Nephropathy In Japan Research Articles

Cost-effectiveness of sodium-glucose cotransporter-2 inhibitors in the treatment of diabetic nephropathy in Japan.

To assess the cost-effectiveness of diabetic nephropathy treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors in Japanese clinical practice, considering diabetes-related complications. A population-based Monte Carlo simulation was used to estimate the cost-effectiveness for people with diabetic nephropathy who initiated pharmacotherapy with an SGLT2 inhibitor plus conventional treatment or conventional treatment alone, based on quality-adjusted life-years (QALYs) and healthcare costs. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation study (CREDENCE) and the Japanese Society for Dialysis Research statistical survey were the primary sources of probability and mortality, while Japanese Health Insurance Claims Data were the cost source. The state transition model included diabetic nephropathy, hospitalization due to cardiovascular disease, dialysis, and death. One-way and probabilistic sensitivity analyses were used to explore model uncertainty. Using the threshold of JPY 5 000 000 per QALY, SGLT2 inhibitor plus conventional treatment was more cost-effective than conventional treatment alone, with an incremental cost-effectiveness ratio of JPY 654 309 per QALY. Treating 100 000 people, SGLT2 inhibitor plus conventional treatment prevented 2234 deaths and reduced 5793 fewer heart failure cases, 3967 fewer myocardial infarctions and stroke events. Sensitivity analysis affirmed the robustness of these results for patients aged under 70 years. The SGLT2 inhibitor treatment appeared to be cost-effective for the overall population of our study and particularly for younger patients (<70 years old). For older patients (≥70 years old), the cost-effectiveness was less clear and may require further evaluation. Decision-makers should consider this age-based heterogeneity when making recommendations about SGLT2 inhibitor treatment.

Cost-Effectiveness of School Urinary Screening for Early Detection of IgA Nephropathy in Japan

The evidence for and against screening for chronic kidney disease in youths who are asymptomatic is inconsistent worldwide. Japan has been conducting urinary screening in students for 50 years, allowing for a full economic evaluation that includes the clinical benefits of early detection and intervention for chronic kidney disease. To evaluate the clinical effectiveness and cost-effectiveness of school urinary screening in Japan, with a focus on the benefits of the early detection and intervention for IgA nephropathy, and to explore key points in the model that are associated with the cost-effectiveness of the school urinary screening program. This economic evaluation with a cost-effectiveness analysis used a computer-simulated Markov model from the health care payer's perspective among a hypothetical cohort of 1 000 000 youths aged 6 years in first grade in Japanese elementary schools, followed up through junior and high school. The time horizon was lifetime. Costs and clinical outcomes were discounted at a rate of 2% per year. Costs were calculated in Japanese yen and 2020 US dollars (¥107 = US $1). School urinary screening for IgA nephropathy was compared with no screening. Outcomes were costs and quality-adjusted life-years (QALYs). Cost-effectiveness was determined by evaluating whether the incremental cost-effectiveness ratio (ICER) per QALY gained remained less than ¥7 500 000 (US $70 093). In the base case analysis, the ICER was ¥4 186 642 (US $39 127)/QALY, which was less than the threshold. There were 60.3 patients/1 000 000 patients in the no-screening strategy and 31.7 patients/1 000 000 patients in the screening strategy with an end-stage kidney disease. Cost-effectiveness improved as the number of screenings decreased (screening frequency <3 times: incremental cost, -¥75 [US $0.7]; incremental QALY, 0.00025; ICER, dominant), but the number of patients with end-stage kidney disease due to IgA nephropathy increased (40.9 patients/1 000 000 patients). Assuming the disutility due to false positives had a significant impact on the analysis; assuming a disutility of 0.01 or more, the population with no IgA nephropathy had an ICER greater than the threshold (¥8 304 093 [US $77 608]/QALY). This study found that Japanese school urinary screening was cost-effective, suggesting that it may be worthy of resource allocation. Key factors associated with cost-effectiveness were screening cost, the probability of incident detection outside of screening, and IgA nephropathy incidence, which may provide clues to decision-makers in other countries when evaluating the program in their own context.

