Decision Factors on Mycophenolic Acid Dose after Renal Transplantation / 대한이식학회지

BACKGROUND: Triple immunosuppressant therapy including anti-metabolites is the representative immunosuppressive therapy after renal transplantation. This study is to evaluate the factors that influence Mycophenolate sodium (MPS, Myfortic, Novartis, Basel, Switzerland) dosage patterns in renal transplantation patients who take MPS as an inosine monophosphate dehydrogenase (IMPDH) among antimetabolites. METHODS: From May 2007 to April 2008, 16 clinical departments of 14 transplantation centers in Korea retrospectively performed a survey on 650 renal transplantation recipients taking MPS. This survey collected personal information, clinical factors related to transplantation and immunosuppressive therapy. RESULTS: The mean age of the patients was 43.0+/-12.0 (7~75) and the study included 364 males (56.0%) and 286 females (44.0%). The average follow up period after renal transplantation was 49.5+/-53.4 (1~307) months. There were 366 (56.3%) living related cases, 145 (22.3%) living non-related cases and 139 (21.4%) deceased donor cases. Cyclosporine was the most common calcineurin inhibitor (CNI) used in combination therapy with MPS (476 cases, 73.2%) followed by tacrolimus (169 cases, 26.0%). The mean daily dose of MPS was 909.7+/-336.3 (180~1,620)mg and the mean daily dose per kg was 15.3+/-5.9 (2.65~32.73)mg/kg. The daily dose showed significant positive correlation with patient body weight but the daily dose per kg showed negative correlation. The daily dose of MPS was significantly higher in the combination therapy with cyclosporine than that with tacrolimus. The daily dose and the dose per kg decreased with increment of recipient age and post-transplant period. CONCLUSIONS: Our study concluded that MPS dosages correlated with the combined type of CNI, post-transplant period and age.

A Case of Imipenem Resistance Acinetobacter baumannii Peritonitis Successfully Treated with Colistin Therapy / 대한신장학회지

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) is a major cause of technical failure in peritoneal dialysis. The major pathogen is gram positive bacteria, and other main pathogens include gram negative bacteria, mixed microorganisms and fungi. The case of imipenem resistance Acinetobacter baumannii (IRAB) peritonitis are not common. We report a case of peritonitis by IRAB that was not responsive to the empirical antibiotics for CAPD-associated peritonitis. A 56-year-old male with a CAPD catheter inserted 2 weeks before visited our hospital for abdominal pain and turbid peritoneal fluid. He had been diagnosed as having an end stage renal disease (ESRD) about a month before. White blood cell and neutrophil count were elevated at the initial peritoneal fluid analysis, so we diagnosed him as having CAPD-associated peritonitis. Antibiotic therapy was initiated with intraperitoneal injections of ceftazidime/cefamezine which were soon changed to vancomycin/ceftazidime. However, vancomycin/ceftazidime regimen proved ineffective. On the fifth and sixth hospital day, IRAB was cultured from the CAPD catheter exit site swab and peritoneal fluid sampled on the first visiting day. Accordingly, we changed the antibiotics to colistin and removed the CAPD catheter, which led to clinical and laboratory improvement. In the cases of CAPD associated peritonitis in patients who have a history of ICU stay, exposure to the 3rd generation cephalosporin or imipenem, or who are elderly, we must suspect unusual pathogen or multi-drug resistance pathogen such as IRAB.

