Euy Jin Choi

Calcitriol regresses cardiac hypertrophy and QT dispersion in secondary hyperparathyroidism on hemodialysis.

Background: Sudden cardiac death is common in patients on hemodialysis (HD), and its rate is as high as 25% of all cardiac deaths associated with left ventricular hypertrophy (LVH) and secondary hyperparathyroidism. A prolonged QT interval on standard electrocardiography is related to an increase in sudden death in various patient groups. It is also well known that LVH has been noted in uremic patients with high parathyroid hormone levels. Methods: To evaluate the response of intravenous calcitriol treatment on the QT interval and LVH in HD patients with secondary hyperparathyroidism (intact parathyroid hormone, iPTH, >450 ng/ml), echocardiographic, electrocardiographic (ECG), and biochemical assessments were performed over a 15-week period in 25 HD patients before and after intravenous calcitriol treatment. We also evaluated 25 age-, sex-, HD duration-, and BMI-matched HD control patients with secondary hyperparathyroidism. Results: In patients receiving intravenous calcitriol, a significant reduction in iPTH levels (p < 0.05) and alkaline phosphatase levels (p < 0.01) was found without changes in values of serum calcium and ionized Ca2+, phosphorus, Na+, K+, Mg2+, hematocrit, blood pressure, or other hemodynamic changes. Echocardiograms showed significant decreases in the thickness of the interventricular septum (p < 0.05), left posterior wall thickness (p < 0.05), and left ventricle mass index (LVMi, p < 0.01). In addition, sequential ECG measurement in patients with calcitriol treatment showed significant reductions in QTcmax (QTmax interval corrected for heart rates, p < 0.01) and QTc dispersion (QT dispersion corrected for heart rates, p < 0.01). However, in the control patients, biochemical, hemodynamic, and ECG changes, as well as myocardial structural and functional changes were not seen. Multiple regression analysis in all patients indicated that iPTH and LVMi levels were independent predictors of QTcmax while the LVMi level was the only independent predictor of QTc dispersion (p < 0.05). Conclusions: Our study showed a significant correlation between LVMi and QT dispersion in HD patients with secondary hyperparathyroidism. Intravenous calcitriol treatment, to be used for the control of secondary hyperparathyroidism, was found to cause regression of myocardial hypertrophy and a reduction in the QTc interval and dispersion, without biochemical and hemodynamic changes. These findings suggest that an active vitamin D metabolite has a cardioprotective action in HD patients.

Oral Supplementation of L-Arginine Prevents Chronic Cyclosporine Nephrotoxicity in Rats

This study was performed to evaluate the effect of L-arginine (L-Arg) on the prevention of chronic cyclosporine (CsA) nephrotoxicity in rats. Rats pair-fed a low-salt diet (0.05%) were given CsA (15 mg/kg/day s.c.), CsA and L-Arg (L-Arg group, 1.25 g/l water), CsA and N-nitro-L-arginine methyl ester (L-NAME group, 70 mg/l water) or vehicle. After 28 days, the L-Arg group had a higher glomerular filtration rate compared to the CsA (0.42±0.05 vs. 0.31±0.06 ml/min/100 g, p < 0.05) and the L-NAME groups (vs. 0.19± 0.04 ml/min/100 g, p < 0.05) and a significantly lower serum creatinine level compared to the CsA (0.70±0.06 vs. 0.92±0.12 mg/dl, p < 0.05) and the L-NAME groups (vs. 1.21±0.17 mg/dl, p < 0.05). The L-Arg group had less fibrosis, tubular injury (TI), and arteriolopathy than the CsA (fibrosis 0.39±0.14 vs. 0.74±0.15; TI 1.3±0.3 vs. 2.0±0.1; arteriolopathy 33±7 vs. 48±17, p < 0.05, respectively) and the L-NAME groups (fibrosis vs. 1.67±0.32, TI vs. 2.6±0.3, arteriolopathy vs. 63±10, p < 0.05, respectively). Plasma renin activity in the L-Arg group was less than in the CsA (18±2 vs. 23±3 ng Ang I/ml/h, p < 0.05) and the L-NAME groups (vs. 30±3 ng Ang I/ml/h, p < 0.05). Nitric oxide production in L-Arg group was higher than in the CsA (24.2±1.7 vs. 11.1±1.5 µmol/24 h, p < 0.05) and the L-NAME groups (vs. 8.4±1.0 µmol/24 h, p < 0.05). In conclusion, the nitric oxide pathway is associated with the pathogenesis of chronic CsA nephrotoxicity, and exogenous L-Arg supplementation is effective in reducing chronic CsA nephrotoxicity in rats.

