Young Rim Song

Prevention of Acute Kidney Injury by Erythropoietin in Patients Undergoing Coronary Artery Bypass Grafting: A Pilot Study

Background/Aims: Depending on the specific definition, acute kidney injury (AKI) occurs in 7–40% of patients undergoing cardiac surgery. Even small changes in serum creatinine (SCr) levels are associated with increased mortality after cardiac surgery. However, there are no current methods for preventing AKI after cardiac surgery. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in various experimental models. In this pilot trial, we evaluated the effectiveness of EPO in the prevention of AKI after coronary artery bypass grafting (CABG). Methods: 71 patients scheduled for elective CABG randomly received either 300 U/kg of EPO or saline intravenously before surgery. AKI was defined as a 50% increase in SCr levels over baseline within the first 5 postoperative days. Estimated glomerular filtration rate (eGFR) was calculated from the Cockcroft-Gault equation. Results: Of 71 patients, 13 developed postoperative AKI: 3 of the 36 patients in the EPO group (8%) and 10 of the 35 patients in the placebo group (29%; p = 0.035). The increase in postoperative SCr concentration and the decline in postoperative eGFR were significantly lower in the EPO group than in the placebo group. Conclusions: In our small, pilot trial, prophylactic administration of EPO prevents AKI and improves postoperative renal function. These data are preliminary and require confirmation in a larger clinical trial.

Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney

BACKGROUNDnChronic hypoxia in the kidney has been suggested as a final common pathway to end-stage renal disease. Hypoxia-inducible factor (HIF) is a transcription factor that regulates cellular hypoxic responses, and it is a promising target with therapeutic potential in various kidney disease models. In this study, we investigated whether HIF activation could attenuate renal injury in the rat remnant kidney model.nnnMETHODSnTwo weeks after a subtotal nephrectomy, rats received a continuous infusion of dimethyloxalylglycine (DMOG) for 4 weeks to activate HIF.nnnRESULTSnThe DMOG infusion halted the progression of proteinuria. A histological evaluation revealed that the glomerulosclerosis and tubulointerstitial injury were significantly decreased by DMOG treatment. DMOG increased renal HIF-1alpha protein. The expression of glucose transporter-1 (GLUT-1) and prolyl hydroxylase 3 (PHD3) and the immunostaining of vascular endothelial growth factor (VEGF) were increased by DMOG. DMOG-treated rats showed less podocyte injury manifested by decreased immunostaining of desmin and the restoration of podoplanin staining. Furthermore, plasma malondialdehyde (MDA), a marker of oxidative stress, showed a tendency to decrease, and the renal expression of catalase, an antioxidant, was significantly increased by DMOG. The DMOG treatment decreased macrophage infiltration and reduced fibrosis, as manifested by decreased type IV collagen and osteopontin expression.nnnCONCLUSIONSnActivation of HIF by DMOG halted the progression of proteinuria and attenuated structural damage by preventing podocyte injury in the remnant kidney model. This renoprotection was accompanied by a reduction of oxidative stress, inflammation and fibrosis.

Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease.

BACKGROUND & AIMSnWe investigated the prevalence of sarcopenia in elderly patients with end-stage renal disease (ESRD) and its relationship with various markers of nutrition, cognitive function, depressive symptoms, inflammation and β2-microglobulin.nnnMETHODSnA cross-sectional study was conducted with 95 patients having ESRD aged over 50 years. Sarcopenia was defined as a decline in both muscle mass and strength.nnnRESULTSnThe mean age was 63.9 ± 10.0 years; 56.8% were men and 52.6% had diabetes. Sarcopenia was highly prevalent in elderly patients with ESRD (37.0% in men and 29.3% in women). Subjective Global Assessment (SGA), inflammatory markers and β2-microglobulin levels were significantly associated with sarcopenia, even after adjustment for age, gender, diabetes, and body mass index. Additionally, patients with depressive symptoms showed a higher risk of sarcopenia relative to those without depressive symptoms (odds ratio, OR = 6.87, 95% confidence interval, CI = 2.06-22.96) and sarcopenia was more likely to be present in patients with mild cognitive dysfunction (OR = 6.35, 95% CI = 1.62-34.96).nnnCONCLUSIONSnSarcopenia is highly prevalent in elderly patients with ESRD and is closely associated with SGA, inflammatory markers, β2-microglobulin, depression and cognitive dysfunction.

Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis.

OBJECTIVESnThe soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis.nnnMETHODSnA cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen.nnnRESULTSnPlasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p=0.007) and IL-6 (p=0.002), whereas sRAGE was negatively associated with those inflammatory markers (p=0.001, p=0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β=-0.230, p=0.037, β=0.155, p=0.045) and VCS (β=-0.205, p=0.049, β=0.197, p=0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03-1.25, p=0.009), presence of diabetes (OR 13.4, 95% CI: 1.20-150.18, p=0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05-5.11, p=0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT>1.0mm and/or plaque formation).nnnCONCLUSIONSnOur findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.

The Bilirubin Level is Negatively Correlated with the Incidence of Hypertension in Normotensive Korean Population

Reactive oxygen species have been known to be an important factor in the pathogenesis of hypertension. Bilirubin, one of the metabolites of heme degraded by heme oxygenase, is a potent anti-oxidant. We verified the effect of serum bilirubin level on the incidence of hypertension in normotensive subjects. We grouped 1,208 normotensive subjects by the criterion of the highest quintile value of serum bilirubin, 1.1 mg/dL. The incidence of hypertension was higher in group 1 with bilirubin less than 1.1 mg/dL than in group 2 with bilirubin 1.1 mg/dL or more (186/908 vs. 43/300, p=0.018). The relative risk for hypertension was 0.71 (95% confidence interval, 0.51-0.99), p=0.048 in group 2 compared to group 1 by Coxs proportional hazard model. Among the groups stratified by gender, smoking, and liver function status, the group 2 showed a lower risk of hypertension in females and in non-smokers. In conclusion, a mild increase within the physiological range of serum bilirubin concentration was negatively correlated with the incidence of hypertension. The effect of bilirubin on the development of hypertension was more evident in females and in non-smokers.

