Sun Ae Yoon

Access Blood Flow as a Predictor of Early Failures of Native Arteriovenous Fistulas in Hemodialysis Patients

Blood flow imaging using color doppler has proven effective in predicting graft failures in hemodialysis patients, but its effect on native arteriovenous fistulas (AVF) is not well known. This study was performed to investigate whether measurements of the access blood flow can be used as predictors of an early failure of a native AVF in hemodialysis patients. Fifty-three consecutive patients who received native AVF operations were included in this study. Access blood flow was measured at 1 week after operations, and AVF function was followed for 4 months. During the follow-up, access failures developed in 10 patients at 9.8 ± 3.5 weeks. AVF blood flow was significantly lower in the failure group (n = 10) than in the patent group (n = 43) (450 ± 214 vs. 814 ± 348 ml/min, p = 0.003). The incidence of access failures was higher in the patients with a flow <350 ml/min (n = 9) compared to the patients with a flow >350 ml/min (n = 44) (55.5 vs. 11.3%, p = 0.008). The diameters of veins were significantly smaller in the failure group than in the patent group (3.5 ± 0.5 vs. 4.1 ± 0.7 mm, p = 0.018). The incidence of diabetes mellitus was higher in the failure group than in the patent group (90 vs. 51%, p = 0.025). However, age, sex, duration from an operation to first cannulation, and different AVF sites did not make a significant difference between the two groups. Our data suggest that access blood flow measurements using color doppler ultrasound during early postoperative periods are useful parameters in predicting an early failure of a native AVF in hemodialysis patients.

Synergistic effects of mycophenolate mofetil and losartan in a model of chronic cyclosporine nephropathy.

Background. Combined treatments of mycophenolate mofetil (MMF) and losartan (LSRT) have synergistic effects on various renal diseases through their hemodynamic and anti-inflammatory effects. This study investigated whether MMF treatment is effective in inhibiting inflammatory processes in chronic cyclosporine A (CsA) nephrotoxicity, and whether combined treatment using MMF and LSRT affords superior protection compared with the respective monotherapies. Methods. Rats on a low-salt diet were given vehicle (VH group, olive oil, 1 mg/kg per day), CsA (15 mg/kg per day), CsA and LSRT (CsA+LSRT group, 100 mg/L per day), CsA and MMF (CsA+MMF group; 40 mg/kg per day), or CsA, LSRT and MMF (CsA+LSRT MMF group). Control groups received each drug without CsA treatment. Renal function, histologic parameters (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and mediators of CsA-induced nephrotoxicity (angiotensin-II, osteopontin, and transforming growth factor [TGF]-&bgr;1) were studied. Results. The CsA-treated rats showed decreased renal function and increased histologic parameters compared with the VH-treated rats. The CsA+MMF treatment significantly improved renal function and histopathologic parameters compared with the CsA group, and combined treatment with MMF and LSRT further improved those parameters compared with the CsA+LSRT and CsA+MMF groups. At a molecular level, increased expression of angiotensin II protein, osteopontin, and TGF-&bgr;1 mRNAs in the CsA group were significantly decreased with MMF, and further decrease was observed with the combined treatment using MMF and LSRT. Conclusions. MMF treatment decreases CsA-induced nephrotoxicity, and combined treatment with LSRT has a synergistic effect in preventing chronic CsA nephrotoxicity.

The Impact of Intima-media Thickness of Radial Artery on Early Failure of Radiocephalic Arteriovenous Fistula in Hemodialysis Patients

This study was performed to investigate the impact of intima-media thickness (IMT) of radial artery on early failure of radiocephalic arteriovenous fistula (AVF) in hemodialysis (HD) patients. Ninety uremic patients undergoing radiocephalic AVF operation were included in this study. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. And then AVF patency was followed up for 1 yr after the operation. Of the total 90 patients, 31 patients (34%) had AVF failure within 1 yr after the operation. Mean IMT was thicker in failed group (n=31) than in patent group (n=59) (486±130 µm vs. 398±130 µm, p=0.004). The AVF patency rate within 1 yr after the operation was lower in patients with IMT ≥500 µm (n=26) than in patients with IMT <500 µm (n=64) (p=0.017). Age was an independent risk factor of IMT. Diabetes mellitus tended to be independent risk factor but not statistically significant. Our data suggest that increased radial artery IMT is closely associated with early failure of radiocephalic AVF in HD patients.

