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.
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.
Renal Dialysis , Japan , Humans , Conservation of Natural Resources , Surveys and Questionnaires , Ambulatory Care Facilities , Climate Change , East Asian People
As an economic activity, any medical practice involves greenhouse gas (GHG) emissions. In Japan, healthcare accounts for approximately 5% of GHG emissions estimated based on economic costs. In the medical sector, pharmaceuticals account for a large proportion of these emissions. GHG produced during drug manufacturing is generally estimated in three scopes. Scope 1 encompasses direct emissions from equipment and business activities owned by the company; Scope 2 encompasses indirect emissions from the production of energy used in the company's activities; and Scope 3 encompasses GHG emissions outside the scope of the company's ownership or control but related to its supply chain (i.e., material procurement, logistics, sales, and disposal). Japanese pharmaceutical companies, similar to companies in other countries, strive to build a sustainable industry. Their efforts have been objectively evaluated, and several companies have been certified by organizations, such as the Carbon Disclosure Project. Regarding biotechnology and the healthcare and pharmaceuticals sectors, 6 of the 14 highest-ranking companies in the world are located in Japan, compared to one or two companies in other nations. Each pharmaceutical company has generally set high emissions goals, although these goals do not necessarily match due to operational differences between companies. Typical strategies to reduce GHG emissions include consolidation of plant facilities, use of renewable energy and eco-cars, simplified packaging of drugs, and shortening of the supply chain. If consumers ignore such companies' efforts, it could put the brakes on environmental conservation activities in the pharmaceutical sector. Stakeholders, including healthcare providers, could further encourage movement toward environmentally friendly pharmaceuticals by market mechanism through proactively prescribing drugs with less environmental burden. Any clinicians can recognize corporate efforts to protect the environment and contribute to developing environmentally friendly medicine for sustainable growth.
Introduction: Obesity and inappropriate lifestyle is the major risk factors for liver dysfunction and proteinuria. Nevertheless, previous studies have not described the differential impacts of body weight changes and lifestyle modification on already developed liver dysfunction and proteinuria. Methods: The original cohort was 933,490 individuals from the Japanese general population. In this investigation, we included 36,256 obese individuals with elevated levels of aspartate aminotransferase and/or alanine aminotransferase (≥31 IU/L) or positive proteinuria (+/- or more) in both the first and second years. Outcomes were the first normalization of these data defined as improvement in liver dysfunction and proteinuria. Times to outcomes were assessed using the Cox proportional hazards modeling for -1 kg/m2/year change in body mass index (BMI) changes in exercise and alcohol intake. Results: The multivariable-adjusted hazard ratio (HR) for incident improvement in liver dysfunction with BMI change -1.0 kg/m2/year was 1.07 (95% confidence interval [CI] 1.05-1.09) in obesity and that with improved proteinuria was 1.04 (95%CI 1.02-1.07). Compared to subjects without exercise habits, subjects who gained exercise habits exhibited a higher rate of improvement in liver dysfunction (HR 1.08; 95%CI 1.01-1.15) but not in proteinuria (HR 0.98; 95%CI 0.88-1.08). Compared to subjects with continuous alcohol intake habits, subjects who quit alcohol intake also showed a higher rate of improvement in liver dysfunction (HR 1.20; 95%CI 1.09-1.32). Conclusions: This study suggested that weight loss greater than 1 kg/m2/year improves liver dysfunction and dipstick proteinuria in obesity. Particularly, liver dysfunction can be remedied by acquiring an exercise habit and quitting alcohol intake.
In Japan, non-farmers and people living in urban areas have not been greatly affected by environmental changes. In contrast, primary producers living in rural areas increasingly suffering from declining crop yields and drastically reduced catches of wild animals and seafood because of recent environmental changes. Studies, mainly from overseas, have reported that farming is an especially stressful occupation associated with high rates of depression and suicide, and the relationship between climate change and depression, as well as between climate change and suicide, is almost certain in rural communities. Particularly striking examples include the impact on the mental health of farmers in rural Australia and the Inuit in the Canadian Arctic, who are losing their livelihoods because of ecological collapse; this mental distress is known as "ecological grief". Such mental distress may be a major cause of depression and suicide among people in rural areas and Japan is no exception. I hoped that the concept of mental distress due to environmental changes will be recognized in Japan, leading to more eco-friendly attitudes that can promote the health of people living in rural areas and protect the surrounding ecosystem.
