• Korea-Australia Rheology Journal
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• v.17 no.3
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• pp.117-123
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• 2005

Background: Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day­to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. Methods: We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemo-dialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. Results: We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy: control (P = 0.0001). Conclusions: The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes. In diabetic patients, early impairment in RBC deformability appears in patients with normal renal function.

• Journal of Digestive Cancer Research
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• v.4 no.1
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• pp.36-38
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• 2016

Biliary tract cancer, a relatively rare disease, is usually found in an unresectable stage. Weekly cisplatin plus gemcitabine has been applied as a standard first-line therapy for advanced biliary tract cancer, but almost up to 3-5% patients experience drug induced renal impairment. Many anticancer medication guidelines recommend drug adjustment when kidneys are damaged, but weekly cisplatin is somewhat low dose so that there is a controversy on reducing the dose. And it is known that the cumulative dose of cisplatin is the most important factor contributing to renal impairment. Therefore, clinicians face troubles whether or not to maintain the chemotherapy. Here, we reported a patient whose renal function (eGFR) had been decreased as the number of chemotherapy increased, so her chemotherapy should be stopped. Since we held the chemotherapy on her, the disease progressed aggressively. Weekly cisplatin regimen is just 25 mg/m², so it may be meaningless to reduce this dose, and it is well known that cumulative dose of cisplatin is the most important factor contributing to renal impairment, it is better not to use cisplatin anymore. Therefore, we recommend that if the patient responds well to weekly cisplatin plus gemcitabine regimen, it would be beneficial to use gemcitabine alone.

• Biomedical Science Letters
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• v.17 no.4
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• pp.337-345
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• 2011

It is well recognized that conventional coronary artery bypass grafting (ONCAB) often leads to major organ dysfunction including renal injury. Diabetes mellitus is a major cause of nephropathy and poor clinical outcomes. The aim of this retrospective study was to evaluate the occurrence of adverse outcomes including renal impairment between diabetic (n=75, DM group) and non-diabetic patients (n=72, Non-DM group) underwent off-pump coronary artery bypass grafting surgery (OPCAB). Fasting glucose, hemoglobin A1c, fructosamine, fibrinogen and serum osmolality levels in the DM group were higher than those of the Non-DM group at pre-operative (Pre-OP) period ($P$ <0.05). History of hypertension and renal impairment in the DM group was higher than that of the Non-DM group ($P$ <0.05). Potassium ($K^+$), blood urea nitrogen and creatinine levels were higher, whereas sodium ($Na^+$) and glomerular filtration rate (GFR) levels were lower in the DM group than the Non-DM group at peri-operative period ($P$ <0.05). Fasting glucose levels at Pre-OP period had positive correlations with blood urea nitrogen and creatinine levels at peri-operative period, but negative correlations with GFR levels at peri-operative period in the DM group ($P$ <0.05). Incidences of renal impairment, diuretic therapy or continuous renal replacement therapy and fever in the DM group were higher than those of the Non-DM group at post-operative period ($P$ <0.05). These results suggest that blood glucose level should be tightly controlled at peri-operative period to avoid renal dysfunction in diabetic patients.

• Journal of Korean Medical Science
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• v.33 no.53
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• pp.298.1-298.10
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• 2018

Background: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of $4{\beta}$-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. Methods: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers ($6{\beta}$-OH-cortisol/cortisol, $6{\beta}$-OH-cortisone/cortisone, $4{\beta}$-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the $4{\beta}$-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. Results: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary $6{\beta}$-OH-cortisol/cortisol and $6{\beta}$-OH-cortisone/cortisone as well as plasma $4{\beta}$-OH-cholesterol and $4{\beta}$-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. Conclusion: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.

• The Journal of Internal Korean Medicine
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• v.18 no.1
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• pp.147-155
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• 1997

This study was undertaken to determine whether Salviae-radix (SVR) exraction exerts benefical effect against oxidant-induced inhibition of tetraethylammonium (TEA) uptake which is actively secreted by renal proximal tubules. TEA uptake increased as function of incubation time to 60 min. When renal cortical slices were exposed to 50 mM $H_2O_2$, TEA uptake was significantly inhibited. The inhibition was significantly protected by addition of 0.5% SVR extraction. The benefical effect of SVR was dose-dependent over the concentration range of 0.1-1%; $H_2O_2$ (50 mM)-induced inhibition of TEA uptake was completely protected by 0.5-1% SVR extraction. $H_2O_2$ increased LDH release which was accompanied by an increase in lipid peroxidation in renal cortical slices. These changes were prevented by 0.5% SVR. These results suggest that SVR exerts benefical effect against oxidant-induced impairment of membrane transport function, this effect may be due to by an antioxidant action.

