Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits during Annual Health Checkups: The Yamagata-Takahata Study.

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Immune thrombocytopenia secondary to primary cytomegalovirus infection after renal transplantation treated with a thrombopoietin receptor agonist: a case report.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired disorder characterised by a low platelet count due to immune-mediated destruction and impaired platelet production. Here we report a rare case of primary cytomegalovirus (CMV) infection followed by thrombocytopenia after renal transplantation (RT). CASE PRESENTATION: A 24-year-old male patient with end-stage kidney disease secondary to hereditary focal segmental glomerulosclerosis was treated with peritoneal dialysis and received ABO-compatible living-related RT from his aunt. Nine months after the RT, the patient was diagnosed with primary CMV infection. After initiating treatment for primary CMV infection, the patient developed thrombocytopenia. After excluding other diseases or drugs that may cause thrombocytopenia, the patient was finally diagnosed with ITP, administered prednisolone (PSL), and started on Helicobacter pylori eradication therapy. Tapering the PSL dose was difficult, but thrombopoietin receptor agonists (TPO-RAs) were effective. CONCLUSIONS: In this case, the patient was diagnosed with ITP, and other causes of thrombocytopenia after RT were successfully ruled out. This case report demonstrates that RT recipients can develop ITP after CMV infection, and, in such cases, TPO-RAs may be an attractive option as a second-line therapy.

Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation.

Acute kidney injury (AKI) is a frequent complication of allogeneic hematopoietic cell transplantation (allo-HCT). There are many causes of AKI after allo-HCT, but it is unknown whether renal acute graft-versus-host disease (aGVHD) caused by direct allogeneic donor T-cell-mediated renal damage contributes. Here, we tested whether allogeneic donor T cells attack kidneys in murine models of aGVHD. To avoid confounding effects of nephrotoxic agents, we did not administer immunosuppressants for GVHD prophylaxis. We found that urinary N-acetyl-ß-D-glucosaminidase, a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allogeneic bone marrow transplantation. Donor major histocompatibility complex-positive cells were present and CD3+ T cells were increased in the glomerulus, peritubular capillaries, interstitium, and perivascular areas in the kidneys of allo-HCT recipient mice. These T cells included both CD4+ and CD8+ cells with elevated activation markers, increased exhaustion markers, and greater secretion of proinflammatory cytokines and cytotoxic proteins. Consistent with allo-T-cell-mediated renal damage, expression of neutrophil gelatinase-binding lipocalin, a marker of AKI, and elafin, a marker of aGVHD, were increased in renal tissue of allogeneic recipients. Because apoptosis of target cells is observed on histopathology of aGVHD target tissues, we confirmed that alloreactive T cells increased apoptosis of renal endothelial and tubular epithelial cells in cytotoxic T-lymphocyte assays. These data suggest that immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell injury in allo-HCT recipients and that aGVHD may contribute to AKI after allo-HCT.

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

The impact of physical activity on cardiovascular mortality in the general population.

The beneficial effect of moderate physical activity (PA) on morbidity and mortality has been observed in the general population. However, the ideal intensity of PA for improving cardiovascular longevity in Japanese general population is uncertain. The aim of this study was to investigate the relationship between the PA and cardiovascular mortality in the general population. This longitudinal cohort study included 1,826 apparently healthy subjects who participated in a community-based health checkup. There were 31 cardiovascular deaths during 10-year follow-up. Subjects were divided into 4 groups based on the quartiles of PA (low, mild, moderate and high). Kaplan-Meier analysis and multivariate Cox proportional hazard analysis demonstrated that the most favorable cardiovascular prognosis was observed in subjects with moderate PA followed by those with mild PA. High PA as well as low PA were associated with higher cardiovascular mortality compared with mild and moderate PA. Noteworthy, in subjects with high PA, Cox hazard analysis revealed that previous cardiovascular disease, smoking, brain natriuretic peptide levels, and Framingham risk score were associated with cardiovascular mortality. The results suggest a U-shaped association between cardiovascular mortality and PA. Mild to moderate PA was associated with favorable cardiovascular outcomes in the Japanese general population. High PA might be associated with poor cardiovascular outcomes in subjects with a history of heart disease and high coronary risk factors.

