Soluble ST2 and Galectin-3 as Predictors of Chronic Kidney Disease Progression and Outcomes.

BACKGROUND: Soluble suppression of tumorigenicity-2 (sST2) and galectin-3, novel biomarkers of heart failure and cardiovascular stress, predict cardiovascular events (CVEs) and mortality. However, their relationship with kidney function and adverse outcomes in CKD are uncertain. The purpose of this study was to determine the association between sST2 and galectin-3 with CKD progression and adverse clinical outcomes. METHODS: We measured baseline sST2 and galectin-3 levels in the CKD patient cohort at our institution between October 2013 and December 2014. The primary outcome was CKD progression (kidney failure with replacement therapy or ≥50% reduction in estimated glomerular filtration rate from the baseline). The secondary outcome was the composite of CVEs and death. We used a Cox proportional hazards model to evaluate the associations between sST2 and galectin-3 levels, with kidney and clinical outcomes. RESULTS: In total, 352 patients were enrolled in this study. At baseline, log sST2 and galectin-3 were directly associated with the serum creatinine (Cr) and urine protein-to-Cr ratio. Cox regression analysis showed that the baseline log sST2 level independently predicted CKD progression and composite outcome after adjustment for age, sex, smoking, diabetes mellitus, hypertension, cardiovascular disease, renin-angiotensin system blocker, calcium channel blocker, ß-blocker, diuretics, antiplatelet agents, anemia, and hypoalbuminemia. The baseline log galectin-3 level was independently associated with CKD progression, but not with the composite outcome after adjustment for confounding variables. CONCLUSIONS: Elevated levels of sST2 and galectin-3 are significantly associated with CKD progression, but only sST2 is associated with adverse clinical outcomes.

Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease.

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.

Associations between Soluble Receptor for Advanced Glycation End Products (sRAGE) and S100A12 (EN-RAGE) with Mortality in Long-term Hemodialysis Patients.

Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612-2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566-1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.

Outcomes of hepatitis B surface antigenaemia in patients with incident end-stage renal disease.

AIM: Hepatitis B virus (HBV) infection is an important risk factor for morbidity and mortality in the general population. However, limited data are available on the progression of HBV infection in patients with end-stage renal disease (ESRD), and available data are controversial. Therefore, we investigated the association between hepatitis B surface antigen (HBsAg) seropositivity and mortality in patients with incident ESRD. METHODS: All adult patients (≥18 years of age) starting dialysis for ESRD from January 2000 to December 2011 were included. A total of 1090 patients with ESRD were analyzed. HBsAg-positive patients were paired 1:6 with HBsAg-negative patients using propensity score matching. RESULTS: Eighty one (7.4%) patients were HBsAg positive. No differences in the survival rates of the HBsAg-positive and HBsAg-negative patients with ESRD were detected in either the entire cohort or the propensity score matched cohort. No differences in survival were detected between the groups of HBsAg-positive patients based on the hepatitis B envelope antigen, hepatitis B envelope antibody, HBV DNA status, or use of antiviral agents. No difference in mortality was found between the haemodialysis (HD) and peritoneal dialysis (PD) subgroups among HBsAg-positive patients. CONCLUSION: Our results suggest that hepatitis B surface antigenaemia is not related to increased mortality in patients with incident ESRD. Survival of HBsAg-positive patients undergoing PD was comparable to that of patients undergoing HD.

Renin-Angiotensin-Aldosterone System Blockade in Critically Ill Patients Is Associated with Increased Risk for Acute Kidney Injury.

Acute kidney injury (AKI) is a major clinical problem and a predictor of outcomes in critically ill patients who frequently required treatments in the intensive care unit (ICU). Renin-angiotensin-aldosterone system (RAAS) blockers are commonly used for treating hypertension but demands caution because of accompanying illnesses including AKI. The aim of this study was to evaluate whether the use of RAAS blockers affected the incidence of AKI in ICU patients. From a total of 26,287 patients who were admitted to the ICU from January 2003 to December 2013 were included in the final analyses. The primary outcome was the incidence of AKI based on the prescription of RAAS blockers. The secondary outcomes were all-cause mortality. RAAS blocker users were more likely to develop AKI (P < 0.001) and remained an independent risk factor for AKI (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.37-1.79; P < 0.001) after adjusting confounding factors. There was no significant difference in the cumulative 90-day survival rate between the RAAS blocker users and non-users (P = 0.381). However, the adjusted mortality risk associated with AKI was 1.38 (95% CI, 1.22 to 1.56; P < 0.001) and increased as the severity of AKI stage increased from 1 to 3: 1.17 (1.02 to 1.36), 1.77 (1.45 to 2.16), and 1.93 (1.55 to 2.41; P < 0.01 for the trend). RAAS blockers may have a harmful influence to increase the incidence of AKI and temporary withholding of these medications may deserve careful consideration in ICU patients.