The Study of Glutathione S-Trasferase M1 and T1 Genetic Polymorphism in Korean Type 2 Diabetic Nephropathy Patients / 대한신장학회잡지

BACKGROUND: Oxidative stress possiby contributes to the development of diabetic nephropathy. Glutathione S-transferases (GSTs) can work as one of endogenous antioxidants to protect cells from oxidative stress. The activity of GSTM1 or GSTT1 are determined genetically. The homologous deletion of the gene (null genotype) which reduced the GSTM1/T1 activity, may be associated with diabetic nephropathy development in diabetic patients. METHODS: We examined 94 patients with diabetic nephropathy and 102 patients without diabetic nephropathy in Korean type 2 diabetic patients. We used multiplex polymerase chain reaction (PCR) to analyze polymorphisms of two endogenous antioxidant genes, GSTM1 and GSTT1. RESULTS: The two patients groups were well matched with regard to age, body mass index, duration of diabetes and HbA1c. GSTM1 null genotype was observed in 50% of patients with nephropathy versus 51% of patients without nephropathy. GSTT1 null genotype was observed in 48.9% of patients with nephropathy versus 51% of patients without nephropathy. No association between homozygous deletion of GSTM1 or GSTT1 and development of diabetic nephropathy in diabetic patients. CONCLUSION: This study is the first to investigate the association of GSTM1/TT1 gene polymorphism which development of diabetic nephropathy in Korean type 2 diabetic patients. The present result suggest that GSTM1/TT1 null genotype does not contribute to the development of diabetic nephropathy in Korean type 2 diabetic patients.

Risk Factors for Early Access Failure of Arteriovenous Fistula in Hemodialysis Patients / 대한신장학회잡지

BACKGROUND: Early failure of vascular access for hemodialysis is not uncommon. It has been known that DM, hypertension, age, sex and some abnormal laboratory findings at the surgery are the risk factors. We designed this study to analyze the risk factors for the early access failure of arteriovenous fistula (AVF). METHODS: Among 111 patients who underwent vascular access surgery and hemodialysis at KHMC from 2000 to 2004, 106 patients with AVF were enrolled. The rate of early access failure of AVF was evaluated. Histories of DM, hypertension, cardiovascular disease, and ipsilateral central venous catheterization, medication and laboratory findings were investigated through the medical records, retrospectively and statistically analyzed. RESULTS: The rate of early access failure of AVF was 21.3%, higher than that of AV grafts. The number of patients older than 50 years of age was greater in early access failure group. Early access failure group showed higher incidence of cardiovascular disease. Early access failure group showed higher incidence of ipsilateral central venous catheterization. Early access failure group also showed higher level of hemoglobin and hematocrit. Logistic regression analysis showed that higher hemoglobin and history of ipsilateral central venous catheterization are independent risk factors for early access failure of AVF. CONCLUSION: Older age at the time of surgery, history of ipsilateral central venous catheterization or cardiovascular disease and higher level of hemoglobin were associated with early access failure of AVF. History of ipsilateral central venous catheterization and higher level of hemoglobin are independent risk factors.

Renoprotective Effect of the Combined Use of Steroid and Angiotensin II Receptor Blocker in IgA Nephropathy / 대한신장학회잡지

BACKGROUND: Several studies have examined the role of angiotensin II receptor blocker (ARB) or steroid treatment in decreasing proteinuria and preserving renal function in IgA nephropathy (IgAN). METHODS: We designed a prospective, randomized trial to assess the effects of combination therapy of steroid (daily high-dose for 6 months) and ARB in IgAN patients with proteinuria >or=1.0 g/d and serum creatinine (SCr)or=1.4 mg/dL at the last visit had older age and higher proteinuria level at 6 mo than those with SCror=1g/d that the combination of ARB and prednisolone was more effective in preserving renal function as well as in decreasing proteinuria than the ARB alone therapy.

Polymorphism of Plasminogen Activator Inhibitor-1 and Development of Diabetic Renal Failure in Koreans / 대한신장학회잡지

