A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice

Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

Risk of ventricular tachycardia and its outcomes in patients undergoing continuous renal replacement therapy due to acute kidney injury

Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes. Methods: This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables. Results: VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting <30 seconds). The occurrence of sustained VT was associated with a higher mortality rate than a nonoccurrence (OR, 2.04 and 95% confidence interval [CI], 1.23–3.39 for the 30- day mortality; OR, 4.06 and 95% CI, 2.04–8.08 for the 90-day mortality). The mortality risk did not differ between patients with non-sustained VT and nonoccurrence. A history of myocardial infarction, vasopressor use, and certain trends of blood laboratory findings (such as acidosis and hyperkalemia) were associated with the subsequent risk of sustained VT. Conclusion: Sustained VT occurrence after starting CRRT is associated with increased patient mortality. The monitoring of electrolytes and acid-base status during CRRT is essential because of its relationship with the risk of VT.

Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study

Background@#The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. @*Methods@#Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed. @*Results@#Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. @*Conclusion@#Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.

System of integrating biosignals during hemodialysis: the CONTINUAL (Continuous mOnitoriNg viTal sIgNdUring hemodiALysis) registry

Appropriate monitoring of intradialytic biosignals is essential to minimize adverse outcomes because intradialytic hypotension and arrhythmia are associated with cardiovascular risk in hemodialysis patients. However, a continuous monitoring system for intradialytic biosignals has not yet been developed. Methods: This study investigated a cloud system that hosted a prospective, open-source registry to monitor and collect intradialytic biosignals, which was named the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry. This registry was based on real-time multimodal data acquisition, such as blood pressure, heart rate, electrocardiogram, and photoplethysmogram results. Results: We analyzed session information from this system for the initial 8 months, including data for some cases with hemodynamic complications such as intradialytic hypotension and arrhythmia. Conclusion: This biosignal registry provides valuable data that can be applied to conduct epidemiological surveys on hemodynamic complications during hemodialysis and develop artificial intelligence models that predict biosignal changes which can improve patient outcomes.

Additive harmful effects of acute kidney injury and acute heart failure on mortality in hospitalized patients

Organ crosstalk between the kidney and the heart has been suggested. Acute kidney injury (AKI) and acute heart failure (AHF) are well-known independent risk factors for mortality in hospitalized patients. This study aimed to investigate if these conditions have an additive effect on mortality in hospitalized patients, as this has not been explored in previous studies. Methods: We retrospectively reviewed the records of 101,804 hospitalized patients who visited two tertiary hospitals in the Republic of Korea over a period of 5 years. AKI was diagnosed using serum creatinine-based criteria, and AHF was classified using International Classification of Diseases codes within 2 weeks after admission. Patients were divided into four groups according to the two conditions. The primary outcome was all-cause mortality. Results: AKI occurred in 6.8% of all patients (n = 6,920) and AHF in 1.2% (n = 1,244). Three hundred thirty-one patients (0.3%) developed both conditions while AKI alone was present in 6,589 patients (6.5%) and AHF alone in 913 patients (0.9%). Among the 5,181 patients (5.1%) who died, 20.8% died within 1 month. The hazard ratio for 1-month mortality was 29.23 in patients with both conditions, 15.00 for AKI only, and 3.39 for AHF only. The relative excess risk of interaction was 11.85 (95% confidence interval, 2.43–21.27), and was more prominent in patients aged <75 years and those without chronic heart failure. Conclusion: AKI and AHF have a detrimental additive effect on short-term mortality in hospitalized patients.

