Jong Hoon Chung

Acute Renal Failure Due to Acute Tubular Necrosis Caused by Direct Invasion of Orientia tsutsugamushi

ABSTRACT We describe a scrub typhus patient with acute renal failure for whom a diagnosis was made based on serology as well as immunohistochemical (IHC) staining and an electron microscopic examination (EM) of a renal biopsy specimen. For our case, we demonstrated by IHC staining and EM that renal failure was caused by acute tubular necrosis due to a direct invasion of Orientia tsutsugamushi.

Protective effects of chitosan oligosaccharide on paraquat-induced nephrotoxicity in rats.

We investigated the apoptotic pathway during paraquat (PQ)-induced nephrotoxicity as well as renoprotective effects of chitosan oligosaccharide (COS) in male Sprague-Dawley rats because increasing evidences suggest that antioxidants may prevent PQ-induced apoptosis. Animals were pretreated with normal saline or COS (500 mg/kg, p.o.) 3 days before PQ (60 mg/kg, i.p.) administration, and were sacrificed at scheduled times after PQ administration. Rats administered PQ showed increased serum PQ concentrations, blood urea nitrogen, and creatinine levels in a time-dependent manner and creatinine clearance was decreased compared with control rats. All of these parameters were reversed significantly by COS pretreatment. After the PQ injection, cell deaths occurred in the proximal renal tubules with increased APE, PUMA, and cleaved caspase-3 expression, while APE and cleaved caspase-3 were immunolocalized mainly in the proximal tubules of control kidneys. COS-pretreated rat kidneys showed increased expression of the above parameters before PQ injection. APE and cleaved caspase-3 were immunolocalized ubiquitously in the renal cortex of COS-pretreated rats until 24h after the PQ injection. These results showed that PQ-induced nephrotoxicity may be caused by apoptosis in rat kidneys and that COS could protect kidneys from PQ-induced toxicity in association with the basal higher level of APE.

Protective effects of epigallocatechin gallate (EGCG) on streptozotocin-induced diabetic nephropathy in mice.

There is increasing evidence suggesting that antioxidants in green tea extracts may protect kidneys on the progression of end-stage renal disease. We investigated the protective impacts of (-)-epigallocatechin 3-O-gallate (EGCG) against streptozotocin (STZ)-induced diabetic nephropathy in mice. The mice were divided into 5 groups (n=10 per group): control (saline, i.p.), STZ (200mg/kg, i.p.), EGCG50 (50mg/kg, S.Q.), EGCG100 (100mg/kg, S.Q.), and EGCG200 (200mg/kg, S.Q.). Animals were sacrificed at scheduled times after EGCG administration and then quantitative and qualitative analysis were performed. Compared with the control group, the STZ group showed an increase in levels of blood glucose, blood urea nitrogen, creatinine and urine protein amounts with a decrease in body weight. All the above parameters were significantly reversed with EGCG treatment, especially in the EGCG100 group. After STZ injection, there was a mesangial proliferation with increased renal osteopontin accumulation and its protein expression in the glomeruli and the proximal tubules. Mice kidneys after EGCG-treatment showed a reduced expression of above parameters and relatively improved histopathological findings. These results indicated that EGCG 100mg/kg might provide an effective protection against STZ-induced diabetic nephropathy in mice by osteopontin suppression.

Endothelium-dependent vasodilation by ferulic acid in aorta from chronic renal hypertensive rats

Background Ferulic acid (FA) is a naturally occurring nutritional compound. Although it has been shown to have antihypertensive effects, its effects on vascular function have not been intensively established. The aim of this study was to assess the vasoreactivity of FA in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. Methods Hypertension was induced in 2K1C rats by clipping the left renal artery and age-matched rats that received a sham treatment served as a control. Thoracic aortas were mounted in tissue baths to measure isometric tension. The effects of FA on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine in the aortic rings obtained from both 2K1C and sham rats. Basal nitric oxide (NO) bioavailability in the aorta was determined by the contractile response induced by NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME). Results FA induced concentration-dependent relaxation responses which were greater in 2K1C hypertensive rats than in sham-clipped control rats. This relaxation induced by FA was partially blocked by the removal of endothelium or by pretreating with l-NAME. l-NAME-induced contractile responses were augmented by FA in 2K1C rats, while no significant differences were noted in sham rats. FA improved acetylcholine-induced endothelium-dependent vasodilation in 2K1C rats, but not in sham rats. The simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA. Conclusion These results suggest that FA restores endothelial function by altering the bioavailability of NO in 2K1C hypertensive rats. The results explain, in part, the mechanism underlying the vascular effects of FA in chronic renal hypertension.