The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.

Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study.

BackgroundElevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.ObjectivesThe CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.DesignMulticenter, open-labeled, randomized controlled study.SettingSeven university-affiliated hospitals in Korea.ParticipantsOverall, 66 peritoneal dialysis patients were enrolled.InterventionSixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.Main outcome measuresAchievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).Results72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (− 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.ConclusionCinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.Trial registrationControlled trials NCT01101113

Cardiac risk assessment by gated single-photon emission computed tomography in asymptomatic end-stage renal disease patients at the start of dialysis

ObjectivesThis study assessed the impact of cardiac risk assessment using gated single-photon emission computed tomography (SPECT) on cardiac events in end-stage renal disease (ESRD) patients.MethodsWe evaluated 215 asymptomatic patients who began dialysis between January 2005 and April 2009. Baseline electrocardiography and echocardiography were performed in all the patients. The subjects were stratified into low- and high-risk groups according to the baseline cardiac status, and gated SPECT was additionally recommended for the high-risk patients.ResultsThe study population consisted of 50 low- and 165 high-risk patients undergoing SPECT. Among the high-risk patients, 75 (45.5%) showed perfusion defects on SPECT and their overall cardiac-event rate per person-year of follow-up was 15.0%, significantly higher than 4.5% in high-risk group without perfusion defect and 1.2% in low-risk group. The presence of perfusion defect was a significant independent predictor of adverse cardiac events [hazard ratio (HR) 2.11; 95% confidence interval (CI) 1.05-4.24; Pxa0=xa0.035]. When gated SPECT was added to the clinical and the echocardiographic variables, the prognostic stratification significantly improved (Pxa0<xa0.001). However, coronary revascularization was not associated with improved cardiac event-free survival (HR 0.62; 95% CI 0.26-1.52; Pxa0=xa0.296).ConclusionsGated SPECT may provide additional prognostic information for cardiac risk stratification, particularly among high-risk patients starting dialysis.

Left Ventricular Diastolic Dysfunction as a Predictor of Rapid Decline of Residual Renal Function in Patients with Peritoneal Dialysis

BACKGROUNDnThe aim of this study was to evaluate whether diastolic dysfunction at the start of dialysis could influence renal and cardiovascular survival rates in 82 patients undergoing peritoneal dialysis.nnnMETHODSnDiastolic dysfunction was determined using left ventricular hypertrophy, the ratio of early peak transmitral inflow velocity to peak diastolic mitral annular velocity (E/E), and left atrial volume index (LAVI). Residual renal function (RRF) was measured with 24-hour urine collections at baseline (within 1 month of beginning peritoneal dialysis) and thereafter at 6-month intervals for 2 years. To evaluate the long-term prognostic significance of diastolic dysfunction, the 4-year cardiac event-free survival was also evaluated.nnnRESULTSnThe median slope of RRF decline was -0.07 mL/min/mo/1.73 m(2). Forty-five patients (54.9%) with rapid RRF declines (< -0.07 mL/min/mo/1.73 m(2)) had a higher prevalence of diabetes and eccentric left ventricular hypertrophy, as well as significantly elevated E/E ratios and LAVIs. There was a close relationship between baseline E/E ratio (r = -0.221, P = .048), LAVI (r = -0.276, P = .015), and RRF decline rate, and both E/E > 15 (odds ratio, 3.61; 95% confidence interval, 1.07-12.12) and LAVI > 32 mL/m(2) (odds ratio, 3.54; 95% confidence interval, 1.08-11.58) were significant independent predictors of the loss of RRF. Furthermore, E/E > 15 also provided additional prognostic value in predicting future cardiac events (hazard ratio, 6.74; 95% confidence interval, 1.07-12.12; P = .023).nnnCONCLUSIONSnLeft ventricular diastolic dysfunction may be a significant predictor of rapid decline in RRF and adverse cardiac outcomes in patients starting peritoneal dialysis.

Association between cardiac valvular calcification and myocardial ischemia in asymptomatic high-risk patients with end-stage renal disease

OBJECTIVEnValvular calcification is associated with significant morbidity and mortality in patients with end stage renal disease (ESRD). This study examined the hypothesis that valvular calcification is a marker of myocardial ischemia in asymptomatic high-risk patients with ESRD.nnnMETHODSnEchocardiography and myocardial perfusion single-photon emission computed tomography were performed in 285 asymptomatic high-risk patients with ESRD at initiation of dialysis. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS) and defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. The presence of cardiac valvular calcification was assessed by echocardiography and defined as aortic valve calcification or mitral valve calcification.nnnRESULTSnEighty-five (29.9%) patients had echocardiographic evidence of cardiac valvular calcification. The presence of myocardial ischemia was significantly associated with aortic valve calcification (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.76-5.78; p < 0.001), mitral valve calcification (OR = 3.31; 95% CI = 1.74-6.28; p < 0.001), and cardiac valvular calcification (OR = 3.18; 95% CI = 1.79-5.65; p < 0.001). The presence of moderate to severe myocardial ischemia (SDS ≥ 8) was independently associated with cardiac valvular calcification (OR = 2.86; 95% CI = 1.12-7.27; p = 0.028).nnnCONCLUSIONnValvular calcification was significantly associated with the presence of inducible myocardial ischemia in asymptomatic patients with ESRD, and may be a potential marker of patients at high-risk for the presence of silent myocardial ischemia.