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades

Background@#Peritoneal dialysis (PD) is improving as a renal replacement therapy for end-stage renal disease (ESRD) patients. We analyzed the main outcomes of PD over the last three decades at a single large-scale PD center with an established high-quality care system. @*Methods@#As a retrospective cohort study, we included participants (n = 1,203) who began PD between 1990 and 2019. Major PD-related outcomes were compared among the three 10-year cohorts. @*Results@#The 1,203 participants were 58.3% male with a mean age of 47.9 ± 13.8 years. The median PD treatment duration was 45 months (interquartile range, 19–77 months); 362 patients (30.1%) transferred to hemodialysis, 289 (24.0%) received kidney transplants, and 224 (18.6%) died. Overall, the 5- and 8-year adjust patient survival rates were 64% and 49%, respectively. Common causes of death included infection (n = 55), cardiac (n = 38), and cerebrovascular (n = 17) events. The 5- and 8-year technique survival rates were 77% and 62%, respectively, with common causes of technique failure being infection (42.3%) and solute/water clearance problems (22.7%). The 5-year patient survival significantly improved over time (64% for the 1990–1999 cohort vs. 93% for the 2010–2019 cohort). The peritonitis rate also substantially decreased over time, from 0.278 episodes/patient-year (2000–2004) to 0.162 episodes/patient-year (2015–2019). @*Conclusion@#PD is an effective treatment option for ESRD patients. There was a substantial improvement in the patient survival and peritonitis rates over time. Establishing adequate infrastructure and an effective system for high-quality PD therapy may be warranted to improve PD outcomes.

Renal Safety of Repeated Intravascular Administrations of Iodinated or Gadolinium-Based Contrast Media within a Short Interval

Objective@#We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI). @*Materials and Methods@#This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0–4-hour group) or between 4 to 48 hours (4–48-hour group).Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA. @*Results@#When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0–4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4–48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 . AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0–4-hour, and 4–48-hour groups, respectively. In the 0–4-hour and 4–48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all p values > 0.05). @*Conclusion@#Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m2 .

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Renal Safety of Repeated Intravascular Administrations of Iodinated or Gadolinium-Based Contrast Media within a Short Interval

Objective@#We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI). @*Materials and Methods@#This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0–4-hour group) or between 4 to 48 hours (4–48-hour group).Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA. @*Results@#When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0–4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4–48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 . AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0–4-hour, and 4–48-hour groups, respectively. In the 0–4-hour and 4–48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all p values > 0.05). @*Conclusion@#Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m2 .

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Expansion of Myeloid-Derived Suppressor Cells Correlates with Renal Progression in Type 2 Diabetic Nephropathy

Type 2 diabetic nephropathy (T2DN) progresses with an increasingly inflammatory milieu, wherein various immune cells are relevant. Herein, we investigated the levels of myeloid-derived suppressor cells (MDSCs) and their clinical implication in patients with T2DN. A total of 91 subjects (T2DN, n=80; healthy, n=11) were recruited and their PBMCs were used for flow cytometric analysis of polymorphonuclear (PMN-) and monocytic (M-) MDSCs, in addition to other immune cell subsets. The risk of renal progression was evaluated according to the quartiles of MDSC levels using the Cox model. The proportion of MDSCs in T2DN patients was higher than in healthy individuals (median, 6.7% vs. 2.5%). PMN-MDSCs accounted for 96% of MDSCs, and 78% of PMN-MDSCs expressed Lox-1. The expansion of PMN-MDSCs was not related to the stage of T2DN or other kidney disease parameters such as glomerular filtration rate and proteinuria. The production of ROS in PMN-MDSCs of patients was higher than in neutrophils of patients or in immune cells of healthy individuals, and this production was augmented under hyperglycemic conditions. The 4th quartile group of PMN-MDSCs had a higher risk of renal progression than the 1st quartile group, irrespective of adjusting for multiple clinical and laboratory variables. In conclusion, PMN-MDSCs are expanded in patients with T2DN, and may represent as an immunological biomarker of renal progression.

