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ABSTRACT: INTRODUCTION: Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated. METHODS: Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008-2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables. RESULTS: Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019-1.777; P=0.037); 4th quartile, 1.52 (1.140-2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224-3.160; Ptrend=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses. DISCUSSION: The present study shows that high cadmium exposure is associated with a risk of hematuria.
Environmental Research 05/2013; · 3.40 Impact Factor
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ABSTRACT: Background: Previous epidemiological studies have focused on the prevalence of primary glomerulonephritis (GN), but few have explored long-term patient outcomes. This study was conducted to investigate the long-term patient and renal outcomes of primary GN. Methods: A total of 1,943 biopsy-proven primary GN patients were included. The outcomes were mortality and end-stage renal disease (ESRD) progression. The relative mortality rate was expressed by the standardized mortality ratio (SMR) and the 95% confidence interval (CI). Results: During the median follow-up of 90 months, 325 (16.7%) patients progressed to ESRD and 164 (8.4%) patients died. Patients with minimal change disease exhibited the best renal and patient outcomes, whereas those with membranoproliferative GN had the worst. IgA nephropathy patients appeared to have a good survival rate in spite of their considerable progression to ESRD, and focal segmental glomerulosclerosis patients showed poor renal and patient outcomes. Mortality was 67% higher in primary GN patients than in the age- and sex-matched general population (SMR, 1.67; 95% CI, 1.42-1.95). The difference was more prominent in women (SMR, 2.95; 95% CI, 2.27-3.77) than in men (SMR, 1.31; 95% CI, 1.07-1.60). Renal risk factors, e.g. hypertension, proteinuria and initial renal dysfunction, were all associated with higher mortality, and the relative mortality rate increased with the number of risk factors. Conclusions: In patients with primary GN, mortality is significantly higher than in the age-/sex-matched general population, especially in women. Moreover, the presence of renal risk factors is positively associated with both relative mortality and progression to ESRD.
American Journal of Nephrology 01/2013; 37(1):74-83. · 2.54 Impact Factor
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ABSTRACT: The data were presented in abstract form at the 45(th) meeting of the American Society of Nephrology, October 30-November 04 2012, San Diego, CA, USA. Circulating autoantibodies against M-type phospholipase A2 receptor (PLA2R) are important pathogenic antibodies of idiopathic membranous nephropathy (MN) in adults. However, previous studies on the clinical impact of anti-PLA2R antibodies demonstrated several limitations, including insufficient numbers of study subjects and different time points and methods for anti-PLA2R antibody measurement. To verify the clinical significance of anti-PLA2R antibodies in Korean patients with MN, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 100 patients with idiopathic MN who had not yet received immunosuppressive treatment. We detected anti-PLA2R antibody in 69 patients, and we observed that autoantibody reactivity reflected the severity of disease activity. Proteinuria and hypoalbuminemia were more severe in patients with anti-PLA2R than in those without the autoantibodies (2.95 g/g vs. 6.85 g/g, P = 0.003; 3.1 g/dL vs. 2.5 g/dL, P = 0.004, respectively). Additionally, the clinical severities worsened proportionally as the levels of anti-PLA2R antibodies increased (P = 0.015 and P for trend <0.001 for proteinuria and hypoalbuminemia, respectively). However, neither the levels nor the presence or absence of anti-PLA2R antibody showed a significant correlation with clinical outcomes, such as remission rate and time to remission. In conclusion, we observed that anti-PLA2R antibodies are highly prevalent in Korean patients with idiopathic MN and that they reflect the clinical disease activity before the administration of immunosuppressive treatment. However, the levels of anti-PLA2R antibody at the time of kidney biopsy may not predict the clinical outcomes in current clinical practice.
