Jong Hyun Jhee

High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial

BACKGROUND Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. STUDY DESIGN Prospective, randomized, controlled, open-label trial. SETTING & PARTICIPANTS Septic patients with AKI receiving CVVHDF for AKI. INTERVENTION Conventional (40mL/kg/h) and high (80mL/kg/h) doses of CVVHDF for the duration of CRRT. OUTCOMES Patient and kidney survival at 28 and 90 days, circulating cytokine levels. RESULTS 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P=0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P=0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. LIMITATIONS Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. CONCLUSIONS High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.

Serum Ferritin Predicts Mortality Regardless of Inflammatory and Nutritional Status in Patients Starting Dialysis: A Prospective Cohort Study

Background: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated. Methods: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations. Results: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003). Conclusion: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis.

Electrolyte and mineral disturbances in septic acute kidney injury patients undergoing continuous renal replacement therapy.

AbstractElectrolyte and mineral disturbances remain a major concern in patients undergoing continuous renal replacement therapy (CRRT); however, it is not clear whether those imbalances are associated with adverse outcomes in patients with septic acute kidney injury (AKI) undergoing CRRT. We conducted a post-hoc analysis of data from a prospective randomized controlled trial. A total of 210 patients with a mean age of 62.2 years (136 [64.8%] males) in 2 hospitals were enrolled. Levels of sodium, potassium, calcium, and phosphate measured before (0 hour) and 24 hours after CRRT initiation. Before starting CRRT, at least 1 deficiency and excess in electrolytes or minerals were observed in 126 (60.0%) and 188 (67.6%) patients, respectively. The excess in these parameters was greatly improved, whereas hypokalemia and hypophosphatemia became more prevalent at 24 hours after CRRT. However, 1 and 2 or more deficiencies in those parameters at the 2 time points were not associated with mortality. However, during 28 days, 89 (71.2%) deaths occurred in patients with phosphate levels at 0 hour of ≥4.5 mg/dL as compared with 49 (57.6%) in patients with phosphate levels <4.5 mg/dL. The 90-day mortality was also significantly higher in patients with hyperphosphatemia. Similarly, in 184 patients who survived at 24 hours after CRRT, hyperphosphatemia conferred a 2.2-fold and 2.6-fold increased risk of 28- and 90-day mortality, respectively. The results remained unaltered when the serum phosphate level was analyzed as a continuous variable. Electrolyte and mineral disturbances are common, and hyperphosphatemia may predict poor prognosis in septic AKI patients undergoing CRRT.

High dietary phosphorus density is a risk factor for incident chronic kidney disease development in diabetic subjects: a community-based prospective cohort study

Background: High serum phosphorus concentrations are associated with an increased risk of cardiovascular disease and progression of chronic kidney disease (CKD). However, the relation between dietary phosphorus intake and CKD development has not been well evaluated.Objective: In this study, we investigated the impact of dietary phosphorus density on the development of incident CKD in a cohort of subjects with normal renal function.Design: Data were retrieved from the Korean Genome and Epidemiology Study, a prospective community-based cohort study. The study cohort consisted of subjects aged 40-69 y, who were followed up biennially from 2001 to 2014. A total of 873 subjects with diabetes mellitus (DM) and 5846 subjects without DM (non-DM) were included in the final analysis. The primary endpoint was incident CKD, defined as a composite of estimated glomerular filtration rate <60 mL · min-1 · 1.73 m-2 and/or the development of proteinuria.Results: In the DM and non-DM groups, the mean ages of the participants were 55.6 ± 8.7 and 51.4 ± 8.6 y, the numbers of male subjects were 454 (52.0%) and 2784 (47.6%), and the mean estimated glomerular filtration rates were 91.6 ± 14.0 and 94.5 ± 14.0 mL · min-1 · 1.73 m-2, respectively. The mean values of dietary phosphorus density, defined as the ratio of a single-day dietary phosphorus amount to the total daily calorie intake, were 0.51 ± 0.08 mg/kcal in the DM group and 0.51 ± 0.07 mg/kcal in the non-DM group. During the follow-up, CKD newly developed in 283 (32.4%) and 792 subjects (13.5%) in the DM and non-DM groups, respectively. When the subjects were divided into quartiles according to the dietary phosphorus density in each group, the highest quartile was significantly associated with the development of incident CKD by multiple Cox proportional hazard analysis in the DM group (P = 0.02) but not in the non-DM group (P = 0.72).Conclusions: High dietary phosphorus density is associated with an increased risk of CKD development in DM patients with normal renal function. The causality in this association needs to be tested in a randomized controlled trial.

Warfarin Use in Patients with Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study

Background and Purpose— The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Methods— Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score–matched cohorts were analyzed by Cox proportional hazards models. Results— Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09–1.91; P=0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10–2.22; P=0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78–1.15; P=0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90–1.26; P=0.470). Conclusions— Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy

Background Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. Methods We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. Results Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37–0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43–0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44–0.97; P = 0.03). Conclusion This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.