Association of hypoalbuminemia with short-term and long-term mortality in patients undergoing continuous renal replacement therapy

Background@#Hypoalbuminemia reflects several pathological conditions, including nutritional deficiencies and chronic inflammation. However, its relationship with short-term and long-term mortality in patients undergoing continuous renal replacement therapy (CRRT) remains unclear. The present study aimed to assess the effect of hypoalbuminemia on mortality in a large cohort of patients undergoing CRRT. @*Methods@#The study retrospectively reviewed 1,581 patients who underwent CRRT for the treatment of acute kidney injury from 2010 to 2016. The patients were categorized by tertiles of serum albumin levels at CRRT initiation. The odds ratios and hazard ratios for the risk of all-cause mortality were calculated before and after adjustment for multiple covariates. @*Results@#The mean albumin level was 2.7 ± 0.6 g/dL at CRRT initiation. During a median follow-up period of 14 days (maximum, 4 years), 1,040 patients (65.8%) died. The risk of overall mortality was higher in the first tertile group than in the third tertile group (hazard ratio, 1.9 [1.63-2.21]). When the mortality rate was stratified by timeframe, the risk was steadily higher in the first tertile group than in the third tertile group (odds ratios: 3.0 [2.34-3.87] for 2-week mortality, 2.7 [2.12-3.52] for 1-month mortality, 2.7 [2.08-3.53] for 6-month mortality, and 2.8 [2.11- 3.62] for 1-year mortality). Additionally, the rates of intensive care unit mortality and in-hospital mortality were higher in the first tertile group than in the third tertile group. @*Conclusion@#The initial hypoalbuminemia was independently associated with short-term and long-term mortality in patients undergoing CRRT. Thus, the serum albumin level should be monitored during CRRT.

Risk of Graft Failure in Kidney Recipients with Cured Post-Transplant Cancer

Background@#Post-transplant cancer (PTC) is a critical complication after kidney transplantation. However, whether successfully cured PTC affects the long-term graft outcome remains unclear. @*Methods@#We retrospectively reviewed 1,629 kidney transplant recipients from 1995 to 2017 after excluding patients with post-transplant hematologic or advanced non-curable cancers and who underwent allograft nephrectomy because of cancer. Cured PTCs were defined as cancers treated with curative methods and/or adjuvant therapy without recurrence during ≥ 2 years. Propensity score matching was performed to match cured PTC patients with cancer-naïve patients (i.e., non-PTC group). @*Results@#During the median period of 7 years (maximum, 23 years), 70 patients (4.3%) had cured PTCs. The PTC group showed significantly higher risks of death-censored graft failure (adjusted hazard ratio [HR], 2.56 [1.05–6.23]), class II donor-specific antibodies (adjusted HRs, 3.37 [1.30–8.71]), estimated glomerular filtration rate 1 g (adjusted HR, 3.61 [1.92–6.79]) compared to non-PTC group. However, the risk of mortality was not different between the PTC and non-PTC groups. According to the cancer type, only urogenital cancer had a significant association with graft failure (adjusted HR, 4.26 [1.19–15.22]) and the gastrointestinal cancer showed elevated risk of T cell mediated rejection compared to non-PTC (adjusted HR, 20.44 [6.02–69.39]). @*Conclusion@#Appropriate monitoring of graft function is necessary in patients with cured PTCs.

Monitoring globotriaosylsphingosine in a Korean male patient with Fabry disease

No abstract available.

Differential Signature of Obesity in the Relationship with Acute Kidney Injury and Mortality after Coronary Artery Bypass Grafting

BACKGROUND: Obesity is related to several comorbidities and mortality, but its relationship with acute kidney injury (AKI) and long-term mortality remain undetermined in patients undergoing coronary artery bypass grafting. METHODS: Data from 3,018 patients (age ≥ 18 years) who underwent coronary artery bypass graft surgery from two tertiary referral centers were retrospectively reviewed between 2004 and 2015. Obesity was defined using the body mass index, according to the World Health Organization's recommendation. The odds and hazard ratios in post-surgical, AKI, and all-cause mortality were calculated after adjustment for multiple covariates. Patients were followed for 90 ± 40.9 months (maximum: 13 years). RESULTS: Among the cohort, 37.4%, 2.4%, 21.1%, 35.1%, and 4.0% of patients were classified as normal weight, underweight, overweight-at-risk, obese I, and obese II, respectively. Post-surgical AKI developed in 799 patients (26.5%). Patients in the obese groups (overweight-at-risk to obese II) had a higher risk of AKI than did those in the normal-weight group. During the follow-up period, 787 patients (26.1%) died. Underweight patients had a higher risk of mortality than did normal-weight patients, whereas overweight-at-risk, obese I, and obese II patients showed better survival rates. CONCLUSION: After coronary artery bypass graft surgery, obese patients encountered a high risk of AKI, and underweight patients exhibited a low chance of survival. Awareness of both obese and underweight statuses should be raised in these patients.