BACKGROUND: An elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration has been identified as a factor for the development of macroangiopathy including myocardial infarction, and an association between polymorphism of the PAI-1 promoter and plasma PAI-1 levels has been described. PAI-1 gene is thought to be one of candidate genes in development of diabetic nephropathy. We studied association between polymorphism of PAI-1 promoter and the development of diabetic renal failure in type 2 DM. METHODS: We reviewed the past clinical records of 4, 500 diabetic patients who were registered in KyungHee university hospital. We selected 85 diabetic patients without nephropathy for more than 10 years and 92 diabetic patients in which Kidney failure was developed within 20 years. We investigated promoter -675 and -844 region polymorphisms in type 2 DM patients with ESRD compared with patients without nephropathy by using PCR-RLFP. RESULTS: The genotypes of group of type 2 DM with ESRD and control group were consistent with Hardy-Weingerg equation. There was no significant difference between two groups in the polymorphisms of PAI-I promoter -675 region. Similarly, there was no significant difference between two groups in the polymorphisms of PAI-I promoter -844 region. CONCLUSION: The results suggest that the polymorphisms of PAI-1 gene are not associated with development of diabetic renal failure in Korean patients with type 2 DM.

A Case of Metformin-associated Lactic Acidosis / 대한신장학회잡지

A 76-year-old female admitted with nausea, anorexia, vague abdominal pain, and malaise. Her past medical history included an 15-year history of type 2 diabetes mellitus and hypertension. She had been taking metformin, glipizid, and amlodipine for past 2 years. One week previously, she underwent gastroscopy to evaluate epigastic pain, and she was diagnosed Helicobacter pylori positive duodenal ulcer, for which she was treated with amoxicillin, clarithromycin, and omeprazole. At admission, laboratory test revealed lactic acidosis (pH 7.23, bicarbonate 8.3 mEq/L, and lactate 5.51 mmol/L) and acute renal failure with a serum creatinine of 7.4 mg/dL. We diagnosed meformin-associated lactic acidosis and the patient made a complete recovery following therapy with bicarbonate-based hemodialysis and supportive care. It is the first report of metformin-associated lactic acidosis in Korea.

Aristolochic Acid Induced Fanconi's Syndrome / 대한신장학회잡지

A unique type of rapidly progressive interstitial fibosis of the kidney designated Chinese herb nephropathy (CHN) has been reported in Belgian woman after intake of Chinese herbs. CHN contains variable clinical features from progressive renal failure with severe anemia to adult-onset Fanconi's syndrome which have been reported mostly in Asian countries. We are reporting a case of 43 years-old female patient. The patient visited our hospital with symptoms of polyuria, polydipsia and generalized weakness and laboratory investigation showed hypokalemia, hyperchloremic metabolic acidosis, hypophosphatemia consitent with Fanconis's syndrome. We found out her intake of Chinese herbal mixture by history taking. The Fanconi's syndrome seemed to be revrersible but it progressed to renal failure after four months in spite of only ten days intake. Renal biopsy resulted typical findings of aristolochic acid induced nephrophathy. Aristolochic acids were also detected in herbal mixture by high performance chromatography. This case shows variable clinical course of aristolochic acid-induced nephrophathy. It is important to bear in mind that CHN could present variable clinical pattern and herbal mixture that include aristolochic acid should be avoided.

Association of the Tumor Necrosis Factor-alpha Gene Polymorphism with End-Stage Kidney Failure / 대한신장학회잡지

BACKGROUND: It is evident that cytokines play a role in the pathogenesis as well as the progression of renal diseases. The purpose of this study was to determine whether cytokine gene polymorphism is a marker of susceptibility to end-stage kidney failure (ESKF) in Korean populations. METHODS: -308 G/A polymorphism of tumor necrosis factor-alpha (TNF-alpha) gene was genotyped in 257 dialysis patients and 277 age-matched healthy controls, 86 NIDDM patients with kidney failure and 102 NIDDM controls without nephropathy. RESULTS: We found a decreased frequency of TNF-alpha allele 2 (TNF2, 2.9%) in ESKF patients compared to healthy controls (7.5%, p<0.05). We also found a decreased frequency of TNF-alpha allele 2 (TNF2, 2.3%) in NIDDM patients with kidney failure compared to NIDDM controls without nephropathy (7.6%, p<0.05). The carriage rate of TNF2 was significantly lower in NIDDM patients with kidney failure than in NIDDM controls without nephropathy (4.4% vs. 13.2%, p<0.05). In addition, allele frequency of TNF2 were remarkably different from those previously reported, indicating a significant ethnic difference. CONCLUSION: There is a significant ethnic difference in the polymorphism of TNF-alpha gene. The non-carriage TNF2 was more prevalent in the kidney failur group. But, we could not determine any association between the TNF-alpha gene polymorphism and the development of kidney failure.

