Young Ki Son

Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis

Background Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. Methods We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. Results Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B) = 1.72, 95% CI = 1.12–2.63, p = 0.013) and sodium bicarbonate administration (Exp (B) = 6.27, 95% CI = 1.10–35.78, p = 0.039). Conclusions Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality.

Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients

Erythrocyte membrane fatty acids (FA), such as oleic acid, are related to acute coronary syndrome. There is no report about the effect of omega-3 FA on oleic acid in peritoneal dialysis (PD) patients. We hypothesized that omega-3 FA can modify erythrocyte membrane FA, including oleic acid, in PD patients. In a double-blind, randomized, placebo-controlled study, 18 patients who were treated with PD for at least 6 months were randomized to treatment for 12 weeks with omega-3 FA or placebo. Erythrocyte membrane FA content was measured by gas chromatography at baseline and after 12 weeks. The erythrocyte membrane content of eicosapentaenoic acid and docosahexaenoic acid was significantly increased and saturated FA and oleic acid were significantly decreased in the omega-3 FA supplementation group after 12 weeks compared to baseline. In conclusion, erythrocyte membrane FA content, including oleic acid, was significantly modified by omega-3 FA supplementation for 12 weeks in PD patients.

Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients

Vitamin D deficiency, low levels of fetuin-A, and fibroblast growth factor 23 (FGF-23) are related to vascular calcification, which is associated with cardiovascular disease. We hypothesized that omega-3 fatty acid (FA), which has cardioprotective properties, modifies vitamin D status, fetuin-A, and FGF-23 levels in dialysis patients. In a randomized, open-label, controlled study, a total of 47 patients treated with dialysis for at least 1 year were randomized to treatment for 6 months with omega-3 FAs (Omacor, 3 g/d; Pronova, Sandefjord, Norway) or a control group. Levels of fetuin-A and FGF-23 were measured by enzyme-linked immunoassay, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured by radioimmunoassay. The mean age of the enrolled patients was 57.4 ± 10.4 years, and mean dialysis duration was 46.5 ± 28.1 months. Twenty-seven hemodialysis patients and 16 peritoneal dialysis patients finished this trial. After 6 months, the levels of 1,25-dihydroxyvitamin D and fetuin-A were significantly increased in the group taking the omega-3 FA supplement compared with baseline. Levels of calcium, phosphorous, parathyroid hormone, 25-hydroxyvitamin D, FGF-23, and lipid profiles were not significantly changed in the omega-3 FA-supplemented group after 6 months compared with baseline. The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were significantly increased, and oleic acid content was significantly decreased in the omega-3 FA-supplemented group after 6 months compared with baseline. Regarding vascular calcification and cardiovascular disease, omega-3 FA supplementation may have a clinical benefit caused by activating vitamin D, increasing fetuin-A levels, and modifying erythrocyte membrane FA contents in dialysis patients.

Association of adiponectin and leptin with serum lipids and erythrocyte omega-3 and omega-6 fatty acids in dialysis patients.

AIMS Besides regulating energy metabolism, leptin promotes and adiponectin suppresses inflammation which is a common feature of end-stage renal disease (ESRD). Omega-3 fatty acids (n-3FA) exert anti-inflammatory actions by inhibiting pro-inflammatory signal transduction pathways whereas arachidonic acid (an n-6FA) facilitates inflammation by mediating inflammatory signals and serving as precursor of pro-inflammatory eicosanoids. Given the functional overlap between adipokines and n-3FA and n-6FA, we sought to explore their interrelationship in patients with ESRD. METHODS 44 ESRD patients maintained on hemodialysis (HD), 29 patients receiving peritoneal dialysis (PD), and 10 healthy subjects were enrolled. Body mass index (BMI), plasma leptin, adiponectin, lipids and CRP and erythrocyte fatty acids were measured. RESULTS Compared to controls adiponectin was elevated and leptin level was reduced in the ESRD group. Adiponectin levels were comparable among PD and HD patients, but leptin and BMI were higher in PD than in HD patients. Despite comparable BMIs, female patients had higher leptin than male patients. Leptin levels were positively associations with BMI, total and LDL cholesterol whereas adiponectin was inversely related with BMI, triglycerides and CRP and directly associated with HDL cholesterol in ESRD patients. Plasma adiponectin was directly associated with erythrocyte n-3 FA (r = 0.581, p = 0.023) and inversely associated with n-6FA (r = -0.640, p = 0.010) in the HD patients. CONCLUSION A direct association was found between plasma levels of adiponectin and HDL and erythrocyte n-3FA in ESRD patients. Prospective trials are needed to explore the effect of n-3FA supplementation on plasma adipokines and markers of oxidative stress and inflammation in this population.

