Breakfast Frequency and Smoking Initiation in University Students: A Retrospective Cohort Study.

Smoking causes various health problems. Limited studies have reported a clinical effect of skipping breakfast on smoking initiation among adolescents. This retrospective cohort study aimed to assess the dose-dependent association between skipping breakfast and smoking initiation in university students. This study included 17,493 male and 8880 female students aged 18-22 years at a national university in Japan. The association between breakfast frequency (eating every day and skipping occasionally, often, and usually) and smoking initiation was evaluated using Cox proportional hazards models adjusted for clinically relevant factors. Smoking initiation was observed in 2027 (11.6%) male and 197 (2.2%) female students over the median observational period of 3.0 and 3.1 years. Skipping breakfast was significantly associated with smoking initiation in a dose-dependent fashion in male students (the adjusted hazard ratios [95% confidence interval] of eating breakfast every day and skipping occasionally, often, and usually: 1.00 [reference], 1.30 [1.15, 1.46], 1.47 [1.21, 1.79], and 1.77 [1.40, 2.25], respectively). Female students skipping breakfast occasionally and often were more vulnerable to smoking initiation than those who ate breakfast every day (1.00 [reference], 1.86 [1.24, 2.78], 2.97 [1.66, 5.32], and 1.76 [0.55, 5.64], respectively). Breakfast frequency may be useful to identify university students at risk of smoking initiation who need improvement in their health literacy.

Cigarette smoking and progression of kidney dysfunction: a longitudinal cohort study.

INTRODUCTION: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established. METHOD: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis. RESULTS: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001). CONCLUSION: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria.

Short sleep duration and smoking initiation in university students: a retrospective cohort study.

PURPOSE: The aim of this study was to clarify an association between short sleep duration and smoking initiation. METHODS: Participants eligible for this retrospective cohort study were university students who were admitted to a single national university in Japan between 2007 and 2015. Baseline sleep duration and smoking status were measured using general questionnaires at health checkups at admission. During a 6-year observation period, smoking initiation was assessed using general questionnaires at annual health checkups. Cox proportional hazards models adjusted for clinically relevant factors were used to assess the association between sleep duration and smoking initiation. RESULTS: Of 17,493 men, including 540, 5,568, 8,458, 2,507, and 420 men with sleep duration of < 5, 5-6, 6-7, 7-8, and ≥ 8 h, respectively, smoking initiation was observed in 16.1%, 12.5%, 11.2%, 10.0%, and 11.7%, respectively, during a median observation period of 3.0 years. Men with shorter sleep duration were at a higher risk of smoking initiation (adjusted hazard ratio 1.49 [95% confidence interval 1.19-1.85], 1.11 [1.01-1.22], 1.00 [reference], 0.92 [0.80-1.06], and 1.00 [0.75-1.34], respectively). Of 8,880 women, including 267, 3,163, 4,220, and 1,230 women with sleep duration of < 5, 5-6, 6-7, and ≥ 7 h, respectively, smoking initiation was observed in 4.9%, 2.3%, 2.0%, and 2.2%, respectively, during a median observation period of 3.0 years. A similar dose dependent association was ascertained in women (2.50 [1.39-4.49], 1.18 [0.86-1.62], 1.00 [reference], and 1.22 [0.79-1.89], respectively). CONCLUSION: This study clarified that university students with short sleep duration were vulnerable to smoking initiation.

Efficacy of corticosteroid therapy for IgA nephropathy patients stratified by kidney function and proteinuria.

