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Hyoung Rae Kim,
Bo Young Nam,
Dong Wook Kim,
Min Woong Kang,
Jae-Hyun Han,
Mi Jung Lee,
Dong Ho Shin,
Fa Mee Doh,
Hyang Mo Koo,
Kwang Il Ko,
Chan Ho Kim,
Hyung Jung Oh,
Tae-Hyun Yoo,
Shin-Wook Kang, Dae Suk Han,
Seung Hyeok Han
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ABSTRACT: BACKGROUND: α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown. STUDY DESIGN: Post hoc analysis of a prospective cohort study. SETTING & PARTICIPANTS: 243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study. PREDICTOR: Baseline α-klotho levels. OUTCOMES: Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy. MEASUREMENTS: Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay. RESULTS: Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data (P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (β = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03). LIMITATIONS: Uncontrolled dietary phosphorus intake and use of frozen samples. CONCLUSIONS: This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings.
American Journal of Kidney Diseases 03/2013; · 5.43 Impact Factor
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Fa Mee Doh,
Tae-Ik Chang,
Hyang Mo Koo,
Mi Jung Lee,
Dong Ho Shin,
Chan Ho Kim,
Kwang Il Ko,
Hyung Jung Oh,
Tae-Hyun Yoo,
Shin-Wook Kang, Dae-Suk Han,
Seung Hyeok Han
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ABSTRACT: BACKGROUND: Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease (ESRD). Although statins exert pleiotropic effects, it is uncertain whether statin therapy improves insulin resistance in these patients. In this prospective randomized controlled trial, we aimed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis (PD). METHODS: Patients were randomized into a statin group (n = 35) or a control group (n = 35). The statin group received 10 mg per day of rosuvastatin for 6 months. We determined insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) index. Serum concentrations of adipokines such as adiponectin, leptin, and resistin were measured using enzyme-linked immunosorbent (ELISA) assay. As inflammatory markers, high sensitive C-reactive protein (hsCRP) and interleukin-6 were also measured. RESULTS: There were no significant differences in baseline characteristics between the two groups. Compared to baseline value, statin treatment significantly decreased HOMA-IR index from 2.37 ± 1.08 to 2.05 ± 0.82 (P = 0.014). There was a concordant decrease in hsCRP levels in the statin group (2.05 ± 1.57 to 1.21 ± 0.84 mg/L, P < 0.001), but such improvements were not observed in the control group. When between-group differences in these parameters were compared, hsCRP levels were more decreased in the statin group than in the control group (P = 0.021 for between-group difference), whereas HOMA-IR index was not (P = 0.189 for between-group difference). During this period, statin treatment did not result in the improved adipokine profiles. CONCLUSION: This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment. Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients.
Cardiovascular Drugs and Therapy 09/2012; · 3.13 Impact Factor
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Jung Tak Park,
Tae-Hyun Yoo,
Jwa-Kyung Kim,
Hyung Jung Oh,
Seung Jun Kim,
Dong Eun Yoo,
Mi Jung Lee,
Dong Ho Shin,
Seung Hyeok Han, Dae-Suk Han,
Shin-Wook Kang
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ABSTRACT: BACKGROUND: The leptin/adiponectin (L/A) ratio has been suggested to be an atherosclerotic index for diabetic patients and a useful marker of insulin resistance in patients with and without diabetes. Even though end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) are well characterized by abnormal adipocytokine metabolism, the significance of alterations in the L/A ratio is largely unexplored in these patients. In this prospective study, we investigated the associations of leptin, adiponectin, and the L/A ratio with clinical outcomes in nondiabetic PD patients. ♢ METHODS: The study included 131 stable nondiabetic ESRD patients who had been on PD for more than 3 months. Serum leptin and adiponectin levels were determined at baseline. Mortality was evaluated over a 5-year follow-up period. ♢ RESULTS: During the follow-up