Concomitant with nephrotic syndrome and multicentric castleman's disease (MCD) has only been described in a limited number of small studies and case reports. Among those, none confirmed the renal pathology prior to the onset of MCD, and none of the cases had a history of nephrotic syndrome. A 76 year-old Japanese man visited a nephrologist because of incident nephrotic syndrome. He had previously experienced three episodes of nephrotic syndrome, the last one 13 years ago, and had been diagnosed with membranous nephropathy by renal biopsy. Apart from these previous episodes, he also suffered from systemic lymphadenopathy, anemia, elevated C-reactive protein, polyclonal hypergammopathy, and elevated interleukin (IL)-6. An inguinal lymph node biopsy revealed CD138-positive plasma cells in the interfollicular region. Based on these findings, MCD was diagnosed. Renal biopsy indicated primary membranous nephropathy with spike lesions and bubbling in the basement membranes and deposition of immunoglobulin (Ig) G, IgA, IgM, and phospholipase A2 receptor along the glomerular basement membrane. Corticosteroid monotherapy successfully reduced the edema, proteinuria, and IL-6, but hypoalbuminemia was not sufficiently improved due to castleman's disease and remission of the nephrotic syndrome was not achieved. Later, tocilizumab was administered for remission induction in another facility. To the best of our knowledge, this represents the first report of Castleman's disease with previously diagnosed membranous nephropathy. This case does not provide a causal mechanism for the pathophysiology, but it may be worth suggesting possible involvement of MCD as a trigger for recurrence of membranous nephropathy.
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.
Immunosuppressive Agents , Nephrotic Syndrome , Humans , Immunosuppressive Agents/therapeutic use , Nephrotic Syndrome/drug therapy , Network Meta-Analysis , Rituximab/therapeutic use , Cost-Effectiveness Analysis , Calcineurin Inhibitors/therapeutic use , Steroids/therapeutic use , Recurrence , Treatment Outcome
Objective The relationship between obesity and risk of death in chronic kidney disease (CKD) patients remains controversial. In addition, no clear evidence has been accumulated regarding whether or not exercise improves mortality in CKD patients. Methods The original cohort was based on a Japanese general population of 685,889 people from 40 to 74 years old who had undergone annual specific health checkups. The number of all-cause deaths during follow-up (mean, 4.7 years) in this study was 1,490. Information on walking and exercise habits was obtained by questionnaires. The study population was divided into 4 categories by the combination of CKD and obesity [body mass index (BMI) ≥25.0 kg/m2]. Changes in the BMI and walking and exercise habits were determined by results for the first year and following year. Results Obese CKD patients with weight gain (BMI increase by more than +1.0 kg/m2/year) showed a higher crude mortality (1.32%) than those with a stable BMI (within ±1.0 kg/m2/year; 0.69%). In the obese CKD population, mortality was higher with loss of exercise habits (0.96%) than in those continuously maintaining exercise habits (0.52%). The age- and sex-adjusted hazard ratio for all-cause death was 2.23 in the group with weight gain compared to the group with stable weight (p<0.01) and 2.08 in the group with loss of exercise habits compared to those who maintained exercise habits (p<0.01). Conclusion This observational cohort study suggested that loss of exercise habits as well as weight gain of more than 1 kg/m2/year might worsen all-cause mortality in the obese CKD population.
East Asian People , Exercise , Obesity , Renal Insufficiency, Chronic , Adult , Aged , Humans , Middle Aged , Body Mass Index , Cohort Studies , Obesity/complications , Obesity/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/mortality , Risk Factors , Weight Gain
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.
Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Creatinine , Renal Dialysis , Peritoneum , Kidney/physiology , Kidney Failure, Chronic/therapy
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.