Weight loss has an additive effect on the proteinuria reduction of angiotensin II receptor blockers in hypertensive patients with chronic kidney disease

BACKGROUND: Weight reduction is a lifestyle intervention that has been introduced for prevention and management of chronic kidney disease (CKD). We investigate the additive anti-proteinuric effect of weight reduction on the usage of angiotensin II receptor blockers (ARBs) and its potential mechanisms in hypertensive CKD patients. METHODS: This study is a subanalysis of data from an open-label, randomized, controlled clinical trial. Among the 235 participants, 227 were assigned to subgroups according to changes in body weight. RESULTS: Fifty-eight participants (25.6%) were assigned to group 1 (≥1.5% decrease in body weight after 16 weeks), 32 participants (14.1%) were assigned to group 2 (1.5–0.1% decrease in body weight), and 136 participants (59.9%) were assigned to group 3 (≥ 0.0% increase in body weight). Characteristics at enrollment were not different among the three groups, but mean differences in weight and percent changes in urinary sodium excretion over the period were statistically different (P < 0.001 and P = 0.017). Over the study period, unintentional weight loss independently increased the probability of reduced albuminuria (group 1, relative risk 6.234, 95% confidence interval 1.913–20.315, P = 0.002). Among urinary cytokines, only podocalyxin level decreased significantly in participants who lost weight (P = 0.013). CONCLUSION: We observed that weight loss had an additive effect on the anti-proteinuric effects of ARBs in nondiabetic hypertensive CKD patients, although it was minimal. An additive effect was shown in both obese and non-obese participants, and its possible mechanism is related to reduction of podocyte damage.

Heart rate is associated with mortality in patients undergoing continuous renal replacement therapy

BACKGROUND: Heart rate (HR) is an essential vital sign based on the finding that HR beyond its normal range is associated with several conditions or diseases, including high mortality in several clinical settings. Nevertheless, the clinical implications of HR remain unresolved in patients undergoing continuous renal replacement therapy (CRRT). METHODS: This retrospective cohort study included 828 patients who underwent CRRT due to acute kidney injury between 2010 and 2014. HR and other baseline parameters at the time of CRRT initiation were retrieved. The odds ratio (OR) of 30-day mortality was calculated using a multivariate logistic model. RESULTS: CRRT significantly lowered the HR of patients such that the pre- and post-CRRT HRs (average 6 hours) were 107 beats/min and 103 beats/min, respectively (P < 0.001). When we explored the relationship with 30-day mortality, only HR at the time of CRRT initiation, but not pre- or post-CRRT HR, had a significant relationship with mortality outcome. Based on this result, we divided patients into quartiles of HR at the time of CRRT initiation. Mortality OR in the 4th quartile HR group was 2.6 (1.78–3.92) compared with the 1st quartile HR group. This relationship remained consistent despite adjusting for 28 baseline covariates: OR, 1.7 (1.09–2.76); P = 0.020. However, HR was not associated with the weaning rate from CRRT. CONCLUSION: High HR at the time of CRRT initiation is subsequently related with high mortality. These results can be a basis for a future predictive model of CRRT-related mortality.

