Ha Young Oh

Decreased Number and Impaired Angiogenic Function of Endothelial Progenitor Cells in Patients With Chronic Renal Failure

Objective—Increased risk of cardiovascular disease in patients with chronic renal failure (CRF) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPCs) may play key roles. We hypothesized that altered EPC biology may contribute to the pathophysiology of CRF. Methods and Results—EPCs were isolated from CRF patients on maintenance hemodialysis (n=44) and from a normal control group (n=30). CRF patients showed markedly decreased numbers of EPC (44.6%) and colonies (75.3%) when compared with the controls (P <0.001). These findings were corroborated by 30.5% decrease in EPC migratory function in response to vascular endothelial growth factor (VEGF) (P =0.040) and 48.8% decrease in EPC incorporation into human umbilical vein endothelial cells (HUVEC) (P <0.001). In addition, Framingham’s risk factor score of both CRF (r = −0.461, P =0.010) and normal group (r = −0.367, P =0.016) significantly correlated with the numbers of EPC. Indeed, the number of circulating EPC was significantly lower in CRF patients than in normal group under the same burden of risk factors (P <0.001). A significant correlation was also observed between dialysis dose (Kt/V) and EPC incorporation into HUVEC (r =0.427, P =0.004). Conclusions—EPC biology, which is critical for neovascularization and the maintenance of vascular function, is altered in CRF. Our data strongly suggest that dysfunction of circulating EPC has a role in the progression of cardiovascular disease in patients with CRF.

Serum Uric Acid Is Associated With Microalbuminuria in Prehypertension

Serum uric acid is associated with cardiovascular disease. However, the independent role of uric acid in the development of cardiovascular disease is uncertain. This study examined the cross-sectional association of serum uric acid level with microalbuminuria among 6771 subjects without diabetes or hypertension. Blood pressure was categorized as prehypertension (systolic blood pressure, 120 to 140 mm Hg or diastolic blood pressure, 80 to 90 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Microalbuminuria was found in 4.0% of normotensive subjects (n=4819) and in 7.9% of prehypertensive subjects (n=1952). Prehypertensive subjects with microalbuminuria had higher uric acid level than those with normoalbuminuria (men, 387 [68] mmol/L versus 371 [69] mmol/L; P=0.017; women 286 [56] mmol/L versus 262 [54] mmol/L; P=0.006). However, the difference in serum uric acid level according to the presence or absence of microalbuminuria was not found in the normotensive group. Multiple logistic regression models showed that, in the prehypertensive group, after adjustment for other cardiovascular risk factors, the highest uric acid quartile entailed >2 times greater risk for microalbuminuria than the lowest quartile in both men (odds ratio, 2.12; 95% CI, 1.16 to 3.87) and women (odds ratio, 3.36; 95% CI, 1.17 to 9.69). In the normotensive group, serum uric acid quartile did not show the independent association with microalbuminuria. In conclusion, serum uric acid level was strongly associated with microalbuminuria in prehypertensive subjects.

Effect of an Electronic Alert on Risk of Contrast-Induced Acute Kidney Injury in Hospitalized Patients Undergoing Computed Tomography

BACKGROUND Prophylaxis against contrast-induced acute kidney injury (AKI) in hospitalized patients is underused. We evaluated the impact of a computerized alert program for contrast-induced AKI for hospitalized patients undergoing contrast-enhanced computed tomography (CT). STUDY DESIGN Quality improvement report. SETTING & PARTICIPANTS 463 adult inpatients in a single center with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). QUALITY IMPROVEMENT PLAN We developed a computer alert program in which the responsible physician was alerted to a patients risk of contrast-induced AKI in the form of a warning message box and was recommended to consider prophylactic measures for contrast-induced AKI when he or she ordered contrast-enhanced CT for patients with eGFR <60 mL/min/1.73 m(2). The intervention was applied simultaneously to all hospitalized patients from March 18, 2010. The hospitals contrast-induced AKI preventive guidelines included prehydration, posthydration, and oral N-acetylcysteine. OUTCOME & MEASUREMENTS Use of prophylactic interventions, development of contrast-induced AKI. Contrast-induced AKI was defined as an increase in serum creatinine level (≥0.3 mg/dL or ≥50%) 24-72 hours after contrast medium exposure. RESULTS 258 adult inpatients with eGFR <60 mL/min/1.73 m(2) were identified as undergoing contrast-enhanced CT before application of the computer alert program (from October 28, 2009, to March 17, 2010), and 205, after its application (from March 18, 2010, to August 5, 2010). Individuals in the postalert group received contrast-induced AKI prophylaxis more often than those in the prealert group (55% vs 25% for total prophylaxis; P < 0.001). The incidence of contrast-induced AKI was lower in the postalert group than in the prealert group (3% vs 10%; P = 0.02). LIMITATIONS Observation bias; only 61.5% of participants were evaluated for contrast-induced AKI. CONCLUSIONS Implementation of a computerized alert program in hospitalized patients was followed by increased use of prophylaxis and decreased risk of contrast-induced AKI.

Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients

Abstract:  Human parvovirus B19 (B19) infection has been known to cause chronic anemia, pure red cell aplasia (PRCA), glomerulopathy, and allograft dysfunction in kidney transplant (KT) recipients. The aim of this study was to evaluate the incidence and clinical significance of B19 infection in KT recipients. A total of 537 serum samples from 167 KT recipients were included in the present study. The incidence of B19 infection was based on either qualitative polymerase chain reaction (PCR) or quantitative PCR with LightCycler Parvovirus B19 Quantitation kit. Clinical significance of B19 infection was investigated by a retrospective review of hemoglobin (Hb) levels and the results of kidney and bone marrow biopsies. The overall PCR positive rate was 18.3% (98/537), and 52 of 167 (31.1%) KT recipients showed at least one positive PCR. In addition, 20 of 167 subjects (12.0%) showed PCR‐positivity more than two consecutive times, and they had significantly lower Hb levels than those with negative or one positive PCR (p < 0.0001). Furthermore, two patients suffered from PRCA, which was confirmed by bone marrow biopsy. However, B19 infection did not seem to affect the graft outcome. In conclusion, the B19 infection in KT recipients was not uncommon and was associated with low Hb levels and PRCA after KT.

Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation.

Background. Human (H) cytomegalovirus (CMV) infections are a major cause of morbidity and mortality among kidney transplants. We performed a prospective study to evaluate the clinical usefulness of HCMV antigenemia assay for preemptive treatment after kidney transplantation. Methods. A total of 100 patients were followed up by HCMV antigenemia assay at posttransplantation weeks 1, 3, 5, 7, 9, 13, 17, and 21. Asymptomatic patients with positive antigenemia were observed without specific antiviral therapy. Results. Most patients had been given cyclosporine A- and prednisolone-based immunosuppressive therapy (99.0%) and were HCMV seropositive before transplantation (99.0%). A positive antigenemia assay was detected in 41 patients among 97 eligible patients. Symptomatic CMV diseases were observed in 10 of 41 patients. HCMV infections were related to history of acute rejection and use of antithymocyte globulin. HCMV-related symptoms and signs were clearly correlated with the level of antigenemia. All patients who had an HCMV antigenemia titer of higher than 50 per 400,000 leukocytes developed HCMV-related symptoms and signs during the follow-up period. This criterion showed the highest positive predictive value and specificity in the development of symptomatic HCMV infection. Conclusions. Data suggest that HCMV antigenemia titer can be used as a useful guide to preemptive treatment of HCMV infection after kidney transplantation in HCMV-positive donor and recipient.

Incidence, Risk Factors, and Prediction of Acute Kidney Injury After Off-Pump Coronary Artery Bypass Grafting

Background: Acute kidney injury (AKI) is a serious complication after coronary artery bypass grafting and is closely associated with high mortality. The objective of the present study was to identify the incidence and risk factors for AKI after off-pump coronary artery bypass grafting (OPCAB) and to construct a risk model for prediction of AKI after OPCAB. Methods: We retrospectively studied 448 adult patients who underwent isolated OPCAB between April 2006 and July 2007. AKI was defined as an increase in serum creatinine of 0.3 mg/dL or 50% within 48 h after surgery. Multivariate analysis was used to evaluate risk factors for AKI after OPCAB and a risk model was developed with a weighted score based on the odds ratio. Results: The incidence of AKI was 7.6% (n = 34). Most patients (97%) had mild AKI. Independent preoperative risk factors of postoperative AKI were identified as high systolic blood pressure, decreased glomerular filtration rate, and coronary angiography (CAG) less than 7 days prior to OPCAB. The incidence of AKI across each increasing score level increased from 2.2% to 60%. Conclusion: AKI after OPCAB was common. High systolic blood pressure, renal dysfunction, and CAG less than 7 days prior to cardiac surgery were associated with AKI after OPCAB. Our risk model may provide information to clinicians and patients about the risk of postoperative AKI.

Association between Changes in N-Terminal Pro-Brain Natriuretic Peptide Levels and Changes in Left Ventricular Mass Index in Stable Hemodialysis Patients

Background/Aims: Left ventricular (LV) hypertrophy is a powerful predictor of mortality in dialysis patients. Serial measurements of LV mass provide prognostic information. We evaluated the association between changes in biomarkers and changes in LV mass index (LVMI) in hemodialysis (HD) patients. Methods: This was a prospective study of 21 stable HD patients with preserved LV ejection fraction (≧50%). Echocardiography and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and cardiac troponin T were performed on the same day and repeated 6 and 12 months later. Results: At baseline, the NT-proBNP and BNP levels correlated with LVMI. Percent changes in LVMI were positively associated with those in log-transformed NT-proBNP levels during both the first (baseline vs. month 6, r = 0.78, p < 0.001) and the second 6 months (months 6 vs. 12, r = 0.73, p < 0.001). Among the 3 biomarkers, NT-proBNP was the only one that was related to changes in LVMI by multivariate correlation analysis, including age, sex, blood pressure, predialysis weight and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Conclusion: Our results show that changes in LVMI are closely correlated with variation in NT-proBNP levels in HD patients. These data have significant implications for the application of NT-proBNP as a biomarker for assessing changes in LVMI in HD patients.

