Byoung Geun Han

Markers of glycemic control in the mouse: comparisons of 6-h- and overnight-fasted blood glucoses to Hb A1c

The present studies examined the relationship between fasting blood glucose and Hb A(1c) in C57BL/6J, DBA/2J, and KK/HlJ mice with and without diabetes mellitus. Daily averaged blood glucose levels based on continuous glucose monitoring and effects of 6-h vs. overnight fasting on blood glucose were determined. Daily averaged blood glucose levels were highly correlated with Hb A(1c), as determined with a hand-held automated device using an immunodetection method. R(2) values were 0.90, 0.95, and 0.99 in KK/HIJ, C57BL/6J, and DBA/2J, respectively. Six-hour fasting blood glucose correlated more closely with the level of daily averaged blood glucose and with Hb A(1c) than did blood glucose following an overnight fast. To validate the immunoassay-determined Hb A(1c), we also measured total glycosylated hemoglobin using boronate HPLC. Hb A(1c) values correlated well with total glycosylated hemoglobin in all three strains but were relatively lower than total glycosylated hemoglobin in diabetic DBA/2J mice. These results show that 6-h fasting glucose provides a superior index of glycemic control and correlates more closely with Hb A(1c) than overnight-fasted blood glucose in these strains of mice.

Superior Outcome of Nafamostat Mesilate as an Anticoagulant in Patients Undergoing Maintenance Hemodialysis with Intracerebral Hemorrhage

Aims. The incidence of complications associated with cerebrovascular diseases in patients who receive hemodialysis for a long-term period is higher than that of other complications. It is known that mortality due to cerebral hemorrhage is two times higher compared to non-dialysis patients. Anti-coagulants used for hemodialysis are essential. Accordingly, in cases in which the cerebral hemorrhage occurred, the selection of anti-coagulants for the prevention of further bleeding poses a great challenge to physicians. The change of hematoma and patient prognosis has a direct relationship. Many ongoing studies are conducted to examine the causative factors causing the increased hematoma and their related prognostic factors. In the current study, we examined the effect of nafamostat mesylate (a serine protease inhibitor) on the change of hematoma compared to heparin in hemodialysis patients. Methods. The current study was conducted in 17 hemodialysis patients who developed a cerebral hemorrhage. These patients were assigned to two groups based on the type of anti-coagulants that they used (i.e., nafamostat mesylate and heparin). Then, the factors affecting the change of hematoma following the onset of cerebral hemorrhage were examined. The prognosis of hematoma was assessed based on brain CT scans, which were performed two weeks after the onset of cerebral hemorrhage in four groups. Following this, groups 1 (the decreased hematoma) and 2 (the decreased delay) were merged to group A (resolving group), and groups 3 (the increased hematoma) and 4 (the death following the aggravation) were merged to group B (the expansion group) for further analysis. Results. There were no significant differences in baseline characteristics between the nafamostat group and the heparin group. A comparison between the resolving group and the expansion group also showed that there were no significant differences in baseline characteristics. In the anti-coagulants and the change of hematoma, however, there were significant differences between the two groups (p = 0.024). A comparison of the change of hematoma between the four groups was also made. This showed that platelet counts and BUN level were significant factors (Platelet; p = 0.042, BUN; p = 0.043 ANOVA with resolving group). Conclusions. Nafamostat mesylate has a similar profile of anti-coagulative activity to heparin. It is assumed, however, that nafamostat has an affirmative effect on the recovery of damaged sites following the onset of cerebral hemorrhage. It is an anti-coagulant that can be safely used for hemodialysis following the onset of cerebral hemorrhage.

A Case of Henoch-Schönlein Purpura in Disseminated Tuberculosis

Tuberculosis is still a common disease, even in some parts of developing countries. Although its major impact is pulmonary, the tuberculosis is actually a disseminated disease. An unusual form of renal involvement of tuberculosis is glomerulonephritis, as a part of systemic vasculitis, Henoch-Schönlein Purpura (HSP). A 41-year-old man, being treated with antituberculous agents for pulmonary tuberculosis, was transferred to our hospital because of newly developed generalized purpura and pretibial edema. Renal manifestations were proteinuria and hematuria. Renal biopsy disclosed interstitial chronic granulomatous inflammation with caseous necrosis and strong nodular mesangial Ig A deposit, along with trace granular Ig G deposition and perivascular C3 deposit. Skin lesions were nonthrombocytopenic palpable purpurae, proved leukocy toclastic vasculitis by skin biopsy. All clinical symptoms and signs were relieved by antituberculous medication. We concluded that disseminated tuberculosis might be a cause of HSP, an immune complex mediated disease.

