• Korean Journal of Clinical Pharmacy
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• v.13 no.1
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• pp.1-4
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• 2003

Cyclosporine (CsA) has become well established as a potent immunosuppressive agent in the renal transplantation. However, therapy is complicated by large intraindividual and interindividual variability in pharmacokinetics of CsA and frequent undesirable clinical outcomes such as graft rejection and nephrotoxicity. The objective of this study was to determine the CsA trough blood concentrations that were associated with acute graft rejection and renal toxicity in renal transplant patients. Also, the ability of the current recommendation of therapeutic range for CsA to prevent graft rejections and CsA-associated renal toxicity was assessed. The clinical courses of the patients on CsA as an immusuppressive agent for preventing the graft rejection with renal ransplantation performed at Seoul National University Hospital from January 1995 to September 1998 were retrospectively reviewed. Total of 78 patients were included and three of them were retransplantation cases. Twenty-two acute episodes of rejection were identified, but only 16 episodes were clinically significant. Of these all the episodes occurred during the first month after transplantation except one. Mean daily doses of CsA were $427.2\pm72.1,\;352.6\pm56.8,\;308.62\pm48.3\;and\;268.47.1\;mg$ at posttransplant 1, 3, 6, and 12 months, respectively. Mean CsA whole blood though levels were $259.8\pm36.2,\;238.5\pm39,\;200.8\pm45.8\;and\;161.9\pm25.8\;ng/ml$ at posttransplant 1, 3, 6 and 12 months, respectively. Mean daily doses/weight were $7.9\pm1,\;6.4\pm1,\;5.3\pm0.7\;and\;4.6\pm0.7\;mg/kg$ at posttransplant 1, 3, 6 and 12 months, respectively. CsA doses decreased significantly as months progressed (p<0.001). During the first month after transplantation, only $12.5\%$ of the patients in rejection group had CsA concentration in therapeutic range, and 87.5, 93.8, and $100\%$ were within the therapeutic range at posttransplant 3, 6, and 12 months, respectively. These results suggested that CsA concentrations of $250\sim300\;ng/ml$ might be appropriate for preventing the acute rejection during the first posttransplant month.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.466-474
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• 2013

Despite the reports on safety concerns regarding the relationship between aluminum salts and neurological and bone disease, many countries continue to use aluminum as phosphate binders among patients with renal failure. In search for a diet supplement that could reduce aluminum toxicity related to renal failure, we carried out this prospective animal study in which the fenugreek seeds were assessed for their effects on rats nephrotoxicity induced by aluminum chloride ($AlCl_3$). Oral $AlCl_3$ administration during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) led to plasma biochemical changes, an inhibition of alkaline phosphatase (ALP), a decrease of total antioxidant status (TAS), and an induction of lipid peroxidation (LPO) in the blood and brain, in addition to kidney atrophy and morphological alterations at the level of Bowman's capsule, the glomerulus and different sorts of tubules, reminiscent of some known kidney disease. The treatment with the whole fenugreek seed powder (FSP) (5% in the diet) during the last 2 months showed its effectiveness in restoring normal plasma values of urea, creatinine, ALP and glucose, as well as re-increasing the TAS, inhibiting LPO and alleviating histopathological changes in the injured kidneys. This study highlights the induced nephrotoxicicity, as well as the related toxicity in the brain and bone, by chronic oral ingestion of the aluminum salts. However, the maintenance of a diet supplemented with fenugreek seeds could offer protection for the kidney, bone and brain, at the same time.

• 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.

• Toxicological Research
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• v.30 no.2
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• pp.99-107
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• 2014

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.580-584
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• 2003

Diabetic Nephropathy is one of the major causes of chronic renal failure. It is a common microvascular complication and clinically defined as the presence of persistent Proteinuria. We studied the effects and change of the renal function of Complex Herbal medication of the 20Diabetic Nephropathy patients. We measured the initial levels of Total Protein, Creatinine Clearance Rate(Ccr), Serum Creatinine(Serum-Cr), Urine Creatinine(Urine-Cr) and HbA1C on admission and followed up the level changes of Total Protein, Ccr, Serum-Cr and Urine-Cr on discharge. The results are following : Complex Herbal Medication does not cause the renal toxicity. The longer hypertension period is, the higher Serum-Cr level and Urine-Cr level. In an older age group, Urine-Cr is lower. 4.From the 'Deficiency in Origin and Excess in Superficiality(本虛表實)'points of view, Complex Herbal Medication improves the Serum-Cr in Diabetic Nephropathy patients. According to this results, it could be suggested that Complex Herbal Medication does not cause the renal toxicity in Diabetic Nephropathy patients and intensive controls of blood sugar, blood pressure and Complex Herbal Medication prevent the renal failure in Diabetic Nephropathy patients with early stage of Microalbumiuria.