BACKGROUND: Steroid therapy is one of the important therapies for IgA nephropathy (IgAN), but the features of the IgAN patients who have the benefit from this therapy remained unclear. METHODS: This retrospective observational study, using data of 874 patients with IgAN analyzed the proteinuria and kidney function of IgAN patients who had beneficial effect by steroid therapy. Two advantages of the present study were a large cohort and a long observational period. RESULTS: Corticosteroid therapy had ameliorated the kidney prognosis [incident rate ratio (IRR) 0.57 (95%CI 0.34-0.92), P = 0.029]. Because of interaction between kidney function and use of corticosteroid (P = 0.047), stratification analysis by kidney function revealed that prognosis of kidney function in IgAN patients whose eGFR was less than 60 ml/min/1.73m2 was ameliorated by corticosteroid therapy [IRR 0.50 (95%CI 0.26-0.97), P = 0.015); while, there was no change of kidney prognosis in IgAN patients whose eGFR was above 60 ml/min/1.73 m2. To make the target of corticosteroid therapy for IgAN patients more clear, IgAN patients, whose eGFR were less than 60 ml/min/1.73 m2, were stratified by proteinuria (1 g/day). In IgAN patients whose eGFR were under 60 ml/min/1.73 m2 and whose proteinuria were over 1.0 g/day, corticosteroid therapy seemed to ameliorate kidney function [IRR 0.39 (95%CI 0.19-0.86), P < 0.05]; while, there was obviously no change by corticosteroid therapy in IgAN patients whose eGFR were less than 60 ml/min/1.73 m2 and whose proteinuria were less than 1.0 g/day. CONCLUSION: Our results suggested that steroid therapy was especially effective for IgAN patients whose eGFR was less than 60 ml/min/1.73 m2 and whose proteinuria was more than 1.0 g/day.

Sleep Quality and Sleep Duration with CKD are Associated with Progression to ESKD.

BACKGROUND AND OBJECTIVES: Shorter or longer sleep duration and poor sleep quality are risk factors for numerous cardio-metabolic diseases, cardiovascular disease, and mortality in subjects with normal kidney function. The association of sleep duration and sleep quality with health outcomes in patients with CKD remains uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A 4-year prospective cohort study in 17 nephrology centers in Japan, the CKD Japan Cohort (CKD-JAC) Study, assessed an association of self-reported sleep duration and sleep quality, on the basis of the Pittsburgh Sleep Quality Index (PSQI) questionnaire, with incidence of ESKD in 1601 patients with eGFR 10-59 ml/min per 1.73 m2 using multivariable-adjusted Cox proportional hazards models. RESULTS: Baseline sleep duration and PSQI global score for the 1601 patients were mean±SD 7.0±1.3 hours and median 4 (interquartile range, 3-7), respectively. Poor sleep quality (PSQI global score ≥6) was common (n=588 [37%]). During a median of 4.0 (2.6-4.3) years of the follow-up period, 282 (18%) patients progressed to ESKD. After adjusting for age, sex, eGFR, urinary albumin excretion, smoking status, body mass index, history of diabetes and cardiovascular disease, systolic BP, blockade of the renin-angiotensin system, use of hypnotics, and Beck depression inventory score, both shorter (≤5 hour) and longer (>8 hour) sleep duration were associated with ESKD (adjusted hazard ratios [95% confidence intervals] for ≤5.0, 5.1-6.0, 6.1-7.0, 7.1-8.0, and ≥8.0 hours were 2.05 [1.31 to3.21], 0.98 [0.67 to 1.44], 1.00 [reference], 1.22 [0.89 to 1.66], and 1.48 [1.01 to 2.16]), suggesting a U-shaped relationship between sleep duration and ESKD. PSQI global score ≥6 was also associated with incidence of ESKD (adjusted hazard ratios [95% confidence intervals] for PSQI global score ≤5 and ≥6 were 1.00 [reference] and 1.33 [1.03 to 1.71]). CONCLUSIONS: Shorter (≤5 hour) and longer (>8 hour) sleep duration and poor sleep quality (PSQI global score ≥6) were associated with ESKD in patients with CKD.

Alcohol consumption and incidence of proteinuria: a retrospective cohort study.

