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The clinical characteristics and treatment of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after initiating chronic hemodialysis remain unknown. We retrospectively enrolled 11 adult patients with AAV receiving chronic hemodialysis in our hospital from 2000–2016. We collected data describing each patient's clinical findings and treatment before and after initiating hemodialysis. Patients with AAV with and without post-hemodialysis AAV relapse were compared statistically. The average observation period was 6.8 ± 4.1 years, and the interval between diagnosis and initiating chronic hemodialysis was 1.9 ± 2.6 years. Before initiating chronic hemodialysis, five patients (45%) experienced 12 AAV relapses, with diagnoses made serologically or symptomatically. After initiating chronic hemodialysis, four patients experienced nine relapses, with no significant difference between the number of relapses and the number of patients experiencing relapse (p = 0.067 and 0.083, respectively). For patients' entire clinical courses before initiating chronic hemodialysis, the average steroid dose was 11.6 ± 6.9 g/y. Comparing before and after initiating chronic hemodialysis, the steroid dose decreased significantly to 3.3 ± 1.4 g/y after initiating chronic hemodialysis (p = 0.0012). Two of 11 patients died of serious infections after initiating chronic hemodialysis. Our results showed that the number of relapses tended to be lower despite a significantly different lower amount of steroid after initiating hemodialysis compared with before initiating hemodialysis, and the burn-out phenomenon specific to uremic patients was inferred. We believe that early tapering of steroids should be considered to avoid death rather than focusing only on relapse.

Background/Aims: Aortic arch calcification (AoAC) is a fatal complication in dialysis. AoAC progression-related molecules in continuous ambulatory peritoneal dialysis (CAPD) remain unclear. Methods: AoAC was estimated using plain chest radiography scoring (AoACS) in 30 CAPD patients (age 49.3 ± 13.4 years). AoAC progression was defined as increased AoACS on follow-up chest X-ray at the end of the study (progressors). Fibroblast growth factor-23 and osteoprotegerin (OPG) were measured. Results: Median follow-up was 38.5 months. Progressors were older, had shorter PD vintage, higher body mass index, and higher serum OPG levels (255.6 ± 109.2 pg/mL) than nonprogressors (183.4 ± 68.2 pg/mL; p = 0.0400). Progressors also showed higher pulse pressure (62.4 ± 20.0 mm Hg) and pulse wave velocity (1,909.9 ± 310.6 cm/s) than nonprogressors (48.5 ± 13.6 mm Hg; p = 0.0030 and 1,390.1 ± 252.8 cm/s; p = 0.0005, respectively). Conclusion: AoAC progression was associated with increased aortic stiffness. OPG may be associated with AoAC progression in CAPD.

Changes over time have been shown in renal manifestations in individuals with diabetes in the United States; however, whether the trends are shared across ethnicities is unknown. We conducted this single-center serial cross-sectional study to determine temporal changes in albuminuria and reduced kidney function in Japanese patients with type 2 diabetes. This study included adult Japanese patients with type 2 diabetes who first visited our institute between 2004 and 2013. Temporal changes during the 10 years in the frequency of albuminuria ( ≥ 30 mg/g creatinine) and reduced eGFR (

To explore novel genetic loci for diabetic nephropathy, we performed genome-wide association studies (GWAS) for diabetic nephropathy in Japanese patients with type 2 diabetes. We analyzed the association of 5,768,242 single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes, 2,380 nephropathy cases and 5,234 controls. We further performed GWAS for diabetic nephropathy using independent Japanese patients with type 2 diabetes, 429 cases and 358 controls and the results of these two GWAS were combined with an inverse variance meta-analysis (stage-1), followed by a de novo genotyping for the candidate SNP loci (p < 1.0 x 10^) in an independent case-control study (Stage-2; 1,213 cases and 1,298 controls). After integrating stage-1 and stage-2 data, we identified one SNP locus, significantly associated with diabetic nephropathy; rs56094641 in FTO, P = 7.74 x 10^. We further examined the association of rs56094641 with diabetic nephropathy in independent Japanese patients with type 2 diabetes (902 cases and 1,221 controls), and found that the association of this locus with diabetic nephropathy remained significant after integrating all association data (P = 7.62 x 10^). We have identified FTO locus as a novel locus for conferring susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes., 論文