Residual urinary volume is a predictor of overhydration in patients on peritoneal dialysis.

Fluid overload is linked to hypertension and cardiovascular diseases in patients on peritoneal dialysis (PD). It is important to monitor the residual urinary volume in patients with end-stage renal disease (ESRD). In fact, fluid overload and residual urinary volume have been considered the risk factors of mortality in ESRD patients on PD. However, the relationship between residual urinary volume and fluid overload was still controversial. Therefore, the objective of this cross-sectional study was to evaluate the association between residual urinary volume and the volume status of PD patients. Body composition was measured using a portable multifrequency whole-body bioimpedance assessment. Relative overhydration was defined when the ratio of overhydration to extracellular water was > 0.15. We examined 75 patients, with a mean age of 50.7 years and mean body mass index of 23.5 kg/m(2). Dialysis vintage was 46.5 months. The patients were divided into the anuric group (n = 30; urine output ≤ 100 mL/day) and the group of urine output > 100 mL/day (n = 45). The anuric group showed higher degree of relative overhydration compared to the patients with the urine output of > 100 mL/day (p = 0.020). In a multivariable linear regression analysis, anuria, diabetes, and serum albumin level were independently associated with relative overhydration. In conclusion, volume status should be closely monitored in anuric patients, and the preservation of residual urinary volume is one of important goals to maintain volume status in PD patients.

The Fatty Liver Index's Association with Incident Chronic Kidney Disease in Korean Middle-Aged Adults: A Community-Based Cohort Study.

(1) Background: The relationship between nonalcoholic fatty liver disease (NAFLD) and incident chronic kidney disease (CKD) is unclear, and long-term follow-up data are limited. Therefore, this study aimed to evaluate whether NAFLD, as assessed by the fatty liver index (FLI), could predict the development of CKD in a community-based Korean cohort over 16 years. (2) Methods: Among the 10,030 total participants, 7778 patients without CKD were selected from the Korean Genome and Epidemiology Study (KoGES). The FLI grade ranged from 0 to 100 and was divided into three groups: low (FLI, <30), intermediate (FLI, 30-59), and high (FLI, ≥60). An estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or the development of proteinuria was considered to indicate incident CKD. (3) Results: During the 16-year follow-up period, 919 individuals (11.8%) developed CKD. The HRs of incident CKD in the intermediate FLI group (30-59) and high FLI group (≥60) increased compared with the reference low FLI group (<30) after adjusting for potentially confounding variables. NAFLD, as assessed by the FLI, was an independent risk factor for CKD. (4) Conclusions: Our findings suggest that the FLI, a simple surrogate biomarker of fatty liver disease, may be used to identify people at high risk of incident CKD in clinical practice.

Hyperuricemia is an independent risk factor for mortality only if chronic kidney disease is present.

BACKGROUND/AIMS: Hyperuricemia has been considered a risk factor for renal disease and cardiovascular disease. However, the potential contribution of hyperuricemia to mortality remains uncertain, and the results in the available literature vary according to kidney function. The aim of this study was to determine the association between hyperuricemia and mortality in patients undergoing percutaneous coronary intervention (PCI) across the interaction of kidney function. METHOD: We retrospectively reviewed patients who underwent PCI from 2003 to 2009. Propensity scores for hyperuricemia (>7 mg/dl for males and >6 mg/dl for females) were used to assemble a matched cohort of 693 pairs of patients with and without hyperuricemia for analysis from the 3,201 patients who fulfilled the inclusion criteria among the 4,842 patients who underwent PCI. RESULTS: Of the 3,201 patients who underwent PCI and for whom data were available regarding their baseline serum uric acid level, 763 (23.8%) had hyperuricemia. The hyperuricemia-associated hazard ratios (HRs) [95% confidence intervals (CIs)] for all-cause mortality were 1.780 (1.270-2.495) in the unmatched cohort and 1.655 (1.109-2.468) in the matched cohort. The HRs (95% CI) for all-cause mortality among those with and without chronic kidney disease (CKD) were 2.080 (1.318-3.283) and 1.592 (0.778-3.256), respectively (p for interaction, 0.001). CONCLUSIONS: Hyperuricemia is an independent risk factor for all-cause mortality in those patients with CKD but not in those without CKD.