Current Status of Treatments for IgA Nephropathy in Japan: A Descriptive Study Using Claims Database

Current Status of Treatments for IgA Nephropathy in Japan: A Descriptive Study Using Claims Database

Current treatment status of IgA nephropathy in Japan: a questionnaire survey

BackgroundIn 2020, the Committee of Clinical Practical Guideline for IgA Nephropathy (IgAN) revised the clinical practice guidelines. Herein, we conducted a questionnaire survey to assess the potential discrepancies between clinical practice guidelines and real-world practice in Japan.MethodsA web-based survey of members of the Japanese Society of Nephrology was conducted between November 15 and December 28, 2021.ResultsA total of 217 members (internal physicians: 203, pediatricians: 14) responded to the questionnaire. Of these respondents, 94.0% answered that the clinical practice guidelines were referred to “always” or “often.” Approximately 66.4% respondents answered that histological grade (H-Grade) derived from the “Clinical Guidelines for IgA nephropathy in Japan, 3rd version” and the “Oxford classification” were used for pathological classification. Moreover, 73.7% respondents answered that the risk grade (R-grade) derived from the “Clinical Guidelines for IgA nephropathy in Japan, 3rd version” was referred to for risk stratification. The prescription rate of renin–angiotensin system blockers increased based on urinary protein levels (> 1.0 g/day: 88.6%, 0.5–1.0 g/day: 71.0%, < 0.5 g/day: 25.0%). Similarly, the prescription rate of corticosteroids increased according to proteinuria levels (> 1.0 g/day: 77.8%, 0.5–1.0 g/day: 52.8%, < 0.5 g/day: 11.9%). The respondents emphasized on hematuria when using corticosteroids. In cases of hematuria, the indication rate for corticosteroids was higher than in those without hematuria, even if the urinary protein level was 1 g/gCr or less. Few severe infectious diseases or serious deterioration in glycemic control were reported during corticosteroid use.ConclusionOur questionnaire survey revealed real-world aspects of IgAN treatment in Japan.

Epipharyngeal Abrasive Therapy for Patients with Immunoglobulin A Nephropathy: A Retrospective Study

Immunoglobulin A nephropathy (IgAN) is the most frequent type of primary glomerulonephritis [1]. Moreover, it is currently the second most frequent indication for dialysis after diabetic nephropathy in Japan [2]. Approximately 30%–40% of patients with IgAN who do not receive treatment develop end-stage renal failure [3]. Focal infections of the palatine tonsils are associated with IgAN development, and bilateral palatine tonsillectomy is effective against IgAN. Combined bilateral palatine tonsillectomy and steroid pulse therapy has good clinical outcomes among patients with IgAN [4].

Clinical and histological features and therapeutic strategies for IgA nephropathy.

Chronic glomerulonephritis is the second most common reason, after diabetic nephropathy, for initiation of dialysis in Japan and IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis. In the half century since IgAN was initially reported, our understanding of the long-term prognosis, clinical and histological features, pathogenesis of onset and progression, risk factors for progression, and appropriate treatment under different clinical and histological conditions, has steadily increased. Strong experimental and clinical evidence, the Clinical Practice Guidelines for IgA Nephropathy in Japan, the Oxford Classification, and the Kidney Disease Improving Global Outcomes guidelines have all contributed to the appropriate treatment of IgAN. Several intensive therapies, such as tonsillectomy, steroid therapy, and their combinations, can result in clinical remission, and prevent the progression to end stage renal disease (ESRD). However, some IgAN patients still progress to ESRD even when treated with intensive therapies. In this review, we discuss the clinical and histological features of IgAN, focusing primarily on our previous reports, and our opinions on therapeutic strategies for IgAN.

Progress in the Prevention of Diabetic Nephropathy in Japan

Progress in the Prevention of Diabetic Nephropathy in Japan

Construction of a simulation model and evaluation of the effect of potential interventions on the incidence of diabetes and initiation of dialysis due to diabetic nephropathy in Japan