Aim The first clinical manifestation of diabetic kidney disease is usually the development of microalbuminuria. However, recent studies have focused on diabetic patients with reduced glomerular filtration rate (GFR) without albuminuria. To evaluate the association of albuminuria and GFR with renal outcomes, we performed an observational study. Methods A total of 3231 type 2 diabetic patients were included in this study between 2003 and 2005. There were 1249 women and the mean age was 59 ± 12 years. The renal endpoints were defined as the initiation of renal replacement therapy (RRT) or 50% reduction from the baseline of estimated GFR (eGFR). Results At baseline, 669 (20.7%) patients had eGFR

Tumors producing IGF-2 (IGF-2oma) are a major cause of spontaneous hypoglycemia. The treatment mainstay is surgical resection. Many case reports note resolution of hypoglycemia after IGF-2oma resection; however, outcomes are variable according to tumor type. We report a case of resolving hypoglycemia, observed on continuous glucose monitoring, after resection of an IGF-2-producing solitary fibrous tumor of pleura and review the current literature.A 69-year-old woman presented with impaired consciousness because of hypoglycemia. An IGF-2oma was diagnosed as the cause for hypoglycemia because of decreased serum insulin and IGF-1, the presence of a pleural tumor, and a high-molecular-weight form of serum IGF-2 detected by Western immunoblot. Surgical resection was performed; pathological examination demonstrated a solitary fibrous tumor with low-grade malignancy. Continuous glucose monitoring showed reversal of hypoglycemia after tumor resection. Approximately 2 years after resection, the patient has no signs of tumor recurrence or hypoglycemia.An IGF-2-producing solitary fibrous tumor of pleura in this case caused hypoglycemia. From a search of the literature of 2004-2014, 32 cases of IGF-2oma with hypoglycemia that underwent radical surgery were identified; in 19 (59%) patients, hypoglycemia was reversed, and there was no subsequent recurrence. The remaining 13 (41%) patients experienced tumor recurrence or metastasis an average of 43 months after initial tumor resection. The tumor of the present case was a low-grade malignancy. Regular follow-up with biomarker monitoring of glucose metabolism and assessment of hypoglycemic symptomatology, in conjunction with imaging tests, is important for detecting possible tumor recurrence and metastasis.

Aims/Introduction Obesity has been shown to be a modifier of the association between leptin levels and cardiovascular events. We examined whether obesity modifies the association between serum leptin levels and the progression of diabetic kidney disease. Materials and Methods This was an observational longitudinal study on patients with type 2 diabetes. We enrolled 410 and 348 patients in the eGFR and ACR cohorts, respectively. Patients were classified into three groups by sex-specific tertile of leptin levels. Obesity was defined as body mass index ≥25 kg/m2. Outcomes were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria. Results In the eGFR cohort, the mean eGFR change during the median follow-up period of 4.7 years was −1.4 mL/min/1.73 m2/year. An interaction between leptin levels (low, medium or high) and obesity (present or absent) on the change in eGFR was detected (P interaction = 0.003). In the lean group, adjusted eGFR decline in patients with low leptin was steeper than that in patients with medium leptin (2.1 and 0.8 mL/min/1.73 m2/year, P = 0.023). In the obese group, patients with high leptin had a steeper adjusted eGFR decline than those with medium leptin (1.7 and 0.6 mL/min/1.73 m2/year, P = 0.044). In the ACR cohort, 29 patients showed progression of albuminuria during the median follow-up period of 3.9 years. There was no interaction between leptin levels and obesity on the outcome (P interaction = 0.094). Conclusions Obesity might modify the effects of leptin on kidney function decline in patients with type 2 diabetes.

Aims/Introduction: To reveal whether visit-to-visit variability in HbA1c is associated with higher risk of cardiovascular disease (CVD) in patients with type 2 diabetes. Materials and Methods: The study was conducted on 689 Japanese patients with type 2 diabetes [295 women, 394 men; mean (±standard deviations (SD)) age 65 ± 11 years]. Variability in HbA1c was evaluated as the intrapersonal SD of serial measurements of HbA1c during the follow-up period for at least 12 months. Patients were divided into quartiles according to the SD of HbA1c, and the primary endpoint was defined as incident CVD. Cox’s proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: During a median follow-up period of 3.3 years (range 1.0–6.3 years), 26 ± 14 measurements of HbA1c were obtained per patient and 61 episodes of incident CVD were recorded. The 5-year cumulative incidence of CVD in patients across the first, second, third, and fourth quartiles of SD in HbA1c was 4.9, 8.7, 17.1, and 26.2%, respectively (P

