Association between fatty liver index and risk of end-stage renal disease stratified by kidney function in patients with type 2 diabetes: A nationwide population-based study.

OBJECTIVE: The effects of nonalcoholic fatty liver disease on the risk of end-stage renal disease (ESRD) remain unclear. We investigated the association between the fatty liver index (FLI) and risk of ESRD in patients with type 2 diabetes. METHODS: This population-based observational cohort study enrolled patients with diabetes who underwent health screening between 2009 and 2012 and utilized data from the Korean National Health Insurance Services. The FLI functioned as a surrogate marker for the presence of hepatic steatosis. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m² calculated using the Modification of Diet in Renal Disease equation. We performed Cox proportional hazards regression. RESULTS: Incident ESRD developed in 19,476 of 1,900,598 patients with type 2 diabetes during a median follow-up of 7.2 years. After adjusting for conventional risk factors, patients with high FLI scores had a higher risk for ESRD: FLI, 30-59 [hazard ratio (HR) = 1.124; 95% confidence interval (CI), 1.083-1.166]; FLI ≥ 60 [HR = 1.278; 95% CI, 1.217-1.343] compared with those with FLI < 30. The association between a high FLI score (≥ 60) and incident ESRD was more prominent in women than in men (male, FLI ≥60: HR, 1.106; 95% CI = 1.041-1.176 and female, FLI ≥ 60: HR, 1.835; 95% CI = 1.689-1.995). The association between a high FLI score (≥ 60) and the risk of ESRD differed according to baseline kidney function. High FLI scores increased the risk of ESRD (HR = 1.268; 95% CI, 1.198-1.342) in patients with CKD at baseline. CONCLUSION: High FLI scores are associated with a greater risk of ESRD in patients with type 2 diabetes with CKD at baseline. Close monitoring and appropriate management of hepatic steatosis may aid in preventing the progression of kidney dysfunction in patients with type 2 diabetes and CKD.

Association of intraabdominal fat with the risk of incident chronic kidney disease according to body mass index among Korean adults.

BACKGROUND: The association between abdominal visceral adipose tissue and the risk of incident chronic kidney disease according to body mass index in the Asian population, remains unclear. We evaluated the impact of abdominal adiposity stratified by body mass index on the risk of incident chronic kidney disease. METHODS: A cohort study included 11,050 adult participants who underwent health check-ups and re-evaluated the follow-up medical examination at a single university-affiliated healthcare center. Cross-sectional abdominal adipose tissue areas were measured using computed tomography. The primary outcome was progression to chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2). The highest quartile of visceral adipose tissue was used for the cut-off of central obesity. RESULTS: During the mean of 5.6 follow-up years, 104 incident chronic kidney disease cases were identified. The risk for chronic kidney disease incidence was significantly increased in the 3rd and 4th quartile ranges of visceral adipose tissue [hazard ratio (95% confidence interval)]: 4.59 (1.48-14.30) and 7.50 (2.33-24.20), respectively. In the analysis stratified by body mass index, the chronic kidney disease incidence risk was increased in the highest quartile range of visceral adipose tissue in the normal weight group: 7.06 (1.35-37.04). However, there was no significant relationship between visceral adipose tissue and chronic kidney disease in the obese group. Compared to the subjects with normal weight and absent central obesity, the hazard ratio for chronic kidney disease incidence was 2.32 (1.26-4.27) among subjects with normal weight and central obesity and 1.81 (1.03-3.15) among subjects with obesity and central obesity. CONCLUSION: Visceral adipose tissue was a significant risk factor for subsequent chronic kidney disease progression, and the association was identified only in the normal weight group. Normal-weight central obesity was associated with excess risk of chronic kidney disease, similar to the risk in the group with obesity and central obesity.

Combined Effects of Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease on the Risk of Cardiovascular Disease in Patients with Diabetes.

