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Background Although it is well known that low bone mineral density (BMD) is associated with an increased risk of cardiovascular disease (CVD) and mortality in the general population, the prognostic role of bone mineral density (BMD) has not been established in the chronic kidney disease (CKD) population. Therefore we aimed to evaluate the association between BMD and the risk of CVD and cardiovascular mortality in patients with predialysis CKD. Methods This prospective cohort study was conducted with 1957 patients with predialysis CKD Stages 1–5. BMD was measured using dual-energy X-ray absorptiometry and coronary arterial calcification (CAC) scores were evaluated using coronary computed tomography. The primary outcome was a major adverse cardiovascular event (MACE). Results When patients were classified based on total hip BMD T -score tertiles stratified by sex, the lowest BMD tertile was significantly associated with an increased risk of MACE {hazard ratio 2.16 [95% confidence interval (CI) 1.25–3.74]; P = 0.006}. This association was also shown with BMD at the femur neck but not with BMD at lumbar spine. In the subgroup of 977 patients with follow-up CACs at their fourth year, 97 (9.9%) showed accelerated CAC progression (>50/year), and BMD was inversely associated with accelerated CAC progression even after adjusting for the baseline CAC score [odds ratio 0.75 (95% CI 0.58–0.99); P = 0.039]. In addition, baseline CAC was associated with an increased risk of MACEs after adjusting for total hip T -score. Conclusions Low BMD was significantly associated with CAC progression and MACEs in patients with predialysis CKD. [ABSTRACT FROM AUTHOR]

Background Urinary chloride is regulated by kidney transport channels, and high urinary chloride concentration in the distal tubules can trigger tubuloglomerular feedback. However, little attention has been paid to urinary chloride as a biomarker of clinical outcomes. Here, we studied the relationship between urinary chloride concentration and chronic kidney disease (CKD) progression. Methods We included 2086 participants with CKD from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease. Patients were categorized into three groups, according to baseline urinary chloride concentration tertiles. The study endpoint was a composite of ≥50% decrease in estimated glomerular filtration rate from baseline values, or end-stage kidney disease. Results During a median follow-up period of 3.4 years (7452 person-years), 565 participants reached the primary endpoint. There was a higher rate of CKD progression events in the lowest and middle tertiles than in the highest tertile. Compared with the lowest tertile, the highest tertile was associated with 33% [95% confidence interval (CI) 0.49–0.90] lower risk for the primary outcome in a cause-specific hazard model after adjustment for confounding variables. In addition, for every 25 mEq/L increase in urinary chloride concentration, there was 11% (95% CI 0.83–0.96) lower risk for CKD progression. This association was consistent in a time-varying model. Urinary chloride concentration correlated well with tubule function and kidney injury markers, and its predictive performance for CKD progression was comparable to that of these markers. Conclusions In this hypothesis-generating study, low urinary chloride concentration was associated with a higher risk for CKD progression. [ABSTRACT FROM AUTHOR]

Introduction: In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce.Aims and Methods: We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation.Results: There were 967 never-smokers and 369, 276, and 339 smokers who smoked <15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4-63.5), 46.9 (35.9-61.4), 69.2 (52.9-90.6), and 76.3 (60.7-96.0) events per 1,000 person-yr in never-, <15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73-1.63), 1.48 (1.00-2.18), and 1.94 (1.35-2.77) fold increased risk (95% CI) of primary outcome in <15, 15-29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR < 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers.Conclusions: These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD.Implications: Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression. [ABSTRACT FROM AUTHOR]

Background The association between fibroblast growth factor 23 (FGF23) and coronary artery calcification (CAC) was inconclusive. Recently it was shown that adiponectin modulates renal handling of calcium and phosphorus. We hypothesized that adiponectin plays a role in the effect of FGF23 on CAC and explored whether the association between FGF23 and CAC is modified by serum adiponectin level in chronic kidney disease (CKD) patients. Methods This cross-sectional study analyzed 1435 predialysis CKD patients from the Korean Cohort Study for Outcome in Patients with CKD cohort. Participants were divided into two groups according to their serum adiponectin (upper half and lower half). Each group was further divided into three groups according to their FGF23 levels as follows: low (<5.0 RU/mL), middle (5.0–29.9 RU/mL) and high (≥30.0 RU/mL). The coronary artery calcium score (CACS) was assessed using cardiac computed tomography and CAC was defined as a CACS >100. Results The median CACS did not differ between the low and high adiponectin groups {3.2 [interquartile range (IQR) 0.0–98.1] versus 0.5 [0.0–99.5], P = 0.988}. The CACS ratio comparing high FGF23 to low FGF23 was significantly increased in the high adiponectin group, but not in the low adiponectin group [2.35 (IQR 1.14–4.85) versus 1.10 (0.60–2.03)]. The odds ratio for CAC in the high FGF23 group compared with the low group was 1.97 (IQR 1.10–3.53). The association between FGF23 and CAC was modified significantly by adiponectin level (P for interaction = 0.023). Conclusions High serum FGF23 was associated with CAC in CKD patients with high adiponectin, but not in those with low adiponectin. Further studies are warranted to verify the role of adiponectin in FGF23-related CAC. [ABSTRACT FROM AUTHOR]