Prevalence and Clinical Course of Hepatitis B and Hepatitis C Liver Disease in Ciclosporin-Treated Renal Allograft Recipients

We performed this study to evaluate prevalence and clinical course of hepatitis B surface antigen (HBsAg)-positive and anti-hepatitis C virus (HCV)-positive renal transplant recipients. HBsAg positivity was 13.7 and anti-HCV positivity 12.8%. Before transplantation, the HBsAg positivity was observed in in 83.5% of the patients, and 16.4% of the patients acquired HBsAg after renal transplantation. In the HCV group, anti-HCV positivity was observed in 47.1% before transplantation, and 19.6% acquired anti-HCV after renal transplantation. The prevalence of chronic hepatitis in the hepatitis B virus (HBV) and in the HCV groups was not different (25.7 vs. 25.5%). Among those with chronic hepatitis in the HBV group, 4 cases progressed to fulminant hepatic failure, 1 case progressed to the end-stage liver cirrhosis, and 1 case to hepatocellular carcinoma. However, in the HCV group, no case showed progression of chronic hepatitis. The overall mortality in the HBV and HCV groups was 25.3 and 7.8%, respectively (p = 0.001). Among 20 fatal cases in the HBV group 9, cases were liver disease related, but no liver disease related death occurred in the HCV group. In conclusion, HCV as well as HBV infections are quite prevalent and important causes of posttransplant chronic hepatitis, and the clinical course of anti-HCV-positive recipients is less aggressive than that of HBsAg-positive recipients.

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

BACKGROUND AND OBJECTIVES The notion that oral intestinal sorbent AST-120 slows renal disease progression has not been evaluated thoroughly. In this study, we investigated the long-term effect of AST-120 on renal disease progression (doubling of serum creatinine, eGFR decrease >50%, or initiation of RRT) in patients with advanced CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We prospectively recruited 579 patients (CKD stage 3 or 4) from 11 medical centers in Korea from March 4, 2009 to August 31, 2010 and randomized them into an AST-120 arm and a control arm. Patients in the AST-120 arm were given 6 g AST-120 in three divided doses per day, and those in the control arm received only standard conventional treatment (open-label design) for 36 months or until the occurrence of primary outcomes. RESULTS Levels of serum and urine indoxyl sulfate and β2-microglobulin decreased throughout the study period in both treatment arms; however, there was not a significant difference in change in uremic toxins in the AST-120 and control arms. The two arms were not different in the occurrence of composite primary outcomes (100 events in 272 individuals in the AST-120 arm and 100 events in 266 individuals in the control arm; hazard ratio, 1.12; 95% confidence interval, 0.85 to 1.48; log-rank P=0.45). The decline in eGFR and change in proteinuria were similar in the two treatment arms over time (Prandomization-time=0.64 and Prandomization-time=0.16, respectively). There was no difference in mortality (nine deaths in the AST-120 arm and 11 deaths in the control arm; log-rank P=0.73) or unplanned hospitalizations (102 in the AST-120 arm and 109 in the control arm; log-rank P=0.76) in the two treatment arms. There was no significant difference of the health-related quality of life score between the two arms. CONCLUSIONS Long-term use of AST-120 added to standard treatment did not change renal disease progression, proteinuria, mortality, and health-related quality of life in patients with advanced renal dysfunction.

Association between blood pressure and target organ damage in patients with chronic kidney disease and hypertension: results of the APrODiTe study

Blood pressure control is the most established practice for preventing the progression of chronic kidney disease. Evidence addressing blood pressure control status or nocturnal blood pressure dipping in Korean hypertensive patients with chronic kidney disease is scarce. We recruited 1317 hypertensive patients (chronic kidney disease stages 2–4, median age 58) from 21 centers in Korea. These patients underwent office and ambulatory blood pressure monitoring. High office and ambulatory blood pressure were defined as >140/90 mm Hg and >135/85 mm Hg (daytime)/ >120/70 mm Hg (nighttime), respectively. The blood pressure control status was as follows: true controlled (19%), white-coat (4.3%), masked (33.9%) and sustained uncontrolled (42.3%) hypertension. The dipping status was as follows: extreme-dipping (14.9%), dipping (33.3%), non-dipping (34.5%) and reverse-dipping (17.3%). Masked and sustained hypertension as well as non-dipping/reverse-dipping was more apparent in proportion to renal dysfunction and the extent of proteinuria. Ageing (⩾58 years), male gender, obesity, diabetic nephropathy and proteinuria (>300 mg g−1 Cr or dipstick proteinuria⩾1+) were independently associated with sustained uncontrolled hypertension. Diabetic nephropathy, old age, a history of stable angina/heart failure, advanced renal dysfunction and higher proteinuria levels were also significantly associated with non-dipping and reverse-dipping. Half of Korean chronic kidney disease patients had uncontrolled blood pressure and a non-dipping nocturnal blood pressure pattern. Future studies are warranted to assess the predictive values of ambulatory blood pressure for cardiorenal events in Korean chronic kidney disease patients.