Circulating levels of soluble receptor for advanced glycation end product are inversely associated with vascular calcification in patients on haemodialysis independent of S100A12 (EN-RAGE) levels.

AIM: The receptor for advanced glycation end products (RAGE) has emerged as a central regulator of vascular inflammation and atherosclerosis. Soluble RAGE (sRAGE) has an anti-inflammatory effect by quenching ligands for RAGE. On the other hand, extracellular RAGE-binding protein S100A12 (EN-RAGE) shows a pro-inflammatory effect in a way, but may play pleiotropic roles related to inflammatory process. Therefore, we determined the levels of sRAGE and S100A12 in haemodialysis (HD) patients and evaluated their relationship with vascular calcification. METHODS: We performed a cross-sectional study with 199 HD patients. Plain X-ray images of the lateral lumbar spine from all subjects were studied to calculate semiquantitative vascular calcification scores (VCS), as described by Kauppila. Commercially available enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentration of sRAGE and S100A12. RESULTS: The patients were 57.1 ± 13.7 years of age; 54.3% were male, 49.2% were diabetic, and 36.2% had a history of cardiovascular disease. In a univariate analysis, serum sRAGE was negatively associated with VCS (log sRAGE, r=-0.208, P=0.003), whereas S100A12 showed a positive tendency (log S100A12, r=0.235, P=0.085). Even after adjustments for confounding risk factors, sRAGE was independently associated with VCS (ß=-1.679, P=0.002). CONCLUSION: This study demonstrated that the circulating sRAGE level was inversely associated with VCS in HD patients independent of the S100A12 level and the severity of systemic inflammation.

Calcitriol treatment increases serum levels of the soluble receptor of advanced glycation end products in hemodialysis patients with secondary hyperparathyroidism.

Cardiovascular disease is common in the patients with end-stage renal disease, who often suffer from secondary hyperparathyroidism (SHP). Vitamin D is considered for the first-line therapy managing SHP in hemodialysis (HD) patients and has a beneficial effect in the chronic inflammation and development of cardiovascular disease. The soluble receptor for advanced glycation end products (sRAGE) may be protective by binding AGE in the pathogenesis of atherosclerotic vascular complications, whereas extracellular RAGE-binding protein (EN-RAGE) represents pro-inflammatory ligands for RAGE. We have hypothesized that vitamin D treatment may alter the levels of sRAGE and EN-RAGE in HD patients. Therefore, this prospective observational study was performed in 51 HD patients with SHP who had low serum 1,25 dihydroxyvitamin D3 (1,25D) levels and elevated intact parathyroid hormone (PTH) levels. We evaluated the changes in the values of sRAGE, EN-RAGE, and other inflammatory marker, interleukin-6 (IL-6), before and at the end of the 8-week calcitriol treatment. After calcitriol treatment, the serum levels of 1,25D were increased, whereas the serum intact PTH levels were decreased. In addition, the sRAGE levels were increased, whereas those of IL-6 were decreased after calcitriol treatment. A positive correlation between 1,25D and sRAGE levels (r = 0.609, P < 0.001) and a negative correlation between sRAGE and EN-RAGE levels (r = -0.368, P = 0.020) were detected after calcitriol treatment. This study suggests that calcitriol treatment could play an anti-inflammatory role through the increasing sRAGE in HD patients with SHP.

Serum calcification propensity and its association with biochemical parameters and bone mineral density in hemodialysis patients.

