Alcohol Consumption and a Decline in Glomerular Filtration Rate: The Japan Specific Health Checkups Study.

Previous studies have reported conflicting results on the clinical impact of alcohol consumption on the glomerular filtration rate (GFR). This retrospective cohort study aimed to assess the dose-dependent association between alcohol consumption and the slope of the estimated GFR (eGFR) in 304,929 participants aged 40-74 years who underwent annual health checkups in Japan between April 2008 and March 2011. The association between the baseline alcohol consumption and eGFR slope during the median observational period of 1.9 years was assessed using linear mixed-effects models with the random intercept and random slope of time adjusting for clinically relevant factors. In men, rare drinkers and daily drinkers with alcohol consumptions of ≥60 g/day had a significantly larger decline in eGFR than occasional drinkers (difference in multivariable-adjusted eGFR slope with 95% confidence interval (mL/min/1.73 m2/year) of rare, occasional, and daily drinkers with ≤19, 20-39, 40-59, and ≥60 g/day: -0.33 [-0.57, -0.09], 0.00 [reference], -0.06 [-0.39, 0.26], -0.16 [-0.43, 0.12], -0.08 [-0.47, 0.30], and -0.79 [-1.40, -0.17], respectively). In women, only rare drinkers were associated with lower eGFR slopes than occasional drinkers. In conclusion, alcohol consumption was associated with the eGFR slope in an inverse U-shaped fashion in men but not in women.

Severe leukocytopenia due to copper deficiency induced by zinc supplementation in a patient on peritoneal dialysis: a case report.

Zinc deficiency is one cause of anemia. However, it has been reported that some patients who were treated with zinc supplementation to resolve this anemia subsequently experienced copper deficiency, which lead to continued anemia, as well as leukocytopenia and other symptoms. However, only two patients with copper deficiency induced by zinc supplementation undergoing peritoneal dialysis have been reported. Here, we report the case of a 59 year-old man with copper deficiency after zinc supplementation undergoing peritoneal dialysis (PD). He took meals only once a day and drank about 750 mL/day of wine every day. He had been receiving zinc supplementation for 4 months. He was diagnosed with severe leukocytopenia and worsening anemia at a planned outpatient visit; in addition, his copper levels had markedly decreased. Thus, zinc supplementation was discontinued, and the patient was instructed to take cocoa for copper supplementation. Because of severe leukocytopenia, he was admitted to our hospital, and granulocyte colony-stimulating factor was administered. Red blood cell transfusions were performed for anemia. After discontinuing zinc supplementation, his white blood cell count and hemoglobin levels improved.To avoid Cu deficiency, patients' dietary history should be checked in detail and Cu should be monitored carefully when Zn is supplemented in patients undergoing PD.

Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics.

Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

A Formula for the Estimation of 24-Hour Urinary Creatinine Excretion: A Derivation and Validation Study.

OBJECTIVE: Twenty-four-hour urinary creatinine (Cr) excretion (24h-uCr) is the basis of Cr clearance and urinary protein-Cr ratio, and it is related to frailty, worsening kidney function, and mortality in patients with chronic kidney disease. Although subjects with lower estimated glomerular filtration rate (eGFR) tend to have lower 24h-uCr, previous formulae for the estimation of 24h-uCr did not include Cr as a predictor. METHODS: This retrospective study included patients admitted to the Department of Nephrology at our hospital (derivation cohort and validation cohort: patients admitted between April 2016 and March 2020). The prediction formula of 24h-uCr was calculated using a multivariate linear regression model with the bootstrap method. Age, height, weight, sex, Cr, and cystatin C were used as predictors. RESULTS: The derivation and validation cohorts included 187 and 63 patients, respectively. The characteristics of the derivation and validation cohorts were as follows: age 73 (61-79.5) years and 70 (58.5-79) years; males, 61.5% and 60.3%; eGFRCr 27.0 (13.7-48.6) mL/min/1.73 m2 and 26.3 (14.0-51.5) mL/min/1.73 m2; and 24-hour urinary protein excretion 0.79 (0.17-2.12) g/day and 1.08 (0.26-2.55) g/day, respectively. Seven prediction formulae were derived. In all models, the Pearson's correlation coefficient was relatively high and statistically significant. However, previous models tended to overestimate the 24h-uCr. Furthermore, the predicted 24h-uCr calculated by the models that do not include Cr as a predictor fluctuates depending on the eGFRCr. CONCLUSION: The best formula for predicting 24h-uCr (mg/day) in a wide range of eGFR populations is a Cr-containing formula: [-9.04 × age (years) + 8.03 × weight (kg) + 0.66 × height (cm) + 188.59 (if male) - 32.11 × Cr (mg/dL) + 779.14].