Background To date, there has been much controversy about the role of crescentic lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN). This study evaluated whether crescentic lesions predict adverse renal outcomes in IgAN patients. Methods A total of 430 patients with biopsy-proven IgAN between January 2000 and December 2009 were included. Histological variables of the Oxford classification (Oxford-MEST) and the presence of crescents were assessed. The primary endpoint was a 50% decline in estimated glomerular filtration rate. Results Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with crescents compared with 40 (11.5%) patients without crescents (P = 0.01). A Kaplan–Meier plot showed that the 10-year renal survival rate was significantly lower in patients with crescents than patients without crescents (P = 0.01). However, in a multivariable Cox analysis which included clinical factors and the Oxford-MEST, crescents were not significantly associated with an increased risk of developing the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36–1.41, P = 0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the discriminative ability for the prediction of renal outcomes [c-statistic: 0.86 (0.81–0.91) vs. 0.86 (0.80–0.91), P = 0.21]. Conclusion Crescentic lesion was not an independent prognostic factor, suggesting that crescents have limited value in predicting renal outcomes of IgAN. [ABSTRACT FROM AUTHOR]

Background. A potential independent association was recently demonstrated between high red blood cell distribution width (RDW) and the risk of all-cause mortality in patients with cardiovascular disease, although the mechanism remains unclear. However, there have been no reports on the relationship between RDW and mortality in acute kidney injury (AKI) patients treated with continuous renal replacement therapy (CRRT). In this study, we assessed whether RDW was associated with mortality in AKI patients on CRRT treatment in the intensive care unit (ICU). Methods. We enrolled 470 patients with AKI who were treated with CRRT at the Yonsei University Medical Center ICU from August 2007 to September 2009 in this study. We performed a retrospective analysis of demographic, biochemical parameters and patient outcomes. Following CRRT treatment, 28-day all-cause mortality was evaluated. Results. At the initiation of CRRT treatment, RDW level was significantly correlated with white blood cell count, hemoglobin (Hb) and total cholesterol. Patients with high RDW levels exhibited significantly higher 28-day mortality rates than patients with low RDW levels (P < 0.01). Baseline RDW level, Sequential Organ Failure Assessment (SOFA) score, low mean arterial pressure (MAP) and low cholesterol levels were independent risk factors for mortality. In multivariate Cox proportional hazard analyses, RDW at CRRT initiation was an independent predictor for 28-day all-cause mortality after adjusting for age, gender, MAP, Hb, albumin, total cholesterol, C-reactive protein and SOFA score. Conclusion. Our study demonstrates that RDW could be an additive predictor for all-cause mortality in AKI patients on CRRT treatment in the ICU. [ABSTRACT FROM AUTHOR]

Background. Patients with end-stage renal disease (ESRD) have a greatly increased risk of premature cardiovascular disease. Peritoneal dialysis (PD) patients have more atherogenic lipid profiles than haemodialysis patients. In this retrospective cohort study, we evaluated whether statin use is associated with improved mortality in incident PD patients.Methods. The study population included consecutive new PD patients (≥18 years old) from seven PD centres in Korea, between January 2003 and December 2008. The clinical outcome was mortality. A propensity score (PS) comprising demographic, clinical and laboratory variables was used to select a 1:1 matched cohort.Results. Statins were prescribed for 37.8% of incident PD patients. Cumulative survival probabilities for statin user versus non-user were 87 versus 80% and 76 versus 69% at 3 and 5 years, respectively (P = 0.01). Statin prescription was associated with a 41% lower adjusted hazard ratio (HR) of death in the unmatched cohort [95% confidence interval (CI) = 0.42–0.82; P = 0.002]. The protective effect of statins was also observed in a subgroup analysis of patients with diabetic ESRD (HR = 0.53, 95% CI = 0.36–0.80; P = 0.002). After PS matching, the use of statins was also associated with improved survival (HR = 0.55, 95% CI = 0.38–0.79; P = 0.001) in incident PD patients.Conclusions. The use of statins was associated with a reduced risk of all-cause mortality. This association was independent of a history of cardiovascular disease or total cholesterol level. Future randomized clinical trials are warranted to confirm the beneficial effect of statin on PD patients. [ABSTRACT FROM PUBLISHER]