BACKGROUND: Previous studies report conflicting results of a dose-dependent association between alcohol consumption and incidence of chronic kidney disease. Only a few studies have assessed the clinical impact of > 45-65 g/day of critically high alcohol consumption. METHODS: This retrospective cohort study included 88,647 males and 88,925 females with dipstick urinary protein ≤ ± and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 at their first annual health examinations between April 2008 and March 2010 in Japan. The exposure was the self-reported alcohol consumption. The outcome was proteinuria defined as dipstick urinary protein ≥ 1 + or ≥ 2 +. RESULTS: During median 1.8 years (interquartile range 1.0-2.1) of the observational period, 5416 (6.1%) males and 3262 (3.7%) females developed proteinuria defined as dipstick urinary protein ≥ 1 +. In males, a U-shape association between alcohol consumption and proteinuria was observed in a multivariable-adjusted Poisson regression model [incidence rate ratio (95% confidence interval) of rare, occasional, and daily drinkers with ≤ 19, 20-39, 40-59, and ≥ 60 g/day: 1.00 (reference), 0.86 (0.79-0.94), 0.70 (0.64-0.78), 0.82 (0.75-0.90), 1.00 (0.90-1.11), and 1.00 (0.85-1.17), respectively], whereas a J-shape association was observed in females [1.00 (reference), 0.81 (0.75-0.87), 0.74 (0.64-0.85), 0.93 (0.78-1.11), 1.09 (0.83-1.44), and 1.45 (1.02-2.08), respectively]. Similar associations with dipstick urinary protein ≥ 2 + were shown in males and females. CONCLUSIONS: Moderate alcohol consumption was associated with lower risk of proteinuria in both males and females. Females with ≥ 60 g/day of high alcohol consumption were at higher risk of proteinuria, whereas males were not. Females were more vulnerable to high alcohol consumption, than males.

Perioperative Steroid Use for Tonsillectomy and Its Association With Reoperation for Posttonsillectomy Hemorrhage: A Retrospective Cohort Study.

BACKGROUND: Steroids reduce postoperative complications after tonsillectomy such as nausea and vomiting, pain, and delayed recovery. However, steroids may also increase the risk of severe posttonsillectomy bleeding requiring reoperation. METHODS: To evaluate the risk of postoperative bleeding requiring reoperation related to perioperative steroid use, we conducted a retrospective cohort study of 6149 patients treated at 68 hospitals using a hospital-based claims database. The primary outcome was reoperation for bleeding within 14 postoperative days. We estimated odds ratios (ORs) between perioperative steroid use and reoperation by multivariable logistic regression analysis adjusted for confounders. We also estimated differences in the adjusted risk. Subgroup analyses after dividing patients into adults and children were also performed. RESULTS: The incidence of reoperation did not differ significantly between patients who received steroids on the day of tonsillectomy and those who did not (1.8%, n = 15 vs 1.5%, n = 79; adjusted OR 0.81, 95% confidence interval [CI], 0.45-1.43; P = .46). We also found nonsignificant associations in both adults (OR, 0.73; 95% CI, 0.38-1.38; P = .33) and children (OR, 1.18; 95% CI, 0.34-4.11; P = .80). The adjusted risk differences estimated by the logistic regression model were -0.30% (95% CI, -1.05 to 0.45) in all patients, -0.64% (95% CI, -1.82 to 0.54) in adults, and 0.13% (95% CI, -0.93 to 1.19) in children. CONCLUSIONS: Steroid use on the day of tonsillectomy was not associated with an increased risk of reoperation for bleeding. Although the wide range of CIs for the ORs could not eliminate the possibility of increased risk, especially in children, the incremental risks of reoperation for steroid use were within an acceptable range for both adults and children. Our results support the safety of perioperative steroid use for tonsillectomy, considering the magnitude of risk of reoperation because of bleeding.

Clinical characteristics of adrenal crisis in adult population with and without predisposing chronic adrenal insufficiency: a retrospective cohort study.