PLoS ONE 01/2013; 8(4):e62151. · 4.09 Impact Factor
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ABSTRACT: Hyponatremia is prevalent before liver transplantation and generally corrected immediately after transplantation. However, the clinical significance of correction rate of hyponatremia is not well investigated. The prognostic impact of pre-transplant serum sodium concentrations and post-transplant correction rate of hyponatremia were assessed. A total of 512 patients who received orthotopic liver transplants were enrolled. The correction rate of hyponatremia (delta sodium, ΔNa) was calculated based on the data collected during the first 48 hours following liver transplantation. Outcomes, including in-hospital mortality, delirium, neurological complications, acute kidney injury, and infections, were compared according to the serum sodium levels (sNa < 125, 125-135, and ≥ 135 mmol/L), and the risk factors for in-hospital mortality and neurological complications were analyzed using multivariate logistic regression methods. Patients with severe hyponatremia (sNa < 125 mmol/L) had higher rates of in-hospital mortality (9.6%, P = 0.010), delirium (54.8%, P = 0.003), neurological complications (24.7%, P = 0.003), and acute kidney injury (57.5%, P = 0.005). In multivariate analysis, serum sodium levels (OR = 0.975, P = 0.402) and delta sodium (OR = 1.097, P = 0.066) were not independent risk factors for in-hospital mortality. However, delta sodium (OR = 1.093, P = 0.003) and fast correction rate of hyponatremia (ΔNa ≥ 12 mmol/L/24h, OR = 3.397, P = 0.023) were significantly associated with post-transplant neurological complications. Pre-transplantation hyponatremia was not independently associated with clinical outcomes. However, rapid correction of hyponatremia is an independent risk factor for the development of post-transplant neurological complications.
The Tohoku Journal of Experimental Medicine 01/2013; 229(2):97-105. · 1.24 Impact Factor
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Hajeong Lee,
Yun Jung Oh,
Myounghee Kim,
Ho Kim,
Jung Pyo Lee,
Sejoong Kim,
Kook-Hwan Oh,
Ho Jun Chin,
Kwon Wook Joo,
Chun Soo Lim,
Suhnggwon Kim,
Yon Su Kim, Dong Ki Kim
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ABSTRACT: Only a few large-scale studies have investigated the association between health-related quality of life (HRQOL) and renal function. Moreover, the HRQOL of patients with moderate renal dysfunction is frequently underestimated by healthcare providers. This study assessed the impact of renal function on preference-based HRQOL in Korean adult population.
We analyzed data for 5,555 adults from the 3(rd) Korean National Health and Nutritional Examination Survey 2005. The EuroQol-5D (EQ-5D) utility score was used to evaluate HRQOL. The study subjects were stratified into three groups based on their estimated glomerular filtration rates (eGFRs): ≥ 90.0, 60.0-89.9 and 30.0-59.9 mL/min/1.73 m(2). Individuals with advanced renal dysfunction were excluded from the analysis.
The proportions of participants who reported problems in each of the five EQ-5D dimensions increased significantly with decreasing eGFR. However, a significant decrease in the EQ-5D utility score was observed among participants with an eGFR of 30.0-59.9 mL/min/1.73 m(2). Participants with an eGFR of 30.0-59.9 mL/min/1.73 m(2) had an almost 1.5-fold higher risk of impaired health utility (the lowest quartile of EQ-5D utility score) compared with those participants with eGFRs ≥ 90.0 mL/min/1.73 m(2), after adjustment for age, gender, health-related behaviors, socioeconomic and psychological variables, and other comorbidities. Among the five dimensions of the EQ-5D, an eGFR of 30.0-59.9 mL/min/1.73 m(2) was an independent determinant of self-reported problems in the mobility and pain/discomfort dimensions.
Although age affects the association between renal dysfunction and the EQ-5D, moderate renal dysfunction seems to be an important determinant of impaired health utility in a general population and may affect the mobility and pain/discomfort dimensions of health utility.
BMC Nephrology 04/2012; 13:19. · 2.18 Impact Factor
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ABSTRACT: Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone.