Occupational sedentary behavior and prediction of proteinuria in young to middle-aged adults: a retrospective cohort study.

BACKGROUND: Although sedentary behavior is a risk factor of cardiometabolic diseases and mortality, little information is available about a clinical impact of occupational sedentary behavior on chronic kidney disease (CKD). METHODS: The present retrospective cohort study included 10,212 workers of a national university in Japan who underwent annual health checkups between April 2006 and March 2013. Main exposure of interest was self-reported occupational sedentary behavior at the baseline visit. The outcome was the incidence of proteinuria defined as dipstick urinary protein of 1 + or more. The association between sedentary workers and the incidence of proteinuria was assessed using Cox proportional hazards models adjusting for clinically relevant factors, including television viewing time, the major home sedentary behavior. RESULTS: During median 4.8 years (interquartile range 2.1-7.9) of the observational period, the incidence of proteinuria was observed in 597 (12.0%) males and 697 (13.3%) females. In males, sedentary workers were identified as a significant predictor of proteinuria (multivariable-adjusted hazard ratio of non-sedentary and sedentary workers: 1.00 [reference] and 1.35 [1.11-1.63]), along with longer television viewing time (< 30 min, 30-60 min, 1-2 h, 2-3 h, and > 3 h/day: 1.15 [0.93-1.42], 1.00 [reference], 1.24 [1.00-1.53], 1.41 [1.03-1.93], and 1.77 [1.13-2.76]), whereas not daily exercise time. In females, neither sedentary workers nor television viewing time was associated with the incidence of proteinuria. CONCLUSIONS: In conclusion, male sedentary workers were at high risk of proteinuria. Occupational sedentary behavior may be a potentially modifiable target for the prevention of CKD.

Frequency of Breakfast, Lunch, and Dinner and Incidence of Proteinuria: A Retrospective Cohort Study.

Although multiple studies have revealed a close association of skipping breakfast with cardiometabolic diseases, few studies have reported its association with chronic kidney disease (CKD). Furthermore, there is scant reporting on the clinical impacts that skipping lunch and dinner has on cardiometabolic diseases and CKD. This retrospective cohort study, including 5439 female and 4674 male workers of a national university in Japan who underwent annual health checkups between January 2005 and March 2013, aimed to assess an association of frequencies of breakfast, lunch, and dinner with incidence of proteinuria (dipstick urinary protein ≥1+). The incidence of proteinuria was observed in 763 (14.0%) females and 617 (13.2%) males during the median 4.3 and 5.9 years of the observational period, respectively. In females, skipping breakfast as well as skipping dinner, but not lunch, were associated with the incidence of proteinuria (adjusted hazard ratios of breakfast frequency of "every day", "sometimes", and "rarely": 1.00 (reference), 1.35 (1.09-1.66), and 1.54 (1.22-1.94), respectively; those of dinner frequency of "every day" and "≤sometimes": 1.00 (reference) and 1.31 (1.00-1.72), respectively). However, no association was observed in male workers. Skipping breakfast and skipping dinner were identified as risk factors of proteinuria in females, but not in males.

Lactate predicts the 28-day survival rate in patients with septic shock treated with the combination of PMX-DHP and rTM.

