[show abstract][hide abstract] ABSTRACT: Host and viral factors interplay in the spontaneous clearance of hepatitis C virus (HCV) infection. We aimed to explore the roles of interleukin-28B genotypes and hepatitis B virus (HBV) infections in spontaneous HCV seroclearance.
Interleukin-28B rs8099917 genotypes, HCV and HBV markers were determined in 290 patients who were seropositive for HCV antibodies from 1681 total uremic patients on maintenance hemodialysis.
Persistent HCV viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed that the strongest factors associated with spontaneous HCV seroclearance were carriage of rs8099917 TT-type (odds ratio/ 95% confidence intervals [OR/CI]: 6.22/1.41-27.35, P=0.016), followed by concurrent hepatitis B surface antigen (HBsAg) seropositivity (OR/CI: 2.37/1.06-5.26, P=0.035). The clearance rate was highest among patients with both positive-HBsAg/rs8099917 TT-type (44.8%, OR/CI: 20.88/3.5-402.5), followed by positive-HBsAg/rs8099917 non-TT-type (28.6%, OR/CI: 8.86/1.8-160.8), and negative-HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0-319.4), compared to 4% of negative-HBsAg/rs8099917 non-TT-type (trend P=0.0002). HBsAg levels, but not HBV DNA levels, were significantly associated with spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in patients with HBsAg >200 IU/mL/rs8099917 TT-type (OR/CI: 42.54/5.7-908.4), 28.0% in patients with HBsAg <200 IU/mL/rs8099917 TT-type or HBsAg >200 IU/mL/rs8099917 non-TT-type (OR/CI: 11.12/2.3-201.0), compared to only 3.3% in those with HBsAg <200 IU/mL/rs8099917 non-TT-type (trend P=0.0004). Five of 214 (2.3%) HCV viremic patients at enrollment had spontaneous HCV seroclearance during one-year follow-up, which was associated with baseline HCV RNA and HBsAg levels.
High HBsAg levels and favorable interleukin-28B genotype were additively associated with spontaneous HCV seroclearance in uremic patients.
Journal of Hepatology 10/2013; · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: X-linked agammaglobulinaemia (XLA) is the most common inherited humoural immunodeficiency disorder. Mutations in the gene coding for Bruton's tyrosine kinase (BTK) have been identified as the cause of XLA. Most affected patients exhibit a marked reduction of serum immunoglobulins, mature B cells, and an increased susceptibility to recurrent bacterial infections. However, the diagnosis of XLA can be a challenge in certain patients who have near-normal levels of serum immunoglobulin. Furthermore, reports on XLA with renal involvement are scant.
We report an atypical XLA patient who presented with selective immunoglobulin M (IgM) immunodeficiency and nephropathy. He was diagnosed with selective IgM immunodeficiency, based on his normal serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels but undetectable serum IgM level. Intravenous immunoglobulin was initiated due to increased infections and persistent proteinuria but no improvement in proteinuria was found. A lupus-like nephritis was detected in his kidney biopsy and the proteinuria subsided after receiving a mycophenolate mofetil regimen. Although he had a history of recurrent bacterial infections since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted.
We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM deficiency to rule out atypical XLA.
[show abstract][hide abstract] ABSTRACT: Malnutrition and/or inflammation may modify the risk relationship of total cholesterol with cardiovascular disease in CKD patients. However, it is unclear whether the relationship of total cholesterol with cardiovascular events and mortality varies by proteinuria.
This study enrolled 3303 patients with CKD stages 3-5 from a medical center and a regional hospital between November of 2002 and May of 2009 and followed the patients until July of 2010.
During a median 2.8-year follow-up, there were 471 (14.3%) deaths and 545 (16.5%) cardiovascular events. In an adjusted Cox model, the two highest quartiles of total cholesterol (hazard ratio, 1.90; 95% confidence interval, 1.16 to 3.13 and hazard ratio, 2.00; 95% confidence interval, 1.18 to 3.39 versus quartile 1, respectively) were associated with a significant higher risk of all-cause mortality in patients with urine protein-to-creatinine ratio<1 g/g (n=1535), but this higher risk was not seen in those patients with urine protein-to-creatinine ratio≥1 g/g (n=1768; hazard ratio, 0.75; 95% confidence interval, 0.53 to 1.07 and hazard ratio, 0.70; 95% confidence interval, 0.49 to 1.02 versus quartile 1, respectively). The interaction between total cholesterol and proteinuria with all-cause mortality was significant (interaction, P=0.05). However, the relationship between total cholesterol and cardiovascular events did not significantly differ by proteinuria (interaction, P=0.91).