BACKGROUND: Adrenal crisis (AC) occurs in various clinical conditions but previous epidemiological studies in AC are limited to chronic adrenal insufficiency (AI) and sepsis. The aim of this study was to investigate characteristics of AC patients, including predisposing diseases and to describe candidate risk factors for AC such as comorbidities and glucocorticoid (GC) therapy. METHODS: We conducted a retrospective cohort study using a claims database on 7.4 million patients from 145 acute care hospitals between January 1, 2003 and April 30, 2014. We identified AC patients who met the following criteria: 1) disease name with ICD-10 corresponded with AI; 2) therapeutic GC administration (hydrocortisone equivalent dose ≥100 mg/day); 3) admission; and 4) age ≥18 years. RESULTS: We identified 504 patients with AC (median age, 71 years; interquartile range, 59 to 80; 50.6% male). As predisposing conditions, primary AI and central AI accounted for 23 (4.6%) and 136 patients (27.0%), respectively. In the remaining AC patients (68.5%), comorbidities such as cancer, autoimmune diseases, and renal failure were frequent. The most frequent indication for hospitalization was AC (16.3%), followed by pituitary disease (14.7%), cancer (14.7%), AI-related clinical symptoms (11.5%), and infection (11.1%). Admission under oral GC treatment was reported in 104 patients (20.6%). Twenty-six patients were admitted within 14 days after GC cessation (5.2%). CONCLUSIONS: These findings present an overview of patients with AC in general practice settings, clarifying that predisposing factors for AC were complicated and that patients other than those with chronic AI were older and had more comorbid conditions than those with primary and central AI.

The association of alcohol and smoking with CKD in a Japanese nationwide cross-sectional survey.

Chronic kidney disease (CKD) is characterized by a reduced glomerular filtration rate (GFR) and proteinuria. Modifiable lifestyle factors such as smoking and alcohol contribute to CKD. Recent cohort studies have shown that moderate alcohol consumption attenuates the decline of the GFR and smoking has been previously shown to be associated with CKD. However, the association of smoking and alcohol consumption on CKD is not entirely clear. To examine whether there is evidence to assume that smoking is an effective modifier of the association between CKD and alcohol consumption, we conducted a cross-sectional study of a population of people who presented for a health checkup under a program that targets the insured population aged ≧40 years using data from the Specific Health Check and Guidance in Japan between April 2008 and March 2009. Of the 506 807 participants aged ⩾40 years, 292 013 (57.6%) were included in the present analysis. Outcomes were kidney dysfunction, as an eGFR of <60 ml/min/1.73 m2, and proteinuria. In nonsmokers, drinking a small amount was associated with a lower prevalence of proteinuria, but in smokers, the association between alcohol and proteinuria was not observed. The analysis regarding eGFR <60 ml/min/1.73 m2 revealed that in both smokers and nonsmokers, alcohol consumption was inversely associated with the risk of CKD. Mild to moderate alcohol consumption might be associated with a lower risk of CKD (proteinuria and eGFR), especially among nonsmokers, because smoking might have modified the potential benefits of alcohol to prevent CKD.

Maternal Smoking during Pregnancy, Household Smoking after the Child's Birth, and Childhood Proteinuria at Age 3 Years.