Background. Echocardiography is an established technique to estimate the risk for cardiovascular complications in patients with end-stage renal disease (ESRD). An enlarged left atrium (LA) has recently emerged as a marker of adverse cardiovascular outcomes in various pathologic conditions. However, there have been few studies to evaluate its prognostic value in patients with ESRD, particularly those receiving continuous ambulatory peritoneal dialysis (CAPD).Methods. We conducted an observational cohort study to investigate whether enlarged LA can predict patient outcome in 216 patients with CAPD. Study outcomes were all-cause and cardiovascular mortality.Results. Increased left atrium volume index (LAVI > 32 mL/m2) was observed in 99 (45.8%) of the CAPD patients. During the follow-up (26.3 ± 18.6 months), 20 patients (9.3%) died. Kaplan–Meier analysis revealed that the 5-year survival rate was significantly lower in patients with LAVI > 32 mL/m2 than those with LAVI ≤ 32 mL/m2 (69 versus 82%, P = 0.024). In multivariate analyses adjusted for echocardiographic parameters and clinical and laboratory data, increased LAVI was an independent predictor of all-cause mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01–1.10, P = 0.03] and cardiovascular mortality (HR 1.08, 95% CI 1.02–1.14, P = 0.006). Furthermore, increased LAVI provided the highest predictive value for all-cause mortality [area under the receiver operating characteristic curve (AUC) = 0.766, P < 0.001] and cardiovascular mortality (AUC = 0.836, P < 0.001) among the measured echocardiographic parameters.Conclusions. We showed that increased LAVI predicted adverse outcomes better than other echocardiographic parameters in patients with CAPD. [ABSTRACT FROM AUTHOR]

Background. Statins and angiotensin receptor blockers (ARBs) are known to improve vascular dysfunction in patients with chronic kidney disease. However, these effects have been inconsistent in dialysis patients. Moreover, it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients.Methods. We conducted a prospective open randomized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis (PD). Initially, all patients received 80 mg/day of valsartan for 6 months. Excluding 10 patients who dropped out during this period, patients were randomly assigned to continue ARB treatment alone (n = 57) or to receive 10 mg/day of rosuvastatin (n = 57) added to ARB for the next 6 months. To assess vascular function, endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV), respectively.Results. Compared to baseline values, ARB treatment for the first 6 months significantly improved FMD% (2.97 ± 2.64 to 3.57 ± 2.58 %, P < 0.001). In addition, there was a small but significant decrease in baPWV during this period (1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s, P = 0.048). After randomization, add-on treatment further improved FMD% (3.57 ± 2.73 to 4.24 ± 2.77 %, P = 0.003), whereas ARB monotherapy did not (P = 0.02 for between-group difference). Further slight improvement in baPWV (1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s, P = 0.021) was observed only in the combined treatment group (P = 0.28 for between-group difference).Conclusions. Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients. However, whether such limited improvements can lead to better clinical outcomes requires further investigation. [ABSTRACT FROM AUTHOR]

Background. The prevalence of glomerular diseases differs according to geographic area, race, age and indications for a renal biopsy. This study was conducted to evaluate the distribution and changing patterns of renal diseases during the past 20 years in a large patient population in Korea. Methods. Patients aged 16 years or older who underwent a renal biopsy at Severance Hospital in the Yonsei University Health System from 1987 to 2006 were enrolled. All medical records were reviewed retrospectively. Results. In total, 1818 patients (M:F = 1.02:1) were reviewed. Glomerulonephritis (GN) comprised 85.9% of the total biopsied cases. The most common primary GN was IgA nephropathy (IgAN) (28.3%), which was followed by minimal change disease (MCD) (15.5%), membranous nephropathy (MN) (12.3%), focal segmental glomerulosclerosis (FSGS) (5.6%) and membranoproliferative GN (MPGN) (4.0%). The most common secondary GN was lupus nephritis (8.7%). The most common idiopathic nephrotic syndrome was MCD (38.5%), which was followed by MN and IgAN. Among 128 (7.4%) patients who were HBsAg-positive, MN (30.5%) and MPGN (21.1%) were the most common GN. When the incidence rates between 1987–91 and 2002–06 were compared, IgAN increased from 25.6 to 34.5%, while MCD (from 23.2 to 7.0%) and MPGN (from 6.7 to 1.7%) decreased significantly (P Conclusions. IgAN was the most common primary GN, and MCD was the most common cause of nephrotic syndrome. In the 5-year quartile comparison, the relative frequency of IgAN increased, while the relative frequency of MCD and MPGN decreased significantly during the past 20 years. [ABSTRACT FROM AUTHOR]