Journal of Korean medical science 02/2012; 27(2):170-6. · 0.84 Impact Factor
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Yun Jung Oh,
Myounghee Kim,
Hajeong Lee,
Jung Pyo Lee,
Ho Kim,
Sejoong Kim,
Kook-Hwan Oh,
Kwon Wook Joo,
Chun Soo Lim,
Suhnggwon Kim,
Yon Su Kim, Dong Ki Kim
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ABSTRACT: Vitamin D deficiency is known as an important risk factor for mortality in patients with chronic kidney disease (CKD). Nevertheless, the association of renal function itself with vitamin D status or serum 25-hydroxyvitamin D (25OHD) level has not been investigated thoroughly.
We examined the association between the estimated glomerular filtration rate (eGFR) and serum 25OHD levels using data from the 4th Korean National Health and Nutritional Examination Survey 2008. Generalized additive models (GAMs) were used to examine the relationship between eGFR and serum 25OHD levels and to estimate a threshold value of eGFR that predicts changes in serum 25OHD levels.
The mean serum 25OHD level was 20.4 ± 9.1 ng/mL, and the overall prevalence of vitamin D deficiency was 29.9% in this population. The prevalence of vitamin D deficiency began to increase at eGFR levels <45 mL/min/1.73 m(2). After adjustment, the logistic regression of dichotomized eGFR levels with a cut-point of 45 mL/min/1.73 m(2) yielded an increased odds ratio for vitamin D deficiency. Additionally, the continuous relationship between eGFR and 25OHD levels was explored using GAMs adjusted for various confounding factors. In this analysis, the difference from the mean serum 25OHD started to increase below an eGFR threshold of 55.4 mL/min/1.73 m(2), which suggests that renal function is directly related to the serum 25OHD levels in patients with CKD Stages 3-5.
Although moderate renal dysfunction (eGFR < 45 mL/min/1.73 m(2)) is an important predictor of vitamin D deficiency, serum 25OHD levels start to decrease below an eGFR level of ~60 mL/min/1.73 m(2) independent of other risk factors. These results suggest that more careful attention to 25OHD levels may be needed when patients reach Stage 3 CKD.
Nephrology Dialysis Transplantation 01/2012; 27(6):2396-403. · 3.40 Impact Factor
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ABSTRACT: Subtle fluid imbalance can cause poor clinical outcomes among hemodialysis patients. However, the traditional subjective assessment of fluid status may be inadequate. We evaluated whether the objective measurement and optimization of fluid status could be beneficial for hemodynamic and biochemical parameters in hemodialysis patients. We enrolled 120 hemodialysis patients, who were clinically euvolemic for at least 3 months. Based on the results of a body composition monitor, we divided the patients into the following two groups: the hyperhydrated group (post hemodialysis fluid overload ≥ 1.1 L) and the dehydrated group (post hemodialysis fluid overload < -1.1 L). We reduced the patient's body weight in the hyperhydrated group and raised the body weight in the dehydrated group towards normohydration (-1.1 L ≤ fluid overload < 1.1 L) for 16 weeks. Forty-four of 120 patients were in the hyperhydrated group, and 18 of 120 patients in the dehydrated group. After 16 weeks, systolic blood pressure and pulse pressure decreased in the hyperhydrated group, while there was no increase in blood pressure in the dehydrated group after the intervention. Serum levels of monocyte chemotactic protein-1, an inflammatory marker, gradually decreased in the hyperhydrated group, and serum adiponectin levels, an anti-atherogenic biomarker, increased in the two groups. We found that hyperhydrated patients contributed over 1/3 of the participants despite enrolling clinically euvolemic patients and that body composition monitor-guided optimization of body fluid status may lead to improvement of inflammatory markers and anti-atherogenic adipokines as well as hemodynamic parameters in hemodialysis patients.