BACKGROUND AND OBJECTIVES: Smoking is a well known risk factor of proteinuria in adults; however, clinical studies in children are limited. The purpose of this study is to clarify the associations of maternal smoking during pregnancy and household smoking after the child's birth with the risk of proteinuria at age 3 years old. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a population-based retrospective cohort study on 44,595 children using data on prenatal health checkups, home visit neonatal health checkups, and health checkups at 4, 9, and 18 months and 3 years of age in Kobe City, Japan. Maternal smoking status (nonsmoker, past smoker, or current smoker) was collected with standardized questionnaires. The outcome of interest was the presence of proteinuria at 3 years of age defined as urinary protein ≥1+. To evaluate the association between child proteinuria and smoking status, we performed multivariate logistic regression model analyses adjusted for confounding factors. RESULTS: The prevalence rates of children in the maternal smoking groups (none, past, and current) were 78.9%, 4.4%, and 16.7%, respectively. The frequencies of child proteinuria defined as ≥1+ urinary protein were 1.7% in the current smoking group, 1.6% in the past smoking group, and 1.3% in the nonsmoking group. Maternal smoking during pregnancy was associated with child proteinuria (odds ratio, 1.24; 95% confidence interval, 1.00 to 1.52; P=0.05) in the multiple logistic regression model, although nonmaternal family smoking during pregnancy was not significantly associated with child proteinuria (odds ratio, 0.97; 95% confidence interval, 0.79 to 1.19; P=0.77). We also found a similar association with household smoking after the child's birth (odds ratio, 1.23; 95% confidence interval, 0.99 to 1.54; P=0.06), although this observation was not significant. CONCLUSIONS: Maternal smoking during pregnancy was one of the risk factors of childhood proteinuria. We also found a similar association with household smoking after the child's birth, although this observation was not significant.

Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. PREDICTOR: Uric acid levels at renal biopsy. OUTCOMES: The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". MEASUREMENTS: The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. RESULTS: An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. LIMITATIONS: A cohort analyzed retorospectively. CONCLUSIONS: This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients.

IFI27 Is a Useful Genetic Marker for Diagnosis of Immunoglobulin A Nephropathy and Membranous Nephropathy Using Peripheral Blood.

Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs. This result was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover, qRT-PCR analysis revealed that the IFI27 mRNA level was reduced in PBMCs of patients with other types of chronic glomerulonephritis. IFI27 immunohistochemical staining of biopsied specimens also confirmed reduced expression of IFI27 protein in IgAN and MN patients. Based on these results, we propose that IFI27 could serve as a noninvasive diagnostic marker for CGNs using peripheral blood.

Secondhand smoke and incidence of dental caries in deciduous teeth among children in Japan: population based retrospective cohort study.

STUDY QUESTION: Does maternal smoking during pregnancy and exposure of infants to tobacco smoke at age 4 months increase the risk of caries in deciduous teeth? METHODS: Population based retrospective cohort study of 76 920 children born between 2004 and 2010 in Kobe City, Japan who received municipal health check-ups at birth, 4, 9, and 18 months, and 3 years and had information on household smoking status at age 4 months and records of dental examinations at age 18 months and 3 years. Smoking during pregnancy and exposure of infants to secondhand smoke at age 4 months was assessed by standardised parent reported questionnaires. The main outcome measure was the incidence of caries in deciduous teeth, defined as at least one decayed, missing, or filled tooth assessed by qualified dentists without radiographs. Cox regression was used to estimate hazard ratios of exposure to secondhand smoke compared with having no smoker in the family after propensity score adjustment for clinical and lifestyle characteristics. STUDY ANSWER AND LIMITATIONS: Prevalence of household smoking among the 76 920 children was 55.3% (n=42 525), and 6.8% (n=5268) had evidence of exposure to tobacco smoke. A total of 12 729 incidents of dental caries were observed and most were decayed teeth (3 year follow-up rate 91.9%). The risk of caries at age 3 years was 14.0% (no smoker in family), 20.0% (smoking in household but without evidence of exposure to tobacco smoke), and 27.6% (exposure to tobacco smoke). The propensity score adjusted hazard ratios of the two exposure groups compared with having no smoker in the family were 1.46 (95% confidence interval 1.40 to 1.52) and 2.14 (1.99 to 2.29), respectively. The propensity score adjusted hazard ratio between maternal smoking during pregnancy and having no smoker in the family was 1.10 (0.97 to 1.25). WHAT THIS STUDY ADDS: Exposure to tobacco smoke at 4 months of age was associated with an approximately twofold increased risk of caries, and the risk of caries was also increased among those exposed to household smoking, by 1.5-fold, whereas the effect of maternal smoking during pregnancy was not statistically significant. FUNDING, COMPETING INTERESTS, DATA SHARING: This study was supported by a grant in aid for scientific research 26860415. The authors have no competing interests or additional data to share.