The association between cholesterol and mortality is different among patients with different levels of proteinuria. Large-scale clinical trials to evaluate the mortality benefit should specifically target lowering hypercholesterolemia in CKD patients with different levels of proteinuria.
Clinical Journal of the American Society of Nephrology 08/2013; · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: The 5th congress of International Society for Hemodialysis took place last August 3-5, 2012 at the Grand Hotel in Taipei and focused on "Save Life and Improve Quality." It attracted a total of 927 participants from 18 countries. The full spectrum of hemodialysis was covered with plenary lectures and symposiums delivered by experts from different subspecialties in nephrology starting from the history of hemodialysis, mineral bone disease, microinflammation and advanced techniques in hemodialysis. It was followed by critical care in nephrology, anemia, and nutrition in dialysis. Last but not the least, natural disasters and medical economics in hemodialysis were also discussed extensively. This special article will highlight the authentic contributions and innovative clinical presentations from the meeting.
Hemodialysis International 07/2013; · 1.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background/Aims: Impaired left ventricular diastolic function and increased left ventricular filling pressure are frequently noted in patients with chronic kidney disease (CKD), even in early stages. The association of increased left ventricular filling pressure with cardiovascular and renal outcomes remains uncertain in CKD. This study is designed to assess whether the ratio of transmitral E-wave velocity (E) to early diastole mitral velocity (Ea) is associated with cardiovascular events and progression to dialysis in patients with CKD stages 3-5. Methods: This longitudinal study enrolled 356 predialysis CKD patients. Cardiovascular events were defined as cardiovascular death, hospitalization for unstable angina, nonfatal myocardial infarction, ventricular tachycardia, hospitalization for congestive heart failure, transient ischemia attack, and stroke. The renal endpoint was defined as commencement of dialysis. The relative cardiovascular events and renal endpoints risks were analyzed by Cox regression methods. Results: The high E/Ea was independently associated with old age, cerebrovascular disease, congestive heart failure, high systolic blood pressure, hypertriglyceridemia, low hemoglobin, proteinuria, and worse echocardiographic profiles. Besides, the high E/Ea increased the risk of cardiovascular events (hazard ratio (HR) 1.067; 95% confidence interval (CI) 1.017-1.119; p = 0.008) and progression to dialysis (HR 1.042; 95% CI 1.000-1.085; p = 0.048). Conclusions: Our study in patients of CKD stages 3-5 demonstrated the high E/Ea was associated with increased cardiovascular events and progression to dialysis. Assessment of the E/Ea by Doppler echocardiography is useful for predicting the risk of adverse cardiovascular and renal outcomes in CKD patients.
Nephron Clinical Practice 06/2013; 123(1-2):52-60. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIM: The Framingham Risk Score (FRS), calculated by considering conventional risk factors of cardiovascular diseases, was developed to predict coronary heart disease in various populations. However, reverse epidemiology has been raised concerning these risk factors in predicting high cardiovascular mortality in hemodialysis patients. Our objectives are to determine whether FRS is associated with overall and cardiovascular mortality and the role of new risk markers when they were added to a FRS model in hemodialysis patients. METHODS: This study enrolled 201 hemodialysis patients aged 20-80 years old. The FRS is used to identify individuals categorized as low (< 6% 10-year risk), intermediate (6-20% risk) or high risk (> 20% risk). Medical records were reviewed to collect clinical information. Data of ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were obtained by an ABI-form device. RESULTS: The mean follow-up period was 4.4 ± 1.5 years. Intermediate risk predicted overall hazard ratio (HR) (2.157, P = 0.039) and cardiovascular mortality (HR= 5.023; P = 0.004) versus low risk, but "high" risk did not. High risk (versus low risk) predicted cardiovascular events (HR = 2.458, P = 0.05). Besides, addition of ABI < 0.9 (P = 0.021) and baPWV (P = 0.014) to a FRS model significantly improved the predictive value for overall mortality. CONCLUSION: In hemodialysis patients, intermediate risk but not high risk categorization by FRS predicted overall and cardiovascular mortality, and high risk predicted cardiovascular events. ABI < 0.9 and baPWV provided additional predictive values for overall mortality. Future study is needed to develop hemodialysis-specific equations and assess whether risk refinement using ABI < 0.9 and baPWV leads to a meaningful change in clinical outcomes.