The Tohoku Journal of Experimental Medicine 01/2012; 228(2):125-33. · 1.24 Impact Factor
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ABSTRACT: Contrast-induced acute kidney injury (CIAKI) is a common complication after percutaneous coronary artery intervention (PCI). It is urgent to find a novel, easily measurable and accurate predictor for the early detection of CIAKI. Hyperosmolarity and large amounts of contrast media are risk factors for CIAKI. However, there is no study on plasma osmolar gap as a predictor of CIAKI. We enrolled 89 patients undergoing elective PCI and tested changes of serum sodium, osmolar gap, and renal function at 0, 6, 12 and 24 hours. Plasma osmolar gap was calculated using the following formula: measured plasma osmolarity - [2(Na) + serum urea nitrogen/2.8 + glucose/18]. CIAKI was defined as follows: increase in serum creatinine of ≥ 50%, increase in serum creatinine of ≥ 0.3 mg/dL, or decrease in estimated glomerular filtration rate of ≥ 25% within 24 hours after PCI. The incidence of CIAKI was 13.5% (12/89 patients). The CIAKI group had higher plasma osmolar gaps 6 hours after PCI. The adjusted hazard ratio of the plasma osmolar gap from hour 6 (1-mOsm/L increments) to the development of CIAKI was 1.12 (95% confidence interval [CI], 1.01-1.26; P = 0.041). Sensitivity and specificity of 7 mOsm/L or higher plasma osmolar gap at hour 6 were 70.0% and 76.6%, respectively (area under the ROC curve = 0.77 [95% CI, 0.65-0.89]). Increased plasma osmolar gap may precede the development of CIAKI in patients undergoing PCI. In conclusion, plasma osmolar gap may be a useful predictor for the development of CIAKI.
The Tohoku Journal of Experimental Medicine 01/2012; 228(2):109-17. · 1.24 Impact Factor
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ABSTRACT: We retrospectively evaluated demographic and biochemical parameters associated with depression and health-related quality of life (HRQOL) in maintenance peritoneal dialysis (PD) patients. This study included 105 patients maintaining PD at Seoul National University Hospital. Data were collected from electronic medical record. Korean Beck's Depression Inventory and Korean version of Kidney Disease Quality of Life short form, version 1.3 were used to evaluate depression and HRQOL, respectively. Moderate to severe depression was found in 24.8% of patients. Patients with lower normalized protein equivalent of nitrogen appearance (nPNA) (< 1.2 g/kg/day), lower weekly renal Kt/V(urea) (< 0.2), and lower serum albumin level (≤ 4.0 g/dL) were associated with depression (P < 0.05). Among them, lower weekly renal Kt/V(urea) was the only independent risk factor associated with depression (OR = 3.1, P = 0.007). Depressed patients showed significantly lower scores in every dimension of HRQOL (P < 0.001). Lower weekly renal Kt/V(urea) (β = 0.24, P = 0.005) and lower nPNA (β = 0.15, P = 0.03) were the independent risk factors associated with lower kidney dialysis component summary, whereas lower plasma hemoglobin level was the consistent risk factor for lower physical component summary (β = 0.22, P = 0.03) and mental component summary (β = 0.22, P = 0.01). Depression is a prevalent psychological problem in PD population. Residual renal function is the most important factor associated with depression and impaired HRQOL in PD patients.