Urinary and plasma proteomics to discover biomarkers for diagnosing between diabetic nephropathy and minimal change nephrotic syndrome or membranous nephropathy.

The choice of treatment for primary nephrotic syndrome depends on the pathologic type of the disorder. Renal biopsy is necessary for a definitive diagnosis, but it is burdensome for the patients, and can be avoided if tests could be performed using urine or plasma. In this study, we analyzed 100 urinary proteins, 141 plasma proteins, and 57 urine/plasma ratios in cases of diabetic nephropathy (DN; n = 11), minimal change nephrotic syndrome (MCNS; n = 14), and membranous nephropathy (MN; n = 23). We found that the combination of urinary retinol-binding protein 4 and SH3 domain-binding glutamic acid-rich-like protein 3 could distinguish between MCNS and DN, with an area under the curve (AUC) of 0.9740. On the other hand, a selectivity index (SI) based on serotransferrin and immunoglobulin G, which is often used in clinical practice, distinguished them with an AUC of 0.9091. Similarly, the combination of urinary afamin and complement C3 urine/plasma ratio could distinguish between MN and DN with an AUC of 0.9842, while SI distinguished them with an AUC of 0.8538. Evidently, the candidates identified in this study were superior to the SI method. Thus, the aim was to test these biomarkers for accurate diagnosis and to greatly reduce the burden on patients.

Adjuvant heparinization before manipulation of artery reduces early failure in primary arteriovenous fistula for end-stage renal disease patients.

BACKGROUND: Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable complications of this procedure. We retrospectively evaluated whether adjuvant systemic heparinization just before arterial manipulation could reduce early failure of primary AVF. METHODS: Three hundred and fifty-six patients with end-stage renal failure who underwent primary AVF surgery from April 2009 to September 2020 were enrolled in this study. The patients were divided into two groups based on whether they received adjuvant heparinization or not. Patient backgrounds, frequency of early AVF failure, and bleeding events were compared between the two groups. Multivariate Cox regression analysis identified risk factors for early AVF failure. RESULTS: Early failure of AVF was observed in only 2 of 157 patients (1.2%) in the adjuvant group, and the incident was significantly lower than observed in the non-adjuvant group, i.e., 17 of 199 patients (8.5%) (p = 0.002). Bleeding events were not significantly different between the two groups. Seven of 157 patients (4.5%) in the adjuvant group and 7 of 199 patients (3.5%) in the non-adjuvant group experienced bleeding events (p = 0.785). Female sex, use of steroids, hypoalbuminemia, venous stenosis in pre-surgical evaluation, arterial spasm in the perioperative period, new-onset venous stenosis after AVF anastomosis, technical failure of surgery, no early cannulation after surgery, and non-adjuvant heparinization were related to early AVF failure in the multivariate regression analysis. CONCLUSION: Adjuvant systemic heparinization therapy just before arterial manipulation reduced early failure of primary AVF without increasing bleeding events.

The distribution of eGFR by age in a community-based healthy population: the Japan specific health checkups study (J-SHC study).

BACKGROUND: Renal function gradually declines with age. However, the association between changes in renal function and healthy aging has not been determined. This study examined the distribution of estimated glomerular filtration rate (eGFR) values in healthy subjects by age using large-scale cross-sectional data of health check-up participants in Japan. METHODS: Among the 394,180 health check-up participants, 75,217 (19.1%) subjects without hypertension, diabetes, hyperlipidemia, obesity, proteinuria, smoking, past history of cardiovascular diseases, and renal failure/not undergoing dialysis were included in the healthy group. The distribution of eGFR values was determined at each age between 39 and 74 years. RESULTS: in healthy subjects, the mean (± 2 SD range) values of eGFR (mL/min/1.73 m2) at ages 40, 50, 60, and 70 were 88.0 (55.4-121.7), 82.3 (51.2-113.3), 77.8 (48.1-107.6), and 72.9 (44.7-101.1), respectively. The difference in the mean eGFR by age was almost constant across all ages. In the linear regression analysis adjusted for sex, the regression coefficient of mean eGFR for a one-year increase in age was -0.46 mL/min/1.73 m2 in healthy subjects (P < 0.001). By sex, the distribution of eGFR and the 1-year change in eGFR showed similar results in both men and women. CONCLUSIONS: Renal function slowly declined with age in a healthy population; however, it was relatively preserved until the mid 70 s. This result suggests that a decline in renal function often observed in the elderly does not attribute to aging alone, and further examination might be required to clarify the cause of renal impairment.