Acute Kidney Injury by Arsine Poisoning: The Ultrastructural Pathology of the Kidney

Arsenic is a terribly poisonous material. There have been many reports of arsine poisoning in workers, and a few have discussed acute kidney injury by arsine. But literatures which investigated the pathologic findings are uncommon, and especially, the ones describing ultrastructural findings are rare. Here, we report an incident of acute arsine poisoning complicated by acute kidney injury and suggest the characteristics of the renal pathology in arsine-induced renal injury, especially the ultrastructural findings.

Coagulopathy in patients who experience snakebite

Background/Aims Coagulopathy is a common complication of snakebite, but there is little information on the clinical importance of coagulopathy. We analyzed the characteristics of coagulopathy after envenomation. Methods Ninety-eight patients who experienced snakebite were enrolled in this study. We divided all the patients into three groups by the ISTH DIC scoring system: the normal, simple coagulopathy and DIC groups. The coagulopathy group included both the simple coagulopathy and DIC groups. We then conducted a case-control study. Results There was a significant decrease in the Hct, protein, albumin, ALP and cholesterol levels in the coagulopathy group, and only the cholesterol level was deceased in the DIC group (p<0.05). Leukocytosis and rhabdomyolysis were significantly associated with coagulopathy, and hemolysis and rhabdomyolysis were associated with DIC (p<0.05). The presence of rhabdomyolysis was considered a risk factor for coagulopathy (p<0.05). These conditions continued for up to six to seven days after the snakebite. Conclusions Evaluation of coagulopathy with using these characteristics is helpful to properly manage the patients who experience snakebite.

Efficacy of hemocontrol biofeedback system in intradialytic hypotension-prone hemodialysis patients.

We conducted a study to determine whether the hemocontrol biofeedback system (HBS) can improve intradialytic hypotension (IDH) in hypotension-prone hemodialysis (HD) patients compared with conventional HD. In this multicenter prospective crossover study, 60 hypotension-prone patients were serially treated by conventional HD for 8 weeks (period A), by HD with hemoscan blood volume monitoring for 2 weeks (period B0), and by HBS HD for 8 weeks (period B1). The number of sessions complicated by symptomatic IDH during 24 HD sessions (14.9±5.8 sessions, 62.1% in period A vs 9.2±7.2 sessions, 38.4% in period B1, P<0.001) and the number of IDH-related nursing interventions in a session (0.96±0.66 in period A vs 0.56±0.54 in period B1, P<0.001) significantly decreased in period B1 than in period A. Recovery time from fatigue after dialysis was significantly shorter in period B1 than in period A. The patients with higher post-dialysis blood pressure, lower difference between pre- and post-dialysis blood pressure, less frequent IDH, and higher pre- and post-dialysis body weight in period A responded better to HBS in period B1 in regard to the reduction of IDH. In conclusion, HBS may improve the patient tolerability to HD by reducing the IDH frequency and promoting faster recovery from fatigue after dialysis. Graphical Abstract

Effects of a cGMP-specific phosphodiesterase inhibitor on expression of endothelial nitric oxide synthase and vascular endothelial growth factor in rats with cyclosporine-induced nephrotoxicity.

BACKGROUND The mechanism of cyclosporine (CsA)-induced nephrotoxicity has been suggested to be vasoconstriction due to reduced nitric oxide (NO), providing tissue fibrosis by elevation of transforming growth factor beta and vascular endothelial growth factor (VEGF). In this study using a rat model of CsA-induced nephrotoxicity, we administered a phosphodiesterase-5 inhibitor to ameliorate the renal injury and alter the expression of endothelial No synthase (eNOS) and VEGF. METHODS A right nephrectomy was performed in Sprague-Dawley rats (n = 30; 200-250 g, all male). The Ischemia group (n = 6) underwent ligation of the left renal artery for 45 minutes (IR) before observation for 28 days. After IR, the udenafil group (n = 6) was treated with 10 mg/kg drug orally, the CsA group (n = 6) received 15 mg/kg CsA injected subcutaneously and the CsA plus udenafil group (n = 6) received 15 mg/kg CsA injected subcutaneously together with the oral administration of 10 mg/kg udenafil. RESULTS Administration of udenafil significantly decreased serum creatinine either alone (0.21 ± 0.04 mg/dL) or in combination with CsA (1.86 ± 0.35 mg/dL) versus the ischemia (0.85 ± 0.22 mg/dL) and the CsA alone (3. 10 ± 0.77 mg/dL) group. (P = .002; P = .002). Comparing the Hematoxylin-eosin staining of the ischemia (0.41 ± 0.09) and CsA (0.44 ± 0.08) groups showed a significantly decreased loss of nuclei in proximal tubules after the administration of udenafil (0.27 ± 0.05 [P = .004] and 0.26 ± 0.02 [P = .002] respectively). Immunohistochemical staining showed strong eNOS staining in the udenafil and CsA plus udenafil groups. Western blots for eNOS showed decreased expression in the CsA group and increased expression in the udenafil group. Western blots for VEGF revealed reduced expression only in the CsA plus udenafil group. eNOS mRNA was decreased in the CsA (0.017 ± 0.010) compared with the ischemia group (0.048 ± 0.015; P = .000). VEGF mRNA which was decreased in the CsA group (2.026 ± 1.109), showed greater tendency after administration of udenafil (0.440 ± 0.449) (P = .003). CONCLUSION The phosphodiesterase inhibitor ameliorated renal injury in a rat model of CsA-induced nephrotoxicity, possibly related to increased eNOS and reduced VEGF expression.

