Se Won Oh

Trends in the prevalence of chronic kidney disease, other chronic diseases and health-related behaviors in an adult Korean population: data from the Korean National Health and Nutrition Examination Survey (KNHANES)

BACKGROUND Chronic kidney disease (CKD) is an increasing public health problem. However, there have been limited data on the trend of CKD prevalence, along with the changes of health-related behaviors and other chronic diseases in an adult Korean population. METHODS Data from the Korean National Health and Nutrition Examination Survey in 2005 and 2007 were analyzed. The study subjects comprised 8400 participants aged ≥ 20 years with creatinine data. CKD was defined as estimated glomerular filtration rate (GFR) <60 mL/min/1.73m(2). GFR was estimated by the abbreviated Modification of Diet in Renal Disease equation. RESULTS The CKD prevalence was significantly decreased from 2005 to 2007 (8.8 versus 7.2%; P = 0.010). The prevalence of hypertension was stable but that of diabetes was increased. The proportion of blood pressure (BP) <130/80 mmHg in the whole population, and HbA1c <7% in the diabetic participants was increased from 2005 to 2007. Participants in 2007 walked more than those in 2005. The proportion of current smoking and sodium/energy/protein excess was decreased from 2005 to 2007. In subgroup analysis, only hypertensive participants without diabetes revealed a decreasing trend of CKD. CONCLUSIONS The CKD prevalence was decreased from 2005 to 2007. Since increased diabetes and improved diabetic control neutralized their impact on CKD, improved BP was the fundamental reason for the decrease. Various health-related behaviors may have indirectly affected the decrease of CKD through their effect in controlling BP and diabetes.

Hypoxia-Inducible Factor Activation Protects the Kidney from Gentamicin-Induced Acute Injury

Gentamicin nephrotoxicity is one of the most common causes of acute kidney injury (AKI). Hypoxia-inducible factor (HIF) is effective in protecting the kidney from ischemic and toxic injury. Increased expression of HIF-1α mRNA has been reported in rats with gentamicin-induced renal injury. We hypothesizd that we could study the role of HIF in gentamicin-induced AKI by modulating HIF activity. In this study, we investigated whether HIF activation had protective effects on gentamicin-induced renal tubule cell injury. Gentamicin-induced AKI was established in male Sprague-Dawley rats. Cobalt was continuously infused into the rats to activate HIF. HK-2 cells were pre-treated with cobalt or dimethyloxalylglycine (DMOG) to activate HIF and were then exposed to gentamicin. Cobalt or DMOG significantly increased HIF-1α expression in rat kidneys and HK-2 cells. In HK-2 cells, HIF inhibited gentamicin-induced reactive oxygen species (ROS) formation. HIF also protected these cells from apoptosis by reducing caspase-3 activity and the amount of cleaved caspase-3, and -9 proteins. Increased expression of HIF-1α reduced the number of gentamicin-induced apoptotic cells in rat kidneys and HK-2 cells. HIF activation improved the creatinine clearance and proteinuria in gentamicin-induced AKI. HIF activation also ameliorated the extent of histologic injury and reduced macrophage infiltration into the tubulointerstitium. In gentamicin-induced AKI, the activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria, and structural damage through a reduction of oxidative stress, inflammation, and apoptosis in renal tubular epithelial cells.

Additional role of urine output criterion in defining acute kidney injury

BACKGROUND Diagnosis of acute kidney injury (AKI) has been a major concern due to its association with increased morbidity and mortality. However, the clinical implication of the urine output criterion (UOCr) in diagnosing AKI has not been fully established. METHODS We assessed the incidence of AKI among 1625 critically ill patients and analysed the overall survival rates based on the serum creatinine criterion (CrCr) and UOCr, both of which have been defined by the AKI Network (AKIN). RESULTS Within 7 days of admission, the risk rate of AKI was 57.0% and the rate determined by UOCr alone was 25.7%. AKI determined by the UOCr alone increased hazard ratios (HRs) for mortality; 1.81 (Stage 1), 2.96 (Stage 2) and 4.17 (Stage 3) compared to non-AKI. However, the difference in mortality between Stages 2 and 3 using the CrCr alone was not significant (P = 0.881). In patients with Stages 2 and 3 by the CrCr, the UOCr further separated the survival rates (P = 0.001 among the four UOCr stages). The diuretic dose did not alter the discriminative function of the UOCr for survival rates. However, 42.1% of non-AKI cases, as determined by the UOCr, were identified as AKI cases by the CrCr. CONCLUSION Although some AKI cases were not identified by the UOCr alone, the UOCr has an additional role in AKI staging, regardless of diuretic use.

Erythropoietin improves long-term outcomes in patients with acute kidney injury after coronary artery bypass grafting.