BACKGROUND: We investigated the combined effect of chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) on the risk of cardiovascular disease (CVD) in patients with type 2 diabetes. METHODS: Data were obtained from the Korean National Health Insurance Service. Patients with diabetes who participated in health screenings from 2009 to 2011 were included. The fatty liver index (FLI) was used as a surrogate marker for NAFLD. RESULTS: During a mean follow-up of 6.9 years, 40,863 incidents of myocardial infarction (MI), 58,427 strokes, and 116,977 deaths were reported in 1,607,232 patients with type 2 diabetes. After adjusting for conventional risk factors, patients with CKD and NAFLD showed the highest risk of MI and stroke (hazard ratio (HR) = 1.49; 95% confidence interval (CI): 1.42-1.57 and stroke, HR = 1.48; 95% CI: 1.41-1.54, respectively) compared with those without either CKD or NAFLD. Both overall and cardiovascular mortality were highest in the CKD/NAFLD group compared with other groups (HR = 2.00; 95% CI: 1.94-2.06, and HR = 2.20; 95% CI: 2.07-2.35, respectively). Advanced liver fibrosis was significantly associated with an increased risk of CVD in patients with NAFLD. Proteinuria was significantly associated with incidence of CVD events in patients with CKD. CONCLUSIONS: The combination of CKD and NAFLD was associated with an increased risk of CVD and mortality in patients with type 2 diabetes. Close monitoring and appropriate management of CKD and NAFLD may be warranted to prevent CVD in these patients.

The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter.

BACKGROUND: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). METHODS: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. RESULTS: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47-1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44-0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44-0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31-0.87 in Q4 vs. Q1). CONCLUSIONS: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.

Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes.

BACKGROUND: Diabetes is an independent risk factor for atrial fibrillation (AF), which is associated with increases in mortality and morbidity, as well as a diminished quality of life. Renal involvement in diabetes is common, and since chronic kidney disease (CKD) shares several of the same putative mechanisms as AF, it may contribute to its increased risk in individuals with diabetes. The objective of this study is to identify the relationship between CKD and the rates of newly-diagnosed AF in individuals with diabetes taking part in a screening program using a self-applied wearable electrocardiogram (ECG) patch. MATERIALS AND METHODS: The study included 608 individuals with a diagnosis of diabetes among 1738 total actively monitored participants in the prospective mHealth Screening to Prevent Strokes (mSToPS) trial. Participants, without a prior diagnosis of AF, wore an ECG patch for 2 weeks, twice, over a 4-months period and followed clinically through claims data for 1 year. Definitions of CKD included ICD-9 or ICD-10 chronic renal failure diagnostic codes, and the Health Profile Database algorithm. Individuals requiring dialysis were excluded from trial enrollment. RESULTS: Ninety-six (15.8%) of study participants with diabetes also had a diagnosis of CKD. Over 12 months of follow-up, 19 new cases of AF were detected among the 608 participants. AF was newly diagnosed in 7.3% of participants with CKD and 2.3% in those without (P < 0.05) over 12 months of follow-up. In a univariate Cox proportional hazard regression analysis, the risk of incident AF was 3 times higher in individuals with CKD relative to those without CKD: hazard ratios (HR) 3.106 (95% CI 1.2-7.9). After adjusting for the effect of age, sex, and hypertension, the risk of incident AF was still significantly higher in those with CKD: HR 2.886 (95% CI 1.1-7.5). CONCLUSION: Among individuals with diabetes, CKD significantly increases the risk of incident AF. Identification of AF prior to clinical symptoms through active ECG screening could help to improve the clinical outcomes in individuals with CKD and diabetes.

Association between Serum Uric Acid Level and ESRD or Death in a Korean Population.