Cardiovascular Diseases , Renal Insufficiency, Chronic , Humans , Follow-Up Studies , Japan , Kidney , Renal Insufficiency, Chronic/complications , Glomerular Filtration Rate , Primary Health Care , Disease Progression
Malignant pleural mesothelioma is rarely associated with nephrotic syndrome. Cryoglobulinemia is found in various pathological statuses, such as hepatitis C virus infection but rarely in malignant neoplasms. We recently encountered a patient with malignant mesothelioma coincident with nephrotic syndrome and cryoglobulinemia in the course of chemotherapy. A 60-year-old man employed as a building painter was diagnosed with malignant mesothelioma by lung biopsy two years earlier and was started on chemotherapy. Nivolumab seemed effective in controlling mesothelioma, but skin immune-related adverse events occurred during the course of treatment. After discontinuation of nivolumab and administration of gemcitabine as an alternative therapy, the patient was referred to a nephrologist because of the subsequent development of edema, renal injury, and proteinuria. Following the investigation, he was diagnosed with nephrotic syndrome and cryoglobulinemia with C4-dominant cold activation. However, a percutaneous renal biopsy could not be performed due to persistent severe cough induced by pleural involvement. The patient died a little over three years after the pathological diagnosis of pleural mesothelioma. Our case had three key features nephrotic syndrome was possibly associated with malignant mesothelioma; cryoglobulinemia occurred in malignant mesothelioma; and concomitant nephrotic syndrome and cryoglobulinemia occurred after chemotherapy. Unfortunately, our rare case lacks a basis in renal pathology or evidence of links between the pathogenesis of malignant mesothelioma, cryoglobulinemia, and nephrotic syndrome. This case does not provide a causal mechanism, but may be worth adding to the case list as one of the rare renal involvement in a patient with malignant mesothelioma.
Acute tubulointerstitial nephritis (ATIN) can be caused by any number of factors, and it accounts for several percent of renal biopsy cases. In Japan, case reports exist, but there are few single-center series of ATIN cases. Case 1. A teenage male patient developed fever and cough on day X-61 and was found to have normal renal function and positive C-reactive protein (CRP) by his primary care physician. On day X-20, he presented with cough and nasal discharge in addition to low-grade fever, and his doctor noted renal dysfunction with serum creatinine of 2.12 mg/dL, negative urine occult blood, and positive urine glucose. Renal biopsy results showed diffuse interstitial nephritis with scarce glomerular involvement. There was no concurrent uveitis. Renal function normalized after 4 months of treatment with moderate-dose prednisolone. Cases 2-10. Of the 422 cases for which renal biopsies were performed at our institution from 2008 to 2021, acute tubulointerstitial nephritis was confirmed clinically and pathologically in 9 cases in addition to case 1, accounting for 2.4% of all biopsy cases. In the analysis of the 10 patients, the median age was 40 years old, eGFR at diagnosis was 19.4 (3.2-49.1) mL/min/1.73 m2, and 2 of them underwent hemodialysis, but both were weaned from dialysis, and the eGFR after treatment was 53.6 (20.8-110.0) mL/min/1.73 m2; all patients showed improvement (P < 0.001). Treatment consisted of steroids in 8 patients and no steroids in 2 patients, the latter being treated by discontinuation of the suspect drugs and treatment of infection; 7 of the 10 patients were examined for ocular uveitis, and uveitis was diagnosed in 5 patients. The causes and clinical course of ATIN are diverse, but it is treated according to individual judgment in addition to standard treatment, and it generally has a good renal prognosis.
Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes (POEMS) syndrome manifests as elevated levels of vascular endothelial growth factor (VEGF) and monoclonal gammopathy. We treated a case of POEMS syndrome showing monoclonality in both IgA-λ and IgG-κ. Serial renal biopsies before treatment and after normalization of the VEGF levels suggested that glomerular microangiopathy had developed due to VEGF, while biclonal gammopathy was not eliminated. The renal pathology, proteinuria, and renal function all clearly improved. Although severe polyneuropathy limited activities of daily living and enforced a bedridden state, the patient dramatically regained his motor function, achieving crutch walking after induction of remission. This case is highly notable due to the presence of biclonality and repeated biopsies.
Monoclonal Gammopathy of Undetermined Significance , POEMS Syndrome , Paraproteinemias , Activities of Daily Living , Humans , POEMS Syndrome/complications , POEMS Syndrome/diagnosis , Paraproteinemias/complications , Vascular Endothelial Growth Factor A
Both the frequency and severity of heat stress-related health problems have been increasing globally, probably due to global warming. The Intergovernmental Panel on Climate Change published a landmark climate report, the 6th Assessment Report, which shocked the world. It emphasized that anthropogenic activities, such as the combustion of fossil fuels, oil, gas, and coal, were responsible for climate change. The combination of population aging, and increased temperatures has meant that the number of people requiring emergency transport for heatstroke has been increasing in Japan from 2008 to 2020. The increase in ambient temperatures and the number of patients requiring emergency transport were strongly correlated (Spearman correlation coefficient: r=0.669 and P=0.008). Like many human activities, medical care is resource intensive and contributes significantly to climate change through the consumption of energy and water, as well as the emission of greenhouse gases. As healthcare professionals, we need to be cognizant of how our eco-friendly activities both on and off the job can contribute to saving both the patients and us.