Pre-existing Arterial Micro-Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients.

Vascular access micro‐calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vascular access patency is still undetermined. Our study aimed to determine the impact of arterial micro‐calcification (AMiC) on the patency of vascular access in HD patients. One‐hundred fourteen HD patients receiving arteriovenous fistula (AVF) operation were included in this study. During the operation, we obtained partial arterial specimen and performed pathological examination by von Kossa stain to identify AMiC. We compared primary unassisted AVF failure within 1 year between positive and negative AMiC groups, and performed Cox regression analysis for evaluating risk factor of AVF failure. The incidence of AMiC was 37.7% and AVF failure occurred in 45 patients (39.5%). The AVF failure rate within 1 year was greater in the positive AMiC group than those in the negative AMiC group (53.5% vs. 31.0%, p = 0.02). Kaplan–Meier analysis showed that the positive AMiC group had a lower AVF patency rate than the negative AMiC group (p = 0.02). The presence of AMiC was an independent risk factor for AVF failure. In conclusion, preexisting AMiC of the vascular access is associated with primary unassisted AVF failure in incident HD patients.

Morning hypertension and night non-dipping in patients with diabetes and chronic kidney disease

Morning hypertension (HTN) and nocturnal non-dipping (ND) are closely associated with target organ damage and cardiovascular events. However, their importance in diabetics with advanced renal disease is unclear. We evaluated the relationships of morning HTN and ND with estimated glomerular filtration rate (eGFR) and proteinuria, and determined the risk of morning HTN and ND according to presence of diabetes mellitus (DM) and chronic kidney disease (CKD) stage. A total of 1312 patients, including 439 with diabetes, were prospectively recruited at 21 centers in Korea. All patients had HTN and an eGFR of 15–89 ml min−1 per 1.73 m2. Ambulatory 24-h blood pressure was assessed. The rates of morning HTN (25.2% vs. 13.6%, P<0.001) and ND (58.2% vs. 48.2%, P=0.002) were higher in diabetics than in non-diabetics. eGFR was correlated with ND in all patients (P<0.05) and with morning HTN only in non-diabetics (P=0.005). Proteinuria was related to ND in all patients (P<0.05) and to morning HTN only in diabetics (P=0.001). In a regression analysis, the risk of morning HTN was 2.093 (95% confidence interval (95% CI): 1.070–4.094) for the DMCKD2 group, 1.634 (95% CI: 1.044–2.557) for the CKD3–4-only group and 2.236 (95% CI: 1.401–3.570) for the DMCKD3–4 group compared with the CKD2-only group. The risk of ND was high for stage 3–4 CKD: 1.581 (95% CI: 1.180–2.120) for non-diabetics and 1.842 (95% CI: 1.348–2.601) for diabetics. Diabetics showed higher rates of morning HTN, ND and uncontrolled sustained HTN compared with non-diabetics with CKD of the same stages.

Arterial Micro-Calcification of Vascular Access is Associated with Aortic Arch Calcification and Arterial Stiffness in Hemodialysis Patients

Vascular calcification of the coronary arteries or aorta is an independent risk factor for cardiovascular outcome, but clinical significance of arterial micro‐calcification (AMC) of vascular access is unclear in hemodialysis (HD) patients. Sixty‐five patients awaiting vascular access operation were enrolled. We compared surrogate markers of cardiovascular morbidity such as aortic arch calcification (AoAC) by chest radiography, arterial stiffness by brachial‐ankle pulse wave velocity (baPWV) and endothelial dysfunction by flow‐mediated dilatation (FMD) between patients with and without AMC of vascular access on von Kossa staining. AMC of vascular access was detected in 36 (55.4%). The AMC‐positive group had significantly higher incidence of AoAC (63.9% vs. 20.7%, p < 0.001) and higher baPWV (26.5 ± 9.4 m/s vs. 19.8 ± 6.6 m/s, p = 0.006) than the AMC‐negative group. There was no significant difference in FMD between the two groups (5.4 ± 2.6% vs. 5.7 ± 3.5%, p = 0.764). The AMC‐positive group had higher incidence of diabetes mellitus, higher systolic blood pressure and wider pulse pressure than the AMC‐negative group. This study suggests that AMC of vascular access may be associated with cardiovascular morbidity via AoAC and arterial stiffness in HD patients.

The Clinical Association of the Blood Pressure Variability with the Target Organ Damage in Hypertensive Patients with Chronic Kidney Disease

It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score ≥4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 and proteinuria).The mean BPV of the subjects was 15.9±4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients. Graphical Abstract