The origin and the clinical significance of urinary angiotensinogen in proteinuric IgA nephropathy patients.

Abstract Background. Urinary angiotensinogen (AGT) was reported as a marker of renal injury in chronic kidney disease patients. However, the main source of urinary AGT is unknown in proteinuric patients because the disrupted filtration barrier might cause AGT filtration. We investigated the origin and the clinical importance of urinary AGT in proteinuric IgA nephropathy (IgAN) patients. Methods. In patients with biopsy-proven IgAN, urinary and plasma AGT was measured using a sandwich ELISA and compared with intrarenal AGT expression. The patients were followed up for 3 years. Results. Natural logarithm of the urinary AGT/creatinine (ln (urinary AGT/Cr)) was positively correlated with intrarenal expression of AGT (ln (urinary AGT/Cr) versus AGT/β-actin, r = 0.620, P < 0.0001; ln (urinary AGT/Cr) versus AGT density, r = 0.452, P = 0.007). Ln (urinary AGT/Cr) showed a positive correlation with urinary protein/creatinine ratio (PCR) but a negative correlation with estimated glomerular filtration rate (eGFR). Regression analyses showed that ln (urinary AGT/Cr) was a significant determinant of urinary PCR and eGFR 3 years after biopsy. Conclusions. Urinary AGT reflects intrarenal AGT expression and correlates with the extent of proteinuria and renal function. Our study indicates the intrarenal compartment as the main source of urinary AGT, suggesting its clinical implication as an important biomarker in proteinuric IgAN patients.

The Role of Nafamostat Mesylate in Continuous Renal Replacement Therapy among Patients at High Risk of Bleeding

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury. The objectives of this retrospective study were to assess the effect of nafamostat on circuit patency of CRRT and the safety regarding bleeding complications in patients at high risk of bleeding. We conducted a retrospective study of 243 CRRT patients at high risk of bleeding. We started CRRT without anticoagulation, and nafamostat was used if hemofilter lifespan was less than 12 h. The average hemofilter lifespan was measured before and after drug infusion to evaluate the efficacy of nafamostat. The frequency and number of red blood cell (RBC) transfusions were measured to assess the safety of nafamostat. Of the 243 patients, 62 (25.5%) received nafamostat. In nafamostat group, the hemofilter lifespan was lengthened from 10.2 (7.5–13.0) h to 19.8 (12.6–26.6) h after drug infusion (p < 0.001). The hemofilter lifespan was 27.5 (17.5–38.2) h in anticoagulation-free group. The frequency of RBC transfusion during CRRT did not differ between the nafamostat group and the anticoagulation-free group (71% vs. 70%, p = NS). The median number of RBC units transfused per CRRT day was also not different between the two groups [0.7 (0.5–1.0) units/day vs. 0.7 (0.4–1.1) units/day; p = NS]. The use of nafamostat in patients at high risk of bleeding who require CRRT effectively lengthened the filter survival time without an increase in RBC transfusion. However, 74.5% of patients at high risk of bleeding maintained an acceptable CRRT hemofilter lifespan without circuit anticoagulation.

The impact of early and late acute rejection on graft survival in renal transplantation.

Background Advances in immunosuppression after kidney transplantation have decreased the influence of early acute rejection (EAR) on graft survival. Several studies have suggested that late acute rejection (LAR) has a poorer effect on long-term graft survival than EAR. We investigated whether the timing of acute rejection (AR) influences graft survival, and analyzed the risk factors for EAR and LAR. Methods We performed a retrospective cohort study involving 709 patients who underwent kidney transplantation between 2000 and 2009 at the Samsung Medical Center, Seoul, Korea. Patients were divided into three groups: no AR, EAR, and LAR. EAR and LAR were defined as rejection before 1 year and after 1 year, respectively. Differences in graft survival between the three groups and risk factors of graft failure were analyzed. Results Of the 709 patients, 198 (30%) had biopsy-proven AR [EAR=152 patients (77%); LAR=46 patients (23%)]. A total of 65 transplants were lost. The 5-year graft survival rates were 97%, 89%, and 85% for patients with no AR, EAR, and LAR, respectively. These differences were significant (P<0.001 for both by log-rank test). In time-dependent Cox regression analysis, EAR (hazards ratio, 3.37; 95% confidence interval, 1.90–5.99) and LAR (hazards ratio, 5.32; 95% confidence interval, 2.65–10.69) were significantly related to graft failure. When we set LAR as standard and compared it with EAR, there was no statistical difference between EAR and LAR (P=0.21). Conclusion AR, regardless of its timing, significantly worsened graft survival. Treatments to reduce the incidence of AR and improve prognosis are needed.