Su-Young Jung

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.

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.

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.

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.

Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

AbstractAcute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.

Characteristics and Clinical Outcomes of End-Stage Renal Disease Patients on Peritoneal Dialysis for Over 15 Years: A Single-Center Experience

Background: Maintaining peritoneal dialysis (PD) for a long time is problematic owing to a number of factors. This study aimed to clarify the characteristics and examine the clinical outcomes of patients who received PD as a long-term dialysis modality. Methods: All end-stage renal disease (ESRD) patients who initiated PD at Yonsei University Health System between 1987 and 2000 were screened. Patients who maintained PD for over 15 years were classified as the long-term PD group and those who were treated with PD for less than 5 years were included in the short-term PD group. Demographic and biochemical data and clinical outcomes were compared between the groups. Independent factors associated with long-term PD maintenance were ascertained using multivariate logistic regression analysis. Results: Among 1,116 study patients, 87 (7.8%) were included in the long-term group and 293 (26.3%) were included in the short-term group. In the long-term group, the mean patient age at PD initiation was 39.6 ± 11.5 years, 35 patients (40.2%) were male, and the mean PD duration was 205.3 ± 32.7 months. Patients were younger, body weight was lower, the proportion of patients with diabetes or cardiovascular diseases was lower, and the proportion of low to low-average transporters was higher in the long-term group than in the short-term group (p < 0.001). Multiple logistic regression analysis revealed that age, body mass index (BMI), serum creatinine, type of PD solution, and diabetes were significant independent factors associated with long-term PD maintenance. Conclusion: Peritoneal dialysis can be considered as a long-term renal replacement therapy option, especially in non-diabetic, not overweight, and young ESRD patients.

Clinical usefulness of the Oxford classification in determining immunosuppressive treatment in IgA nephropathy

Abstract Background: The Oxford classification has been widely used in IgA nephropathy. However, its clinical usefulness of determining immunosuppression is unknown. Aim: Whether the Oxford classification could predict the development of proteinuria ≥1 g/g Cr and worsening kidney function, as well as the clinical efficacy of corticosteroid treatment according to each histologic variable of the Oxford-MEST. Methods: We included 377 patients with early-stage IgA nephropathy. The study endpoints were the development of a heavy proteinuria and a decline renal function. Results: The results showed that among the Oxford-MEST lesions, only M1 predicted the risk of the development of proteinuria ≥1.0 g/g Cr compared to other lesions in a time-varying Cox model adjusted for multiple confounding factors. In addition, the risk of reaching a 30% decline in eGFR was significantly higher in patients with M1 than in those with M0. Furthermore, patients with M1 had a greater decline of eGFR than patients with M0. However, steroid treatment in M1 lesion was not associated with improving clinical outcomes in the unmatched and propensity score matched cohort. Conclusions: This finding may provide a rationale for using the Oxford classification as a guidance to initiate immunosuppression in the early stages of IgA nephropathy. KEY MESSAGES M1 has independently predictive role among the Oxford lesions in IgA nephropathy. Oxford classification should be defined during pathologic approach. Decision of starting immunosuppression according to the Oxford lesions.

Neck circumference predicts renal function decline in overweight women: A community-based prospective cohort study

AbstractChronic kidney disease (CKD) is characterized by increased risks of morbidity and mortality. Upper-body subcutaneous fat, which is commonly estimated from the neck circumference (NC), was revealed to be the main reservoir of circulating nonesterified fatty acids in overweight patients. Despite a close association between NC and metabolic complications, the relationship of NC with renal function has not been fully investigated. In this study, the impact of NC on the development of incident CKD was elucidated.The data were retrieved from the Korean Genome and Epidemiology Study cohort. The subjects were followed at 2-year intervals from 2003 to 2011. Overweight was defined as a body mass index of ≥23 kg/m2. A total of 4298 cohort subjects were screened. After exclusion, 2268 overweight subjects were included for the final analysis. The primary end point was incident CKD, which was defined as a composite of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or the development of proteinuria.The mean patient age was 36.3 ± 3.0 years, and 1285 (56.7%) were men. They were divided into 2 groups according to the median NC in male and female subjects, separately. In both sexes, hypertension (men, P < 0.001; women, P = 0.009) and diabetes (men, P = 0.002; women, P < 0.001) were significantly more prevalent in the big NC group than in the small NC group. In contrast, eGFR was significantly lower only in male subjects of the big NC group (P < 0.001), whereas it was comparable between the small and big NC groups (P = 0.167). In multivariate Cox proportional hazards regression analysis, NC values were independently associated with incident CKD development in female subjects after adjusting for multiple confounding factors (per 1 cm increase, hazard ratio [95% confidence interval] = 1.159 [1.024–1.310], P = 0.019) but not in male subjects.NC is independently associated with the development of CKD in overweight female subjects, suggesting that it could be a practical risk factor for CKD.