BACKGROUND: Serum uric acid (SUA) is recognized as a risk factor for chronic kidney disease (CKD) and mortality. However, there is controversy as to whether a high or low level of SUA is related to the risk of CKD progression or death, and whether it differs between males and females. METHODS: We included 143,762 adults who underwent voluntary health screening between 1995 and 2009 in Korea. For each sex, we divided participants into sex-specific quintiles according to SUA levels and compared end-stage renal disease (ESRD) incidence and mortality between the groups with low and high SUA levels and those with middle SUA levels. Sex-specific Cox proportional hazard analyses were performed for ESRD and all-cause mortality. RESULTS: Among the 143,762 participants, 0.2% (n = 272) developed ESRD. The hazard ratio (HR) of ESRD was higher in the highest (adjusted HR, 2.13; 95% confidence interval [CI], 1.18-3.84) and lowest (adjusted HR, 1.90; 95% CI, 1.02-3.51) SUA quintiles than in the middle SUA quintile in males and the highest SUA quintile in females (adjusted HR, 2.31; 95% CI, 1.10-4.84). Four-point three percent (n = 6,215) of participants died during a mean follow-up period of 157 months. The hazard ratio (HR) of all-cause mortality was higher in the highest SUA quintile than in the middle SUA quintile in males (adjusted HR, 1.15; 95% CI, 1.03-1.28) and females (adjusted HR, 1.17; 95% CI, 1.01-1.35). CONCLUSION: Elevated levels of SUA are associated with increased risk for ESRD and all-cause mortality in both sexes. Low levels of SUA might be related to ESRD and death only in males, showing U-shaped associations. Our findings suggest sex-specific associations between SUA levels and ESRD development and mortality.

Association between advanced fibrosis in fatty liver disease and overall mortality based on body fat distribution.

BACKGROUND: Studies on association between fatty liver disease and overall mortality have yielded conflicting results. We evaluated the impact of fatty liver disease and advanced fibrosis on overall morality with a focus on body size and abdominal fat distribution measured by computed tomography. METHODS: We performed a prospective cohort study including 34 080 subjects (mean age, 51.4 years; 58.6% men) who underwent abdominal ultrasonography and fat computed tomography, from 2007 to 2015. Fatty liver was diagnosed by ultrasonography, and advanced fibrosis was defined as high probability of advanced fibrosis based on three noninvasive methods, aspartate aminotransferase-to-platelet ratio index, non-alcoholic fatty liver disease fibrosis score, and fibrosis-4 score. Body size was categorized by body mass index into obese (≥ 25 kg/m2 ) or nonobese (< 25 kg/m2 ). Multivariate proportional Cox hazard regression analyses were performed. RESULTS: The prevalence of fatty liver disease was 37.5%, while the prevalence of advanced fibrosis in fatty liver disease was 1.8%. During a median follow-up of 87 months (interquartile range, 62-110), 296 deaths occurred. Fatty liver disease was not associated with higher overall mortality (multivariate-adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.77-1.34), while increased subcutaneous adiposity was associated with decreased mortality (HR 0.72, 95% CI 0.60-0.88). Advanced fibrosis resulted in a 3.5-fold increase in overall mortality (adjusted HR 3.52, 95% CI 1.86-6.65), which was more pronounced in the nonobese. CONCLUSIONS: While fatty liver disease did not impact overall mortality, subcutaneous adiposity was associated with reduced overall mortality. Advanced fibrosis was an independent predictor of increase in overall mortality.

Genome-wide association analysis identifies multiple loci associated with kidney disease-related traits in Korean populations.

Chronic kidney disease (CKD) is an important social health problem characterized by a decrease in the kidney glomerular filtration rate (GFR). In this study, we analyzed genome-wide association studies for kidney disease-related traits using data from a Korean adult health screening cohort comprising 7,064 participants. Kidney disease-related traits analyzed include blood urea nitrogen (BUN), serum creatinine, estimated GFR, and uric acid levels. We detected two genetic loci (SLC14A2 and an intergenic region) and 8 single nucleotide polymorphisms (SNPs) associated with BUN, 3 genetic loci (BCAS3, C17orf82, ALDH2) and 6 SNPs associated with serum creatinine, 3 genetic loci (BCAS3, C17orf82/TBX2, LRP2) and 7 SNPs associated with GFR, and 14 genetic loci (3 in ABCG2/PKD2, 2 in SLC2A9, 3 in intergenic regions on chromosome 4; OTUB1, NRXN2/SLC22A12, CDC42BPG, RPS6KA4, SLC22A9, and MAP4K2 on chromosome 11) and 84 SNPs associated with uric acid levels. By comparing significant genetic loci associated with serum creatinine levels and GFR, rs9895661 in BCAS3 and rs757608 in C17orf82 were simultaneously associated with both traits. The SNPs rs11710227 in intergenic regions on chromosome 3 showing significant association with BUN is newly discovered. Genetic variations of multiple gene loci are associated with kidney disease-related traits, and differences in associations between kidney disease-related traits and genetic variation are dependent on the population. The meanings of the mutations identified in this study will need to be reaffirmed in other population groups in the future.