period, 22 patients died (16.8%), including 10 (45.5%) as a result of cardiovascular disease. The L/A ratio showed a significant positive correlation with body mass index [BMI (r = 0.47, p < 0.001)], high-sensitivity C-reactive protein (r = 0.32, p < 0.001), and triglycerides (r = 0.43, p < 0.001). In addition, we observed significant inverse correlations between the L/A ratio and percentage lean body mass (r = -0.30, p = 0.001) and high-density lipoprotein cholesterol (r = -0.31, p = 0.001). In contrast to individual leptin and adiponectin levels, the L/A ratio was found to be independently associated with an increased mortality risk (relative risk: 1.15; 95% confidence interval: 1.05 to 1.27; p = 0.003) even after adjustments for age and BMI. ♢ CONCLUSIONS: The L/A ratio might be better related to patient outcomes than adipocytokines are individually in nondiabetic patients undergoing PD.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 08/2012;
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ABSTRACT: In patients with end-stage renal disease (ESRD), circulating adipokine levels are increased due to decreased renal clearance, irrespective of obesity. However, whether adipokines play a role in the development of insulin resistance (IR) in non-obese ESRD patients is unknown. We conducted a cross-sectional study to identify factors associated with IR in 62 non-obese patients on peritoneal dialysis (PD). Non-obesity was defined as body mass index (BMI) <25 kg/m². IR was determined using homeostatic model assessment-IR (HOMA-IR). We also measured serum concentrations of adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hsCRP), and IL-6. The average BMI of the study patients was 21.6 kg/m². When patients were divided into two groups according to the median value of HOMA-IR, serum adiponectin levels were significantly lower in patients with HOMA-IR > 1.85 than in those with HOMA-IR ≤1.85, whereas serum concentrations of leptin and resistin did not differ between the two groups. In addition, log-transformed HOMA-IR was negatively correlated with adiponectin (γ = -0.464, P < 0.001) and log-transformed high-density lipoprotein cholesterol (γ = -0.250, P = 0.050) and positively correlated with age (γ = 0.334, P = 0.008) and triglyceride (γ = 0.392, P = 0.002). However, resistin, log-transformed leptin and log-transformed hsCRP were not associated with HOMA-IR. In a multiple linear regression model, adiponectin was independently associated with HOMA-IR (β = -0.023, P = 0.015). In conclusion, this study suggests that low circulating adiponectin levels might be involved in IR even in non-obese patients undergoing PD.
Endocrine Journal 05/2012; 59(8):685-95. · 2.03 Impact Factor
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ABSTRACT: Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD).
This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia.
In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 - 9.64) vs 0.48 (0 - 3.89) mL/min/1.73 m(2), P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = -0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = -0.345, P = 0.003), pulse pressure (γ = -0.341, P = 0.003), and age (γ = -0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017).
This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 03/2012; 32(2):149-58.
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Jwa-Kyung Kim,
Jeong Ho Kim,
Sang Choel Lee,
Ea Wha Kang,
Tae Ik Chang,
Sung Jin Moon,
Soo Young Yoon,
Tae-Hyun Yoo,
Shin-Wook Kang,
Kyu Hun Choi, Dae Suk Han,
Jeong Hae Kie,
Beom Jin Lim,
Hyeon Joo Jeong,
Seung Hyeok Han
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ABSTRACT: Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored.
A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration.
Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P<0.001). The risk of reaching the primary endpoint was significantly higher in the PR (P=0.04) and NR groups (P<0.001) than in the CR group. Among patients with NS, 24 (24%) underwent spontaneous remission (SR). SR occurred more frequently in female patients and in patients with serum creatinine levels ≤1.2 mg/dl and a >50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up.
This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.