BackgroundThe prevalence of diabetes mellitus is a growing public health concern in Japan. We developed a simulation model to predict the number of people with diabetes and those on dialysis due to diabetic nephropathy. In addition, we used the model to simulate the impact of possible interventions on the number of people with diabetes and those on dialysis due to diabetic nephropathy in the near future.MethodsA simulation model with aging chains for diabetes management was built using system dynamics. The model was calibrated to population data from 2000 to 2015 (sex- and age category-specific population, the prevalence of diabetes, and the number of patients on dialysis due to diabetic nephropathy). We extrapolated the model up to 2035 in order to predict future prevalence of diabetes and related dialysis (base run). We also ran the model, hypothesizing that incidence of diabetes and/or related dialysis would be reduced by half from 2015 to 2025 and that this rate would be maintained until 2035, in order to investigate the effects of hypothetical interventions on future prevalence.ResultsThe developed model forecasted the population with diabetes to increase until 2028 (5.58 million males and 3.34 million females), and the population on dialysis due to diabetic nephropathy to increase until 2035 (113,000 males and 48,000 females). Simulation experiments suggested that diabetes prevention interventions would decrease the number of patients on dialysis in 2035 by 13.8% in males and 12.6% in females compared to the base run. In contrast, interventions aiming to avoid dialysis initiation for patients with diabetes would decrease the number of patients on dialysis by 37.8% in males and 38.1% in females.ConclusionsWe successfully developed a simulation model to project the number of patients with diabetes and those on dialysis due to diabetic nephropathy. Simulation experiments using the model suggested that, as far as the perspective of the next 20 years, intervention to prevent dialysis is an important means of bending the increasing curve of dialysis in the population with diabetes. Simulation analysis may be useful when making and evaluating health policies related to diabetes and other chronic diseases.

Nationwide survey on current treatments for IgA nephropathy in Japan.

BackgroundA wide variety of treatments, including tonsillectomy and steroid pulse therapy (TSP), are performed for the various stages of IgA nephropathy (IgAN) in Japan. However, the current status of treatments for IgAN patients in Japan is still unclear. The objective of the present study was to investigate the current status of treatments for IgAN patients.MethodsA nationwide survey was conducted in 2008 by sending questionnaires to the 1,194 teaching hospitals of the Japanese Society of Nephrology (JSN) via Progressive Renal Diseases Research, Research on intractable disease, from the Ministry of Health, Labour and Welfare of Japan.ResultsAmong the total 376 hospitals (31.4 %) that responded, 188 hospitals (66.2 % in the internal medicine departments) performed TSP, out of which 137 hospitals (61.4 %) had begun to perform TSP in the period from 2004 to 2008. The following two major steroid pulse protocols in TSP were used: (1) three cycles over 3 consecutive weeks and (2) three cycles every 2 months. Approximately 68 % of pediatric hospitals (68 hospitals) performed combination therapy with prednisolone, azathioprine, heparin-warfarin and dipyridamole. The clinical remission rates for hematuria and proteinuria after TSP tended to be higher than those following other corticosteroid therapies. Almost all hospitals prescribed antiplatelet agents and renin angiotensin system inhibitor (RAS-I).ConclusionIn addition to popular treatments such as antiplatelet agents and RAS-I, TSP is becoming a standard treatment for adult IgAN patients in Japan.

Japan Diabetic Nephropathy Cohort Study: study design, methods, and implementation

Diabetic nephropathy, leading to end-stage renal disease, has a considerable impact on public health and the social economy. However, there are few national registries of diabetic nephropathy in Japan. The aims of this prospective cohort study are to obtain clinical data and urine samples for revising the clinical staging of diabetic nephropathy, and developing new diagnostic markers for early diabetic nephropathy. The Japanese Society of Nephrology established a nationwide, web-based, and prospective registry system. On the system, there are two basic registries; the Japan Renal Biopsy Registry (JRBR), and the Japan Kidney Disease Registry (JKDR). In addition to the two basic registries, we established a new prospective registry to the system; the Japan Diabetic Nephropathy Cohort Study (JDNCS), which collected physical and laboratory data. We analyzed the data of 321 participants (106 female, 215 male; average age 65 years) in the JDNCS. Systolic and diastolic blood pressure was 130.1 and 72.3mmHg, respectively. Median estimated glomerular filtration rate (eGFR) was 33.3ml/min/1.73m(2). Proteinuria was 1.8g/gCr, and serum levels of albumin were 3.6g/dl. The majority of the JDNCS patients presented with preserved eGFR and low albuminuria or low eGFR and advanced proteinuria. In the JRBR and JKDR registries, 484 and 125 participants, respectively, were enrolled as having diabetes mellitus. In comparison with the JRBR and JKDR registries, the JDNCS was characterized by diabetic patients presenting with low proteinuria with moderately preserved eGFR. There are few national registries of diabetic nephropathy to evaluate prognosis in Japan. Future analysis of the JDNCS will provide clinical insights into the epidemiology and renal and cardiovascular outcomes of type 2 diabetic patients in Japan.