We have previously reported that combination therapy with polymyxin-B direct hemoperfusion (PMX-DHP) and recombinant thrombomodulin (rTM) is effective in patients with septic shock accompanied by disseminated intravascular coagulation (DIC). Two previous studies reporting the favorable effect of early initiation of PMX-DHP for septic shock did not focus on the combination therapy of PMX-DHP and rTM. This retrospective study included 47 consecutive patients who underwent the combination therapy of PMX-DHP and rTM for septic shock with DIC from August 2011 to August 2016. Main exposure was early or late initiation of PMX-DHP. PMX-DHP initiated within 12 hours after catecholamine administration was designated as early group (N = 25) and later than 12 hours as late group (N = 22). Main outcome was 28-day survival rate. The patient characteristics were age median 73 (IQR 68-78) years, 26 men (55%), APACHE II score 32.7 ± 7.7 and lactate 26.0 (18.0-41.0) mg/dL. The 28-day survival rate after PMX-DHP initiation was 76.6% and was not significantly different in the two groups. In the early group, APACHE II score was lower (P = .02), and lactate was higher (P = .005) than in the late group. Lactate was the only predictor of 28-day mortality [odds ratio (95%CI) per 1 mg/dL, 1.08 (1.03-1.19); P = .037] in multivariate logistic regression analysis adjusted with age, sex, APACHE II score, lactate and timing of PMX-DHP initiation. Late PMX-DHP initiation did not lead to statistically worse 28-day survival rate in this combination therapy. The combination therapy of PMX-DHP and rTM may improve the therapeutic effect of PMX-DHP and modify the effect of early PMX-DHP on the prognosis. Lactate may be an appropriate indicator rather than time after catecholamine administration if we discuss when to start PMX-DHP in this combination therapy.

Body mass index modifies the association between frequency of alcohol consumption and incidence of hypertension in men but not in women: a retrospective cohort study.

Alcohol consumption is one of the major modifiable risk factors of hypertension. The aim of the present retrospective study was to assess the clinical impact of obesity on the association between alcohol consumption and the incidence of hypertension. The present study included 5116 male and 6077 female university employees with a median age of 32 (interquartile range 27-39) who underwent annual health checkups between January 2005 and March 2013. Self-reported drinking frequency was recorded at their first checkup and categorized into rarely and 1-3, 4-6, and 7 days/week. During the median observational period of 4.9 years (interquartile range 2.1-8.3), hypertension, defined as systolic/diastolic blood pressure of ≥140/90 mmHg and/or self-reported treatment for hypertension, was observed in 1067 (20.9%) men and 384 (6.3%) women. Poisson regression models adjusted for clinically relevant factors revealed a dose-dependent association between drinking frequency and the incidence of hypertension in men (adjusted incidence rate ratio [95% confidence interval] of men who drank rarely, 1-3, 4-6, and 7 days/week was 1.00 [reference], 1.12 [0.97-1.30], 1.42 [1.19-1.70], and 1.35 [1.14-1.59], respectively; Ptrend < 0.001). However, this association was not observed in women. The dose-dependent association was significant in nonobese men (body mass index (BMI) < 25 kg/m2), but not in obese men (BMI ≥25 kg/m2) (P for interaction between drinking frequency and BMI = 0.072). The present study provides clinically useful evidence to identify the drinkers who may reap the health benefits of abstinence from alcohol consumption.

Sleep debt and prevalence of proteinuria in subjects with short sleep duration on weekdays: a cross-sectional study.

STUDY OBJECTIVE: Short sleep duration is a risk factor of chronic kidney disease, along with cardiovascular diseases and all-cause mortality. Several studies reported that many people sleep longer on weekends than on weekdays, suggesting that they should be compensated for their sleep debt on weekdays on the weekends. Few studies have reported the clinical impact of sleep debt on the kidney. METHODS: This cross-sectional study included 5799 employees of Osaka University who visited its Health Care Center for their annual health examinations and answered ≤ 6 h of sleep duration on weekdays. The independent variable was the sleep debt index defined as a gap in self-reported sleep duration (≤ 5, 5-6, 6-7, 7-8, 8-9, and ≥ 9 h) between weekdays and weekends, which was categorized into ≤ 0, + 1, + 2, + 3 and ≥+4. An association between the sleep debt index and a prevalence of proteinuria defined as dipstick proteinuria of ≥ 1 + was assessed using logistic regression models adjusting for clinically relevant factors. RESULTS: More than four-fifths of the subjects had a positive sleep debt index (≤ 0, + 1, + 2, + 3, and ≥+4 recorded for 19%, 36%, 28%, 11%, and 6%, respectively). The multivariable-adjusted logistic regression models showed the sleep debt index ≥ 3 + was significantly associated with the prevalence of proteinuria (sleep debt index ≤ 0, adjusted odds ratio 1.13 [0.77, 1.65]; + 1, 1.00 [reference]; + 2, 1.29 [0.93, 1.79]; + 3, 1.54 [1.02, 2.33]; ≥ + 4, 1.87 [1.15, 3.05]). CONCLUSIONS: Sleep debt was associated with the prevalence of proteinuria in a dose-dependent manner.

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.