The Protective Effects of Green Tea Extract against L-arginine Toxicity to Cultured Human Mesangial Cells

The aim of this study was to investigate whether green tea extract (GTE) has the protective effects on excess L-arginine induced toxicity in human mesangial cell. Human mesangial cells treated with L-arginine were cultured on Dulbeccos modified eagle medium in the presence and absence of inducible nitric oxide synthase (iNOS) inhibitor and GTE. The cell proliferation was determined by 3 (4,5-dimethylthiazol-2-yl)-2, 5-diphengltetrqzolium bromide, a tetrazole assay. The iNOS mRNA and its protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. The concentration of nitric oxide (NO) was measured by NO enzyme-linced immuno sorbent assay kit. L-arginine significantly inhibited the proliferation of human mesangial cells, and induced the secretion of NO to the media. NO production by L-arginine was significantly suppressed by GTE and iNOS inhibitor (p<0.01). The expression level of iNOS mRNA and its protein that was significantly increased by L-arginine was decreased by iNOS inhibitor but not by GTE. GTE protected the mesangial cells from the NO-mediated cytotoxicity by scavenging the NO rather than by iNOS gene expression. Therefore, we conclude that GTE has some protective effect for renal cells against oxidative injury possibly by polyphenols contained in GTE.

Renoprotective effects of green tea extract on renin-angiotensin-aldosterone system in chronic cyclosporine-treated rats

BACKGROUND Renin-angiotensin-aldosterone system (RAAS) activation plays an important role in cyclosporine (CsA)-induced nephropathy. The main aim of this study was to test whether the administration of green tea extract (GTE) prevents the development of CsA-induced nephrotoxicity. METHODS The rats were treated for 21 days and divided into four groups (n = 6/group): control group (0.9% saline injection), CsA group (30 mg/kg/day by intraperitoneal injection), CsA-GTE group (CsA plus GTE 100 mg/kg/day subcutaneous injection) and GTE group (GTE alone). RESULTS There were significant increased levels of serum blood urea nitrogen and creatinine in the CsA group compared with that of the control group and significantly improved in the CsA-GTE group. Biochemical analysis showed that the plasma renin activity (PRA) and serum concentration of aldosterone were significantly increased in the CsA group compared with the control group and significantly decreased in the CsA-GTE group compared with the CsA group. The total level of renin protein expression was significantly higher in the CsA group than in the control group, and it was lower in the CsA-GTE group than in the CsA group. CONCLUSIONS CsA treatment increases the PRA and intrarenal renin levels and induces nephrotoxicity. The protective effects of GTE on CsA-induced structural and functional alternations of the kidney may be the blockage of RAAS.

Cutoff value of serum procalcitonin as a diagnostic biomarker of infection in end-stage renal disease patients

Background/Aims Serum procalcitonin (PCT) levels are low in healthy individuals but are elevated in patients with a serious bacterial infection or sepsis. In this study, we examined the ability of serum PCT concentration to diagnose infections in end-stage renal disease (ESRD) patients, and sought to determine an appropriate threshold level. Methods Serum PCT levels were measured in ESRD patients on antibiotic therapy for a suspected bacterial infection (ESRD infection [iESRD] group, n = 21), and compared with those of ESRD patients on hemodialysis with no sign of infection (ESRD control [cESRD] group, n = 20). Results The mean serum PCT concentration of the iESRD group was significantly higher than in the cESRD group (2.95 ± 3.67 ng/mL vs. 0.50 ± 0.49 ng/mL, p = 0.006), but serum PCT concentrations did not correlate with severity of infection. The optimized threshold level derived for serum PCT was 0.75 ng/mL, rather than the currently used 0.5 ng/mL; this threshold demonstrated a sensitivity and specificity of 76.2% and 80.0% for infection and 100% and 60.6% for systemic inflammatory response syndrome, respectively, compared with the cutoff of 0.5 ng/mL. Conclusions This study suggests that serum PCT at a cutoff value of 0.75 ng/mL is an appropriate indicator of infection in ESRD patients.

