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 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.

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.

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.

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.

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.

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.

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.

Non-linear association of serum 25-hydroxyvitamin D with urinary albumin excretion rate in normoalbuminuric subjects.

BACKGROUND: Vitamin D deficiencies and increases in urinary albumin excretion (UAE) are both important and potentially related health problems; however, the nature of their relationship has not been established in normoalbuminuric subjects. METHODS: We obtained data from 14,594 normoalbuminuric Korean adults who underwent voluntary health screenings. We used a generalized additive model to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and urinary-albumin creatinine ratio (UACR) levels. We conducted multivariate logistic regression for high-normal UAE (UACR, 10-29 mg/g), according to various categories of vitamin D status. RESULTS: The generalized additive model confirmed a non-linear relationship between serum 25(OH)D and UACR levels, and the threshold concentration of 25(OH)D was 8.0 ng/mL after multivariate adjustment. Comparing subjects who fell into the lowest category of serum 25(OH)D levels with subjects who were in the reference range (the highest category), we observed that the multivariate adjusted odds ratio (OR) for high-normal UAE was significantly increased, regardless of the criteria used to categorize vitamin D levels: OR of the 1st quartile over the 4th quartile, 1.20 (95% CI, 1.04-1.39); OR of the 1.0-4.9th percentile over the 50-100th percentile, 1.56 (95% CI, 1.25-1.93); and OR of vitamin D deficiency group over vitamin D sufficiency group, 1.28 (95% CI, 1.08-1.52). CONCLUSIONS: We demonstrated that there was an inverse relationship between serum 25(OH)D less than 8.0 ng/mL and UACR in normoalbuminuric subjects, suggesting that severe vitamin D deficiency could cause an increase in UAE in subjects with normoalbuminuria.

Alkali therapy attenuates the progression of kidney injury via Na/H exchanger inhibition in 5/6 nephrectomized rats.

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Effects of sodium citrate on salt sensitivity and kidney injury in chronic renal failure.

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Significance of microalbuminuria in relation to subclinical coronary atherosclerosis in asymptomatic nonhypertensive, nondiabetic subjects.

We aimed to investigate the significance of microalbuminuria and its relationship with subclinical atherosclerosis in nonhypertensive and nondiabetic patients, by using coronary artery computed tomography (CT). A total of 1,318 nonhypertensive and nondiabetic subjects who had taken coronary artery CT and measured spot urine albumin to creatinine ratio (UACR) were evaluated. The atherosclerotic changes of coronary arteries were greater in subjects with microalbuminuria, reflected by coronary artery calcium score (CACS) and significant coronary artery stenosis (CACS ≥ 100 in 15.3% vs 7.6% and stenosis ≥ 50% in 11.5% vs 4.9% of patients with vs without microalbuminuria, P = 0.008 and P = 0.011, respectively). Among various parameters that are known as a risk factor or possible biomarkers of coronary artery disease, presence of microalbuminuria, age and Framingham risk score were significantly related to coronary artery stenosis. Among them the presence of microalbuminuria showed stronger correlation than others to the coronary artery stenosis detected by CT, even after adjusting confounding factors (OR 3.397, 95% confidence interval 1.138 to 10.140, P = 0.028). The presence of microalbuminuria by UACR was significantly associated with presence of coronary artery stenosis ≥ 50% in asymptomatic, nonhypertensive and nondiabetic general population. Our study suggests that the presence of microalbuminuria may imply subclinical coronary artery disease, even in asymptomatic population.

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.

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.

Serum phosphorus as a predictor of low-grade albuminuria in a general population without evidence of chronic kidney disease.