Comparison of methylprednisolone plus prednisolone with prednisolone alone as initial treatment in adult-onset minimal change disease: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: Previous studies suggested that intravenous methylprednisolone possibly accelerates remission of proteinuria in adult-onset minimal change disease; its impact on relapse of proteinuria is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This multicenter retrospective cohort study included 125 adult-onset minimal change disease patients diagnosed by kidney biopsy between 2000 and 2009 and treated initially with corticosteroid in five nephrology centers in Japan participating in the Study of Outcomes and Practice Patterns of Minimal Change Disease. Times to first remission and first relapse of proteinuria after initiating the first immunosuppressive therapy were compared between 65 patients with initial use of intravenous methylprednisolone followed by prednisolone and 60 patients with initial use of prednisolone alone using multivariate Cox proportional hazards models. After calculating the probability of receiving methylprednisolone and prednisolone using a logistic regression model (propensity score), the results were ascertained using propensity score-matched and -stratified models. RESULTS: During the median 3.6 years of observation (interquartile range=2.0-6.9), all 65 patients in the methylprednisolone and prednisolone group achieved remission within 11 (8-20) days of the corticosteroid initiation, whereas in the prednisolone group, 58 of 60 patients (96.7%) achieved remission within 19 (12-37) days (P<0.001). After achieving first remission, 32 (49.2%) patients in the methylprednisolone and prednisolone group and 43 (74.1%) patients in the prednisolone group developed at least one relapse. Multivariate Cox proportional hazards models revealed that methylprednisolone and prednisolone use was significantly associated with early remission (multivariate-adjusted hazard ratio, 1.56; 95% confidence interval, 1.06 to 2.30) and lower incidence of relapse (0.50; 95% confidence interval, 0.29 to 0.85) compared with prednisolone use alone. These results were ascertained in propensity score-based models. No significant difference was observed in incidence of adverse events, including infection, aseptic osteonecrosis, cataract, diabetes, and gastrointestinal bleeding. CONCLUSIONS: Initial use of methylprednisolone was associated with earlier remission and lower incidence of relapse in adult-onset minimal change disease patients. Efficacy of methylprednisolone should be evaluated in randomized controlled trials.

Age and prediction of remission and relapse of proteinuria and corticosteroid-related adverse events in adult-onset minimal-change disease: a retrospective cohort study.

BACKGROUND: In adult-onset minimal-change disease (MCD) the predictors of remission and relapse of proteinuria and corticosteroid-related adverse events remain unknown. METHODS: The multicenter retrospective cohort study, the STudy of Outcomes and Practice patterns of Minimal-Change Disease (STOP-MCD), included 142 adult-onset MCD patients in 5 nephrology centers in Japan. Primary outcomes were first remission of proteinuria defined by urinary protein (UP) <0.3 g/day, UP/creatinine ratio (UPCR) <0.3, and/or negative/trace by dipstick test and first relapse of proteinuria defined by UP ≥1.0 g/day, UPCR ≥1.0, and/or dipstick test ≥1+ followed by immunosuppressive therapy. Secondary outcomes were corticosteroid-related adverse events. RESULTS: During the median 3.6 (interquartile range, 2.0-6.9) years of the entire observational period, 136 (95.8 %) and 79 (58.1 %) patients developed at least 1 remission and 1 recurrence within a median of 15 (10-34) days and 0.90 (0.55-1.57) years, respectively. Compared with younger patients aged 15-29 years at kidney biopsy, elderly patients aged ≥60 years developed remission significantly later [hazard ratio 0.53 (95 % confidence interval 0.32-0.88)], while older patients aged ≥45 years were at a significantly lower risk of relapse [45-59 years, 0.46 (0.22-0.96); 60-83 years, 0.39 (0.21-0.74)]. However, older patients were significantly more vulnerable to severe infection, diabetes, and cataract as compared with younger patients. CONCLUSION: Younger patients had a higher risk of relapse while older patients had a lower risk of relapse but a higher risk of corticosteroid-related adverse events.