Persistent Elevation of C-Reactive Protein May Predict Cardiac Hypertrophy and Dysfunction in Patients Maintained on Hemodialysis

Background: C-reactive protein (CRP), which reflects chronic inflammation, is a strong predictor of cardiovascular mortality in hemodialysis patients. We investigated whether persistent elevation of CRP is associatedwith cardiac function and morphology in patients maintained on hemodialysis. Methods: Predialysis high-sensitivity CRP (hs-CRP) was measured twice at an interval of 3 weeks in 52 stable hemodialysis patients, and echocardiographic studies were performed. Results: 25 patients showed persistent elevation of predialysis hs-CRP (>3 mg/l, high CRP group). Patients in the high CRP group had a lower dialysis dose (p < 0.01), higher troponin T (p < 0.01), and higher fibrinogen (p < 0.01). Echocardiographic studies showed that left atrial diameter (LA, p < 0.05), interventricular septal thickness (IVST, p < 0.05), left ventricular end-diastolic volume (LVEDV, p < 0.05), and left ventricular mass index (LVMI, p < 0.05) were higher in the high CRP group. However the ejection fraction (EF) was lower in the high CRP group (p < 0.05), which also contained more patients with low EF (<40%) (p < 0.01). There was no difference in diabetes mellitus, acute infection and type of vascular access between the groups. hs-CRP level was positively correlated with troponin T (r = 0.416, p < 0.01) and fibrinogen (r = 0.560, p < 0.001), and IVST with hs-CRP level (r = 0.291, p < 0.05), whereas the EF was negatively correlated with hs-CRP(r = –0.301, p < 0.05). In addition, the high CRP group correlated positively with IVST (r = 0.281, p < 0.05), LVEDV (r = 0.322, p < 0.05), and LVMI (r = 0.312, p < 0.05) and negatively with EF (r = –0.311, p < 0.05). On multivariate analysis, the high CRP group (β = –0.312, β = 0.238, and β = 0.318, respectively) was a significant predictor of EF (R = 0.62, p = 0.025), LVMI (R = 0.928, p = 0.02) and IVST (R = 0.64, p = 0.01). Conclusions: Persistent elevation of CRP, which is an independent risk factor for EF, LVMI and IVST, may predict cardiac hypertrophy and dysfunction in patients maintained on hemodialysis.

The role of autophagy in unilateral ureteral obstruction rat model

Aim:  Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death or proliferation. Unilateral ureteral obstruction (UUO) is a model of progressive renal fibrosis in the obstructed kidney. And UUO is followed by compensatory cellular proliferation in the contralateral kidney. We investigate the role of autophagy in the obstructed kidney and contralateral kidney after UUO.