BACKGROUND: T50 is a novel serum-based marker that assesses the propensity for calcification in serum. A shorter T50 indicates a greater propensity to calcify and has been associated with cardiovascular disease and mortality among patients with chronic kidney disease. The factors associated with T50 and the correlation between T50 and bone mineral density (BMD) are unknown in hemodialysis (HD) patients. METHODS: This cross-sectional study included 184 patients undergoing HD. Individuals were grouped into tertiles of T50 to compare the demographic and disease indicators of the tertiles. Linear regression was used to evaluate the association between T50 and hip and spinal BMD in a multivariate model. RESULTS: Mineral and inflammatory parameters, including serum phosphate (r = -0.156, p = 0.04), albumin (r = 0.289, p < 0.001), and high-sensitivity C-reactive protein (r = -0.224, p = 0.003) levels, were associated with T50. We found a weak association between T50 and BMD in the total hip area in the unadjusted model (ß = 0.030, p = 0.04) but did not find a statistically significant association with the total hip (ß = 0.017, p = 0.12), femoral neck (ß = -0.001, p = 0.96), or spinal BMD (ß = 0.019, p = 0.33) in multivariable-adjusted models. CONCLUSION: T50 was moderately associated with mineral and inflammatory parameters but did not conclusively establish an association with BMD in HD patients. Broad-scale future studies should determine whether T50 can provide insights into BMD beyond traditional risk factors in this population.

The effect of renin-angiotensin-aldosterone system blockade on contrast-induced acute kidney injury: a propensity-matched study.

BACKGROUND: The role of the angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) in the pathophysiology of contrast-induced acute kidney injury (AKI) is controversial, and the available literature is contradictory. STUDY DESIGN: A retrospective propensity score-matched study to analyze the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI. SETTING & PARTICIPANTS: Using propensity score matching, 1,322 ACE-inhibitor/ARB recipients and nonrecipients were paired for analysis from 5,299 patients and fulfilled the inclusion criteria among 11,447 patients receiving coronary angiography (CAG) or percutaneous coronary intervention. PREDICTORS: ACE-inhibitor/ARB use based on prescription and risk factors for contrast-induced AKI. OUTCOMES: The incidence of contrast-induced AKI defined by AKI Network (AKIN) criteria: an absolute increase in serum creatinine levels ≥0.3 mg/dL or a relative increase ≥50% from baseline values within 48 hours after exposure to the contrast medium. MEASUREMENTS: Baseline serum creatinine, hemoglobin, and albumin levels; volume of contrast agents; preprocedural medication; and post-CAG serum creatinine levels. RESULTS: An ACE inhibitor/ARB was prescribed for 64.0% of patients receiving CAG. ACE-inhibitor/ARB users showed an increased incidence of contrast-induced AKI after propensity score matching (11.4% vs 6.3%; P < 0.001). In multivariable analysis, use of ACE inhibitors/ARBs remained an independent and significant predictor of contrast-induced AKI in an unmatched cohort (OR, 1.39; 95% CI, 1.10-1.76; P = 0.06). In the matched cohort, use of ACE inhibitors/ARBs also was associated with a higher adjusted OR of contrast-induced AKI (OR, 1.43; 95% CI, 1.06-1.94; P = 0.02). LIMITATIONS: A retrospective study at a single center. CONCLUSIONS: Use of ACE inhibitors/ARBs during CAG has a possible influence to increase the incidence of contrast-induced AKI. Further randomized clinical trials are warranted to confirm the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI.

Prognostic implication of interdialytic fluid retention during the beginning period in incident hemodialysis patients.

Patient with end stage renal disease have characteristics in common with heart failure patients, and volume overload in heart failure is associated with poorer outcomes. Fluid removal during the hemodialysis (HD) is the cornerstone of volume management in this population. The objective of this study is to assess the long-term prognostic effect of interdialytic fluid retention (IDFR) and its relationship with cardiovascular (CV) events in incident HD patients who newly started dialysis. IDFR is defined as the difference between the predialysis weight and the weight at the end of the previous dialysis session, and it mainly reflects the consequence of salt and water intake between two consecutive dialysis sessions. We retrospectively reviewed the 172 patients who newly started and maintained HD over 6 months at Gachon University Gil Hospital between 1 January 2003 and 31 December 2008. The average data were collected for 3 months during the beginning period, including total IDFR and IDFR/dry weight (IDFR%), nutritional parameters, blood pressure, and other biochemical parameters. Patients were classified into 3 cohorts according to the tertile of IDFR%; low (T1; ≤ 3.21%), intermediate (T2; 3.21%-4.56%), and high (T3; ≥ 4.56%). The high IDFR% group showed higher prevalence of diabetes and better nutritional status. The adjusted odds ratio for CV events was 1.562 (95% confidence interval, 1.026-2.378) for high IDFR% group, compared with the low IDFR% group. In incident HD patients, greater IDFR% soon after HD initiation showed an independent association with higher risk for CV events.