High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension

The association between salt intake and renal outcome in subjects with preserved kidney function remains unclear. Here we evaluated the effect of sodium intake on the development of chronic kidney disease (CKD) in a prospective cohort of people with normal renal function. Data were obtained from the Korean Genome and Epidemiology Study, a prospective community-based cohort study while sodium intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A total of 3,106 individuals with and 4,871 patients without hypertension were analyzed with a primary end point of CKD development [a composite of estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2 and/or development of proteinuria during follow-up]. The median ages were 55 and 47 years, the proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73 m2 in individuals with and without hypertension, respectively. During a median follow-up of 123 months in individuals with hypertension and 140 months in those without hypertension, CKD developed in 27.8% and 16.5%, respectively. After adjusting for confounders, multiple Cox models indicated that the risk of CKD development was significantly higher in people with hypertension who consumed less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between 2.93-4.03 g/day sodium. However, there was no significant difference in the incident CKD risk among each quartile of people without hypertension. Thus, both high and low sodium intakes were associated with increased risk for CKD, but this relationship was only observed in people with hypertension.

Vitamin D deficiency is significantly associated with depression in patients with chronic kidney disease

Background Depression is reported to be the most common psychological problem in patients with chronic kidney disease (CKD). Several studies have reported that lower levels of serum vitamin D are significantly associated with depression. Both vitamin D deficiency and depression are prevalent in patients with CKD, yet the relationship between these two factors remains poorly understood. This study aimed to investigate the association between vitamin D levels and depression among CKD patients. Methods Totally, 21,257 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES V, VI) from 2010–2014 were screened for the study; 533 CKD patients were included. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D3 [25(OH)D3] ≤10 ng/mL. Patients were divided into vitamin D deficient or sufficient groups. Depression was screened for using the Korean version of the WHO Composite International Diagnostic Interview-Short Form. The association between vitamin D deficiency and depression was evaluated by multivariate logistic regression analysis. Results The mean participant age was 70.1±9.4 years; 262 patients (49.2%) were male. The median 25(OH)D3 level was 19.1±6.9 ng/mL. The prevalence of depression was higher in CKD patients than in the general population (14.3 vs. 11.1%, P = 0.03). Additionally, the prevalence of depression was significantly higher in CKD patients with (vs. without) vitamin D deficiency (32.5% vs. 50.0%, P<0.001). Multivariate logistic regression analysis showed that vitamin D deficiency was a significant independent predictor of depression after adjusting for confounding factors (adjusted odds ratio, 6.15; 95% confidence interval, 2.02–8.75; P = 0.001). Conclusion Depression was highly prevalent in CKD patients, in whom vitamin D deficiency was a significant independent predictor of depression. Therefore, management of vitamin D deficiency might help prevent depression in CKD patients.

Phosphate is a potential biomarker of disease severity and predicts adverse outcomes in acute kidney injury patients undergoing continuous renal replacement therapy

Hyperphosphatemia is associated with mortality in patients with chronic kidney disease, and is common in critically ill patients with acute kidney injury (AKI); however, its clinical implication in these patients is unknown. We conducted an observational study in 1144 patients (mean age, 63.2 years; male, 705 [61.6%]) with AKI who received continuous renal replacement therapy (CRRT) between January 2009 and September 2016. Phosphate levels were measured before (0 h) and 24 h after CRRT initiation. We assessed disease severity using various clinical parameters. Phosphate at 0 h positively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II; P < 0.001) and Sequential Organ Failure Assessment (SOFA; P < 0.001) scores, and inversely with mean arterial pressure (MAP; P = 0.02) and urine output (UO; P = 0.01). In a fully adjusted linear regression analysis for age, sex, Charlson comorbidity index (CCI), MAP, and estimated glomerular filtration rate (eGFR), higher 0 h phosphate level was significantly associated with high APACHE II (P < 0.001) and SOFA (P = 0.04) scores, suggesting that phosphate represents disease severity. A multivariable Cox model also showed that hyperphosphatemia was significantly associated with increased 28-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) and 90-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) mortality. Furthermore, patients with increased phosphate level during 24 h were at higher risk of death than those with stable or decreased phosphate levels. Finally, c-statistics significantly increased when phosphate was added to a model that included age, sex, CCI, body mass index, eGFR, MAP, hemoglobin, serum albumin, C-reactive protein, and APACHE II score. This study shows that phosphate is a potential biomarker that can reflect disease severity and predict mortality in critically ill patients receiving CRRT.

Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy

Abstract Background: Soluble CD89 (sCD89)-IgA complex plays a key role in the pathogenesis of IgA nephropathy (IgAN). However, there is a lack of evidence supporting this complex as a good biomarker for disease progression. This study aimed to evaluate the usefulness of sCD89-IgA complex for risk stratification of IgAN. Methods: A total of 326 patients with biopsy-proven IgAN were included. sCD89-IgA complex was measured by sandwich-enzyme-linked immunosorbent assay. The study endpoints were a 30% decline in estimated glomerular filtration rate (eGFR). Results: sCD89-IgA complex levels were inversely and weakly associated with eGFR at the time of biopsy (r=−0.12, p=0.03). However, the significance between the two factors was lost in the multivariate linear regression after adjustment of clinical factors (β=0.35, p=0.75). In a multivariate Cox model, the highest (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.35–1.61; p=0.45) and middle (HR, 0.93; 95% CI, 0.46–1.89; p=0.84) tertiles of sCD89-IgA complex levels were not associated with an increased risk of developing a 30% decrease in eGFR. Furthermore, the decline rates in eGFR did not differ between groups and C-statistics revealed that the sCD89-IgA complex were not superior to clinical factors in predicting disease progression. Conclusions: This study found no association between sCD89-IgA complex levels and disease progression in IgAN. Although sCD89 can contribute to the formation of immune complexes, our findings suggest that the sCD89-IgA level is not a good predictor of adverse outcomes and has limited clinical utility as a biomarker for risk stratification in IgAN.