Clinical Journal of the American Society of Nephrology 03/2012; 7(3):427-36. · 5.23 Impact Factor
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ABSTRACT: Protein-energy wasting (PEW) is prevalent among patients on dialysis and has emerged as an important risk factor for morbidity and mortality in these patients. Numerous factors, including inflammation, inadequate dialysis, insufficient nutrient intake, loss of protein during dialysis, chronic acidosis, hypercatabolic illness and comorbid conditions, are involved in the development of PEW. The causes and clinical features of PEW in patients on peritoneal dialysis and hemodialysis are comparable; assessment of the factors that lead to PEW in patients receiving peritoneal dialysis is important to ensure that PEW is managed correctly in these patients. For the past 20 years, much progress has been made in the prevention and treatment of PEW. However, the results of most nutritional intervention studies are inconclusive. In addition, the multifactorial and complicated pathogenesis of PEW makes it difficult to assess and treat. This Review summarizes the nutritional issues regarding the causes, assessment and treatment of PEW, with a focus on patients receiving peritoneal dialysis. In addition, an in-depth overview of the results of nutritional intervention studies is provided.
Nature Reviews Nephrology 01/2012; 8(3):163-75. · 7.09 Impact Factor
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ABSTRACT: Many studies have suggested clinical benefits of icodextrin in peritoneal dialysis (PD) patients regarding fluid management, glycaemic control and metabolic improvement. However, reports on whether icodextrin can improve patient and technique survival is sparse.
A total of 2163 patients from 54 centres in Korea who initiated PD from July 2003 to December 2006 were enrolled. Outcomes data were retrieved retrospectively from the Baxter Korea database. Among these patients, 641 patients who had been prescribed icodextrin for >50% of their PD duration were defined as the 'icodextrin' group and the remaining 1522 patients as the 'non-icodextrin' group. Propensity score matching yielded 640 matched pairs of patients. We compared all-cause mortality and technique failure rates between the two groups.
There were no significant differences in age, gender, diabetes, cardiovascular comorbidity, socioeconomic status, biocompatible solution use in short dwells or centre experience between the two groups. Death occurred in 92 (14.4%) patients in the icodextrin group compared with 128 (20.0%) in the non-icodextrin group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.53-0.90; P = 0.006]. In addition, icodextrin use was associated with a significantly lower risk of technique failure (HR, 0.60; 95% CI, 0.40-0.92; P = 0.018). The icodextrin group had fewer technique failures due to non-compliance compared with the non-icodextrin group whereas peritonitis- or ultrafiltration failure-related technique failure was not different between the two groups.
This study further supports previous findings of long-term utilization of icodextrin solution improving patient and technique survival in PD patients. To confirm these results, a large randomized prospective study is warranted.
Nephrology Dialysis Transplantation 10/2011; 27(5):2044-50. · 3.40 Impact Factor
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ABSTRACT: IgA nephropathy (IgAN) can be complicated by nephrotic syndrome. Because the spontaneous resolution of heavy proteinuria is rare, corticosteroid therapy should be considered in such cases, particularly when IgAN is combined with minimal-change disease. Here, we report our experience of spontaneous remission of nephrotic syndrome in patients with IgAN and the long-term outcomes of these patients.
Two hundred and thirty-three patients with biopsy-proven IgAN were enrolled between January 2001 and March 2009. Demographic, clinical and laboratory data were collected retrospectively based on medical records. In addition, pathologic findings were reviewed for glomerular and tubulointerstitial lesions. Outcome data for complete or partial remission, spontaneous remission, relapse, deterioration of renal function, and end-stage renal disease were recorded.
Twenty-four patients (10.3%) presented nephrotic syndrome. Among them, five patients underwent spontaneous remission within 6 months after the presentation of nephrotic syndrome. Interestingly, spontaneous remission occurred even in two patients who had elevated serum creatinine levels and advanced renal damage. During follow-up, neither recurrence nor relapse occurred, and no patients showed progressive deterioration of kidney function. Conclusions. This study suggests that spontaneous remission of nephrotic syndrome may occur in any stage of IgAN and carries a favourable long-term outcome without relapse. Given the possibility of under-reported cases, large-scale studies are required, and careful attention should be paid to such complicated cases.