First Report of Cryptococcus Albidus-Induced Disseminated Cryptococcosis in a Renal Transplant Recipient

Cryptococcus albidus, a non-neoformans species of the genus Cryptococcus, is generally regarded as a rare cause of disease. There have been only 14 previously reported cases in which this organism has been isolated as a pathogen, none of which occurred in a renal transplant recipient. A 23-year-old renal transplant recipient taking medication consisting of cyclosporine and prednisolone was admitted with a 10-day history of dry cough, fever and progressive dyspnea. The next day, his respiratory status deteriorated dramatically, and he developed acute respiratory distress syndrome (ARDS) and fulminant septic shock. On the eighth hospital day, tender macules on both his shins coalesced to form erythematous patches. Cryptococcus albidus was isolated by skin biopsy and tissue culture. We report here the first case of disseminated cryptococcosis caused by C. albidus in a renal transplant recipient who had been successfully treated with fluconazole monotherapy.

Treatment outcomes and predictors in patients with idiopathic membranous nephropathy / 대한내과학회지

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults but the treatment regimen and the prognosis of IMN are controversial issue. Immunosuppresive treatment was preferably used in patients with high risk factors related to renal failure. We studied biopsy-proven idiopathic membranous nephropathy to evaluate clinical predictors for risk stratification and treatment outcomes according to regimens. METHODS: 66 patients (51 male, 15 female) with biopsy-proven IMN at our hospital during the period of 1991 to 2001 were studied retrospectively. Clinical information and data were obtained at the time of presentation and followed up regularly. We used several different treatment regimen according to patients compliance, clinical and laboratory data. Seven patients were treated with conservative management, 12 with oral steroid alone, 47 with oral steroids and combination with oral cyclophosphamide (1~2 mg/kg/day for 6~12 months). The mean follow-up period was 53.4 +/- 34.2 month. Treatment oucomes and predictors were idetified. RESULTS: At presentation, mean age was 45.5 +/- 14.7 years old and patients with nephrotic syndrome was 77.8%. Pathologic stages II (Ehrenreich and Churg classification) was most common (68.2%). After each treatment, 33.3% of the group treated with oral steroid alone showed partial remission (PR) and 33.3% showed complete remission (CR), in combination thrapy group (cyclophosphamide with steroids) 23.4% PR and 38.3% CR. During follow-up period, four patients (6.1%) developed into chronic renal insufficiency. We used multivariate analysis of prognostic factor associated with persistent CR and progression to chronic renal insufficiency (CRI). Initial response within one year after therapy and non smoking were predictior of persistnet CR and increased initial serum creatinine and old age was related to progression to CRI. CONCLUSION: At the end of follow-up, immunosuppresive therapy including oral cyclophosphamide and steroids induced favorable effect and can be used for high risk patients.

Effect of Combined Treatment of Steroid and Angiotensin II Receptor Blocker (ARB) in Proteinuric IgA Nephropathy / 대한신장학회잡지