Journal of Korean medical science 01/2012; 27(1):64-71. · 0.84 Impact Factor
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Bo Young Nam,
Jisun Paeng,
Seung Hye Kim,
Sun Ha Lee,
Do Hee Kim,
Hye-Young Kang,
Jin Ji Li,
Seung-Jae Kwak,
Jung Tak Park,
Tae-Hyun Yoo,
Seung Hyeok Han, Dong Ki Kim,
Shin-Wook Kang
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ABSTRACT: Previous studies have demonstrated the importance of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of diabetic nephropathy in terms of inflammation, but the direct role of the MCP-1/CCR2 system on podocyte apoptosis under diabetic conditions has never been explored. In vitro, mouse podocytes were exposed to a medium containing 30 mM glucose (HG) with or without CCR2 siRNA or CCR2 inhibitor (RS102895). Podocytes were also treated with MCP-1 or TGF-β1 with or without anti-TGF-β1 antibody, CCR2 siRNA, or CCR2 inhibitor. In vivo, 20 db/m and 20 db/db mice were divided into two groups, and ten mice from each group were treated with RS102895. Western blot and Hoechst 33342 or TUNEL staining were performed to identify apoptosis. HG-induced apoptosis and TGF-β1 levels were significantly abrogated by CCR2 inhibition. In addition, treatment with MCP-1 directly induced apoptosis via CCR2. Moreover, TGF-β1- and MCP-1-induced apoptosis were significantly ameliorated by the inhibition of CCR2 and anti-TGF-β1 antibody, respectively. Glomerular expression of cleaved caspase-3 and apoptotic cells within glomeruli were also significantly increased in db/db mice compared to db/m mice, and these increases were significantly attenuated in db/db + RS102895 mice. These results suggest that interactions between the MCP-1/CCR2 system and TGF-β1 may contribute to podocyte apoptosis under diabetic conditions.
Apoptosis 01/2012; 17(1):1-13. · 4.07 Impact Factor
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ABSTRACT: Research on the prognosis of IgA nephropathy (IgAN) has focused on renal survival, with little information being available on patient survival. Hence, this investigation aimed to explore long-term patient outcome in IgAN patients. Clinical and pathological characteristics at the time of renal biopsy were reviewed in 1,364 IgAN patients from 1979 to 2008. The outcomes were patient death and end stage renal disease (ESRD) progression. Overall, 71 deaths (5.3%) and 277 cases of ESRD (20.6%) occurred during 13,916 person-years. Ten-, 20-, and 30-year patient survival rates were 96.3%, 91.8%, and 82.7%, respectively. More than 50% patient deaths occurred without ESRD progression. Overall mortality was elevated by 43% from an age/sex-matched general population (GP) (standardized mortality ratio [SMR], 1.43; 95% confidence interval [CI], 1.04-1.92). Men had comparable mortality to GP (SMR, 1.22; 95% CI, 0.82-1.75), but, in women, the mortality rate was double (SMR, 2.17; 95% CI, 1.21-3.57). Patients with renal risk factors such as initial renal dysfunction (estimated glomerular filgration rate <60 ml/min per 1.73m(2); SMR, 1.70; 95% CI, 1.13-2.46), systolic blood pressure ≥140 mmHg (SMR, 1.88; 95% CI, 1.19-2.82) or proteinuria ≥1 g/day (SMR, 1.66; 95% CI, 1.16-2.29) had an elevated mortality rate. Patients with preserved renal function, normotension, and proteinuria <1 g/day, however, had a similar mortality rate to GP. When risk stratification was performed by counting the number of major risk factors present at diagnosis, low-risk IgAN patients had a mortality rate equal to that of GP, whereas high-risk patients had a mortality rate higher than that of GP. This investigation demonstrated that overall mortality in IgAN patients was higher than that of GP. Women and patients with renal risk factors had a higher mortality than that of GP, Therefore, strategies optimized to alleviate major renal risk factors are warranted to reduce patient mortality.
PLoS ONE 01/2012; 7(12):e51225. · 4.09 Impact Factor
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ABSTRACT: Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.