Background The impact of serum lipid abnormalities on the progression of diabetic kidney disease (DKD) remains conflicting. Furthermore, gender differences in the association between dyslipidaemia and outcome of DKD are largely unknown. We therefore conducted this single-centre observational cohort study to clarify gender differences in the association between serum lipid profiles and the progression of DKD. Methods Seven hundred and twenty-three Japanese type 2 diabetes mellitus (T2DM) patients with normoalbuminuria or microalbuminuria, 280 women and 443 men, with a mean (± SD) age of 63 ± 11 years were studied. The endpoint was the progression to a more advanced stage of albuminuria. For statistical analyses, Cox proportional hazard model analyses were conducted. Results During the mean follow-up period of 4.3 years, 62 of 477 patients with normoalbuminuria and 69 of 246 patients with microalbuminuria reached the endpoint. A significant interaction between high-density lipoprotein (HDL) cholesterol and gender was detected (P(interaction) = 0.04); therefore, separate analyses were conducted for men and women. Overall, in men, the univariate Cox proportional hazard model revealed that higher triglycerides and lower HDL cholesterol levels were significantly associated with higher risk of reaching the endpoint. In the multivariate Cox proportional hazard model, only HDL cholesterol levels remained as an independent predictor of the endpoint (hazard ratio 0.391, P = 0.01). In women, no serum lipid parameters were associated with the endpoint. Conclusions Lower HDL cholesterol levels seem to be associated with the progression of DKD in men but not in women.

Abdominal obesity has been implicated in the pathogenesis of microalbuminuria in patients with diabetes; however, the underlying mechanisms remain unclear. Increased leptin secretion by adipocytes may be one of the factors responsible for the relationship between abdominal obesity and microalbuminuria, because increased leptin secretion has been demonstrated to contribute to renal impairment. We therefore conducted a cross-sectional study to clarify the relationship between increased serum leptin levels associated with abdominal obesity and albuminuria in patients with type 2 diabetes mellitus (T2DM). We studied a total of 502 adult patients with T2DM, 220 women and 282 men, with a mean (±SD) age of 60 ± 13 years. Patients with macroalbuminuria and those with an estimated glomerular filtration rate of

Diabet. Med. 27, 538–543 (2010) Abstract Aims Silent cerebral infarction (SCI) is an independent risk factor for future symptomatic stroke. Although the prevalence of SCI is closely related to kidney function in non-diabetic individuals, evidence is lacking whether albuminuria and/or reduced estimated glomerular filtration rate (eGFR) independently increase the risk of SCI in diabetic patients. We therefore examined the relationships between albuminuria, eGFR and SCI in patients with Type 2 diabetes mellitus (T2DM). Methods We studied 786 T2DM patients with an eGFR ≥ 15 ml/min 1.73/m2, including 337 women and 449 men [mean (± sd), age 65 ± 11 years]. All patients underwent cranial magnetic resonance imaging (MRI) to detect SCI. GFR was estimated using the modified three-variable equation for Japanese subjects. Albuminuria was defined as a first morning urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. Results SCI was detected in 415 (52.8%) of the subjects. The prevalence of SCI was significantly associated with both elevated ACR and decreased eGFR in univariate analysis. In multivariate logistic regression analysis, urinary ACR remained independently associated with SCI after adjusting for conventional cardiovascular risk factors [odds ratio (OR) of urinary ACR per logarithmical value: 1.89, 95% confidence interval (CI) = 1.41–2.51, P

We performed a prospective, randomized, multicenter, parallel-group, per-protocol study to compare the effects of hydrochlorothiazide (HCTZ) and amlodipine as add-on to losartan treatment in hypertensive type 2 diabetic patients. A total of 49 Japanese type 2 diabetic patients with inadequate control of blood pressure while receiving losartan 50 mg were randomly allocated to receive a fixed-dose single-pill combination of HCTZ 12.5 mg plus losartan (N = 26) or a free combination of amlodipine 5 mg plus losartan (N = 23). During 8 weeks of follow-up, changes in blood pressure and laboratory data including HbA1c, uric acid, and potassium were compared between the groups using analysis of covariance. Systolic and diastolic blood pressure decreased in both groups, the reductions of which were greater in the amlodipine group. However, the least square mean (95 % CI) differences between groups were not statistically significant [2.3 (−6.8 to 11.4) mmHg, p = 0.618 and 2.7 (−2.4–7.9) mmHg, p = 0.293, respectively]. HbA1c increased in patients receiving HCTZ but not in the amlodipine group. Uric acid also increased in patients receiving HCTZ but decreased in patients receiving amlodipine, yielding a significant between-group difference of 1.0 (0.5–1.5) mg/dl (p