Possible burden of hyperuricaemia on mortality in a community-based population: a large-scale cohort study.

Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25-1.49] and 1.69 [1.41-2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targets the intestines, liver, and skin. However, recent studies suggest aGVHD may also attack the kidney and contribute to AKI following allo-HCT. For example, severe aGVHD is associated with AKI, suggesting a link between the two. In addition, animal models have shown donor immune cell infiltration and increased expression of inflammatory cytokines in recipient kidneys after allo-HCT. Therefore, aGVHD may also target the kidney and contribute to AKI following allo-HCT. Herein, we describe the etiology, diagnosis, risk factors, pathophysiology, prevention, and treatment of renal injury after allo-HCT. In addition, we highlight emerging evidence that aGVHD may contribute to the development of AKI after allo-HCT.

Association between serum uric acid levels and mortality: a nationwide community-based cohort study.

Hyperuricemia is associated with all-cause and cardiovascular mortality. However, the threshold value of serum uric acid levels for increased risk of mortality has not been determined. This large-scale cohort study used a nationwide database of 500,511 Japanese subjects (40-74 years) who participated in the annual health checkup and were followed up for 7 years. The association of serum uric acid levels at baseline with cardiovascular and all-cause mortality was examined. The Cox proportional hazard model analysis with adjustment for possible confounders revealed that the all-cause and cardiovascular mortality showed a J-shaped association with serum uric acid levels at baseline in both men and women. A significant increase in the hazard ratio for all-cause mortality was noted with serum uric acid levels ≥ 7 mg/dL in men and ≥ 5 mg/dL in women. A similar trend was observed for cardiovascular mortality. This study disclosed that even a slight increase in serum uric acid levels was an independent risk factor for all-cause and cardiovascular mortality in both men and women in a community-based population. Moreover, the threshold values of uric acid for mortality might be different for men and women.

Association among chronic kidney disease, airflow limitation, and mortality in a community-based population: The Yamagata (Takahata) study.

Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) are known risk factors for mortality. In this study, we examined the overlap of CKD and airflow limitation (AFL) that characterises COPD and its effect on 10-year mortality in a community-based population. This study included 1,233 health check-up participants (mean age, 63.7 years; 46.7% men). We defined serum creatinine-based CKD (CKDcr) and serum cystatin C-based CKD (CKDcys) as glomerular filtration rate <60 mL/min/1.73 m2, estimated using serum creatinine or cystatin C, and/or dipstick proteinuria ≥1+. AFL was defined as forced expiratory volume in 1 s to forced vital capacity ratio <70% on spirometry. Compared with subjects without AFL, those with AFL showed a significantly higher prevalence of CKDcys but not of CKDcr. Cox proportional hazard analysis adjusted for confounders showed that the hazard ratio (95% confidence interval) for all-cause mortality was 1.45 (0.77-2.63) in subjects with CKDcys alone, 1.29 (0.60-2.54) in those with AFL alone, and 2.94 (1.33-6.12) in those with both CKDcys and AFL, with subjects without both AFL and CKD as the reference. This study showed that AFL and CKDcys are strongly associated and that their overlap is a significant risk factor for mortality in community-based populations.

The association between genotypes of urate transporter-1, Serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study.