Nephrology Dialysis Transplantation 05/2011; 26(5):1570-5. · 3.40 Impact Factor
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Seung-Jae Kwak,
Jisun Paeng,
Do Hee Kim,
Sun Ha Lee,
Bo-Young Nam,
Hye Young Kang,
Jin Ji Li,
Dong-Sub Jung,
Seung Hyeok Han,
Dong-Ryeol Ryu,
Jung Tak Park,
Tae Ik Chang,
Tae-Hyun Yoo, Dae Suk Han,
Shin-Wook Kang
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ABSTRACT: The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
Apoptosis 03/2011; 16(5):478-90. · 4.07 Impact Factor
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ABSTRACT: Statins and angiotensin receptor blockers (ARBs) are known to improve vascular dysfunction in patients with chronic kidney disease. However, these effects have been inconsistent in dialysis patients. Moreover, it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients.
We conducted a prospective open randomized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis (PD). Initially, all patients received 80 mg/day of valsartan for 6 months. Excluding 10 patients who dropped out during this period, patients were randomly assigned to continue ARB treatment alone (n = 57) or to receive 10 mg/day of rosuvastatin (n = 57) added to ARB for the next 6 months. To assess vascular function, endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV), respectively.
Compared to baseline values, ARB treatment for the first 6 months significantly improved FMD% (2.97 ± 2.64 to 3.57 ± 2.58 %, P < 0.001). In addition, there was a small but significant decrease in baPWV during this period (1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s, P = 0.048). After randomization, add-on treatment further improved FMD% (3.57 ± 2.73 to 4.24 ± 2.77 %, P = 0.003), whereas ARB monotherapy did not (P = 0.02 for between-group difference). Further slight improvement in baPWV (1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s, P = 0.021) was observed only in the combined treatment group (P = 0.28 for between-group difference).
Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients. However, whether such limited improvements can lead to better clinical outcomes requires further investigation.
Nephrology Dialysis Transplantation 03/2011; 26(11):3722-8. · 3.40 Impact Factor
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Seung Hyeok Han,
Sung Hee Choi,
Bong Jun Cho,
Yenna Lee,
Soo Lim,
Young Joo Park,
Min Kyung Moon,
Hong Kyu Lee,
Shin-Wook Kang, Dae Suk Han,
Young-Bum Kim,
Hak C Jang,
Kyong Soo Park
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ABSTRACT: Fibroblast growth factor-21 (FGF-21) is a new metabolic regulator, which is related to antiobesity and insulin sensitivity in vivo. However, the clinical implication of FGF-21 is poorly understood. To investigate whether FGF-21 may play a role as a metabolic regulator in patients with end-stage renal disease, we measured serum concentrations of FGF-21, inflammatory markers, and metabolic parameters in healthy people (n = 63) and nondiabetic patients receiving peritoneal dialysis (PD, n = 72). The patients were treated with angiotensin receptor blocker for 6 months, and the changes in FGF-21 concentration and metabolic parameters were assessed. Compared with controls, serum FGF-21 concentration was 8 times higher in patients undergoing PD (754.2 ± 463.5 vs 86.9 ± 60.2 pg/mL, P < .001). In controls, only lipid parameters correlated positively with FGF-21 concentration. In contrast, inflammatory markers (interleukin-6, fibrinogen, high-sensitivity C-reactive protein) and homeostasis model assessment of insulin resistance (HOMA-IR) correlated positively and residual renal function correlated inversely with serum FGF-21 concentration in PD patients. In a multivariate analysis adjusting these factors, residual renal function, HOMA-IR, and fibrinogen concentration were independent determinants of serum FGF-21 concentration. After 6-month angiotensin receptor blocker treatment, serum FGF-21 concentration declined significantly by 13% and HOMA-IR and inflammatory markers improved in PD patients. These findings suggest that FGF-21 may play a role in insulin resistance in patients with end-stage renal disease.