Membranous nephropathy in Japan: analysis of the Japan Renal Biopsy Registry (J-RBR)

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The J-RBR/J-KDR registry developed by the Japanese Society of Nephrology provides nationwide cohort data for epidemiological studies of MN. MN was present in 36.8% of 1,203 primary nephrotic syndrome patients in Japan. In addition, 633 (77.9%) out of 813 MN patients were referred to as "idiopathic," whereas 22.1% were classified as "secondary" and involved conditions such as systemic lupus erythematosus, drug exposure, infections, cancer, and various collagen diseases. The mean age of the MN patients was 62.2 (2-88) years old, their mean eGFR was 76.7 (7.6-154.6) ml/min/1.73m(2), and 63.3% had hypertension at the time of renal biopsy. On the basis of these findings, half of Japanese idiopathic MN patients have risk factors (age >60, male, or lower eGFR) for end-stage renal failure, and 10% belong to the high-risk group (daily proteinuria of over 8.0g). Further studies with high-grade evidence should resolve the natural history and therapeutic problems of idiopathic MN in elderly Japanese.

Immunoglobulin A nephropathy and chronic kidney disease

Immunoglobulin (Ig)A nephropathy is one of the major causes of chronic kidney disease (CKD) in Japan. Despite statutory urinalysis of industrial workers and school children, Japan unfortunately still ranks among the countries with the highest CKD-5D prevalence in the world. Topics of this review are as follow: (i) early diagnosis and treatment; (ii) influence of the period from onset to medical intervention on renal prognosis; and (iii) epidemiology of IgA nephropathy patients in Japan. Some investigators have discussed the possibility of predicting the diagnosis and prognosis of this disease. We indicated that the frequency of various casts in urinary sediments and total numbers of each type of urinary cast should provide highly convincing data for prediction of the prognosis in IgA nephropathy patients prior to renal biopsy. Furthermore, early medical intervention (anti-platelet agents, anticoagulants, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, corticosteroids and/or tonsillectomy) may lead to better renal prognosis in patients with IgA nephropathy. In a nationwide survey on IgA nephropathy in Japan, predictive factors after 10 years were as follows: (i) male sex; (ii) under 30 years old; (iii) diastolic hypertension; (iv) heavy proteinuria; (v) mild haematuria; (vi) low serum albumin; and (vii) elevated serum creatinine and impaired renal pathology. It appears that substantial renal deterioration can be validly estimated using these predictive factors in patients with IgA nephropathy. In conclusion, early diagnosis, treatment and improvement of predictive factors for a long duration may lead to better renal prognosis in patients with IgA nephropathy.

Virological features of hepatitis B virus‐associated nephropathy in Japan

Hepatitis B virus (HBV)-associated nephropathy is considered as an immune-mediated disorder which is dependent on interactions between viral, host, and environmental factors. But there are few reports that investigated the relationship between the development of HBV-associated nephropathy and HBV genotypes and the mutations. To clarify the relationship between nephropathy and HBV genotype in Japan, six male patients with HBV-associated nephropathy were examined. The complete genome sequences of HBV were determined directly and the specific mutations associated with the development of HBV-associated nephropathy were examined by comparison of the alignments along with consensus sequences [HBV/A1 (Aa), A2 (Ae), B1 (Bj), B2 (Ba), C1 (Cs) and C2 (Ce)] retrieved from international database. The mean age of the six patients was 33.5 years. HBeAg was found in all patients and serum HBV-DNA levels were relatively high. Histological findings of renal tissues indicated five cases of membranous nephropathy and one membranoproliferative glomerulonephritis. HBV genotypes from the six patients were two HBV/A1, two A2 and two C2, suggesting HBV/A was predominant. G1862T mutation was observed in the two HBV/A1 patients, resulting in the pre-core amino acid substitution with a switch from valine (Val) to phenylalanine (Phe). Only one patient had core deletions. It is concluded that HBV/A may be associated with membranous nephropathy, but little relationship between HBV gene mutations and the development of HBV-associated nephropathy was observed.