BACKGROUND: The urate transporter-1 (URAT1) is crucial in developing hyperuricemia via reabsorption of uric acid in renal tubules, and its function is regulated by several single nucleotide polymorphisms (SNPs) within SLC22A12 gene encoding URAT1. This study investigated whether the genetic predisposition of URAT1 is associated with the mortality in general population. METHODS: This study enrolled 1596 participants (male 45%, mean age 61 years) who registered at local health checkup in Takahata, Japan, and the association between the rs505802 genotypes in SLC22A12 gene and the 7-year mortality, was examined. RESULTS: The serum uric acid levels (mean ± SD) at baseline in the subjects with GG and AG + AA genotypes of rs505802 were 5.1 ± 1.3 mg/dL and 5.0 ± 1.5 mg/dL, respectively. Kaplan-Meier analysis revealed that the mortality was nonsignificantly higher in the subjects with GG genotype than in those with AG + AA genotype (P = 0.09). Cox proportional hazard model adjusted with age, gender, renal function, comorbidities, and other possible confounders, demonstrated that the GG genotype was significantly associated with the mortality [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.05-4.85, (vs. AG + AA genotype)]. Furthermore, adjustment with serum uric acid levels, along with aforementioned confounders retained the significant association (HR 2.26, 95% CI 1.05-4.85). CONCLUSIONS: This study revealed that the genetic predisposition of URAT1 was independently associated with mortality in the Japanese community-based population. This association might be due to the mechanism independent of serum uric acid levels.

The association between urinary sodium excretion and blood pressure in a community-based population: the Yamagata (Takahata) study.

BACKGROUND: The association between salt intake and blood pressure levels is still inconclusive, and may be influenced by patient characteristics. We thus conducted a community-based cross-sectional study. METHODS: This study included 2297 subjects aged ≥ 40 years not on antihypertensive medication at the time of a health check-up. We examined the association between blood pressure levels and the estimated amount of 24-h urinary sodium excretion (e24hUNa) stratified by background characteristics. The 24-h urinary excretion levels of sodium and potassium were estimated from Kawasaki's equation using a spot urine sample. RESULTS: The association of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with e24hUNa was significantly positive in a multiple linear regression model adjusted for confounders including age, sex, smoking, alcohol consumption, body mass index, diabetes, hypercholesterolemia, renal function, and potassium excretion. The regression coefficients of changes in SBP and DBP per 1 SD increase in e24hUNa (53 mEq/day) were + 1.91 mmHg and + 0.94 mmHg, respectively. In the subgroup analyses, the increase in SBP was especially greater in the elderly, in subjects with diabetes, and in subjects with reduced renal function compared to those in the counterparts. The association between SBP and e24hUNa was insignificant in subjects with eGFR ≥ 90 ml/min/1.73m2, while the association with progression of renal dysfunction was stronger and significant. CONCLUSIONS: These results demonstrated that the association between blood pressure and urinary sodium excretion was strengthened by characteristics of subjects such as aging, presence of diabetes, and renal impairment in the community-based population.

The Association between Glomerular Filtration Rate Estimated Using Different Equations and Mortality in the Japanese Community-Based Population: The Yamagata (Takahata) Study.

BACKGROUND: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population. METHODS AND RESULTS: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67). CONCLUSIONS: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.

The Association between Serum Uric Acid and Renal Damage: The Takahata Study - New Insights.

BACKGROUND: Hyperuricemia is a risk factor for causing end-stage kidney disease and cardiovascular disease in the general population; however, several aspects, such as the site of kidney damaged by hyperuricemia and the threshold levels of serum uric acid for the development of renal damage, have not been fully clarified. SUMMARY: To examine these aspects, we analyzed data from the Takahata study, a community-based cohort study involving participants of an annual health check-up, and used urinary albumin creatinine ratio (UACR) and urinary ß2-microglobulin creatinine ratio (UBCR) in spot urine as indices of glomerular and tubular damage respectively. In cross-sectional analysis, increased serum uric acid levels were accompanied by higher UACR values and lower UBCR values. Multivariate analysis revealed that albuminuria (UACR ≥30 mg/g), but not elevated UBCR, was independently associated with increased uric acid (≥7 mg/dL for males, ≥6 mg/dL for females). In longitudinal analysis, uric acid at baseline was an independent factor for a 1-year increase in the UACR. Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia was an independent risk factor for all-cause and cardiovascular mortality in females. Key Messages: Our results revealed that elevated uric acid is an independent risk factor for glomerular damage, but not tubular damage, and that the risk for renal damage and mortality might be increased at the high-normal range of uric acid in the community-based population.