Secondary Focal Segmental Glomerulosclerosis: From Podocyte Injury to Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a common cause of proteinuria and nephrotic syndrome leading to end stage renal disease (ESRD). There are two types of FSGS, primary (idiopathic) and secondary forms. Secondary FSGS shows less severe clinical features compared to those of the primary one. However, secondary FSGS has an important clinical significance because a variety of renal diseases progress to ESRD thorough the form of secondary FSGS. The defining feature of FSGS is proteinuria. The key event of FSGS is podocyte injury which is caused by multiple factors. Unanswered questions about how these factors act on podocytes to cause secondary FSGS are various and ill-defined. In this review, we provide brief overview and new insights into FSGS, podocyte injury, and their potential linkage suggesting clues to answer for treatment of the disease.

Copeptin in Hemodialysis Patients with Left Ventricular Dysfunction.

Purpose Copeptin has been considered as a useful marker for diagnosis and prediction of prognosis in heart diseases. However, copeptin has not been investigated sufficiently in hemodialysis patients. This study aimed to investigate the general features of copeptin in hemodialysis and to examine the usefulness of copeptin in hemodialysis patients with left ventricular dysfunction (LV dysfunction). Materials and Methods This study included 41 patients on regular hemodialysis. Routine laboratory data and peptides such as the N-terminal of the prohormone brain natriuretic peptide and copeptin were measured on the day of hemodialysis. Body fluid volume was estimated by bioimpedance spectroscopy, and the E/Ea ratio was estimated by echocardiography. Results Copeptin increased to 171.4 pg/mL before hemodialysis. The copeptin had a positive correlation with pre-dialysis body fluid volume (r=0.314; p=0.04). The copeptin level decreased along with body fluid volume and plasma osmolality during hemodialysis. The copeptin increased in the patients with LV dysfunction more than in those with normal LV function (218.7 pg/mL vs. 77.6 pg/mL; p=0.01). Receiver operating characteristic curve analysis showed that copeptin had a diagnostic value in the hemodialysis patients with LV dysfunction (area under curve 0.737; p=0.02) and that the cut-off value was 125.48 pg/mL (sensitivity 0.7, specificity 0.8, positive predictive value 0.9, negative predictive value 0.6). Conclusion Copeptin increases in hemodialysis patients and is higher in patients with LV dysfunction. We believe that copeptin can be a useful marker for the diagnosis of LV dysfunction in hemodialysis patients.

The Effects of Proteinuria on Urinary Cystatin-C and Glomerular Filtration Rate Calculated by Serum Cystatin-C

Background: The measurement of glomerular filtration rate (GFR) applying serum creatinine (Cr) does not reflect the GFR of patients accurately, and thus recently, studies on the measurement of GFR applying serum cystatin-C (Cys-C) have been conducted. We investigated the relationship between Cys-C and proteinuria in patients with chronic kidney disease. Methods: We compared the biochemical test, including serum Cys-C, the amount of proteinuria and the concentration of Cys-C measured by the 24-h urine test, and the difference of GFR on 105 patients who visited our hospital in 6 months (January to June 2007). Results: Among 105 patients, 58 patients were males, and the mean age was 56.74 ± 16.31 years. With regard to underlying diseases, the group with diabetes had 76 patients and the group showing nephrotic proteinuria [nephrotic syndrome (NS)] had 29 patients. The GFR-Cys-C in the NS group (44.17 ± 26.32 mL/min) was higher than in the non-NS group (33.68 ± 14.29 mL/min; p = 0.041). The fractional excretion (FE) of Cys-C increased according to FE of albumin ( p = 0.000) and GFR-modification of diet in renal disease (MDRD) equation (p = 0.000). Serum Cys-C increased according to corrected urine Cys-C (p = 0.010). The GFR calculated by serum Cys-C decreased according to FE of albumin (p = 0.003). The degree of difference between GFR-Cys-C and GFR-MDRD was negatively correlated according to the FE of albumin (p = 0.001). Conclusion: We confirmed that urinary excretion of Cys-C could be altered by previously known mechanisms such as proteinuria. Difference between GFR-Cys-C and GFR-MDRD was negatively correlated according to FE of albumin.