Metabolism: clinical and experimental 11/2010; 59(11):1656-62. · 2.59 Impact Factor
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ABSTRACT: Although most cases of immunoglobulin A (IgA) nephropathy are idiopathic, several diseases are associated with IgA nephropathy. Of these, chronic liver disease resulting from hepatitis B or C virus infection has been reported as a secondary cause of IgA nephropathy. Recently, hepatitis A virus (HAV)-associated kidney disease has received attention because acute kidney injury can occur as a complication of HAV infection, generally caused by acute tubular necrosis or interstitial nephritis. However, unlike IgA nephropathy related to hepatitis B or C, HAV-associated IgA nephropathy is extremely rare and long-term outcomes have not been reported yet. We describe a case of spontaneous remission of IgA nephropathy associated with serologically documented HAV infection. The patient presented with microhematuria and moderate proteinuria, but acute kidney injury did not occur during active hepatic injury. Kidney biopsy specimens clearly showed mesangial IgA deposits with intact tubules and interstitium. Serum liver enzyme levels returned to reference values 1 month after the onset of acute hepatitis, but urinary protein excretion remained increased. Approximately 1 year later, urinary abnormalities were resolved and a second biopsy showed no mesangial IgA deposits. These findings suggest that IgA nephropathy can transiently accompany HAV infection, but may not progress to chronic glomerulonephritis after recovery from HAV.
American Journal of Kidney Diseases 10/2010; 56(6):1163-7. · 5.43 Impact Factor
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ABSTRACT: End-stage renal disease patients have a higher risk for developing cancer. Although several causes for this increased risk have been proposed, the risk factors for cancer development in this population have not been elucidated. The aim of this study was to determine whether metabolic derangements, including insulin resistance and altered adipokines, increase the risk of developing malignancies in peritoneal dialysis (PD) patients, who are vulnerable to metabolic disorders because of excessive glucose absorbed from the dialysate. Study subjects comprised 106 nondiabetic PD patients who had been on PD for a minimum of 3 months with no overt malignancy. Baseline anthropometry, fasting glucose, insulin, and adiponectin were measured. The development of malignancy was evaluated during the follow-up period. During the mean follow-up of 47.0 ± 23.7 months, malignancy occurred in 15 patients (14.2%). The most common site of cancer was the kidney (26.7%), followed by thyroid (13.3%) and stomach (13.3%). Baseline insulin levels and homeostasis model assessment of insulin resistance were significantly higher, whereas plasma adiponectin levels were significantly lower, in patients who developed malignancy. Cox proportional hazards analysis revealed that insulin levels, homeostasis model assessment of insulin resistance, and lower adiponectin were independent predictors of malignancy. These findings demonstrate that insulin resistance and lower adiponectin levels could be risk factors for malignancy in nondiabetic PD patients.
Metabolism: clinical and experimental 03/2010; 60(1):121-6. · 2.59 Impact Factor
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Sun Ha Lee,
Bo Young Nam,
Ea Wha Kang,
Seung Hyeok Han,
Jin Ji Li,
Do Hee Kim,
Seung Hye Kim,
Seung-Jae Kwak,
Jung Tak Park,
Tae Ik Chang,
Tae-Hyun Yoo, Dae Suk Han,
Shin-Wook Kang
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ABSTRACT: Previous studies have demonstrated that AST-120 (Kremezin((R))), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function.
Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production.
Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05).
In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.
Nephrology Dialysis Transplantation 02/2010; 25(7):2134-41. · 3.40 Impact Factor
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ABSTRACT: A low-protein diet (LPD) is a conservative treatment in patients with chronic kidney disease (CKD) to improve uremic symptoms and slow the progression of renal dysfunction. However, the deleterious effects of protein restriction on nutritional status have raised concern. We investigated whether ketoanalogs supplementation in CKD patients who had training on LPD retards the progression of CKD and maintains nutritional status.