Patients with peripheral artery disease (PAD), defined as having low ankle-brachial pressure index (ABI), have increased risk for incident stroke compared with those without PAD. We aimed to reveal whether ABI abnormality, especially high ABI is associated with prevalent silent cerebral infarction (SCI) in type 2 diabetic patients.We studied 538 Japanese type 2 diabetic patients, 227 women and 311 men, with a mean [±SD] age of 64±11 years. All patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were classified as low (0.9), normal (0.9≤ and1.3), and high (1.3≤). Logistic regression model was used to calculate odds ratio and 95% confidence interval (95% CI) for prevalent SCI.The mean ABI among the overall 538 patients was 1.09±0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%) patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8 (p0.001), respectively. In the multivariate logistic regression analysis, both patients with high and low ABI were significantly increased risk of prevalent SCI (odds ratio 4.53, 95% CI 1.67-12.34, p=0.003 and odds ratio 3.50, 95% CI 1.50-10.29, p=0.005), independently of other traditional cardiovascular risk factors, than those with normal ABI.Both high and low ABI may be strongly associated with prevalent SCI in Japanese patients with type 2 diabetes.

OBJECTIVE To clarify the association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was an observational cohort study of 668 patients with T2D. Patients were classified into three groups by sex-specific tertile of leptin levels. Outcome measurements were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria. RESULTS Patients with low or high leptin levels had a steeper eGFR decline (−2.07 and −2.14 mL/min/1.73 m2/year) than those with midrange leptin levels (−0.82 mL/min/1.73 m2/year; P < 0.01), whereas patients with low leptin levels had an elevated risk of progression of albuminuria as compared with those with high leptin levels (hazard ratio 3.125 [95% CI 1.302–7.499]). CONCLUSIONS Both low and high serum leptin levels were risk factors for kidney function decline. Meanwhile, lower serum leptin levels were associated with progression of albuminuria.

OBJECTIVE To investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 ± 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo- to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis. RESULTS The baseline mean (± SD) cf-PWV was 9.6 ± 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3–8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13–1.33, P < 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate −0.095, P = 0.031). CONCLUSIONS Aortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients.

It is unclear whether albuminuria and reduced glomerular filtration rate (GFR) independently increase the risk of incident stroke and coronary artery disease (CAD) in Japanese patients with diabetes. We investigated the independent effects of albuminuria and estimated GFR (eGFR) on the first occurrence of stroke and CAD in patients with type 2 diabetes mellitus (T2DM). We studied 1002 T2DM patients with eGFR (ml min−1 per 1.73 m2) ⩾15 and had no previous cardiovascular disease (CVD) history. GFR was estimated using the modified three-variable equation for the Japanese. Patients were divided into four eGFR categories: ⩾90, 60–89, 30–59 and 15–29. The end point was an incident stroke and CAD events. The Cox proportional hazard model was used to calculate hazard ratio and 95% confidence interval. During a mean follow-up period of 5.2±2.1 years, 72 episodes of stroke and 90 of CAD were observed. Multivariate Cox analysis revealed no significant association between the eGFR category and incident stroke. The stroke hazard ratio (95% confidence interval) in reference to patients with an eGFR ⩾90 was 0.78 (0.40–1.56) for patients with an eGFR of 60–89, 1.47 (0.70–3.10) for patients with an eGFR of 30–59 and 1.14 (0.39–3.35) for patients with an eGFR of 15–29. Reduced eGFR was a significant risk factor for CAD, with hazard ratios (95% confidence interval) for patients with an eGFRs of 60–89, 30–59 and 15–29 at 1.81 (1.01–3.57), 2.03 (1.04–4.40) and 3.01 (1.13–8.02), respectively. Reduced eGFR is independently associated with incident CAD but not stroke in Japanese patients with T2DM.

Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease in patients with diabetes. The relationship between renal manifestations of CKD (albuminuria and decreased glomerular filtration rate) and silent cerebral infarction (SCI) has attracted attention; however, most studies examined the effects of components of CKD on prevalence of SCI. We sought to assess the relationship between SCI and the development and progression of nephropathy in type 2 diabetic patients. We studied 366 type 2 diabetic patients with normoalbuminuria (urinary albumin-to-creatinine ratio [ACR]30 mg g(-1), N=246) or microalbuminuria (ACR=30-299 mg g(-1), N=120). SCI was defined by cranial MRI. The primary end point was progression from normo- to microalbuminuria or from micro- to macroalbuminuria. The cumulative incidence of the primary end point was estimated using the Kaplan-Meier method. Risk estimates for reaching the end point were calculated using Cox proportional hazard model analyses. During a median follow-up period of 3.9 years, 23 normoalbuminuric and 24 microalbuminuric patients reached the primary end point. Patients with SCI (N=171) had a greater incidence of reaching the end point than those without SCI (N=195, P=0.020 by the log-rank test), with a hazard ratio of 2.02 (95% confidence interval=1.09-3.72, P=0.025) in the multivariate Cox regression model. Although the common pathogenesis of SCI and albuminuria in diabetic patients is still unclear, SCI may be a predictor of progression of nephropathy in type 2 diabetic patients.