PLoS ONE 01/2012; 7(5):e37075. · 4.09 Impact Factor
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ABSTRACT: There is a significant immune response to ischemia-reperfusion injury (IRI), but the role of immunomodulatory natural killer T (NKT) cell subtypes is not well understood. Here, we compared the severity of IRI in mice deficient in type I/II NKT cells (CD1d(-/-)) or type I NKT cells (Jα18(-/-)). The absence of NKT cells, especially type II NKT cells, accentuated the severity of renal injury, whereas repletion of NKT cells attenuated injury. Adoptively transferred NKT cells trafficked into the tubulointerstitium, which is the primary area of injury. Sulfatide-induced activation of type II NKT cells protected kidneys from IRI, but inhibition of NKT cell recruitment enhanced injury. In co-culture experiments, sulfatide-induced activation of NKT cells from either mice or humans attenuated apoptosis of renal tubular cells after transient hypoxia via hypoxia-inducible factor (HIF)-1α and IL-10 pathways. Renal tissue of patients with acute tubular necrosis (ATN) frequently contained NKT cells, and the number of these cells tended to negatively correlate with ATN severity. In summary, sulfatide-reactive type II NKT cells are renoprotective in IRI, suggesting that pharmacologic modulation of NKT cells may protect against ischemic injury.
Journal of the American Society of Nephrology 06/2011; 22(7):1305-14. · 9.66 Impact Factor
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ABSTRACT: Organ shortages lead end stage renal disease patients to seek overseas kidney transplantations (OTs), but the long-term outcomes of OTs have not been evaluated extensively.
Patients who received OT and were followed at Seoul National University Hospital (SNUH) from 2000 to 2009 (n = 87) were compared with patients who received kidneys from local donors (LTs) and were followed at SNUH (n = 577). Furthermore, we matched OT patients and LT patients via a propensity score using operation date, age, renal replacement therapy duration, and donor sources (n = 87 vs 87).
The recipient age was older in the OT group (48 vs 41 years), and donor age was younger in the OT group (29 vs 39 years). The estimated glomerular filtration rates (eGFR) of functioning grafts between the groups were not different throughout the follow-up period. Biopsy-proven acute rejection, infectious disease, and hospitalization were more frequent in the OT group (27/87 vs 141/577, log-rank P < 0.001; 39/87 vs 28/577, log-rank P < 0.001; 66/87 vs 99/577, log-rank P < 0.001). The graft survival rate was lower in the OT group (82/87 vs 542/577, log-rank P = 0.003). Patient survival rate, however, was similar between the groups. After propensity score matching, the donor age was still younger in the OT group (29 vs 38 years). The risks of biopsy-proven acute rejection, infectious disease, and hospitalization were still higher in the OT group (27/87 vs 36/87, log-rank P = 0.04; 39/87 vs 3/87, log-rank P < 0.001; 66/87 vs 19/87, log-rank P < 0.001).
Overseas kidney transplantation connotes risk factors that may negatively affect the long-term graft outcome.
Nephrology 05/2011; 16(7):672-9. · 1.31 Impact Factor
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Jung Pyo Lee,
Seung Hee Yang, Dong Ki Kim,
Hajeong Lee,
Bora Kim,
Joo-Youn Cho,
Kyung-Sang Yu,
Jin Ho Paik,
Myounghee Kim,
Chun Soo Lim,
Yon Su Kim
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ABSTRACT: Epoxyeicosatrienoic acid (EET) regulates the functional integrity of the endothelium. It is hypothesized that the activity of epoxide hydrolase (EPHX2), which determines EET concentration through hydrolysis, may affect the progression of glomerulonephritis. Here, we evaluated the relationship between genetic variations, the in vivo activity of EPHX2, and progression of IgA nephropathy (IgAN). Three single-nucleotide polymorphisms (SNPs) [rs41507953 (K55R), rs751141 (R287Q), and rs1042032] were traced in 401 IgAN patients and 402 normal healthy controls. The in vivo activity of EPHX2 was assessed by measuring substrates/metabolites of the enzyme. None of the polymorphism frequencies differed significantly between patients and controls. However, patients carrying the variant allele (A) of rs751141 possessed better kidney survival than those with the wild-type allele (G; P < 0.001). This association remained significant after adjustment for several risk factors (hazard ratio 1.83, 95% confidence interval 1.13-2.96, P = 0.014). Vascular damage was more prominent in kidney biopsies from patients carrying the G allele of rs751141. The in vivo activity of EPHX2, assessed by the epoxyoctadecenoic acid/dihydroxyoctadecenoic acid ratio using liquid chromatography/mass spectrometry analysis, was elevated in patients with the G allele. The expression of EPHX2 in the human kidney was independent of the sequence variation of the rs751141 allele. Variant rs41507953 was not present in this cohort, and rs1042032 was not associated with progression. Thus the specific measures which regulate EPHX2 activity should be designed for potential therapeutics.