Data were collected retrospectively from 120 consecutive patients in the CKD stages III and IV. Firstly all patients were restricted to LPD alone for 6 months (LPD alone), and then ketoanalogs of essential amino acids (KA) were supplemented for 6 months.
The adequate LPD had not achieved in both periods. The declining slopes of glomerular filtration rate (GFR) during the LPD + KA period were significantly lower than those during the LPD alone period. This improvement in GFR was apparent in both subjects with diabetics and non-diabetic patients. Mean serum total cholesterol levels decreased in LPD + KA compared with LPD alone period. However, serum albumin levels did not change. Responders showed a higher prevalence of diabetes and higher serum albumin levels during the LPD alone period. Multivariate analysis revealed that responsiveness to LPD + KA was independently related to diabetes (p = 0.006) and high serum albumin levels (p = 0.011) in the LPD alone period.
KA supplementation on over LPD delayed the progression of CKD without deteriorating nutritional status, and initial serum albumin levels could be an independent factor.
Nephrology 12/2009; 14(8):750-7. · 1.31 Impact Factor
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Hoon Young Choi,
Jung Eun Lee,
Seung Hyeok Han,
Tae Hyun Yoo,
Beom Seok Kim,
Hyeong Cheon Park,
Shin-Wook Kang,
Kyu Hun Choi,
Sung Kyu Ha,
Ho Yung Lee, Dae-Suk Han
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ABSTRACT: Cardiovascular disease is the main cause of mortality in end-stage renal disease (ESRD) patients. Recent studies have indicated that non-traditional risk factors such as endothelial dysfunction (ED), chronic inflammation and protein-energy wasting (PEW) may contribute significantly to the increased cardiovascular mortality among dialysis patients. To further ascertain this association, we carried out a cross-sectional assessment of nutritional status, inflammatory markers and endothelial dysfunction in peritoneal dialysis (PD) patients.
We measured ED functionally by flow-mediated vasodilatation (FMD) using doppler ultrasonography and biochemically by soluble intercellular adhesion molecule-1 (sICAM-1) in 105 stable PD patients and 32 age- and sex-matched healthy controls. We also simultaneously measured inflammatory markers and performed a subjective global assessment (SGA) of their nutritional status using a seven-point scoring scale. Subjects were subgrouped according to their nutritional and inflammatory status.
In PD patients, FMD was markedly lower (9.9 +/- 4.8% vs. 16.4 +/- 4.8%, P < 0.05), and sICAM-1 was significantly higher than those in controls. The malnourished patients had significantly lower FMD (8.4+/-4.6% vs. 10.8+/-4.7%, P <0.05) and higher sICAM-1 than the nourished patients. The inflamed group had significantly lower FMD (7.1 +/- 3.8 vs.11.1 +/- 4.6%, P < 0.05) and higher sICAM-1 than the non-inflamed group. In all PD patients, lean body mass/body weight %, albumin and SGA correlated positively with FMD (r = +0.207, r = +0.224, r = +0.285, P < 0.05). However, age, log high sensitivity C-reactive protein (hsCRP), log IL-6 and sICAM-1 were negatively correlated with FMD (r = -0.275, r = -0.361, r = -0.360, r = -0.271, P < 0.05). A multiple regression analysis showed that log hsCRP was an independent factor affecting FMD. Endothelial function, demonstrated as FMD and sICAM-1 in the nourished PD patients without inflammation, was well preserved compared to other subgroups.
Our data suggest that chronic inflammation and PEW are closely linked to ED in PD patients.
Nephrology Dialysis Transplantation 11/2009; 25(4):1266-71. · 3.40 Impact Factor
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Sang Choel Lee,
Seung Hyeok Han,
Jin Ji Li,
Sun Ha Lee,
Dong-Sub Jung,
Seung-Jae Kwak,
Seung Hye Kim,
Dong Ki Kim,
Tae-Hyun Yoo,
Jin Hyun Kim,
Se-Ho Chang, Dae Suk Han,
Shin-Wook Kang
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ABSTRACT: Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose-treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose-treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.