[show abstract][hide abstract] ABSTRACT: Double-lumen central venous catheter (CVC) is a rapid access technique for hemodialysis (HD) when an arteriovenous fistula or graft is not available. A variety of procedure-related complications have been reported, such as infection and pneumothorax, but serious cardiac complications are relatively less mentioned. We report a uremic woman with preexisting left bundle branch block who required emergent HD and received jugular double-lumen CVC insertion, which was complicated by short-duration ventricular tachycardia followed by complete atrio-ventricular block and bradycardia. Pharmacological management did not reverse heart rate and rhythm. External pacing was not applied because she remained hemodynamically stable in the course of HD. Heart rate returned to sinus rhythm with left bundle branch block 4 hours later and did not recur through the whole admission period. We speculate that the transient arrhythmia might have been induced by mechanical contact with the ventricular wall during the procedure with the guided metallic wire. In conclusion, physicians responsible for CVC catheterization should pay more attention to patients with preexisting cardiac arrhythmia to prevent such technical mistakes from transpiring.
Hemodialysis International 03/2013; · 1.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND:: Anemia is a common complication in patients with chronic kidney disease (CKD), which may initiate or accelerate left ventricular hypertrophy (LVH). This study is designed to assess whether the coexistence of anemia and LVH is independently associated with the rate of renal function decline and increased cardiovascular events in patients with CKD stages 3 to 5. METHODS:: This longitudinal study enrolled 415 patients, who were classified into 4 groups according to sex-specific median values of hemoglobin and with/without LVH. The change in renal function was measured by estimated glomerular filtration rate slope. Cardiovascular events were defined as cardiovascular death, hospitalization for unstable angina, nonfatal myocardial infarction, sustained ventricular arrhythmia, hospitalization for congestive heart failure, transient ischemia attack, and stroke. The relative risk of cardiovascular events was analyzed by Cox's regression method. RESULTS:: The estimated glomerular filtration rate slope was significantly lower in the group with lower hemoglobin and LVH than in the other groups (P ≤ 0.031). In addition, patients with lower hemoglobin and LVH were independently associated with increased cardiovascular events (hazard ratio, 4.269; 95% confidence interval, 1.402-13.000; P = 0.011). CONCLUSIONS:: Our findings showed that the coexistence of anemia and LVH was independently associated with faster renal function decline and poor cardiovascular outcomes in patients with CKD. Assessments of serum hemoglobin level and LVH by echocardiography may help identify a high-risk group of poor renal and cardiovascular prognosis in patients with CKD stages 3 to 5.
The American Journal of the Medical Sciences 02/2013; · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND Hyperuricemia and left ventricular (LV) hypertrophy are prevalent in chronic kidney disease (CKD), but the association of uric acid (UA) and left ventricular mass index (LVMI) with renal outcomes in patients with CKD is unclear. We conducted a study to assess whether the combination of UA and LVMI is associated with renal outcomes in patients with CKD of stages 3-5. METHODS This longitudinal study enrolled 540 patients, who were classified into four groups according to sex-specific median values of UA and LVMI. The study investigated the associations of the study groups with progression to dialysis, rapid progression of decline in renal function (decline in estimated glomerular filtration rate (eGFR) > 3ml/min/1.73 m(2)/year), and change in eGFR, using Cox proportional hazards modeling, logistic regression analysis, and linear mixed-effects modeling, respectively. RESULTS The follow-up period for the study was 33.4 (19.8-39.6) months. The average number of serum creatinine measurements during the follow-up period was 8 (range, 5-12). Multivariate analyses demonstrated an association of the group with a higher UA and LVMI with an increased rate of progression to dialysis (hazard ratio (HR), 1.830; 95% confidence interval (CI), 1.007 to 3.326; P = 0.048) and with rapid progression of decline in renal function (odds ratio (OR), 2.231; 95% CI, 1.058-4.705; P = 0.04). Additionally, the linear mixed-effects model showed that the decrease in eGFR over time was more rapid in the group with a higher UA and LVMI than in the other groups (P < 0.04). CONCLUSIONS Our findings show that the combination of a higher UA and LVMI is a risk factor for progression to dialysis and rapid progression of decline in renal function in patients with CKD of stages 3-5.
