Nam Ju Heo

Risk factors for consequent kidney impairment and differential impact of liver transplantation on renal function

BACKGROUND Chronic kidney disease (CKD) develops frequently after liver transplantation (LTx), and it is important to identify and correct risk factors that negatively affect kidney function. Risk factors have not been well evaluated in Asian countries where hepatitis B virus (HBV) infection is a dominant cause. METHODS Four hundred thirty-one Korean recipients who underwent LTx between 1997 and 2008 were analysed. CKD was defined as a sustained decrease in estimated glomerular filtration rate (eGFR) of <60 (mL/min/1.73 m(2)) for at least three consecutive months using an abbreviated Modification in Renal Disease (MDRD) formula. RESULTS Eighty percent of the patients had HBV-related underlying diseases. The recipients whose pretransplant eGFR had been low (<30 mL/min/1.73 m(2)) improved their renal function after LTx, but significant functional decline occurred in recipients whose pretransplant eGFR was high (>or=60 mL/min/1.73 m(2)). A multivariate Cox regression analysis revealed that the overall risk of CKD development (eGFR < 60 mL/min/1.73 m(2)) was associated with old age of recipients, cyclosporine, posttransplant acute renal failure (ARF), cause [calcineurin inhibitor (CNI) nephrotoxicity] and severity of posttransplant ARF, low pretransplant eGFR, pretransplant hepatorenal syndrome, pretransplant proteinuria, high Child-Pugh score and high Model for End-Stage Renal Disease (MELD) score. Especially in recipients whose pre-operative eGFR was high (>or=60 mL/min/1.73 m(2)), rapid progression of kidney disease was associated with high tacrolimus level, non-HBV disease, posttransplant ARF, cause (CNI nephrotoxicity) and severity of posttransplant ARF and Child-Pugh score. CNI toxicity and focal segmental sclerosis, but not immune-complex disease, were revealed as significant contributors to CKD after LTx in HBV recipients. CONCLUSION Judicious use of CNIs should be applied to liver recipients to prevent kidney dysfunction.

Visceral obesity is associated with microalbuminuria in nondiabetic Asians

Microalbuminuria is an indicator of renal disease and is known to be related to obesity. The aim of this study is to investigate the association between the cross-sectional area of visceral adipose tissue (VAT) and the prevalence of microalbuminuria. We conducted a cross-sectional study of 1154 subjects who underwent routine checkups, including computed tomography (CT) scans of abdominal adipose tissue. We used the lowest tertile as a reference of abdominal fat. The highest tertile of VAT was related to the highest prevalence of microalbuminuria (odds ratio (OR): 1.96; 95% CI: 1.12–3.43). Subcutaneous adipose tissue (SAT) was not associated with microalbuminuria. In men, the highest tertile for VAT was associated with the highest prevalence of microalbuminuria (OR: 2.74; 95% CI: 1.44–5.22). In women, VAT or SAT was not associated with microalbuminuria. In nondiabetic subjects, the highest tertile for VAT was associated with the highest prevalence of microalbuminuria (OR: 2.23; 95% CI: 1.15–4.32). Among subjects without metabolic syndrome or with body mass index <25 kg m−2, the highest tertile for VAT was associated with microalbuminuria in age- and sex-adjusted model, respectively (OR: 1.62; 95% CI: 1.01–2.31; OR: 2.21; 95% CI: 1.05–4.65). The analysis of the association of VAT and insulin resistance (IR) indicated that a higher VAT was associated with a higher IR (highest tertile for VAT—OR: 2.91; 95% CI: 1.70–4.96). In conclusion, the highest VAT of the current study was significantly correlated with the highest prevalence of microalbuminuria, even in traditionally low-risk subjects without diabetes, and this association is potentially related with a higher IR.