[Clinical characteristics of adult-onset minimal change nephrotic syndrome in our hospital].

OBJECTIVE: Few findings are available regarding adult-onset minimal change nephrotic syndrome (MCNS) with respect to the disease course and complications, such as acute kidney injury (AKI). We therefore performed a retrospective review to characterize the clinical presentations, steroid responsiveness and complications of adult-onset MCNS patients in our hospital. PATIENTS AND METHODS: We retrospectively reviewed 40 cases of idiopathic adult-onset MCNS who had been investigated and treated at a single center. Patients between 18 and 50 years of age (Younger group) at the time of biopsy were compared with those older than 50 years (Older group) with regard to demographic data, clinical features and treatment outcome. RESULTS: Baseline characteristics of the 40 patients were: median age, 42 years (interquartile range: 28-63 years); male, 70%; mean (+/- standard deviation) systolic and diastolic blood pressures, 125 +/- 17 mmHg and 78 +/- 12 mmHg, respectively; estimated glomerular filtration rate (eGFR), 74 mL/min/1.73 m2 (range: 64-94 mL/min/1.73 m2); serum albumin, 1.8 +/- 0.3 g/dL; and urinary protein, 7.8 g/day (range: 3.9-10.4 g/day). All except for one patient received steroid pulse therapy. Time to complete response (CR) was 12 days (range: 8-21 days). Time to CR was significantly longer in the Older group (p = 0.011). The Late-responder group (time to CR > 2 weeks)was significantly older (p < 0.01), with a low eGFR (p < 0.001) and a higher prevalence of interstitial fibrosis in renal biopsy before the initiation of corticosteroid therapy (p < 0.05), compared with the Early-responder group. AKI was observed in 14 patients. Patients with an episode of AKI were significantly older (p = 0.005), with a lower eGFR (p < 0.002) and a higher prevalence of cellular casts (p < 0.05). At the follow-up, 19 patients (51%) had experienced relapses. The relapse rate was significantly lower in the Older group than in the Younger group (p < 0.05). CONCLUSION: The present study revealed that older patients had a longer period to CR and a higher risk of AKI at follow-up.

Self-reported sleep duration and prediction of proteinuria: a retrospective cohort study.

BACKGROUND: Although multiple studies have shown that sleep duration is a predictor of cardiovascular diseases and mortality, few studies have reported an association between sleep duration and chronic kidney disease. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 6,834 employees of Osaka University aged 20-65 years who visited Osaka University Healthcare Center for their mandatory annual health examinations between April 2006 and March 2010 and did not have estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), proteinuria, or treatment for self-reported kidney disease. PREDICTOR: Self-reported questionnaires about life style, including sleep duration, and blood and urine testing at the first examinations during the study period. An association between sleep duration and outcome was assessed using multivariate Poisson regression models adjusting for clinically relevant factors. OUTCOME: Time to the development of proteinuria defined as 1+ or higher by dipstick test. RESULTS: Self-reported baseline sleep duration was 6.0 ± 0.9 hours, which reflected the mean sleep duration during a median of 2.5 (25th-75th percentile, 1.4-3.9) years of the observational period. Development of proteinuria was observed in 550 employees (8.0%). A multivariate Poisson regression model clarified that shorter sleep duration, especially 5 or fewer hours, was associated with the development of proteinuria in a stepwise fashion (vs 7 hours; incidence rate ratios of 1.07 [95% CI, 0.87-1.33; P = 0.5], 1.28 [95% CI, 1.00-1.62; P = 0.05], and 1.72 [95% CI, 1.16-2.53; P = 0.007] for 6, 5, and ≤4 hours, respectively), along with younger age, heavier current smoking, trace urinary protein by dipstick test, higher eGFR, higher serum hemoglobin A(1c) level, and current treatment for heart disease. A stepwise association between shorter sleep duration and the development of proteinuria also was verified in 4,061 employees who did not work the night shift. LIMITATIONS: Self-reported sleep duration might be biased. Results in a single center should be confirmed in the larger cohort including different occupations. CONCLUSION: Short sleep duration, especially 5 or fewer hours, was a predictor of proteinuria.