Risk of Stroke in Elderly Dialysis Patients

Despite the current knowledge about the risk of stroke and its related factors in general population, this issue in elderly patients receiving dialysis remains unresolved. Firstly, to compare the risk of stroke between hemodialysis (HD) and peritoneal dialysis (PD), data on 13,065 incident dialysis patients (aged ≥ 65 years; 10,675 in HD and 2,390 in PD) were retrieved from the Korean Health Insurance dataset. Secondly, to identify the risk factors of stroke amongst various clinical and laboratory parameters in HD, 980 elderly patients were retrospectively analyzed using an independent prospective cohort from 31 dialysis centers. For a mean duration of 1.8 years (maximum of 5 years), the risk of all cardiovascular diseases (ischemic heart disease and stroke) did not differ between HD and PD. However, when analyses were conducted separately by subtype, the risk of stroke, not ischemic heart disease, was significantly higher in HD patients than in PD patients. When the risk factors of stroke were probed after HD for a mean duration of 2.6 years (maximum of 7 years), the absolute dependence on social support, a previous history of cardiovascular disease, high levels of low-density lipoprotein cholesterol, and the use of a high number of anti-hypertensive drugs were identified as being significant. Based on the discrepancy of stroke risk between modalities and the HD-tailored risk factors of stroke, the monitoring and management of these factors may be a key strategy to reduce the risk of stroke in elderly patients receiving dialysis.

The role of local IL6/JAK2/STAT3 signaling in high glucose–induced podocyte hypertrophy

BACKGROUND: Interleukin-6 (IL6) is an important regulator of cellular hypertrophy through the gp130/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. We tested the hypothesis that IL6 and its downstream gp130/JAK2/STAT3 pathway participated in high glucose (HG)–induced podocyte hypertrophy. METHODS: IL6 levels in the media and lysates of podocytes were measured by enzyme-linked immunosorbent assay. Western blots were performed to determine the protein expression levels of gp130/JAK2/STAT3 among podocytes cultured with normal glucose (NG), NG + mannitol, NG + recombinant IL6, HG, and HG + IL6-neutralizing antibodies (IL6NAb). Immunoprecipitation was examined to determine whether gp130 interacted with JAK2 in response to HG or IL6. Podocyte hypertrophy was verified using protein/cell counts and flow cytometry. RESULTS: IL6 levels were significantly increased in the media and lysates of podocytes cultured in HG compared with the NG groups. The nuclear phospho-STAT3/STAT3 ratio was increased by HG and NG + IL6 and was attenuated in the HG + IL6NAb groups, indicating that nuclear STAT3 was activated following JAK2 and cytosolic STAT3 activation in response to IL6 secreted by HG-stimulated podocytes. Immunoprecipitation showed increased phospho-JAK2 recruitment to gp130 in the HG and NG + IL6 groups, and the addition of IL6NAb in the HG group significantly abrogated these increases. Podocyte hypertrophy was significantly increased in the HG and NG + IL6 compared with the NG condition and was diminished by the addition of IL6NAbs to the HG group. CONCLUSION: IL6 might play a prominent role in the local activation of JAK2/STAT3 in podocyte hypertrophy under HG conditions. In vivo studies examining this pathway are warranted.

Predictive Value of Echocardiographic Parameters for Clinical Events in Patients Starting Hemodialysis

Echocardiographic parameters can predict cardiovascular events in several clinical settings. However, which echocardiographic parameter is most predictive of each cardiovascular or non-cardiovascular event in patients starting hemodialysis remains unresolved. Echocardiography was used in 189 patients at the time of starting hemodialysis. We established primary outcomes as follows: cardiovascular events (ischemic heart disease, cerebrovascular disease, peripheral artery disease, and acute heart failure), fatal non-cardiovascular events, all-cause mortality, and all combined events. The most predictable echocardiographic parameter was determined in the Cox hazard ratio model with a backward selection after the adjustment of multiple covariates. Among several echocardiographic parameters, the E/e' ratio and the left ventricular end-diastolic volume (LVEDV) were the strongest predictors of cardiovascular and non-cardiovascular events, respectively. After the adjustment of clinical and biochemical covariates, the predictability of E/e' remained consistent, but LVEDV did not. When clinical events were further analyzed, the significant echocardiographic parameters were as follows: s' for ischemic heart disease and peripheral artery disease, LVEDV and E/e' for acute heart failure, and E/e' for all-cause mortality and all combined events. However, no echocardiographic parameter independently predicted cerebrovascular disease or non-cardiovascular events. In conclusion, E/e', s', and LVEDV have independent predictive values for several cardiovascular and mortality events.