AJP Renal Physiology 03/2011; 300(6):F1283-90. · 4.42 Impact Factor
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ABSTRACT: Although there has been considerable investigation of the general characteristics of contrast-induced nephropathy (CIN), it has not been studied adequately in a computed tomography (CT) population. We assessed the incidence and outcomes of CIN after contrast-enhanced CT in patients with chronic kidney disease pretreated with saline and N-acetylcysteine (NAC).
Quality improvement report.
520 patients registered in a CIN prevention program.
We initiated the CIN prevention program in January 2007. In this program, patients with chronic kidney disease undergoing contrast-enhanced CT in an outpatient setting were automatically referred to nephrologists, and patients received saline and NAC before and after CT. The development of CIN was assessed 48-96 hours after CT.
Incidence of CIN and time to renal replacement therapy.
Baseline serum creatinine, hemoglobin, and serum albumin levels; type and volume of contrast agents; and post-CT serum creatinine level.
Overall, CIN occurred in 13 (2.5%) patients. Incidences of CIN were 0.0%, 2.9%, and 12.1% in patients with an estimated glomerular filtration rate of 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively. The risk of CIN was increased in patients with severely decreased kidney function and diabetes. The development of CIN consequently increased the risk of renal replacement therapy (P < 0.001 by log-rank), and the risk was significantly accentuated in patients with estimated glomerular filtration rate <30 mL/min/1.73 m(2).
A single-center study and comparison with previous studies.
The incidence of CIN was relatively low in patients treated with saline and NAC. The development of CIN predisposed to poor kidney survival in the long term.
American Journal of Kidney Diseases 06/2010; 55(6):1018-25. · 5.43 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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ABSTRACT: The kidney and the brain play a major role in maintaining normal homeostasis of the extracellular fluid by neuroendocrine regulation of sodium and water balance. Therefore, disturbances of sodium balance are common in patients with central nervous system (CNS) disorders and clinicians should focus not only on the CNS lesion, but also on the potentially deleterious complications. Hyponatremia is the most common and important electrolyte disorder affecting patients with critical neurologic diseases. In these patients, the maladaptation to hyponatremia by impaired osmoregulation in pathologic lesions of brain may cause more aggressive cerebral edema and increased intracranial pressure due to hypoosmolality induced by hyponatremia. Furthermore, hyponatremia accompanied by CNS disorders has shown to increase delayed cerebral ischemia and mortality rates. Two main pathophysiologies of hyponatremia, excluding iatrogenic causes, are inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting (CSW) syndrome. Differential diagnosis between these two entities can be difficult due to considerable overlap in the laboratory findings and clinical situations. SIADH is in a volume expanded status due to inappropriately secreted arginine vasopressin (AVP) and requires water restriction. However, CSW syndrome is characterized by renal sodium wasting mainly due to increased natriuretic peptides resulting in volume depletion and follows appropriate secretion of AVP. Therefore, maintenance of volume status and sodium replacement is the mainstay of treatment in CSW syndrome. In this review, we aimed to describe the regulation of sodium and water balance, and pathophysiology, diagnosis and treatment of hyponatremia in neurologic patients, especially focusing on SIADH and CSW syndrome.
Electrolyte & blood pressure: E & BP 12/2009; 7(2):51-7.