Low-Osmolar vs. Iso-Osmolar Contrast Media on the Risk of Contrast-Induced Acute Kidney Injury: A Propensity Score Matched Study.

Objective: Among the various risk factors associated with contrast-induced acute kidney injury (CI-AKI), the importance of osmolality and viscosity is emerging among the characteristics of contrast media (CM) itself. High osmolality CM (HOCM) is deprecated and low osmotic pressure (LOCM) and iso-osmotic pressure (IOCM) are mainly used in clinical situations where the results of studies on their effect on the development of CI-AKI are contradictory. We evaluated the association between the type of CM and the risk of CI-AKI. Materials and Methods: A retrospective observational cohort study to analyze the effect of the type of CM on the development of CI-AKI. Using propensity score (PS) matching, 2,263 LOCM and IOCM groups were paired for analysis from 5,267 patients and fulfilled the inclusion criteria among 12,742 patients who underwent CAG between 1 January 2007, and 31 December 2016. LOCM included iopromide and iopamidol, IOCM was iodixanol. CI-AKI, which was the primary endpoint, was defined based on the Kidney Disease Improving Global Outcomes criteria within 48 h after exposure to the CM. A multivariable logistic regression analysis was used in the unmatched and matched cohorts, respectively. In addition, a stratified model on clinically important variables, including a high Mehran score (≥ 6), was also used in the matched cohort. Results: LOCM users showed an increased incidence of CI-AKI (11.7% vs. 9.3%; p = 0.006), but it lost statistical significance after PS matching (9.9% vs. 9.5%, p = 0.725). In multivariable analyses, the adjusted odds ratio for CI-AKI in the LOCM group were 1.059 [95% confidence interval (CI) = 0.875-1.282; p = 0.555] in unmatched cohort and 0.987 (95% CI = 0.803-1.214; p = 0.901) in matched cohort. These results were also consistent with the high-risk (high Mehran score) group. Conclusions: Although the role of CM types in the development of CI-AKI has been debated, our observation shows that the selection between LOCM and IOCM during CAG has no influence on the incidence of CI-AKI.

Concomitant Mitochondrial Diabetes and Myopathy Mistook for Complications of Immunosuppressants After Kidney Transplant.

Posttransplant diabetes mellitus, presenile deafness, and myopathy are not commonly accompanied symptoms after kidney transplant. We report the case of a 48-year-old woman with diabetes mellitus, sensorineural hearing loss, and severe myopathy without neuropathy after deceased donor kidney transplant. ShehadamitochondrialDNApointmutation at position 3243 (A>G), and mitochondrial diseases such as maternally inherited diabetes deafness or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodeswere suspected.Diabetes andother symptoms following kidney transplant can often be overlooked as complications of immunosuppressants taken after kidney transplant. However, in patients without a known cause of their symptoms, appropriate examinations and consultation for other diseases, including genetic diseases, should be considered.

Adipsic Hypernatremia after Clipping of a Ruptured Aneurysm in the Anterior Communicating Artery: A Case Report.

Adipsia is a rare disorder that occurs due to damage to the osmoreceptor and not feeling thirst despite hyperosmolality. Adipsic hypernatremia can occur when there is damage to the anterior communicating artery that supplies blood to osmoreceptors, and the level of arginine vasopressin secretion varies widely. A 37-year-old woman, suffering from severe headache, was consulted to the nephrology department for hypernatremia and polyuria after clipping of a ruptured aneurysm in the anterior communicating artery. Despite her hypernatremic hyperosmolar state, she denied thirst and did not drink spontaneously. She was diagnosed adipsic hypernatremia by evaluating the osmoregulatory and baroregulatory function tests. Because adipsic hypernatremia is caused by not enough drinking water even for hyperosmolality due to the lack of thirst stimulus, the strategies of treatment are that setting the target body weight when serum osmolality is normal and have the patient drink water until patient reach the target body weight. Adipsic hypernatremia should be considered to be a rare complication of subarachnoid hemorrhage associated with an anterior communicating artery aneurysm.