Gene polymorphisms contributing to hypertension in immunoglobulin A nephropathy.

BACKGROUND: Hypertension, which is affected by genetic and environmental factors, is one of the major risk factors for chronic kidney disease. Identification of the genetic factor contributing to hypertension in patients with chronic kidney disease may potentially refine a therapeutic strategy. METHODS: In the present multicenter cross-sectional study, 240 patients were eligible (aged 15-50 years with urinary protein ≥0.25 g/day) out of 429 patients who were diagnosed as having immunoglobulin (Ig) A nephropathy (IgAN) by renal biopsy between 1990 and 2005 and enrolled in our previous study, PREDICT-IgAN. The outcome was hypertension defined as ≥140 and/or ≥90 mmHg of systolic and diastolic blood pressure and/or use of antihypertensives at renal biopsy. We assessed associations between hypertension and 28 polymorphisms with the frequency of minor genotype ≥10% among 100 atherosclerosis-related polymorphisms using the Chi-squared test in dominant and recessive models. We identified polymorphisms associated with hypertension in multivariate logistic regression models. RESULTS: Baseline characteristics: hypertension 36.3%. Among 28 polymorphisms, the Chi-squared test revealed that CD14 (-159CC vs CT/TT, P = 0.03) and ACE (DD vs DI/II, P = 0.03) were significantly associated with hypertension after Bonferroni correction. Multivariate logistic regression models revealed that CD14 -159CC [vs CT/TT, odds ratio (OR) 3.58 (95% confidence interval (CI) 1.66-7.63)] and ACE DD [vs DI/II, OR 4.41 (95% CI 1.80-10.8), P = 0.001] were independently associated with hypertension. CONCLUSIONS: CD14 C-159T and ACE I/D contributed to hypertension in patients with IgAN.

Effects of nicorandil on the reduction of BNP levels in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) still frequently experience cardiovascular events despite recent progress in treatment. We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events. METHODS: Patients with advanced stage CKD (stage III-V with or without peritoneal dialysis) were included in this trial if they were considered at high risk for cardiovascular events [past history of cardiovascular diseases, past history of coronary angiography, presence of endothelial dysfunction measured by reactive hyperemia peripheral arterial tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients were randomly assigned to be treated with or without oral nicorandil, 15 mg/day. BNP values and endothelial function (augmentation index, pulse wave velocity, and reactive hyperemia peripheral arterial tonometry) before and 1 month after the initiation of the trial were assessed. RESULTS: Nineteen patients (15 men, 4 women) with a mean age of 61 ± 10 (SD) years were included. The median baseline BNP value was 75.3 (interquartile range, 32.1-138.8) pg/ml, and the BNP level was significantly reduced in the nicorandil group (P < 0.05). Regression analysis demonstrated that only the use of nicorandil is related to a decrease of BNP levels [standardized ß coefficient, -75.1 (95% CI, -19.7 to -130.6), P = 0.01]. There were no significant changes in the rest of the parameters in the nicorandil group in comparison to the control group. The change in BNP levels was correlated with changes in the augmentation index (P < 0.01) and central pulse pressure (P = 0.03). CONCLUSIONS: Nicorandil treatment may reduce the level of BNP by reducing the central blood pressure in CKD patients.