Clinical Outcome of Preemptive Kidney Transplantation in Patients With Diabetes Mellitus

End-stage renal disease (ESRD) caused by diabetic nephropathy is increasing throughout the world. The survival of diabetic patients treated by transplantation has improved nowadays. Although recent studies have demonstrated preemptive kidney transplantation to be associated with better graft survival in CKD patients, the effect of pre-transplantation dialysis on graft outcomes among diabetic ESRD patients is unclear. This analysis summarized our experience with preemptive kidney transplantation in diabetic ESRD patients by retrospectively comparing 70 such patients transplanted between 1995 and 2009. These 70 patients were divided into two groups: 30 patients underwent preemptive and the other 40 transplantation after maintenance hemodialysis or peritoneal dialysis. We compared graft survivals, acute rejection episodes, postoperative complications, and delayed graft function rates. The 10-year patient survival of 100% in the preemptive group was similar to that of the nonpreemptive group (85%, P = .11). But the 10 year graft survival was higher among the preemptive than the nonpreemptive group (100% vs 75%, P = .02). Pre-transplantation modality did not affect graft survival. Therefore, preemptive kidney transplantation should be applied to eligible patients with diabetic ESRD.

Rosuvastatin Attenuates Inflammation, Apoptosis and Fibrosis in a Rat Model of Cyclosporine-Induced Nephropathy

Background/Aim: Cyclosporine (CsA)-induced kidney injury is characterized by renal dysfunction with inflammatory cell infiltrations, apoptosis and fibrosis. Pleiotropic effects of statins may exert anti-inflammatory, antiapoptotic and antifibrotic actions beyond lipid control. The aim of this study is to investigate whether rosuvastatin (RUS) has anti-inflammatory, antiapoptotic and antifibrotic effects on chronic CsA-induced nephropathy in a rat model. Methods: Male Sprague-Dawley rats fed a low-sodium diet were divided into three treatment groups: control (0.9% saline injection), CsA (15 mg/kg/day by subcutaneous injection), CsA + RUS (10 mg/kg/day by gastric gavage). Renal function, CsA level and lipid levels were measured at the end of 4 weeks. The expression of ED-1, transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) for inflammation and fibrosis were examined by Western blot analysis. The expression levels of apoptosis-associated factors were examined by Western blot analysis. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling (TUNEL) method. Results: Kidney function was decreased in CsA-treated rats compared with controls, which was attenuated by RUS. RUS did not affect the lipid level or the blood CsA level. TUNEL staining showed that RUS inhibited CsA-induced tubular apoptosis. RUS decreased CsA-induced increased expression of Bax/Bcl-2 ratio. The expressions of ED-1, α-SMA, TGF-β1, Smad2/3, Smad4 and p-JNK were increased in CsA-treated rats, which were attenuated by RUS. Tubular atrophy and interstitial fibrosis in CsA-treated rats were attenuated by RUS supplementation. Conclusion: RUS supplementation attenuates proinflammatory and apoptosis-related factors and inhibits the fibrotic pathways including the smad-dependent and smad-independent pathways in a rat model of CsA-induced nephropathy.

Association Between Vascular Calcification Scores on Plain Radiographs and Fatty Acid Contents of Erythrocyte Membrane in Hemodialysis Patients

OBJECTIVE Vascular calcification (VC) scores determined by using simple plain radiographic films are known to be associated with coronary artery disease and mortality in patients undergoing hemodialysis (HD). Omega-3 fatty acid (FA) has been shown to reduce ectopic calcifications in an animal model, and it has also been shown that erythrocyte membrane omega-3 FA content is an independent discriminator of coronary artery disease. The present study was designed to demonstrate relations between VC scores and erythrocyte membrane FA contents in patients undergoing HD. DESIGN A cross-sectional study was carried out. SETTING The study was carried out at an outpatient hemodialysis unit at Dong-A University Hospital, Busan, Republic of Korea. PATIENTS A total of 31 patients undergoing HD were recruited. Patients with significant malnutrition, a short duration of dialysis (<12 months), a history of recent infection, malignancy, or liver disease were excluded. MAIN OUTCOME MEASURES Plain radiographic films of the feet, hands, pelvis, and lateral lumbar spine were examined and VC scores were determined using previously reported methods. Erythrocyte membrane FA contents were analyzed by gas chromatography. RESULTS The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were not found to be related with VC on simple plain radiographic films. However, erythrocyte membrane contents of oleic acid and total monounsaturated FA (MUFA) were significantly higher in patients with significant VC scores. Furthermore, erythrocyte membrane contents of MUFA and oleic acid were found to be negatively associated with high-density lipoprotein cholesterol level and positively associated with triglyceride level. CONCLUSION Erythrocyte membrane contents of MUFA and oleic acid were found to be associated with VC scores determined using plain radiographs and with dyslipidemia in patients undergoing HD.