Association between renal function and cardiovascular and all-cause mortality in the community-based elderly population: results from the Specific Health Check and Guidance Program in Japan.

BACKGROUND: Chronic kidney disease is a significant risk factor for end-stage kidney disease, cardiovascular events, and premature death. However, the prognostic value of low estimated glomerular filtration rate (eGFR) in the elderly is debatable. METHODS: We determined eGFR using the Japanese equation in 132,160 elderly subjects (65-75 years) who attended the special health checkup (Tokutei-Kenshin) in 2008 and investigated the association between baseline eGFR and 5-year all-cause and cardiovascular mortality. RESULTS: The median (SD) eGFR was 70.5 ± 15.3 mL/min/1.73 m2. During follow-up, we noted 2045 all-cause deaths including 408 from cardiovascular events. A J-shaped curve was obtained when all-cause and cardiovascular mortality rates were compared with decreases in eGFR, with the highest mortality observed for eGFR <45 mL/min/1.73 m2. These trends were statistically significant in the Kaplan-Meier analysis (P < 0.001). In the Cox proportional hazard analysis, after adjusting for possible confounders, those with eGFR <45 mL/min/1.73 m2, but not eGFR 45-59 mL/min/1.73 m2 showed a higher all-cause and cardiovascular mortality than those with eGFR >90 mL/min/1.73 m2 [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.06-1.91 for all-cause mortality, HR 2.28, 95% CI 1.28-4.03 for cardiovascular mortality]. Sex-based subgroup analyses showed similar results for both men and women. CONCLUSIONS: We conclude that eGFR <45 mL/min/1.73 m2 is an independent risk factor for all-cause and cardiovascular mortality in the elderly population.

The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). METHODS: In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. RESULTS: Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. CONCLUSIONS: Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study.

BACKGROUND: Hyperuricemia is an established risk factor for cardiovascular events and mortality. This study investigated the association between serum uric acid and the incidence of nonfatal stroke in a Japanese community-based population. METHODS: We used a nationwide database of 155,322 subjects (aged 40-73, male 39 %) who participated in the annual "Specific Health Check and Guidance in Japan" checkup from 2008 to 2010. We examined the relationship between the quintiles of serum uric acid levels at baseline and the incidence of nonfatal stroke during a 2-year study period using self-reported data. RESULTS: The crude incidence of nonfatal stroke was significantly associated with serum uric acid levels at baseline, showing the lowest values in subjects with the 3rd quintile (Q3: men, 5.0-5.6; women, 3.8-4.3) of uric acid levels (mg/dL) and the highest values in subjects with the highest quintile (Q5: men ≥7.1, women ≥5.5) both in men and women (P < 0.05). In multivariate-adjusted logistic regression analysis, the odds ratio (OR) of the Q5 group was significantly higher than for the Q3 group in both men and women [men: OR 1.26, 95 % confidence interval (CI) 1.04-1.54, women: OR 1.24, 95 % CI 1.00-1.48]. In the subgroup analysis, the OR of the Q5 group of uric acid levels for incident stroke was high, irrespective of characteristics such as age, sex, and renal function. CONCLUSIONS: This study has shown that serum uric acid is independently associated with the incidence of nonfatal stroke in the general Japanese population.

Ruptured Right Sinus of Valsalva Aneurysm Caused by Suspected Takayasu's Arteritis.

A sinus of Valsalva aneurysm (SVA) is a rare aortic anomaly. The most common complication is a rupture into the right ventricle and atrium. An SVA rupture into the left ventricle is a rare event. A 42-year-old man visited an outpatient clinic due to worsening exertional dyspnea. A loud to-and-fro heart murmur was detected, and echocardiography revealed a right SVA that had ruptured into the left ventricle, inducing acute heart failure. Computed tomography imaging allowed us to determine that the right SVA had been caused by asymptomatic Takayasu's arteritis. The patient was treated with prednisolone and the right SVA rupture was surgically repaired.