American Journal of Hypertension 02/2013; 26(2):243-9. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background and Aim: Metabolic syndrome (MetS) and albuminuria increase cardiovascular risk. However, in occupational drivers, the clinical significance of albuminuria and its association with MetS remain unclear. We investigated the prevalence of MetS, albuminuria and cardiovascular risk, and its associated risk factors in occupational drivers; Methods: 441 occupational drivers and 432 age- and sex-stratified matched counterpart controls were enrolled. MetS was defined using Adult Treatment Panel III for Asians. Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g. Cardiovascular disease risk was evaluated by Framingham Risk Score (FRS); Results: A significantly higher prevalence of MetS (43.1% vs. 25.5%, p < 0.001), albuminuria (12.0% vs. 5.6%, p = 0.001) and high FRS risk ≥ 10% of 10-year risk (46.9% vs. 35.2%, p < 0.001) was found in occupational drivers compared with their counterpart controls. Multiple logistic regression analysis showed that old age, a history of diabetes, gout and betel nut chewing, less exercise and albuminuria (odds ratio [OR], 2.75; p = 0.01) were risk factors for MetS, while a history of renal disease, diabetes and hypertension, and MetS (OR, 2.28; p = 0.01) were risk factors for albuminuria in occupational drivers; Conclusions: Our study demonstrated that MetS and albuminuria were public health problems in occupational drivers. An education program for promoting healthy lifestyle and a regular occupational health visit for early detection and interventions should be established.
International Journal of Molecular Sciences 01/2013; 14(11):21997-2010. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated.
2500 participants with CKD stage 1-4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used.
The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m(2). Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03-3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19-2.35) in sK = 3.5-4 mEq/L, respectively, compared with sK = 4.5-5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09-2.34) increased risk of ESRD compared with sK = 4.5-5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range.
In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.
PLoS ONE 01/2013; 8(7):e67140. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as "low" (<10% of 10-year risk), "intermediate" (10-20% risk) or "high" risk (≧ 20% risk). A significant improvement in model prediction was based on the -2 log likelihood ratio statistic and c-statistic. "High" risk (v.s. "low" risk) predicts cardiovascular events either without (hazard ratios [HR] 2.090, 95% confidence interval [CI] 1.144 to 3.818) or with adjustment for clinical, biochemical and echocardiographic parameters (HR 1.924, 95% CI 1.008 to 3.673). Besides, the addition of albumin, hemoglobin, estimated glomerular filtration rate, proteinuria, left atrial diameter >4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction<50% to the FRS model significantly improves the predictive values for cardiovascular events. In CKD patients, "high" risk categorized by FRS predicts cardiovascular events. Novel biomarkers and echocardiographic parameters provide additional predictive values for cardiovascular events. Future study is needed to assess whether risk assessment enhanced by using these biomarkers and echocardiographic parameters might contribute to more effective prediction and better care for patients.
PLoS ONE 01/2013; 8(3):e60008. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dyslipoproteinemia is highly prevalent in diabetes, chronic kidney disease, and diabetic kidney disease (DKD). Both diabetes and chronic kidney disease (CKD) are associated with hypertriglyceridemia, lower high-density lipoprotein, and higher small, dense low-density lipoprotein. A number of observational studies have reported that dyslipidemia may be associated with albuminuria, renal function impairment, and end-stage renal disease (ESRD) in the general population, and especially in CKD and DKD patients. Diabetic glomerulopathy and the related albuminuria are the main manifestations of DKD. Numerous animal studies support the finding that glomerular atherosclerosis is the main mechanism of glomerulosclerosis in CKD and DKD. Some randomized, controlled trials suggest the use of statins for the prevention of albuminuria and renal function impairment in CKD and DKD patients. However, a large clinical study, the Study of Heart and Renal Protection (SHARP), does not support that statins could reduce ESRD in CKD. In this article, we analyze the complex association of dyslipoproteinemia with DKD and deduce its relevance from animal studies, observational studies, and clinical trials. We show that special subgroups could benefit from the statin treatment.
