantly reduced anti-myeloperoxidase autoimmunity. In late autoimmunity, Th1 deficient mice developed reduced autoimmunity and were protected from anti-myeloperoxidase glomerulonephritis. The therapeutic potential of these findings were demonstrated by neutralizing monoclonal antibodies. Targeting IL-23p19 attenuated early Th17 dominated anti-myeloperoxidase autoimmunity and glomerulonephritis but not late phase disease. Targeting IL-12p35 attenuated late phase Th1 dominated anti-myeloperoxidase autoimmunity and glomerulonephritis but not early autoimmunity or glomerulonephritis. Targeting both T helper subsets with an anti-IL-12p40 monoclonal antibody was effective during both early and late phases of anti-myeloperoxidase glomerulonephritis. Thus, definition of dominant T helper differentiating subsets in anti-myeloperoxidase glomerulonephritis by renal CD4+ T-cell cytokine gene expression allows effective proper phase monoclonal antibody treatment of anti-myeloperoxidase glomerulonephritis.

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study.

BACKGROUND: Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)-an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2-has remained largely unexamined. METHODS: We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5 years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event. RESULTS: Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan. CONCLUSIONS: Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

A Case in Which Renal Function and Peritoneal Function Were Maintained for Ten Years by Proactive Combination Therapy with Peritoneal Dialysis and Hemodialysis.

To avoid loss of residual renal function (RRF) and to enhance solute clearance, we sometimes, from the initiation of peritoneal dialysis (PD) therapy, combine PD with hemodialysis (HD) that removes little or no fluid. In one typical valuable case, a 51-year-old woman with diabetic nephropathy who selected combined PD and HD therapy as her first dialysis method has continued on that therapy for 10 years. Her dialysis schedule consists of 5 PD days and 1 HD day without fluid removal weekly. Because this combination therapy was proactively started at dialysis initiation, good fluid control could be kept with urinary excretion and PD ultrafiltration. Stable peritoneal equilibration test data indicate that peritoneal resting might be expected to be beneficial for the preservation of peritoneal function. This case demonstrates that proactive combination therapy can be extremely useful for preserving both RRF and peritoneal function, indicating a good prognosis.

Involvement of pentraxin-3 in anti-neutrophil cytoplasmic antibody production induced by aluminum salt adjuvant.

OBJECTIVES: Pentraxin 3 (PTX3) is a multifunctional soluble factor. PTX3 can be involved in the regulation of vasculitis and is expressed in the cytoplasm of neutrophils. As anti-neutrophil cytoplasmic antibody (ANCA) is recognised as a cause of vasculitis, we aimed to discover the role of PTX3 in ANCA production in vivo. METHODS: To this end, we used aluminum salt (alum), which induces neutrophil extracellular traps, as an adjuvant for producing anti-myeloperoxidase-ANCA (MPO-ANCA). Specifically, we intraperitoneally injected alum and recombinant MPO (rMPO) into MPO-deficient mice and then measured the concentration of anti-MPO IgG in their blood. To show the involvement of extracellular PTX3 in this model, we assessed PTX3 protein content and host double-stranded DNA levels in the mice's peritoneal fluid after alum injection. In addition, we simultaneously administered recombinant PTX3, rMPO and alum to MPO-deficient mice to assess the function of PTX3 in producing anti-MPO IgG in vivo. RESULTS: Anti-MPO IgG was produced by the alum + rMPO immunisation model in MPO-deficient but not wildtype mice. Injection of alum induced extracellular PTX3 as well as double-stranded DNA and dead cells in MPO-deficient mice. Simultaneous injection of recombinant PTX3 with rMPO and alum attenuated the production of anti-MPO IgG in MPO-deficient mice. CONCLUSIONS: Our current findings provide evidence that PTX3 attenuates the production of murine MPO-ANCA.

Peritoneal Dialysis Preserves Residual Renal Function and Reduces Oxidative Stress During the Initial Period of Dialysis Therapy.

Patients with end-stage renal failure are believed to have an increase of oxidative stress. However, any variation in oxidative stress between patients receiving hemodialysis (HD) and those receiving peritoneal dialysis (PD) are still unclear. In the present study, we investigated variation in oxidative stress in 54 HD and 23 PD patients during their initial dialysis period.We measured serum pentosidine and indoxylsulfuric acid as markers of oxidative stress every 6 months from the start of the dialysis therapy to 30 months of treatment. Serum pentosidine was significantly lower in the PD patients than in the HD patients. Serum indoxylsulfuric acid was also significantly lower in the PD group compared with the HD group at 6, 12, and 18 months. Compared with the HD patients, the PD patients maintained significantly higher urine volumes (a marker of residual renal function) throughout the study, except at 24 months.Our findings demonstrate that, compared with HD patients, PD patients experience lower levels of oxidative stress because of higher preserved residual renal function during the initial dialysis period.

Combination Therapy with Peritoneal Dialysis and Hemodialysis from the Initiation of Renal Replacement Therapy Preserves Residual Renal Function and Serum Albumin.

Peritoneal dialysis (PD) and hemodialysis (HD) combination therapy is considered for the improvement of ultrafiltration failure and uremic symptoms in PD patients with loss of residual renal function (RRF). However, a rapid decline in RRF is one of the critical drawbacks to such therapy. In contrast, we started patients on combination therapy as a proactive option at the initiation of dialysis.In patients on HD (n = 52), PD (n = 21), and combination dialysis (n = 13), we studied changes in RRF, blood parameters, and peritoneal permeability for 30 months. Residual renal function was better preserved in patients who received PD and HD combination therapy from the start of the dialysis therapy than in patients who received HD alone, and serum albumin was better preserved in the combination-therapy patients than in the patients who received PD alone. No significant differences in peritoneal permeability were observed between the patients on PD and those on combination therapy. Blood parameters were not significantly different between the three groups.Because our proactive combination therapy option has beneficial effects compared with HD or PD therapy alone, combination therapy should be considered a new modality of renal replacement therapy.