• The Monthly Diabetes
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• s.219
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• pp.69-72
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• 2008

• The Monthly Diabetes
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• s.220
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• pp.83-86
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• 2008

• Journal of Chest Surgery
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• v.31 no.5
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• pp.494-501
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• 1998

From May 1, 1993 to May 31 1995, the authers studied retrospectively 211 patients who underwent cardiovascular operation with cardiopulmonary bypass(CPB). Because we were interested in new development of ARF(prevalence, mortality rate, and main risk factors), we performed a multivariate statistical analysis about data of patients with preoperative serum creatinine values of less than 1.5 mg/dL. Normal renal function before operation(serum creatinine level less than 1.5 mg/dL) was registered in 198(74%) patients. Of these, 27(14%) patients showed postoperative renal complication, including 20(10%) patients classified as renal dysfunction(serum creatinine level between 1.5 and 2.5 mg/dL) and 7(4%) patients as acute renal failure(serum creatinine level higher than 2.5 mg/dL). The mortality rate was 5.8% in normal patients, 5% in patients with renal dysfunction, and 43% when acute renal failure developed(p=0.036). Indeed, the renal impairment proved to be an independent predictor of mortality(odd ratio 2.52∼11.25), along with cardiovascular(odd ratio 4.20) and respiratory(odd ratio 2.18) complications. Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment : advanced age(odd ratio 1), need for emergency operation(odd ratio 3.78), low-output syndrome(odd ratio 3.66), respiratory complication(odd ratio 1.30), need for deep hypothermic circulatory arrest(odd ratio 1.4). The 13 patients(7%) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation. We concluded that the likelihood of severe renal complications is resonably low in the patients undergoing cardiac operation without preexisting renal dysfunction, but associated mortality remains high. A prominant role of hemodynamic factor in the development of postoperative acute renal failure must be recognized during preoperative, intraoperative, and postoperative periods.

• Toxicological Research
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• v.32 no.1
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• pp.57-64
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• 2016

Recently several studies reported that the renal toxicity of lead (Pb) and cadmium (Cd) may exist in even a low level exposure. In terms of the deterioration of tubular function, it affects the loss of divalent metals and leads to other complications, so renal tubular effect of heavy metals should be well managed. Considering the exposure to heavy metals in reality, it is hard to find the case that human is exposed to only one heavy metal. We designed a cross-sectional study using Korean Research Project on the Integrated Exposure Assessment (KRIEFS) data to investigate the renal effects of multiple metal exposure in general population. We used blood Pb and urinary Cd as exposure measures, and urinary N-acetyl-${\beta}$-D-glucosaminidase (NAG) and ${\beta}_2$-microglobulin (${\beta}_2$-MG) as renal tubular impairment outcome. We conducted linear regression to identify the association between each heavy metal and urinary NAG and ${\beta}_2$-MG. And then, we conducted linear regression including the interaction term. Of 1953 adults in KRIEFS (2010~2011), the geometric mean of blood Pb and urinary Cd concentration was $2.21{\mu}g/dL$ (geometric $SD=1.49{\mu}g/dL$) and $1.08{\mu}g/g\;cr$ (geometric $SD=1.98{\mu}g/g\;cr$), respectively. In urinary Cd, the strength of the association was also high after adjusting (urinary NAG: ${\beta}=0.44$, p < 0.001; urinary ${\beta}_2$-MG: ${\beta}=0.13$, p = 0.002). Finally, we identified the positive interactions for the two renal biomarkers. The interaction effect of the two heavy metals of ${\beta}_2$-MG was greater than that of NAG. It is very important in public health perspective if the low level exposure to multiple heavy metals has an interaction effect on kidney. More epidemiological studies for the interaction and toxicological studies on the mechanism are needed.

• Toxicological Research
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• v.17
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• pp.117-125
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• 2001

Envenoming by Russells viper causes a broad spectrum of renal impairment. Renal failure is an important complication in patients bitten by Russells viper. Experimental work in animals and in vitro has elucidated pathophysiological mechanisms that contribute to life threatening complications and have suggested possibilities for therapeutic intervention. The evidence in experimental animals regarding mechanisms of venom action in relation to changes in either extrarenal or intrarenal factors is presented. The cardiovascular system and renal hemodynamics are affected by venom. Reductions of renal function including renal hemodynamics are associated directly with changes in general circulation during envenomation. Possible endogenous mechanisms for releasing the hormone inducing renal vasoconstriction after envenomation are evident. Hormonal factor such as the catecholamine, prostaglandin and renin angiotensin systems induce these changes. Direct nephrotoxicity of venom action is studied in the isolated per-fused kidney. Characteristic polarization of the cell membrane, changes of mitochondrial activity and Na-K ATPase in renal tubular cells are observed. Changes in renal function and the cardiovascular system are observed of ter envenomation and are reversed by the administration of Russells viper antivenom (purified equine immunoglobulin, $Fab_2$ fragment). The neutralizing effects are more efficient when the intravenous injection of antivenom is given within 30 min after the envenomation.