Antiproteinuric Effects of Green Tea Extract on Tacrolimus-Induced Nephrotoxicity in Mice.

INTRODUCTION It has been reported that proteinuria is an early predictive marker in detection of tacrolimus (TAC) nephrotoxicity. The aim of this study was to investigate the antiproteinuric effects of green tea extract (GTE) on TAC-induced acute nephrotoxicity in mice. METHODS The mice (n = 20) were divided into 4 groups (n = 5 per group); control group mice were intraperitoneally (IP) injected with 0.9% saline, TAC group mice were IP injected with TAC 1 mg/kg, and inducible nitric oxide synthase (iNOS) inhibitor group mice were given in addition NG-nitro-L-arginine-methyl ester 12 mmol/L by subcutaneous injection. TAC-GTE group mice were given TAC by IP injection and GTE 100 mg/kg by subcutaneous injection. RESULTS The 24-hour urine protein amounts were significantly increased in TAC group mice (36.1 ± 9.9 mg/d) compared with control group mice (13.3 ± 5.4 mg/d) and significantly decreased in TAC-GTE group mice (19.1 ± 6.9 mg/d, P < .01) compared with TAC group mice. The nitric oxide (NO) production by TAC was significantly suppressed by GTE and iNOS inhibitor injection. Renal tissue malondialdehyde (MDA) level was significantly increased in the TAC group compared with the control group and was significantly decreased in the TAC-GTE group compared with that of the TAC group. The antioxidant enzyme activities of superoxide dismutase and catalase were significantly suppressed in the TAC group compared with the control group and were restored in the GTE injection group. CONCLUSIONS GTE treatment has beneficial antiproteinuric effects on TAC-induced acute renal injury in mice.

Relationship between Serum N-Terminal Pro-Brain Natriuretic Peptide Level and Left Ventricular Dysfunction and Extracellular Water in Continuous Ambulatory Peritoneal Dialysis Patients

This study inquired the relationship between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and left ventricular (LV) dysfunction and extracellular water in continuous ambulatory peritoneal dialysis (CAPD) patients. We conducted a cross-sectional study of 30 CAPD patients. Each patient was admitted to the department of internal medicine, Chosun University Hospital between February and October, 2006. Echocardiography was performed using HDI 5000, allowing M-mode, two-dimensional measurement. A multifrequency bioimpedance analyzer was used; extracellular water was calculated as a percentage of total body water and was understood as the index of volume load of CAPD patients. The mean age was 47±12 years. Underlying causes of renal failure were 14 with diabetes mellitus, 7 with hypertension, and 9 with chronic glomerulonephritis. The mean serum NT-proBNP level was 14236.56 (83-35,000) pg/mL. LV mass index and LV ejection fraction were 151.67±42.5 g/m2 and 57.48±12.9%, respectively. The mean extracellular water was 35.97±1.04%. Serum NT-proBNP levels correlated positively with LV mass index (r=0.768, p=0.01) and extracellular water (r=0.866, p=0.01) and negatively with LV ejection fraction (r=-0.808, p=0.01). Serum NT-proBNP levels significantly correlated with LV mass index, LV ejection fraction, and extracellular water. Therefore, serum NT-proBNP levels can be a clinical predictive marker for LV hypertrophy, LV dysfunction, and volume status in CAPD patients.

Direct vascular actions of quercetin in aorta from renal hypertensive rats.

Background Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. Methods 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. Results Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside–induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. Nw-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of Nw-nitro-L-arginine methyl ester in either 2K1C or sham rats. Conclusion Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.