Elevated levels of soluble ST2 but not galectin-3 are associated with increased risk of mortality in hemodialysis patients.

BACKGROUND: The soluble forms of suppression of tumorigenicity-2 (ST2) and galectin-3 have been proposed as novel biomarkers for cardiac fibrosis and heart failure, as well as predictors of cardiovascular events and mortality. However, there are limited data on the association between soluble ST2 and galectin-3 and clinical outcomes in patients with kidney failure on replacement therapy. To determine this, we examined the associations between soluble ST2 and galectin-3 and all-cause mortality and cardiovascular events in patients on hemodialysis. METHODS: This study included maintenance hemodialysis patients (over 18 years old) who consented to preserve their serum in the Biobank at our institution between March 2014 and March 2015. We used Cox proportional hazards regression analysis to evaluate the associations between soluble ST2, galectin-3 levels, and clinical outcomes. The primary outcome was all-cause mortality, the secondary outcome was cardiovascular disease, and patients were followed for both outcomes until March 2018. RESULTS: A total of 296 patients were analyzed in this study. The mean age was 57 ± 13 years, and 53.0% were male. Serum concentration of soluble ST2 was significantly associated with higher mortality, after adjustment for confounding factors, but was not associated with cardiovascular disease. Serum galectin-3 level was not independently associated with either outcome after adjustment. CONCLUSION: Elevated soluble ST2 is independently associated with an increased risk of mortality, but not with cardiovascular disease, in patients on hemodialysis. Elevated galectin-3 was not associated with mortality or cardiovascular disease.

Low-dose aspirin was associated with an increased risk of cardiovascular events in patients with chronic kidney disease patients and low bodyweight: results from KNOW-CKD study.

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1 < 60.0 kg). Secondary outcomes were not significantly different between aspirin users and non-users. It needs to be individualized of prescribing low-dose aspirin for the prevention of cardiovascular events in patients with chronic kidney disease, particularly patients with low bodyweight (< 60 kg).

Chronic Cadmium Intoxication and Renal Injury Among Workers of a Small-scale Silver Soldering Company.

BACKGROUND: Cadmium exposure may induce chronic intoxication with renal damage. Silver soldering may be a source of cadmium exposure. METHODS: We analyzed working environment measurement data and periodic health screening data from a small-scale silver soldering company with ten workers. Concentrations of cadmium in air from working environment measurement data were obtained. Concentrations of blood and urinary cadmium, urine protein, and urine ß2-microglobulin (ß2M) were obtained. The generalized linear model was used to identify the association between blood and urine cadmium and urine ß2M concentrations. Clinical features of chronic cadmium intoxication focused with toxicological renal effects were described. RESULTS: The mean duration of work was 8.5 years (standard deviation [SD] = 6.9, range = 3-20 years). Cadmium concentrations in air were ranged from 0.006 to 0.015 mg/m3. Blood cadmium concentration was elevated in all ten workers, with a highest level of 34.6 µg/L (mean = 21.288 µg/L, SD = 11.304, range = 9.641-34.630 µg/L). Urinary cadmium concentration was elevated in nine workers, with a highest level of 62.9 µg/g Cr (mean = 22.151 µg/g creatinine, SD = 19.889, range = 3.228-62.971 µg/g creatinine). Urine ß2M concentration was elevated in three workers. Urinary cadmium concentration was positively associated with urine protein concentration (beta coefficient = 10.27, 95% confidence interval = [4.36, 16.18]). Other clinical parameters were compatible with renal tubular damage. CONCLUSION: Cadmium intoxication may occur at quite low air concentrations. Exposure limit may be needed to be lowered.

Mediation of the relationship between proteinuria and serum phosphate: Insight from the KNOW-CKD study.

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.