Potassium Intake and the Prevalence of Metabolic Syndrome: The Korean National Health and Nutrition Examination Survey 2008–2010

Lower potassium intake is considered to be correlated with diabetes incidence. However, few studies have investigated the effect of potassium intake on metabolic syndrome (MetS). Data was taken from the Korean National Health and Nutritional Examination Survey (2008–2010) using weighted adjustment. MetS was defined as per the revised National Cholesterol Education Program criteria. Homeostasis model assessment indices were calculated to diagnosis insulin resistance (IR). A total of 16,637 participants (44±0.25 years) were included. Women ingested lower amounts of potassium (2.71±0.02 g/day) than men (3.45±0.03 g/day). A curvilinear association between potassium intake and MetS prevalence was found among women. Women with less than the Adequate Intake (4.7 g/day) of potassium had an 11% risk reduction for MetS (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.82–0.96; P = 0.004) and a 10% risk reduction for IR (OR, 0.90; 95% CI, 0.82–0.99; P = 0.026) for every 1 g/day potassium increase. Compared with the reference group (3.5–4.5 g/day), potassium intake was inversely associated with an increased risk of MetS (1.5–2.5 g/day; OR, 1.29; 95% CI, 1.02–1.63; P = 0.035; <1.5 g/day; OR, 1.40; 95% CI, 1.06–1.85; P = 0.017) and IR (<1.5 g/day; OR, 1.36; 95% CI, 1.05–1.76; P = 0.021). This relationship was more prominent in postmenopausal women, but not observed among men. Higher potassium intake is significantly associated with a lower MetS prevalence in women, and IR is believed to be connected.

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.

Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria

AIM To investigate the relationship between Helicobacter pylori (H. pylori) seropositivity and the presence of microalbuminuria. METHODS Between December 2003 and February 2010, asymptomatic individuals who visited the Seoul National University Healthcare System Gangnam Center for a routine check-up and underwent tests for H. pylori immunoglobulin G antibodies and urinary albumin to creatinine ratio (UACR) were included. All study subjects completed a structured questionnaire, anthropometric measurements and laboratory tests. Anti-H. pylori immunoglobulin G was identified using an enzyme-linked immunosorbent assay kit. A random single-void urine sample, collected using a clean-catch technique, was obtained to determine the UACR. The presence of microalbuminuria was defined as a UACR from 30 to 300 μg/mg. The presence of diabetes mellitus (DM) was defined as either a fasting serum glucose level greater than or equal to 126 mg/dL or taking anti-diabetic medication. Multiple logistic regression analysis was performed to identify the risk factors. The dependent variable was microalbuminuria, and the independent variables were the other study variables. RESULTS A total of 2716 subjects (male, 71.8%; mean age, 54.9 years) were included. Among them, 224 subjects (8.2%) had microalbuminuria and 324 subjects (11.9%) had been diagnosed with DM. Subjects with microalbuminuria had a significantly higher H. pylori seropositivity rate than subjects without microalbuminuria (60.7% vs 52.8%, P = 0.024). Multivariate analysis after adjustment for age, body mass index (BMI), waist circumference, and glucose and triglyceride levels showed that H. pylori seropositivity was significantly associated with microalbuminuria [odds ratio (OR), 1.40, 95% CI, 1.05-1.89, P = 0.024]. After the data were stratified into cohorts by glucose levels (≤ 100 mg/dL, 100 mg/dL < glucose < 126 mg/dL, and ≥ 126 mg/dL or history of DM), H. pylori seropositivity was found to be significantly associated with microalbuminuria in diabetic subjects after adjusting for age, BMI and serum creatinine level (OR, 2.21, 95% CI, 1.20-4.08, P = 0.011). In addition, the subjects were divided into five groups. Those without microalbuminuria (an UACR of < 30 μg/mg) were divided into four groups in accordance with their UACR values, and subjects with microalbuminuria comprised their own group. Notably, H. pylori seropositivity gradually increased with an increase in UACR (P = 0.001) and was highest in subjects with microalbuminuria (OR, 2.41, 95% CI, 1.14-5.11). This suggests that H. pylori seropositivity is positively associated with microalbuminuria in diabetic subjects. CONCLUSION H. pylori seropositivity was independently associated with microalbuminuria, and the prevalence of H. pylori seropositivity was associated with the severity of UACR in diabetic subjects.