The Review of Diabetic Studies 01/2013; 10(2-3):110-20.
[show abstract][hide abstract] ABSTRACT: Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <-6 ml/min/1.73 m(2)/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3-5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.
PLoS ONE 01/2013; 8(2):e55643. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background and Aim: Echocardiographic left atrial diameter (LAD) has been documented to be an independent predictor of adverse cardiovascular outcomes in various populations. An enlarged left atrium is frequently noted in chronic kidney disease (CKD). We examined the association between albumin and indexed LAD (indexed to height) and assessed whether the combination of indexed LAD and albumin was independently associated with renal outcomes in patients with CKD stages 3-5. Methods: This longitudinal study enrolled 395 patients, who were classified into four groups according to median values of indexed LAD (LAD/height) and albumin. The change in renal function was measured by estimated glomerular filtration rate (eGFR) slope. Rapid renal progression was defined as eGFR slope less than -3 ml/min/1.73 m(2)/year. The renal end point was defined as commencement of dialysis. Results: Albumin was significantly associated with indexed LAD (β = -0.108, P = 0.024). During follow-up period, seventy-four patients started dialysis. After the multivariate analysis, the group with higher indexed LAD and lower albumin was independently associated with rapid renal progression (odds ratio, 7.979; 95% confidence interval [CI], 3.028 to 21.025) and progression to dialysis (hazard ratio, 2.352; 95% CI, 1.078 to 5.131). Conclusions: Our findings show that albumin is independently associated with indexed LAD and suggest that the combination of increased indexed LAD and hypoalbuminemia is independently associated with rapid renal progression and progression to dialysis in patients with CKD. Assessments of serum albumin and indexed LAD by echocardiography are useful for predicting the risk for adverse renal outcomes.
International journal of medical sciences 01/2013; 10(5):575-84. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: : Abnormal ankle-brachial index (ABI) is associated with increased morbidity and mortality in hemodialysis patients. However, whether the decrease in ABI over time carries the prognostic value is unknown. The aim of this study was to assess whether the decrease in ABI over time was a good predictor of poor cardiovascular (CV) prognosis in hemodialysis patients.
: This study enrolled 234 routine hemodialysis patients and 173 patients completed the follow-up. The ABI was measured by an ABI-form device at baseline and at the first year follow-up. The ΔABI was defined as ABI measured at the first year follow-up minus ABI measured at baseline. Progressors of ABI were defined as patients with ΔABI < -0.3. CV events were defined as CV death, hospitalization for unstable angina, nonfatal myocardial infarction, hospitalization for arrhythmia, hospitalization for congestive heart failure and stroke.
: The follow-up period was 37.8 ± 11.1 months. In the multivariate analysis, progressors of ABI (hazard ratio, 2.71; 95% confidence interval, 1.10-6.68, P = 0.03), decreased albumin and increased high-sensitivity C-reactive protein were associated with increased CV events.
: This longitudinal study showed ΔABI < -0.3 was independently associated with an increase in CV events. Hence, a great decrease in ABI over time might be a useful indicator of poor CV prognosis in hemodialysis patients.