Effects of colchicine on renal fibrosis and apoptosis in obstructed kidneys.

BACKGROUND/AIMS: Colchicine is an established drug for microtubule stabilization that may reduce tissue injury. No data were available that its effects may depend on the dosage of colchicine. We investigated the anti-fibrotic and apoptotic effects of various dose of colchicine in a unilateral ureteral obstruction (UUO) model. METHODS: Thirty-six Sprague-Dawley rats were randomly assigned into six groups. Two sham groups were divided into a vehicle-treated or colchicine-treated group (100 µg/kg/day). Four UUO groups were treated with either vehicle or three different doses of colchicine for 7 days (30, 60, and 100 µg/kg/day, intraperitoneally). All of the animals were sacrificed on day 7. RESULTS: Colchicine treatment diminished acetylated α-tubulin and tumor growth factor-ß immunoreactivities in the cortical area of the 7-day obstructed kidneys, which was in dose dependent manner. Colchicine attenuated tubulointerstitial damage and apoptosis in both cortical and medullary area, and beneficial effects of colchicine therapy were dramatically shown at the higher dosage of colchicine. The expression levels of cleaved caspase-3, ED-1, and fibronectin were decreased in UUO animals. CONCLUSIONS: We found that the proper dosage of colchicine may have anti-fibrotic and anti-apoptotic effects in obstructed kidneys. For clinical applications, an optimal dose of colchicine should be evaluated to maximize the prevention of renal disease progression.

Changes in bioimpedance analysis components before and after hemodialysis.

BACKGROUND: This study compared nutritional parameters in hemodialysis (HD) subjects and controls using bioimpedance analysis (BIA) and investigated how BIA components changed before and after HD. METHODS: This cross-sectional study included 147 subjects on maintenance HD from two hospitals and 298 propensity score-matched controls from one healthcare center. BIA was performed pre- and post-HD at mid-week dialysis sessions. RESULTS: Extracellular water/total body water (ECW/TBW) and waist-hip ratio were higher in the HD patients; the other variables were higher in the control group. The cardiothoracic ratio correlated best with overhydration (r = 0.425, P < 0.01) in HD subjects. Blood pressure, hemoglobin, creatinine, and uric acid positively correlated with the lean tissue index in controls; however, most of these nutritional markers did not show significant correlations in HD subjects. Normal hydrated weight was predicted to be higher in the pre-HD than post-HD measurements. Predicted ultrafiltration (UF) volume difference based on pre- and post-HD ECW/TBW and measured UF volume difference showed a close correlation (r 2 = 0.924, P < 0.01). Remarkably, the leg phase angle increased in the post-HD period. CONCLUSION: The estimated normal hydrated weight using ECW/TBW can be a good marker for determining dry weight. HD subjects had higher ECW/TBW but most nutritional indices were inferior to those of controls. It was possible to predict UF volume differences using BIA, but the post-HD increase in leg phase angle, a nutritional marker, must be interpreted with caution.

Body fat distribution is more predictive of all-cause mortality than overall adiposity.