BACKGROUND: High levels of serum phosphorus, even within the normal range, have been associated with cardiovascular (CV) morbidity. Low-grade albuminuria (LGA) was demonstrated to be related to increased CV events in various study populations. The present study aimed to investigate the association between serum phosphorus levels and LGA in the general population. METHODS: We examined the individuals who had undergone health inspections. We evaluated the correlation between serum phosphorus and LGA in 8953 participants (mean age, 47.4 years) with estimated glomerular filtration rates (eGFRs)≥60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratios (UACRs)<30 mg/g. Participants who underwent a colonoscopy were excluded. RESULTS: The mean UACR was significantly higher in the uppermost quartile group of serum phosphorus concentrations than in other quartile groups. In the multivariate regression analysis, serum phosphorus remained an independent predictor of increased UACR (B=0.610, P<0.001). Subgroup analyses showed that this association was maintained irrespective of age, gender, presence of hypertension or diabetes, body mass index and eGFR. CONCLUSIONS: In our population-based study, higher serum phosphorus was independently related to LGA in individuals without evidence of renal dysfunction. Further investigations are warranted to clarify the precise mechanism of the association between serum phosphorus and LGA.

Mild decrease in estimated glomerular filtration rate and proteinuria are associated with all-cause and cardiovascular mortality in the general population.

BACKGROUND: A recent collaborative meta-analysis by Kidney Disease: Improving Global Outcomes reported that an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an albumin-to-creatinine ratio of ≥ 10 mg/g were independent predictors for mortality in the general population. However, selection bias, heterogeneity of the cohorts and measurement issues could be limitations. METHODS: We analyzed the relationship of eGFR and proteinuria with mortality in the Korean general population, represented by 112,115 participants, aged ≥ 20 years, who had a voluntary health check-up with homogenous calibration of creatinine measurement from 2003 to 2009. Proteinuria (trace or more) was determined by urine dipstick. RESULTS: eGFR and proteinuria were independently associated with all-cause mortality (ACM) and cardiovascular mortality (CVM), and progressive increases in risks for mortality were noted according to eGFR level and the presence of proteinuria. Compared with eGFR 90-105 mL/min/1.73 m(2), hazard ratio (HRs) for ACM were 1.60 [95% confidence interval (CI) 1.12-2.30] for eGFR 60-74 mL/min/1.73 m(2) and 3.54 (2.20-5.68) for eGFR <60 mL/min/1.73 m(2) in participants with no proteinuria. In participants with proteinuria, HRs for ACM were 2.10 (1.41-3.12) for eGFR 75-89 mL/min/1.73 m(2), 2.30 (1.50-3.53) for eGFR 60-74 mL/min/1.73 m(2) and 3.77 (2.15-6.38) for eGFR <60 mL/min/1.73 m(2). Similar findings were observed for CVM. CONCLUSIONS: eGFR <75 mL/min/1.73 m(2) and urine dipstick trace or more were independent risk factors of ACM and CVM. The risks of adverse outcomes are greater in the general population with mild renal impairment or mild proteinuria.

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.

Effects of potassium on expression of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

Dietary potassium is an important modulator of systemic blood pressure (BP). The purpose of this study was to determine whether dietary potassium is associated with an altered abundance of major renal sodium transporters that may contribute to the modulation of systemic BP. A unilateral nephrectomy (uNx) was performed in male Sprague-Dawley rats, and the rats were fed a normal-salt diet (0.3% NaCl) for 4 wk. Thereafter, the rats were fed a high-salt (HS) diet (3% NaCl) for the entire experimental period. The potassium-repleted (HS+KCl) group was given a mixed solution of 1% KCl as a substitute for drinking water. We examined the changes in the abundance of major renal sodium transporters and the expression of mRNA of With-No-Lysine (WNK) kinases sequentially at 1 and 3 wk. The systolic BP of the HS+KCl group was decreased compared with the HS group (140.3 ± 2.97 vs. 150.9 ± 4.04 mmHg at 1 wk; 180.3 ± 1.76 vs. 207.7 ± 6.21 mmHg at 3 wk). The protein abundances of type 3 Na(+)/H(+) exchanger (NHE3) and Na(+)-Cl(-) cotransporter (NCC) in the HS+KCl group were significantly decreased (53 and 45% of the HS group at 1 wk, respectively; 19 and 8% of HS group at 3 wk). WNK4 mRNA expression was significantly increased in the HS+KCl group (1.4-fold of control at 1 wk and 1.9-fold of control at 3 wk). The downregulation of NHE3 and NCC may contribute to the BP-attenuating effect of dietary potassium associated with increased urinary sodium excretion.