Relationships between mesangial proliferation and ominous lesions such as sclerosis, tuft adhesion or crescent, and between active and chronic lesions: Proposal for revision of classification by committee of IgA nephropathy in Japan

Relationships between mesangial proliferation and ominous lesions such as sclerosis, tuft adhesion or crescent, and between active and chronic lesions: Proposal for revision of classification by committee of IgA nephropathy in Japan

Long-Term Results of Tacrolimus Therapy for Renal Transplantation in Patients With Diabetic Nephropathy in Japan

In Japan, the number of kidney transplants for the patients with diabetic nephropathy is limited because of an extreme organ shortage and poor patient and graft survival rates. We analyzed the 5-year outcomes in kidney transplant recipients treated with tacrolimus with (group 1; n = 53) and without a diagnosis of diabetic nephropathy (group 2; n = 1432). We also investigated outcomes in patients who received simultaneous pancreas and kidney transplants since 2000 (group 3; n = 15). Patients in group 1 were older than those in group 2, with a shorter duration of pretransplant dialysis ( P = .0001). Five-year patient survival rates in groups 1 and 2 were 89.7% and 97.9%, respectively ( P = .13), and 5-year graft survival rates were 89.6% and 94.8%, respectively ( P = .44). The incidence of acute rejection within 3 months of transplantation was 28.3% in group 1 and 29.2% in group 2 ( P = .98). Tacrolimus-based induction therapy was used in 13 of the 15 group 3 cases. Both kidney and pancreas grafts are surviving to date in all but one of the group 3 patients; one patient had the pancreas removed due to venous thrombosis at 7 days. It was concluded that tacrolimus-based therapy resulted in excellent 5-year outcomes in patients who had kidney transplantation because of diabetic nephropathy, despite the higher risks associated with this condition. Tacrolimus was also beneficial in association with simultaneous pancreas and kidney transplantation. These data encourage us to perform kidney transplantation in patients with diabetic nephropathy.

Revised criteria for the early diagnosis of diabetic nephropathy

The Diabetic Nephropathy Committee recommends the use of revised criteria for the early diagnosis of diabetic nephropathy in Japan. The new criteria are as follows: 1) Urinary albumin should be determined by immunoassay using a morning spot urine sample in diabetic patients without proteinuria or with dipstick-positive(+ 1) proteinuria. 2) A urinary albumin-to-creatinine ratio ranging from 30 to 299 mg/ gCr in 2 or more of 3 specimens may be diagnosed as microalbuminuria. 3) Two alternatives, i.e. the urinary albumin excretion rate of 30-299 mg/24hr in 24hr urine collection or 20-199 microg/min in timed urine collection can be used to detect microalbuminuria. 4) Renal hypertrophy and elevated urinary type IV collagen may indicate the existence of diabetic renal disease. 5) Microalbuminuria originating in non-diabetic diseases should be excluded.

Clinical strategy for the treatment of hypertension in non-diabetic and diabetic nephropathy in Japan.

Clinical strategy for the treatment of hypertension in non-diabetic and diabetic nephropathy in Japan.

Classification of type-2 diabetic nephropathy in Japan.

Classification of type-2 diabetic nephropathy in Japan.

Hematopoietic cell transplantation–related nephropathy in Japan

To clarify the incidence and characteristics of hematopoietic cell transplantation (HCT)-related nephropathy (HCT-N) in Japan, we sent questionnaire letters to 188 hematologic divisions of 91 hospitals and analyzed the responses. Of 2,136 Japanese hematopoietic cell transplant recipients, 51 patients (2.4%) had HCT-N. The early-onset (≤30 days after HCT), middle-onset (31 to 120 days after HCT), and late-onset (>180 days after HCT) groups included 20, 16, and 15 patients, respectively. The early-onset group mainly consisted of patients with acute renal failure (ARF) and hemolytic uremic syndrome and/or thrombotic thrombocytopenic purpura. ARF was the dominant type in the middle-onset group. The main phenotype of the late-onset group was nephrotic syndrome, which correlated with chronic graft-versus-host disease (P = 0.008). The total amounts of irradiation for patients with chronic renal failure and urinary abnormality were significantly greater than those for patients with ARF (P = 0.004). The survival rate of the early-onset and middle-onset groups was 47.2%, whereas 87% of patients in the late-onset group survived (P = 0.002). HCT-N is expected to become a serious and important problem in Japan because of the increasing number of HCTs from unrelated donors.

Microalbuminuria and Associated Factors in Bahraini Patients with Type 2 Diabetes Mellitus

Microalbuminuria and Associated Factors in Bahraini Patients with Type 2 Diabetes Mellitus