AIMS: The relationship between directly measured body fat and all-cause mortality has been rarely studied. The aim of this study was to evaluate the predictive significance of computed tomography (CT)-measured body fat, including both visceral fat area (VFA) and subcutaneous fat area (SFA), for mortality. METHODS: The study included 36 656 participants who underwent abdominal CT as part of a health check-up at a single university-affiliated healthcare center in 2007 to 2015. Of those, 32 593 participants with data regarding vital status as of May 2016 were included in the final analysis. The main factors evaluated were VFA, SFA and visceral-to-subcutaneous fat area ratio (VSR), and the primary outcome was all-cause mortality. RESULTS: There were 253 deaths during a mean follow-up of 5.7 years. Increased SFA was associated with decreased all-cause mortality, whereas an increased VFA and VSR were related to increased all-cause mortality. Compared with the predictive power of body mass index (BMI), SFA and VSR showed a larger area under the curve than did BMI. In Kaplan-Meier survival curve analysis, increased SFA and VSR were associated with decreased and increased hazard of all-cause death, respectively. However, in multivariate Cox proportional hazard regression analysis, only VSR was independently associated with all-cause mortality. Moreover, this relationship was paralleled by the harmful impact of increased VSR on metabolic profiles. CONCLUSION: Increased VSR was an independent predictor of all-cause mortality. This suggests that the location of fat deposits may be more important than the actual amount of body fat.

Factors that influence lower urinary tract symptom (LUTS)-related quality of life (QoL) in a healthy population.

OBJECTIVES: The aim of this study was to evaluate the factors affecting the lower urinary tract symptoms (LUTS) related quality of life (QoL) score. METHODS: This retrospective study analyzed 29,123 men who underwent health check-ups from January 2007 to July 2011 at a single institution. Those patients who completed the American urologic association symptom index (AUA-SI) with QoL, beck depression inventory (BDI) and state-trait anxiety inventory questionnaires were included in the study. Men with a history of medication for LUTS were excluded from the study. Men who submitted QoL scores of 3 or higher in spite of mild LUTS (total AUA-SI score <8) were defined as having a relatively worse QoL. RESULTS: Mean age of 21,390 men was 48.4 ± 9.5 years. Mean total AUA-SI score was 6.4 ± 5.9 points. The QoL score was well correlated with the total AUA-SI score (r = 0.705, p < 0.001). Among all AUA-SI items, AUA-SI item 1 (incomplete emptying, r = 0.600, p < 0.001) had the strongest correlation with QoL scores. On the multivariate analysis, hypertension, total AUA-SI score, BDI score, and trait anxiety score were found to be independent factors that influenced the QoL scores. A lower age, a higher PSA, a higher AUA-SI score and a higher BDI score were risk factors for relatively worse QoL scores in spite of mild LUTS. CONCLUSIONS: Among the seven items of AUA-SI, AUA-SI item 1 has the strongest correlation with a worse LUTS-related QoL. Psychological status also influences the QoL scores.

High Salt Intake Is Associated with Atrophic Gastritis with Intestinal Metaplasia.

Background: Although several studies have investigated excessive salt intake as a risk factor for gastric precancerous lesions, such as atrophic gastritis and intestinal metaplasia, the evidence is insufficient to make a conclusion. We evaluated the association between gastric precancerous lesions and salt intake.Methods: From 2008 to 2015, the medical records of 728 subjects who underwent upper gastrointestinal endoscopy and sodium excretion in 24-hour urine tests were retrospectively reviewed. Sixty-six subjects were excluded due to diuretics use (n = 55), diagnosis with a gastric neoplasm (n = 4), or the cases of intestinal metaplasia in the absence of atrophy (n = 7), so 662 subjects were included. Atrophic gastritis and intestinal metaplasia were diagnosed by endoscopic findings. The subjects were grouped into three levels by tertiles of 24-hour urine sodium excretion.Results: A total of 192 (29.0%) had atrophic gastritis without intestinal metaplasia and 112 (16.9%) had atrophic gastritis with intestinal metaplasia. A total of 276 subjects (61.5%) were infected with Helicobacter pylori (H. pylori). In multivariate analyses, H. pylori infection [OR = 14.17; 95% confidence interval (CI), 7.12-28.22) was associated with atrophic gastritis without intestinal metaplasia. Highest levels of sodium excretion (OR = 2.870; 95% CI, 1.34-6.14), heavy smoking (≥20 pack-years) (OR = 2.75; 95% CI, 1.02-7.39), and H. pylori infection (OR = 3.96; 95% CI, 2.02-7.76) were associated with atrophic gastritis with intestinal metaplasia.Conclusions: Our endoscopy-based study suggested that high salt intake could be associated with an increased risk of atrophic gastritis with intestinal metaplasia.Impact: Low salt diet might be helpful to prevent gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1133-8. ©2017 AACR.