This article reports the result of the questionnaire survey conducted to 258 biomedical researchers and clinicians, which asked three questionnaires about the quality and character of abstracts published as a conference material or in specialty journal pages. The first questionnaire is “How do you think about a reference citation of meeting abstracts in the article?” Twenty-five percent of the respondents show that they believe meeting abstracts can be cited in the articles. Twenty-eight percent, they can do it if the abstract author has not published its full-length article. Forty percent, meeting abstracts should not be cited in a full-length article in any cases. The second questionnaire is “Do you think that paper presenter at a scientific meeting should write a full-length articles with the same theme?” Seventy-two percent of respondents think that presenter should write the full-length article after the meeting. Twenty-three percent, do not think so. The third questionnaire is “How do you think about the content of full-length article is different from the paper presentation of the same theme at the meeting already held?” Sixteen percent of respondents believe that the content of presentation at a meeting must not be changed when it is published as a full-length article. Seventy-two percent, think that small changes are within allowance. Only seven percent, think that there is difference between the paper oral presentation at a meeting and its full-length article written after the meeting as a natural consequence. Many biomedical researchers and clinicians have understood the different role of various meetings, e. g. national, local, and special theme meetings. In other words, they use meeting abstracts at the variety of situations of biomedical meetings.

Background. Nitric oxide (NO) is thought to play an important role in the pathogenesis of diabetic nephropathy. We conducted a prospective, observational cohort study to explore the relationship between plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, and the development and progression of nephropathy in patients with type 2 diabetes. Methods. This was a hospital-based observational cohort study in Japanese type 2 diabetic patients with normoalbuminuria [urinary albumin-to-creatinine ratio (ACR)

Objective To examine the impact of add-on sitagliptin therapy on glucose, endogenous insulin and glucagon concentrations in Japanese patients with type 2 diabetes under insulin therapy.

The surgical implantation of chronic ureter cannula to determine the renal clearance was evaluated using 24 pigs. The silicon tubing was surgically implanted into both ureters of each pigs. Two types of thick tubing (the inside diameter 1.0 or 2.5 mm and the outside diameter 4.0 mm) were used for these cannulas. The tubing was exposed out of the pig's body on the flank, on the hypogastric zone near the umbilicus, or near the groin. The following steps were effective to minimize the opportunity of a bacterial infection in the kidney and to maintain the functional integrity of the chronic ureter cannula for as longer period as possible: 1) to use the tubing of larger opening as the ureter cannula, 2) to expose the tubing from the hypogastric zone near the groin, and 3) to apply the disinfectant frequently to the incision sites, cannula outlets and pig's metabolic cage. The oral ingestion of the GGES solution increased the urinary volume, which might in turn have resulted in the effective rinsing of the kidney and the chronic ureter cannula. The cannula served satisfactorily for more than 3 weeks in 13 of the pigs, up to a maximum of 7 weeks. The PSP clearances values were low during the first week of the postoperative period, which may be attributed to surgical stress. The chronic ureter cannula, associated with the postoperative period of more than 1 week, can be recommended for the evaluation of the renal clearance of drugs in the pig.

The contribution of renal active tubular secretion of N4-acetylsulfamonomethoxine (AcSMM) in renal excretion was examined using 3 conscious pigs with permanent ureter cannulae. AcSMM was the main metabolite of sulfamonomethoxine (SMM) in pigs. When AcSMM (100 mg/kg) was intravenously injected, the renal clearance of AcSMM increased with the decrease of AcSMM plasma concentration. Michaelis-Menten kinetics was demonstrated in the renal excretion of AcSMM. It can be concluded that AcSMM is mostly excreted through active tubular secretion. The decrease of renal clearance of AcSMM may be thought as the causal factor of nonlinear plasma kinetics of SMM in pig.

The renal clearance is an important parameter of the drug disposition. It is calculated from the amount of urinary drug per unit time and plasma concentration. Using experimental animals the exact value of renal clearance cannot be determined, because urine is voided spontaneously (Shimoda et al, 198 6). It may be preferable to collect urine and blood at the same time under the continuous urinary flow, but we report here experience based on the chronic ureter cannulation of pigs.