ISH ADA-03 ADEQUATELY CONTROLLED SYSTOLIC BLOOD PRESSURE IS SIGNIFICANTLY ASSOCIATED WITH BETTER SURVIVAL RATE, IRRESPECTIVE OF NUMBER OF ANTIHYPERTENSIVE AGENTS IN PREVALENT DIALYSIS PATIENTS.

Objective: The object of this study is to investigate optimal BP target and adequate management of BP in prevalent dialysis patients group. Design and Method: The data were retrieved from End-stage Renal Disease-Clinical Research Center (ESRD-CRC) which dialysis patients were prospectively enrolled from 2009 to 2014. Total 2,299 prevalent dialysis patients were analyzed. Eligible patients were assigned to four groups according to distribution of systolic BP (SBP, group as SBP <120, 120–140, 140–160, and >160 mmHg, respectively). The primary outcome was all-cause mortality. Results: Among the study subjects, there were 360, 862, 719, and 358 patients in each SBP groups. The mean SBP in each group was 106.9, 128.6, 146.4 and 170.9 mmHg, respectively (P < 0.001). Baseline characteristics among the groups did not show significant differences except number of AHAs (1.5 ± 1.4, 1.8 ± 1.5, 2.1 ± 1.4, and 2.3 ± 1.3 in each group, P < 0.001). During a median follow up of 4.5 years, all-cause mortality was significantly higher in SBP <120 mmHg group (hazard ratio [HR] 1.44, confidential interval [CI] 1.06–1.94, P = 0.019), and the tendency with higher risk was revealed in >160 mmHg group (HR 1.33, CI 0.94–1.81, P = 0.074) compared to groups, whose BP ranged from 120 to 160 mmHg. Multiple Cox analysis revealed that SBP <120 and >160 mmHg group had significantly higher risk of all-cause mortality after adjustment for multiple confounding factors (HR 1.84, CI 1.27–2.66, P = 0.001; HR 1.69, CI 1.16–2.45, P = 0.006). However, the number of AHAs being taken was not associated with survival rate in subgroup analysis with each BP group. Conclusions: This study showed that lowest (<120) or highest (>160 mmHg) SBP group had significantly higher risk of all-cause mortality, irrespective of number of AHAs. BP control with optimal target is significantly associated with better survival rate. Further study is warranted to determine optimal blood pressure target in dialysis patients.

ISH NIA PS 02-01 Neck Circumference is Associated with Systolic Blood Pressure: A Community-based Prospective Cohort Study

Objective: The association between upper body subcutaneous fat, represented by neck circumference (NC), and blood pressure was explored. Design and Method: The data was retrieved from the Korean Genome and Epidemiology Study (KoGES) cohort. A total of 35,709 cohort subjects were screened. After exclusion, 1,814 male and 1,495 female subjects were eligible for final analysis. The subjects with hypertension was classified as who answered a question which about experience of diagnosed hypertension by any physicians. Multiple linear regression analysis was performed to elucidate the association between NC and cardiovascular risks. Results: A total of 1,814 (54.8%) male and 1,495 (45.2%) female subjects were analyzed. The median NC was 37.6 (36.1–39.0) in male and 32.7 (31.5–34.0) in female, and subjects were divided into two groups according to the median value of NC, respectively. The high NC group showed significantly higher prevalence of hypertension (male: 63 [7.3%] vs 139 [16.4%], P < 0.001; female: 53 [7.4%] vs 109 [15.4%], P < 0.001) and diabetes (50 [5.7%] vs 91 [10.7%], P < 0.001; 13 [1.8%] vs 49 [6.9%], P < 0.001), systolic BP (111.5 ± 16.6 vs 117.1 ± 16.9, P < 0.001; 105.1 ± 15.2 vs 112.5 ± 17.3, P < 0.001), diastolic BP (75.6 ± 12.1 vs 80.0 ± 12.0, P < 0.001; 69.7 ± 10.5 vs 74.2 ± 11.7, P < 0.001), and pulse pressure (36.0 ± 8.5 vs 37.1 ± 9.3, P = 0.008; 35.4 ± 8.6 vs 38.3 ± 10.5, P < 0.001). In multiple linear regression analysis, NC was independently associated with systolic BP in both genders even after adjustment for multiple confounding factors (per 10 mmHg, male: &bgr;=0.049, P = 0.040; female: &bgr;=0.094, P < 0.001). However, a significant relationship was not found with diastolic BP or pulse pressure. Conclusions: NC is independently associated with systolic BP in both gender groups. Upper body subcutaneous fat, chiefly represented by NC, may have a role in hypertension pathophysiology.