Different association between renal hyperfiltration and mortality by sex.

AIM: Renal hyperfiltration (RHF) is a marker of early kidney injury that was recently shown to be a novel marker of mortality. However, it has no clear definition. In this study, we suggested an age- and sex-adjusted RHF definition and explored the association between RHF and mortality by sex. METHODS: We analyzed data from individuals receiving routine health examinations from 1995 to 2009. RHF was defined as an estimated glomerular filtration rate over the 95th percentile matched for age and sex. RESULTS: A total of 114 966 individuals were included. During the 75-month of observation period, 2559 (2.2%) participants died. Among those, 71.4% were men. Because sex and RHF had a significant interaction for mortality (P for interaction < 0.001), we performed survival analysis according to sex. RHF was related to lower body weight and a higher proportion of cigarette smoking in men, whereas these relationships were not found in women. In the Kaplan-Meier curve, RHF was associated with higher mortality rate than non-RHF in both sexes, but this relationship was more prominent in men. In the multivariate analysis, RHF remained as an independent risk factor for all-cause mortality even after adjustment for confounding in men (hazard ratio, 1.34; 95% confidence interval, 1.12-1.59; P = 0.001). In women, RHF was not associated with increased mortality. CONCLUSIONS: We demonstrated that RHF was a significant risk factor for mortality in men but not in women. The mechanisms and clinical implications of these different associations according to sex require a further clarification.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

OBJECTIVES: To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. METHODS: We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. RESULTS: Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 µg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). CONCLUSIONS: Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume.

Low-dose paclitaxel ameliorates renal fibrosis by suppressing transforming growth factor-ß1-induced plasminogen activator inhibitor-1 signaling.

AIM: To investigate the effect of microtubule stabilization with low-dose paclitaxel on renal fibrosis, focusing on the transforming growth factor-ß1 (TGF-ß1)-induced plasminogen activator inhibitor-1 (PAI-1) signaling cascade. METHODS: Forty-eight rats were randomly assigned to four groups: sham/vehicle, sham/paclitaxel, unilateral ureteral obstruction (UUO)/vehicle and UUO/paclitaxel. Rats were treated with a 0.3 mg/kg intraperitoneal dose of paclitaxel or vehicle twice per week for 14 days. Half of the rats in each group were sacrificed respectively on day 7 and 14 after operation. Inner medullar collecting duct (IMCD) cells stimulated with TGF-ß1 were incubated with 0, 1 and 2 nM paclitaxel for 24 and 72 hours. Histological changes were assessed using periodic acid-Schiff and Masson's trichrome. The TGF-ß1-induced PAI-1 signaling and status of extracellular matrix proteins were evaluated by western blot analysis. RESULTS: In the UUO kidneys, paclitaxel significantly attenuated tubular damage and interstitial collagen deposition, as well as α-smooth muscle actin (α-SMA), TGF-ß1 and PAI-1 protein expression. Paclitaxel also inhibited the UUO-induced activation of Smad2/3 and c-Jun N-terminal kinase (JNK). However, paclitaxel treatment did not inhibit extracellular signal-regulated kinase 1/2 (ERK1/2) or p38 expression. In TGF-ß1-treated IMCD cells, treatment with 1 and 2 nM paclitaxel for 72 h reduced fibronectin, α-SMA and PAI-1 protein expression. Moreover, a 2 nM dose of paclitaxel for 24 h significantly inhibited the TGF-ß1-stimulated activation of Smad2/3, JNK and ERK1/2 in IMCD cells. CONCLUSION: Paclitaxel at low non-cytotoxic doses ameliorates renal fibrosis by inhibiting multiple steps in the TGF-ß1-induced PAI-1 signaling including Smads and mitogen-activated protein kinases.

Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome.

Gitelman's syndrome (GS) is caused by loss-of-function mutations in SLC12A3 and characterized by hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia. Long-term prognosis and the role of gene diagnosis in GS are still unclear. To investigate genotype-phenotype correlation in GS and Gitelman-like syndrome, we enrolled 34 patients who showed hypokalemic metabolic alkalosis without secondary causes. Mutation analysis of SLC12A3 and CLCNKB was performed. Thirty-one patients had mutations in SLC12A3, 5 patients in CLCNKB, and 2 patients in both genes. There was no significant difference between male and female in clinical manifestations at the time of presentation, except for early onset of symptoms in males and more profound hypokalemia in females. We identified 10 novel mutations in SLC12A3 and 4 in CLCNKB. Compared with those with CLCNKB mutations, patients with SLC12A3 mutations were characterized by more consistent hypocalciuria and hypomagnesemia. Patients with 2 mutant SLC12A3 alleles, compared with those with 1 mutant allele, did not have more severe clinical and laboratory findings except for lower plasma magnesium concentrations. Male and female patients did not differ in their requirement for electrolyte replacements. Two patients with concomitant SLC12A3 and CLCNKB mutations had early-onset severe symptoms and showed different response to treatment. Hypocalciuria and hypomagnesemia are useful markers in differentiation of GS and classical Bartter's syndrome. Gender, genotypes or the number of SLC12A3 mutant alleles cannot predict the severity of disease or response to treatment.

Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function.

BACKGROUND: High serum phosphorus levels are associated with cardiovascular morbidity and mortality in kidney disease. Although serum phosphorus levels possibly influence on mortality in individuals without kidney disease, this is uncertain because of the variable sex- and age-based distribution of serum phosphorus levels. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Clinical and biochemical data were collected from 138,735 adults undergoing routine health checkups in 3 tertiary hospitals. Individuals with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urine dipstick albumin ≥ 1+ were excluded. PREDICTOR: Sex-specific quartiles of serum phosphorus and sex. OUTCOMES: All-cause mortality. RESULTS: The study included 92,756 individuals. Generally, women showed higher serum phosphorus levels than men. In women, serum phosphorus levels increased with age until 60 years old, then decreased with age. Men with higher serum phosphorus levels were younger and less likely to have hypertension, whereas women with higher serum phosphorus levels were older and more likely to have diabetes and hypertension. During a median follow-up of 75 months, 1,646 participants died. In the overall population, higher serum phosphorus levels were an independent predictor for all-cause mortality after adjustment (adjusted HR for the highest vs. lowest quartile, 1.34; 95% CI, 1.15-1.56; P<0.001). We observed that this increased risk was present in men but not in women (adjusted HR of 1.43 [95% CI, 1.22-1.68] vs. 1.01 [95% CI, 0.76-1.33]), but interaction by sex was not significant (P=0.8). LIMITATIONS: A single phosphorus measurement and low power to test for interactions by sex and age. CONCLUSIONS: We demonstrated that higher serum phosphorus levels influenced all-cause mortality in individuals with normal kidney function. Our findings suggest that the association may differ by sex, but future studies with adequate power to test for effect modification are needed to confirm our findings.

Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT) in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61), P for trend 0.016, for the comparisons of lowest vs. highest quartile) and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75), P for trend < 0.001) in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2), male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80), P for trend = 0.009). Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49), P for trend = 0.002). After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25), P for trend = 0.013). Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post-menopausal women, visceral adipose tissue area shows significant positive association with glomerular hyperfiltration as in men.