• Environmental Analysis Health and Toxicology
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• v.10 no.3_4
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• pp.1-5
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• 1995

The general toxicological study of new platinum(II) compounds, KHPC-002, KHPC-005 and KHPC-006 were investigated in rats. The effects of these Pt(II) complexes on renal, hematopoietic and hepatic system in rats showed lower toxicity compared with cisplatin. In the consideration of the maximal dose of these Pt(II) complexes using in this experiment is 4-8 times higher than cisplatin, these novel compounds will have the less general toxicity in vivo.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.133-137
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• 1998

Purpose : To investigate renal toxicity of high-dose intravenous immunoglobulin(IVIG) in children with Kawasaki disease and idiopathic thrombocytopenic purpura. Methods : 23 children with Kawasaki disease and 7 children with idiopathic thrombocytopenic purpura who were treated with high-dose IVIG(2 g/kg) were evaluated for the change of urine output, blood urea nitrogen(BUN), serum creatinine(Scr), creatinine clearance(Ccr), tubular reabsorption of phosphorus(TRP), fractional excretion of sodium(FENa), 24hour urine ${\beta}_2$-microglobulin/creatinine(${\beta}_{2}MG/cr$) ratio and urine microalbumin/creatinine(MA/cr) ratio at post-IVIG 1 and 3 day. Results : There was no significant change of urine output, BUN, Scr, Ccr, TRP, 24hour urine ${\beta}_{2}MG/cr$ and MA/cr ratio after high-dose IVIG treatment. Transient increase of FENa at post-IVIG 1 day was the only significant change. Conclusion : There was no significant renal toxicity of high-dose IVIG in children with Kawasaki disease and idiopathic thrombocytopenic purpura who had normal renal function.

• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.61-70
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• 2004

Heptaplatin is a new platinum derivative with antitumor activity against gastric cancer. Preclinical studies showed that it is less toxic than other platinum analogues. The purpose of this study is to evaluate the efficacy and toxicity of the combination therapy of heptaplatin and 5-fluorouracil in Korean advanced gastric cancer patients. This study was investigated retrospectively. The patients group consisted of 65 advanced gastric cancer patients with no prior radiotherapy. All patients received heptaplatin $400\;mg/m^2$ by 2-3 hour infusion on Day 1 and 5-FU $1000\;mg/m^2by 12-24 hour continuous infusion for 5 days. After the first cycle, subsequent doses were adjusted according to the toxicity. Courses were repeated every 28 days. As results, objective response occurred in 16 patients $(24.6\%)$. Two were complete and 14 were partial response. Median progression free survival was 32 weeks with $29\%$ of patients progression free at 1 year. The most common hematologic toxicity was anemia. Grade 3 or 4 anemia was seen at $2.7\%$ of treatment cycles. Grade 3 or higher leucopenia was seen at $1.2\%$ of cycles. Grade 3 or 4 neutropenia and thrombocytopenia occurred at $6.1\%\;and\;1.5\%$ of cycles, respectively. The most common nonhematologic toxicity was proteinuria. Though no patients experienced grade 3 or 4 proteinuria, proteinuria was a considerable factor for this chemotherapy. Grade 3 or higher gastrointestinal toxicities were nausea and vomiting ($4.6\%$ of patients) and diarrhea ($1.5\%$ of patients). Grade 2 renal toxicity with elevation of serum creatinine was seen in $0.3\%$ of cycles, which is less than that of other platinum analogues. This study showed that combination therapy of heptaplatin and 5-FU have modest antitumor activity against advanced gastric cancer without severe renal toxicity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.25 no.1
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• pp.104-111
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• 2012

Objective : The aim of this study is to report the effect and safety of Traditional Korean Medicine on the treatment of erythrodermic psoriasis which appeared after stopping high potency topical steroids. Methods : A patient with psoriasis stopped topical steroids after the first outpatient care and was treated with herbal medicine, acupuncture, moxibustion for eight months. The severity of psoriasis was assessed with Psoriasis Area and Severity Index. Liver and renal functions were tested to observe the hepatic and renal toxicity of the treatment. Results : PASI score were 6.2 on the first visit and three months after it increased to 30 and the patient showed symptoms of erythrodermic psoriasis. And seven months after the first visit, it decreased to 0.6. There was no hepatic and renal toxicity of the treatment. Conclusion : These findings suggest that Traditional Korean Medicine might be effective and safe for the treatment of erythrodermic psoriasis.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.125-132
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• 1997

Cisplatin, a platinum-complex, is currently one of the most effective compounds used in the treat-ment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. We synthesized new Pt (II) complex analogue containing 1,2-diaminocyclohexane (DACH) as carrier ligand and 1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(cia-DACH)(DPPE)] . $2NO_3$ (PC) was synthes-ized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $_{13}$carbon nuclear magnetic resonance (NMR)] .PC demonstrated acceptable and significant antitumor activity against SKOV-3 and OVCAR-3 human ovarian carcinoma cell lines as compared with that of cisplatin. The cytotoxicity of PC in normal cells was found quite less than that of cisplatin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ($^3$H)thymidine uptake and glucose consumption tests in rabbit renal proximal tubular cells, human renal cortical cells and tissues. In conclusion, PC is considered to be more selective cytotoxicity toward human ovarian cancer cells than normal human/rabbit kidney cells.