Comparison of Erythrocyte Membrane Fatty Acid Contents in Renal Transplant Recipients and Dialysis Patients

BACKGROUND Alterations of erythrocyte membrane fatty acid (FA) composition play important roles in cellular function because they change the membrane microenvironment, including transmembrane receptors. The erythrocyte membrane oleic acid content is higher among patients with acute coronary syndrome and also in dialysis patients. However, available data are limited concerning erythrocyte membrane FA content in kidney transplant recipients (KTP). We sought to test the hypothesis that erythrocyte membrane FA content among KTP were different from those in dialysis patients. METHODS In this cross-sectional study, we recruited 35 hemodialysis, 33 peritoneal dialysis 49 KTP, and 33 normal control subjects (CTL). Their erythrocyte membrane FA content were measured by gas chromatography. RESULTS The mean ages of the enrolled dialysis patients, KTP, and CTL were 56.4 ± 10.1, 48.9 ± 10.4, and 49.5 ± 8.3 years, respectively. Mean kidney transplant duration was 89.8 ± 64.8 months and mean dialysis duration, 49.0 ± 32.6 months. The intakes of vegetable lipid and vegetable protein including total calories were significantly increased among KTP versus dialysis patients. Total cholesterol (P < .001) and high density lipoprotein cholesterol (HDL; P < .001) levels were significantly higher and C-reactive protein was significantly lower among KTP compared with dialysis patients. The erythrocyte membrane content of palmitoleic acid (P < .001) was significantly higher but oleic acid (P < .001) significantly lower in KTP compared with dialysis patients. The erythrocyte membrane contents of arachidonic acid and docosahexaenoic acid were significantly higher, and linoleic acid and the omega-6 FA to omega-3 FA ratio (P < .001) significantly lower in KTP compared with dialysis patients. The erythrocyte membrane content of oleic acid was independently associated with monounsaturated fatty acid (beta = 0.771, P < .001), eicosapentaeonic acid (beta = -0.244, P = .010), and HDL (beta = -0.139, P = .049) in KTP. CONCLUSIONS FA contents of erythrocyte membranes were significantly different in KTP compared with dialysis patients. These differences may have been associated with improved dietary intake and immunosuppression after kidney transplantation.

Vascular calcification on plain radiographs is associated with carotid intima media thickness, malnutrition and cardiovascular events in dialysis patients: a prospective observational study

BackgroundVascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular (CV) disease. We hypothesized that significant VC on plain radiographs is associated with CIMT and CV events in dialysis patients. In addition, we evaluated risk factors for VC progression on plain radiographs in dialysis patients.MethodsIn this 2-year observational, prospective study, 67 dialysis patients were included. We checked plain radiographs at baseline and after 2 years. Laboratory tests and malnutrition score were obtained at baseline, after 12 months, and after 24 months.ResultsThe mean age of patients was 56.3 ± 10.3 years and duration of dialysis was 41.3 ± 34.5 months. The prevalence of significant VC was 61.2% and the prevalence of carotid artery atheromatous plaques was 55.6%. Mean CIMT, malnutrition scores, CRP level and prevalence of carotid atheromatous plaques were significantly higher in patients with significant VC. Serum albumin and total iron binding capacity were significantly lower in patients with significant VC compared to patients without significant VC. During a mean observational period of 22 months, patients without significant VC showed lower CV events by the Kaplan-Meyer method (p = 0.010). Progression of VC was found in 35.7% among 56 patients followed up. Hemoglobin after 24 months was an independent factor for progression of VC (Exp(B) = 0.344, 95% Confidence Interval = 0.13 – 0.96, p = 0.034).ConclusionsSignificant VC on plain radiograph was associated with CIMT, malnutrition, inflammation, and CV events in dialysis patients. Conditions which increase hemoglobin level may retard progression of VC in dialysis patients.

The effects of omega-3 fatty acid on vitamin D activation in hemodialysis patients: a pilot study.

The high incidence of cardiovascular disease and vitamin D deficiency in chronic kidney disease patients is well known. Vitamin D activation by omega-3 fatty acid (FA) supplementation may explain the cardioprotective effects exerted by omega-3 FA. We hypothesized that omega-3 FA and 25-hydroxyvitamin D (25(OH)D) supplementation may increase 1,25-dihydroxyvitamin D (1,25(OH)2D) levels compared to 25(OH)D supplementation alone in hemodialysis (HD) patients that have insufficient or deficient 25(OH)D levels. We enrolled patients that were treated for at least six months with 25(OH)D < 30 ng/mL (NCT01596842). Patients were randomized to treatment for 12 weeks with cholecalciferol supplemented with omega-3 FA or a placebo. Levels of 25(OH)D and 1,25(OH)2D were measured after 12 weeks. The erythrocyte membrane FA contents were also measured. Levels of 25(OH)D were increased in both groups at 12 weeks compared to baseline. The 1,25(OH)2D levels at 12 weeks compared to baseline showed a tendency to increase in the omega-3 FA group. The oleic acid and monounsaturated FA content decreased, while the omega-3 index increased in the omega-3 FA group. Omega-3 FA supplementation may be partly associated with vitamin D activation, although increased 25(OH)D levels caused by short-term cholecalciferol supplementation were not associated with vitamin D activation in HD patients.