The relationship between the regional abdominal adipose tissue distribution and the serum uric acid levels in people with type 2 diabetes mellitus

BackgroundHyperuricemia is associated with obesity. The visceral adiposity and subcutaneous adiposity may be associated with the differential metabolic risk, and the distribution of abdominal adipose tissue was significantly altered in people with type 2 diabetes mellitus (DM) compared to healthy people. Our study was performed to determine to the association between the regional abdominal adipose tissue distribution and serum uric acid levels in people with type 2 DM.MethodsA total of 699 people with type 2 DM and who had undergone abdominal computed tomography assessment of the visceral fat area and subcutaneous fat area were included. The serum uric acid levels were measured by the uricase method. Hyperuricemia was defined by cut-off value of > 7 mg/dl for men and > 6 mg/dl for women.ResultsThe visceral fat area was positively associated with the serum uric acid levels after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, serum creatinine, hemoglobin, serum albumin, serum high-density lipoprotein, serum triglyceride and hemoglobin A1c (β-coefficient = 0.117, p < 0.001). The logistic regression analysis showed that the visceral fat area was the significant independent predictor of hyperuricemia (OR 2.33, 95% CI, 1.21-4.50, p = 0.012). But there was no significant association between the subcutaneous fat area and the serum uric acid levels (β-coefficient = 0.061, p = 0.255).Conclusionsour data shows that the visceral fat area was positively associated with the serum uric acid levels, but the subcutaneous fat area was not in people with type 2 DM.

Natural History and Renal Pathology in Patients with Isolated Microscopic Hematuria

Background/Aims No definite conclusions have been reached about the natural history of patients with isolated microscopic hematuria (IMH). In this study, we observed the natural history of patients with IMH and examined factors related to a pathologic diagnosis and subsequent prognosis. Methods We retrospectively evaluated 156 subjects with IMH who had a renal biopsy performed. Of the 156 subjects, 33.3% were diagnosed with IgA nephropathy, 23.7% with mesangial proliferative glomerulonephritis, 15.4% with glomerular minor lesion, and 12.8% with thin basement membrane nephropathy; 6.4% had normal biopsies. Results We followed up with 100 subjects for about 31 months. During this follow-up period, two subjects who had received a pathologic diagnosis of IgA nephropathy developed chronic kidney disease. During the course of the study, one of these subjects presented with proteinuria and hypertension and the other with proteinuria. The overall incidences of proteinuria and hypertension were 6% and 5% respectively. Conclusions The prognosis for patients with IMH was relatively favorable, but patients developing proteinuria and/or hypertension require careful observation and management during the follow-up period.

Relationship between erythropoietin resistance index and left ventricular mass and function and cardiovascular events in patients on chronic hemodialysis

The response to erythropoietin (EPO) treatment varies considerably in individual patients on chronic hemodialysis. The EPO resistance index (ERI) has been considered useful to assess the EPO resistance and can be easily calculated in the clinic. The aim of this study was to investigate the association between ERI and left ventricular mass (LVM) and function and to determine whether ERI was associated with cardiovascular events in patients on hemodialysis. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on hemodialysis. The ERI was determined as the weekly weight‐adjusted dose of EPO (U/kg/week) divided by hemoglobin concentration (g/dL). Patients were divided into three groups by tertiles of ERI. Patients with higher tertiles of ERI had a higher LVM index and lower LV ejection fraction compared with those with lower tertiles of ERI (P = 0.019 and P = 0.030, respectively). The median follow‐up period was 53 months. The Kaplan–Meier plot showed increased frequency of cardiovascular events in patients with higher tertiles of ERI, compared with those with lower tertiles of ERI (P = 0.011, log‐rank test). The multivariate Cox proportional hazard models showed that the ERI was the significant independent predictor of cardiovascular events (HR 3.00, 95% CI, 1.04–8.62, P = 0.042). Our data show that ERI was related with LVM index, LV systolic function and cardiovascular events in patients with hemodialysis. By monitoring of ERI, early identification of the EPO resistance may be helpful to predict the cardiovascular risk in hemodialysis patients.