Previous studies reported the beneficial effect of erythropoietin (EPO) in acute injuries. We followed patients with and without acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and evaluated the effect of EPO on long-term outcome. We also assessed the efficacy of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. Seventy-one patients scheduled for elective CABG were randomly given either 300 U/kg of EPO or saline before CABG. The primary outcome was AKI, and the secondary outcome was the all-cause-mortality and composite of all-cause-mortality and end stage renal disease (ESRD). Twenty-one patients had AKI, 14 (66.7%) in the placebo group and 7 (33.3%) in the EPO group (P = 0.05). Also, uNGAL was higher in the patients with AKI than in those without AKI at baseline, 2, 4, 24, and 72 hr after CABG (P = 0.011). Among patients with AKI, 2-week creatinine (Cr) was not different from baseline Cr in the EPO group, but 2-week Cr was significantly higher than baseline Cr in the placebo group (P = 0.009). All-cause-mortality (P = 0.022) and the composite of all-cause-mortality and ESRD (P = 0.003) were reduced by EPO. EPO reduces all-cause-mortality and ESRD in patients with AKI, largely due to the beneficial effect of EPO on recovery after AKI.

Mild decrease in estimated glomerular filtration rate and proteinuria are associated with all-cause and cardiovascular mortality in the general population

BACKGROUND A recent collaborative meta-analysis by Kidney Disease: Improving Global Outcomes reported that an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an albumin-to-creatinine ratio of ≥ 10 mg/g were independent predictors for mortality in the general population. However, selection bias, heterogeneity of the cohorts and measurement issues could be limitations. METHODS We analyzed the relationship of eGFR and proteinuria with mortality in the Korean general population, represented by 112,115 participants, aged ≥ 20 years, who had a voluntary health check-up with homogenous calibration of creatinine measurement from 2003 to 2009. Proteinuria (trace or more) was determined by urine dipstick. RESULTS eGFR and proteinuria were independently associated with all-cause mortality (ACM) and cardiovascular mortality (CVM), and progressive increases in risks for mortality were noted according to eGFR level and the presence of proteinuria. Compared with eGFR 90-105 mL/min/1.73 m(2), hazard ratio (HRs) for ACM were 1.60 [95% confidence interval (CI) 1.12-2.30] for eGFR 60-74 mL/min/1.73 m(2) and 3.54 (2.20-5.68) for eGFR <60 mL/min/1.73 m(2) in participants with no proteinuria. In participants with proteinuria, HRs for ACM were 2.10 (1.41-3.12) for eGFR 75-89 mL/min/1.73 m(2), 2.30 (1.50-3.53) for eGFR 60-74 mL/min/1.73 m(2) and 3.77 (2.15-6.38) for eGFR <60 mL/min/1.73 m(2). Similar findings were observed for CVM. CONCLUSIONS eGFR <75 mL/min/1.73 m(2) and urine dipstick trace or more were independent risk factors of ACM and CVM. The risks of adverse outcomes are greater in the general population with mild renal impairment or mild proteinuria.

Serum phosphorus as a predictor of low-grade albuminuria in a general population without evidence of chronic kidney disease

BACKGROUND High levels of serum phosphorus, even within the normal range, have been associated with cardiovascular (CV) morbidity. Low-grade albuminuria (LGA) was demonstrated to be related to increased CV events in various study populations. The present study aimed to investigate the association between serum phosphorus levels and LGA in the general population. METHODS We examined the individuals who had undergone health inspections. We evaluated the correlation between serum phosphorus and LGA in 8953 participants (mean age, 47.4 years) with estimated glomerular filtration rates (eGFRs)≥60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratios (UACRs)<30 mg/g. Participants who underwent a colonoscopy were excluded. RESULTS The mean UACR was significantly higher in the uppermost quartile group of serum phosphorus concentrations than in other quartile groups. In the multivariate regression analysis, serum phosphorus remained an independent predictor of increased UACR (B=0.610, P<0.001). Subgroup analyses showed that this association was maintained irrespective of age, gender, presence of hypertension or diabetes, body mass index and eGFR. CONCLUSIONS In our population-based study, higher serum phosphorus was independently related to LGA in individuals without evidence of renal dysfunction. Further investigations are warranted to clarify the precise mechanism of the association between serum phosphorus and LGA.

Glycated haemoglobin and the incidence of end-stage renal disease in diabetics.