CRP Level and HDL Cholesterol Concentration Jointly Predict Mortality in a Korean Population

BACKGROUND C-reactive protein (CRP) and high-density lipoprotein (HDL) cholesterol are well-known cardiovascular predictors. However, the joint effect of these parameters on long-term mortality has not been established. METHODS We studied a total of 92,500 subjects older than 20 years who underwent routine health examination at the three health care centers affiliated with Seoul National University. High-sensitivity CRP and the lipid profile were obtained at baseline. Subjects were followed for a median of 45.5 months. Mortality data were obtained from the National Statistics Office of Korea. RESULTS There were 649 deaths (0.7%) during the follow-up. The leading cause of death was cancer. The subjects who died were significantly older, had a male predominance, and had increased levels of inflammatory markers. A significant mortality difference was identified according to the CRP and HDL cholesterol levels. Considering both parameters jointly, subjects with a CRP ≥1.4 mg/L (highest quartile) and HDL cholesterol <45 mg/dL (lowest quartile) were at the highest risk for all-cause mortality, even after adjusting for covariates (hazard ratio 2.29, 95% confidence interval, 1.83~2.87). After matching on the propensity score, 6304 subjects with a high CRP and low HDL cholesterol were at high risk of death (hazard ratio 2.52, 95% confidence interval, 1.59~4.01). Interestingly, the joint effect of CRP and HDL cholesterol was observed for cardiovascular as well as cancer-related mortality prediction. CONCLUSIONS Elevated CRP and low HDL cholesterol jointly contribute to the prediction of all-cause, cancer, and cardiovascular mortality in Koreans. The interactive relationship between them in mediating inflammatory processes might explain these results.

Effects of potassium on expression of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy

Dietary potassium is an important modulator of systemic blood pressure (BP). The purpose of this study was to determine whether dietary potassium is associated with an altered abundance of major renal sodium transporters that may contribute to the modulation of systemic BP. A unilateral nephrectomy (uNx) was performed in male Sprague-Dawley rats, and the rats were fed a normal-salt diet (0.3% NaCl) for 4 wk. Thereafter, the rats were fed a high-salt (HS) diet (3% NaCl) for the entire experimental period. The potassium-repleted (HS+KCl) group was given a mixed solution of 1% KCl as a substitute for drinking water. We examined the changes in the abundance of major renal sodium transporters and the expression of mRNA of With-No-Lysine (WNK) kinases sequentially at 1 and 3 wk. The systolic BP of the HS+KCl group was decreased compared with the HS group (140.3 ± 2.97 vs. 150.9 ± 4.04 mmHg at 1 wk; 180.3 ± 1.76 vs. 207.7 ± 6.21 mmHg at 3 wk). The protein abundances of type 3 Na(+)/H(+) exchanger (NHE3) and Na(+)-Cl(-) cotransporter (NCC) in the HS+KCl group were significantly decreased (53 and 45% of the HS group at 1 wk, respectively; 19 and 8% of HS group at 3 wk). WNK4 mRNA expression was significantly increased in the HS+KCl group (1.4-fold of control at 1 wk and 1.9-fold of control at 3 wk). The downregulation of NHE3 and NCC may contribute to the BP-attenuating effect of dietary potassium associated with increased urinary sodium excretion.

Differential white blood cell count and all-cause mortality in the Korean elderly.