Evaluation of Acute Renal Failure in Bacterial Allograft Pyelonephritis Using Abdominal CT and Graft Biopsy

The causes of acute renal failure in bacterial allograft pyelonephritis were evaluated using abdominal CT and graft biopsy. Twenty-one recipients, who showed a poor response to antibiotic therapy, comprised this study group. The diagnostic approach taken with this poor responder group was first to perform abdominal CT. If a focal lesion was identified on abdominal CT, a diagnosis of acute focal bacterial nephritis or renal abscess was made. If no focal lesion was found, a graft biopsy was performed for diagnosis. Abdominal CT revealed focal lesions in 9 of the 21 recipients, and renal biopsy showed superimposed acute rejection in 8 of the 12 recipients biopsied. In conclusion, acute renal failure in allograft pyelonephritis is associated with not only severe infection but also a superimposed acute rejection process. Therefore, imaging study and graft biopsy are recommended in the poor responder group.

Effect of preload on left atrial function: evaluated by tissue Doppler and strain imaging

AIMS Both strain and strain rate (SR) measure the regional myocardial deformation and can assess phasic left atrial (LA) function. However, there is still a lack of evidence for their volume independency. In this study, strain and SR determined by tissue Doppler imaging were used to evaluate the effect of preload reduction in end-stage renal disease patients who were undergoing regular haemodialysis (HD). METHODS AND RESULTS Forty-one subjects who underwent transthoracic echocardiography just before and after HD were enrolled. LA strain was measured during late systole, and LA peak tissue velocity and SR were measured during systole and during early and late diastolic periods. The values of tissue velocity, strain, and SR were obtained in the basal septal, lateral, inferior, and anterior walls of the LA. The mean strain value was 23.89 ± 7.29% at baseline and decreased to 21.88 ± 5.85% after HD (P = 0.019). SR during systole (before HD 1.55 ± 0.40; after HD 1.38 ± 0.35, P = 0.001) and early diastole (before HD -1.41 ± 0.54; after HD -1.16 ± 0.45, P = 0.001) also changed. However, the acute preload change caused by HD did not affect the peak tissue velocity (before HD -6.34 ± 1.58 cm/s; after HD -6.46 ± 1.54 cm/s, P = 0.436) and the SR (before HD -1.36 ± 0.45/s; after HD -1.34 ± 0.29/s, P = 0.621) measured during late diastole. CONCLUSION Both tissue velocity and SR during late diastole, representing the contractile function of the LA, are relatively preload-independent parameters and are available for the evaluation of the LA function.

Predictors for diabetic retinopathy in normoalbuminuric people with type 2 diabetes mellitus.

BackgroundPrevious studies have reported that microalbuminuria is an independent risk factor for the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). For this reason, the clinical significance of DR in normoalbuminuric type 2 DM patients may be overlooked. The aim of this study was to investigate the prevalence of DR and predictors for DR in normoalbuminuric patients with type 2 DM.MethodsA total 310 patients with type 2 DM and normoalbuminuria, who were referred to the Department of Ophthalmology for screening of DR were included in this study. DR was clinically graded according to the International Clinical Diabetic Retinopathy guidelines. The urinary albumin excretion rate (UAER) was assessed via 24-hour urine collection and measured by immunoturbidimetric assay. Normoalbuminuria was defined as a UAER < 20 μg/min in 2 out of 3 consecutive tests taken within 2–3 months.ResultsDR of any grade was present in 64/310 (20.7 %) patients. Mild non-proliferative diabetic retinopathy (NPDR) was most prevalent in patients with DR of any grade (36/64, 56 %). The duration of diabetes (OR 1.01, 95 % CI, 1.01 – 1.02, p < 0.001), hemoglobin levels (OR 0.73, 95 % CI, 0.59 – 0.91, p = 0.004) and a higher tertile of UAER (OR 4.04, 95 % CI, 1.71 – 9.57, p = 0.001) had independently significant association with DR. NPDR as well as PDR was more prevalent in patients with higher tertile of UAER compared with those with lower tertile of UAER (NPDR, p = 0.002 and PDR, p = 0.027, respectively).ConclusionsOur findings suggest that patients with normoalbuminuric type 2 DM also require close monitoring for the early detection of DR, especially if they have a higher UAER, longer duration of diabetes, or lower hemoglobin levels.