BACKGROUND The relationship between glycated haemoglobin and the incidence of end-stage renal disease (ESRD) in patients with diabetes remains uncertain, especially in those with decreased glomerular filtration rate (GFR). The aim of this study was to assess the appropriate HbA(1c) level for diabetics for minimizing the incidence of ESRD and all-cause mortality. METHODS A cohort of patients aged 25 years or older who had been treated for diabetes was generated from the Seoul National University Bundang Hospital database using diagnosis code and prescribed medication during 2004. The 4474 patients were classified into three groups according to the baseline HbA(1c) in 2004 (HbA(1c) < 6.50%, 6.50-7.49% and ≥ 7.50%; termed groups 1, 2 and 3, respectively). The outcomes were extracted from the database of Statistics Korea for mortality and registry in the Korean Society of Nephrology for ESRD incidence. RESULTS Ninety patients developed ESRD during 5.29 ± 1.22 years of mean follow-up period. Group 1 patients showed the lowest incidence of ESRD (P = 0.003). Compared with this group, the adjusted hazard ratio of ESRD was 2.915 and 4.219 in groups 2 and 3, respectively. The incidence of ESRD increased in patients with HbA(1c) ≥ 6.50% compared with the patients with HbA(1c) < 6.50%, regardless of GFR. However, HbA(1c) < 6.50% showed no benefit on ESRD development in patients older than 80 years and in patients with diabetic duration > 10 years. All-cause mortality was not associated with the level of HbA(1c). CONCLUSIONS HbA(1c) < 6.50% was associated with reduced development of ESRD in all patients and later stages of chronic kidney disease.

Higher hemoglobin level is associated with subtle declines in renal function and presence of cardiorenal risk factors in early CKD stages

BACKGROUND Patients with advanced renal dysfunction have comorbidities, including anemia, as a consequence of reduced production of erythropoietin. However, little is known about the renal response to early decreases in estimated glomerular filtration rate (eGFR) before the onset of anemia. We therefore investigated the hemoglobin concentration across subtle declines in renal function stratified by cardiorenal risk factors, in subjects with eGFR ≥50 mL/min/1.73 m(2). METHODS Based on the data from routine health checkups in tertiary university hospitals during the last 15 years, 145 865 adult subjects were identified. RESULTS Hemoglobin levels among eGFR Groups 2-6 (50 ≤ eGFR < 100 mL/min/1.73m(2)) were significantly higher compared to eGFR group ≥100 mL/min/1.73m(2) (P < 0.001), and the highest level of mean hemoglobin was seen at eGFR 50-59 mL/min/1.73m(2). The mean hemoglobin level of subjects with eGFR 50-59 mL/min/1.73m(2) and eGFR ≥ 100 mL/min/1.73m(2) were 13.36 [95% confidence interval (CI): 13.33-13.40] g/dL versus 12.92 (95% CI: 12.88-12.95) g/dL in women (P < 0.001); in men, 15.60 (95% CI: 15.57-15.63) g/dL versus 15.15 (95% CI: 15.11-15.18) g/dL (P < 0.001). Among each eGFR group, hemoglobin levels were higher in subjects with hypertension (P < 0.001 in both genders), diabetes mellitus (P < 0.001 in both genders) and components of MS (P < 0.003 in both genders) compared to subjects without these conditions. CONCLUSION Hemoglobin concentration may be slightly higher across subtle declines in renal function and the presence of cardiorenal risk factors in early CKD stages.

Associations of sodium intake with obesity, metabolic disorder, and albuminuria according to age

Sodium intake is associated with obesity and metabolic disorder in the general population. However, sodium intake is significantly reduced according to the decrease of energy intake in older adults although the prevalence of obesity is higher than younger adults. We evaluate the association of sodium excretion (UNa) with blood pressure, obesity, metabolic disorders, and albuminuria according to age. An observational study using data from the Korean National Health and Nutrition Examination Survey IV-V (2008–2011) was performed (N = 18,146). The 24 hour UNa was estimated from a single fasting urine sample.Participants aged≥75 years showed the highest risk for hypertension (HTN) in the highest quartile of UNa (1.769, 95% CI, 1.174–2.665), and the risks for HTN increased with advancing age. Obesity was not associated with UNa in participants aged≥75 years, and hypertriglyceridemia and body fat were not related to UNa in participants aged≥65 years, although these values were significantly associated with UNa in participants aged<65 years. Impaired fasting glucose (IFG) and insulin resistance (IR) were associated with UNa only in participants aged 20–39 years. The highest quartile of UNa showed a 3.777 fold increased risk for albuminuria in those aged 20–39 years (95% CI, 1.130–12.630), and a 1.885 fold increased risk (95% CI, 1.156–3.075) among participants aged 40–64 years. In participants aged≥65 years, albuminuria was not associated with UNa. In contrast with HTN, UNa was not associated with albuminuria, obesity, hypertriglyceridemia, IFG, and IR in older adults despite a strong association in younger adults.