The circulating white blood cell (WBC) count has been considered a good biomarker of systemic inflammation, but the predictive value of this inexpensive and universally obtained test result has not been fully explored in the elderly. The objective of this study was to assess the independent association of WBC count and its individual components with mortality in an elderly population. We studied a total of 9996 participants (age ≥65 years) who underwent routine health examinations at the 2 healthcare centers affiliated with Seoul National University. Mortality data were obtained from the National Statistics Office of Korea. The mean age of the study population was 69.7 (SD 4.3) years, and 5491 of the subjects (54.9%) were male. The median length of follow-up was 44.9 months (range, 1.2-78.7 months). There were 118 deaths (1.2%) during the follow-up period. The leading cause of death was cancer. Compared with the survivors, the deceased subjects were older, predominantly male, had increased levels of inflammatory markers, and had poor nutritional status. A significant difference in mortality was identified among patients in different WBC and WBC subtype quartile groups. Cox proportional hazards analysis indicated that monocyte count (HR: 5.18, 95% CI: 2.44-11.02) was a strongest predictor of all-cause mortality than total WBC count (HR: 1.57, 95% CI: 0.88-2.80), granulocyte count (HR: 2.11, 95% CI: 1.15-3.88), and lymphocyte count (HR: 1.11, 95% CI: 0.66-1.86), even after adjusting for possible confounding variables. Monocyte counts were associated with an increased risk of cardiovascular and cancer-related mortality in the elderly population. In conclusion, the total WBC count is an independent predictor of mortality in older adults, but the monocyte subtype provides greater predictive ability.

Changes in the Sodium and Potassium Transporters in the Course of Chronic Renal Failure

Background: In chronic renal failure (CRF), residual nephrons can increase their excretion of sodium (Na) and potassium (K). However, the mechanisms of renal Na and K regulation in late-stage CRF have not been clearly investigated. Methods: We examined altered expression of major renal Na and K transporters in Sprague-Dawley rats at 4 and 12 weeks after a 5/6 nephrectomy. Results: CRF rats were azotemic and had gradually increased levels of urinary Na and K excretion over time. At 4 weeks, the abundance of Na-K-2Cl cotransporter (NKCC2), and Na-Cl cotransporter (NCC) in CRF rats increased significantly (477 and 222% of the control, respectively). In contrast, expression of NKCC2 and NCC decreased markedly at 12 weeks (55.4 and 30.8%, respectively). Expression of epithelial Na channel-α increased throughout the whole period. The abundance of renal outer medullary K-channel (ROMK) and Na-K-ATPase did not decrease at 4 weeks, but it was reduced at 12 weeks. Conclusion: We suggest that increased urinary Na excretion in late-stage CRF may be associated with decreased expression of renal Na transporters except ENaC compared to early-stage CRF, and that increased urinary K excretion in the late stage of CRF may not be related to expression of ROMK.

Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function

BACKGROUND High serum phosphorus levels are associated with cardiovascular morbidity and mortality in kidney disease. Although serum phosphorus levels possibly influence on mortality in individuals without kidney disease, this is uncertain because of the variable sex- and age-based distribution of serum phosphorus levels. STUDY DESIGN Observational cohort study. SETTING & PARTICIPANTS Clinical and biochemical data were collected from 138,735 adults undergoing routine health checkups in 3 tertiary hospitals. Individuals with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urine dipstick albumin ≥ 1+ were excluded. PREDICTOR Sex-specific quartiles of serum phosphorus and sex. OUTCOMES All-cause mortality. RESULTS The study included 92,756 individuals. Generally, women showed higher serum phosphorus levels than men. In women, serum phosphorus levels increased with age until 60 years old, then decreased with age. Men with higher serum phosphorus levels were younger and less likely to have hypertension, whereas women with higher serum phosphorus levels were older and more likely to have diabetes and hypertension. During a median follow-up of 75 months, 1,646 participants died. In the overall population, higher serum phosphorus levels were an independent predictor for all-cause mortality after adjustment (adjusted HR for the highest vs. lowest quartile, 1.34; 95% CI, 1.15-1.56; P<0.001). We observed that this increased risk was present in men but not in women (adjusted HR of 1.43 [95% CI, 1.22-1.68] vs. 1.01 [95% CI, 0.76-1.33]), but interaction by sex was not significant (P=0.8). LIMITATIONS A single phosphorus measurement and low power to test for interactions by sex and age. CONCLUSIONS We demonstrated that higher serum phosphorus levels influenced all-cause mortality in individuals with normal kidney function. Our findings suggest that the association may differ by sex, but future studies with adequate power to test for effect modification are needed to confirm our findings.