Kidney International 09/2009; 76(8):838-48. · 6.61 Impact Factor
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Jung Tak Park,
Tae Ik Chang,
Dong Ki Kim,
Jung Eun Lee,
Hoon Young Choi,
Hyun Wook Kim,
Jae Hyun Chang,
Sun Young Park,
Eunyoung Kim,
Tae-Hyun Yoo, Dae-Suk Han,
Shin-Wook Kang
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ABSTRACT: Metabolic syndrome is associated with higher morbidity and mortality in the general population, but the corresponding effects in patients on dialysis have not been clearly defined. In this study, we prospectively investigated the effect of metabolic syndrome and its individual components on outcome in non-diabetic peritoneal dialysis (PD) patients. Method. The study subjects included 106 stable non-diabetic PD patients who had been on PD for >3 months. We measured baseline characteristics, blood pressure, fasting blood glucose, lipid profiles and high-sensitivity CRP (hsCRP), and defined metabolic syndrome using the modified National Cholesterol Education Program (Adult Treatment Panel III) criteria. Mortality, technical failure and hospitalization were evaluated during the follow-up period.
Metabolic syndrome was present in 50 patients (47.2%), and these showed higher baseline hsCRP levels (0.67; 95% CI: 0.50-0.94 versus 1.78 mg/dl; 95% CI: 1.21-2.57; P < 0.001). Patients with metabolic syndrome experienced significantly lower 5-year survival rates than patients without (90% versus 67%, P = 0.02), although these groups did not differ in peritonitis rates, technical failure or hospitalization. A Cox proportional hazards analysis identified the following as predictors of mortality: metabolic syndrome (RR: 3.39; 95% CI: 1.16-9.94; P = 0.02), baseline albumin (RR: 0.06; 95% CI: 0.01-0.30; P = 0.001) and baseline hsCRP levels (RR: 1.14; 95% CI: 1.07-1.22; P < 0.001).
Metabolic syndrome is prevalent and is a risk factor influencing long-term survival in non-diabetic PD patients.
Nephrology Dialysis Transplantation 09/2009; 25(2):599-604. · 3.40 Impact Factor
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Sun Young Park,
Jae Hyun Chang,
Hyun-Wook Kim,
Dong Ki Kim,
Eun Young Kim,
Jung Tak Park,
Tae Ik Chang,
Jung Won Park,
Hyeon Joo Jeong, Dae-Suk Han,
Shin-Wook Kang
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ABSTRACT: Renal involvement in Churg-Strauss syndrome (CSS) is not uncommon, but nephrotic syndrome is rarely reported in patients with CSS. A 25-year-old woman with a long history of bronchial asthma presented to our hospital with a chief complaint of generalized edema. Laboratory studies revealed normocytic normochromic anemia, marked eosinophilia, positive anti-neutrophil cytoplasmic antibody, hypoalbuminemia, and hypercholesterolemia. Urinalysis showed heavy proteinuria (4+) without significant casts. The 24-hour urinary protein excretion was 6.5 g with a selective index of 0.35. Echocardiography and X-ray of the paranasal sinuses suggested restrictive cardiomyopathy and maxillary sinusitis, respectively. Diagnoses of CSS and nephrotic syndrome were made on the basis of clinical and laboratory findings. Renal biopsy was performed, and pathologic findings revealed focal segmental glomerulosclerosis with mesangiolysis. The patient's clinical symptoms and proteinuria improved markedly after combined treatment with corticosteroids and cyclophosphamide. Herein, we report a case of nephrotic syndrome in a patient with CSS.
Rheumatology International 09/2009; 30(10):1385-8. · 1.88 Impact Factor