The American Journal of the Medical Sciences 12/2012; 344(6):457-61. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Chronic hypoxia has been recognized as a common mechanism driving the progression of many glomerular diseases. Glomerular cells, though susceptible to hypoxic injuries, are less studied to unravel the hypoxia-related influences. In the present study, we showed that both lipopolysaccharide (LPS) and hypoxia induced B7-1 and hypoxia-inducible factor (HIF)-1α expression in podocytes. B7-1, an essential player in the regulation of podocytes stress fibers, interacted directly with the N-terminal oxygenation domain of HIF-1α protein and therefore, might interfere with the HIF-related oxidative events. The suggestion was supported by the changes in the expression of inducible nitric oxide synthase and nitric oxide. The orderly arranged stress fibers in differentiated podocytes were disrupted by either LPS or hypoxic stimulation, and the disruption could be rescued if they were brought back to normal oxygen tension. Cell motility increased with the stimulation by LPS and hypoxia, most probably mediated by the induction of B7-1 and HIF-1α, respectively. We generated a B7-knockdown podocytes cell line using the lentiviral siRNA system. The LPS- and hypoxia-induced stress fibers disruption was largely prevented in the B7-knockdown podocytes. The increased cell motility by LPS and hypoxia stimulations was also ameliorated in the B7-knockdown podocytes. In summary, we found that both B7-1 and HIF were up-regulated by LPS and hypoxic stimulations in podocytes and they interacted with each other. Hypoxia disrupted the abundant stress fibers and increased cell motility. These hypoxia-induced changes were prevented in B7-knockdown podocytes and it highlighted the importance of B7-1 expression in the hypoxia-related podocytes injuries.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The inevitable post-inflammatory fibrosis and adhesion often compromises future treatment in peritoneal dialysis patients. Here, we describe a patient who experienced an unusual form of peritoneal adhesion that made her give up peritoneal dialysis. However, its unique pattern also saved her from infection caused by bowel perforation. CASE PRESENTATION: The female patient discontinued peritoneal dialysis due to gradual dialysis inadequacy. Two months after shifting to hemodialysis with generally improved sense of well-being and no sign of abdominal illness, she was admitted to remove the Tenckhoff catheter. The procedure was smooth, but fever and abdominal pain not at the site of operation developed the next day. Abdominal ultrasound showed the presence of ascites and aspiration revealed slimy, green-yellowish pus that gave a negative result on bacterial culture. Abdominal computed tomography (CT) with oral contrast medium was performed, but failed to demonstrate the suspected bowel perforation. The examination, however, did show accumulation of pus inside the abdomen but outside the peritoneal cavity. We drained the pus with two 14-F Pig-tail catheters and the total amount of drainage approached 4000 ml. The second CT was performed with double dose of the contrast medium and found a leak of the contrast from the jejunum. She then received laparotomy and had the perforation site closed. CONCLUSIONS: In summary, this uremic patient suffered from pus accumulation inside her abdomen without obvious systemic toxic effect. The bowel perforation and pus formation might be caused by repeated peritonitis, but the peritoneal adhesion itself might also isolate her peritoneal cavity from the anticipated toxic injuries of bowel perforation.
[show abstract][hide abstract] ABSTRACT: An interarm BP difference has been associated with atherosclerosis and adverse cardiovascular outcomes. This study investigated whether an interleg BP difference was associated with peripheral vascular disease and overall and cardiovascular mortality in hemodialysis patients.
This study enrolled 210 hemodialysis patients from December 2006 to January 2007. Bilateral leg BPs were measured simultaneously by an ankle-brachial index (ABI)-form device before hemodialysis.
The mean follow-up period was 4.4±1.5 years. ABI <0.9 and high brachial-ankle pulse wave velocity were independently associated with an interleg difference in systolic BP of ≥15 mmHg or diastolic BP of ≥10 mmHg. Furthermore, this difference was an independent predictor for overall mortality (hazard ratio [HR], 3.36; 95% confidence interval [CI], 1.68-6.72; P<0.01) and cardiovascular mortality (HR, 4.84; 95% CI, 1.84-12.71; P<0.01) after adjustment for demographic, clinical, and biochemical parameters. After further adjustment for ABI <0.9 and brachial-ankle pulse wave velocity, the relation remained significant to overall mortality (HR, 2.91; 95% CI, 1.28-6.64; P=0.01) and cardiovascular mortality (HR, 3.15; 95% CI, 1.05-9.44; P=0.04).
A difference in systolic BP of ≥15 mmHg or diastolic BP of ≥10 mmHg between legs was associated with peripheral vascular disease and increased risk for overall and cardiovascular mortality in hemodialysis patients. Detection of an interleg BP difference may identify hemodialysis patients at increased risk of peripheral vascular disease and overall and cardiovascular mortality.
Clinical Journal of the American Society of Nephrology 08/2012; 7(10):1646-53. · 5.07 Impact Factor