BACKGROUND: It has been reported that prednisolone (PDL) therapy favorably influences proteinuria and renal function in the patients with IgAN in whom ARB as well as ACE inhibitor has an anti- proteinuric effect. Therefore, we did a controlled prospective trial to test the effect of treatment with PDL (daily high-dose for 6 months) and ARB in proteinuric adult patients with IgAN. METHODS: Forty-two patients with proteinuria > or =1.0 g/day and serum Cr < or =2.0 mg/dL were randomized to treatment with PDL and ARB and to that with ARB alone. RESULTS: The follow-up period lasted 15.4+/-3.5 months in combination group (n=18) and 19.8+/-7.4 months in ARB group (n=20). Proteinuria was significantly reduced in the both groups (ARB group: from 4.31+/-2.85 g to 1.38+/-1.09 g vs. combination group: from 4.67+/-5.33g to 0.78+/-0.99 g). The rate of complete remission was 10% in ARB group and 44% in combination group at the final follow-up (p<0.05). There were no differences of mean serum Cr between groups before and after treatment. The number of patient with aggravation in renal function was five (25%) in ARB group and one (5%) in combination group. CONCLUSION: This study shows that the urinary protein excretion was effectively reduced by both groups and the rate of complete remission was higher in combination group than in ARB group. Long- term follow-up may be helpful to define the effect on the renal function in IgAN patients.

Quinupristin/Dalfopristin-induced Sweet's Syndrome

Quinupristin/Dalfopristin is a new combination of streptogramin antibiotics designed specifically to treat clinically significant infections due to Vancomycin-resistant Enterococcus Faecium. Sweet's syndrome is characterized by painful skin plaques, which is associated with dermal neutrophilic infiltration, fever and peripheral blood leukocytosis. Drug-induced Sweet's syndrome has a temporal relationship between drug ingestion, clinical presentation and the temporally-related resolution of lesions following drug withdrawal or on treatment with systemic corticosteroids. A 63-year-old woman received Quinupristin/Dalfopristin for acute pyelonephritis developed fever, arthralgia, vomiting, and painful erythematous skin plaques. A skin biopsy showed neutrophilic dermatosis, and there was rapid resolution of the symptoms and cutaneous lesions after discontinuation of Quinupristin/Dalfopristin, consistent with drug-induced Sweet's syndrome. To date, there has been no reported case of Sweet's syndrome associated with the use of Quinupristin/Dalfopristin.

A case of Goodpasture syndrome with diffuse pulmonary hemorrhage / 대한내과학회지

Goodpasture syndrome is an autoimmune disease with a triad of acute renal failure due to rapidly progressive glomerulonephritis (RPGN), pulmonay hemorrhage and circulating anti-glomerular basement membrane antibody (anti-GBM Ab). It was commonly reported from Europe in male with a peak incidence in their 20's. If patients are affected with the disease, relief of symptoms can be expected by eliminating the anti-GBM Ab from the circulatory system through hemodialysis, plasmapheresis and immunoadsorption. However, if the diagnosis or treatment is delayed, the patients usually die from massive pulmonary hemorrhage. It has been revealed that the main target of anti-GBM Ab's is NC1 domain on the alpha3 chain of type IV collagen. Currently there are many studies underway using this information as a basis to identify the pathogenesis of Goodpasture syndrome and to develop new therapeutic approach. The patient was a 20-year-old male with a chief complaint of edema. Unlike patients in the two previous cases, reported in Korea who had massive hemorrhage, he showed diffuse pulmonary hemorrhage which improved in only one week by hemodialysis. Renal biopsy demonstrated crescents in over 90% of glomeruli and showed signs of acute renal failure due to RPGN, with 618 U/mL (normal range <19.9 U/mL) of anti-GBM Ab titer.

Prevalence of Cancers in Korean Recipients of Renal Transplant / 대한신장학회잡지

No abstract available.

Effect of Native and Modified Lipoproteins, and Albumin on Human Mesangial Cell Proliferation / 대한신장학회잡지

BACKGROUND: Modified lipoproteins may be involved in nephro- and glomerulosclerosis. Diabetic nephropathy-like lesions have also been induced in a rat model by glycated and glycoxidized albumin. In cultured rat or human mesangial cells, enhanced cell proliferation and production of mesangial matrix in response to lipoproteins and their modified forms have been demonstrated by [3H]-thymidine incorporation and cell counting assays. But these methods are relatively complex and most of them have used only one or two of the lipoprotein, albumin and their modified forms. METHODS: We investigated the effects of native and modifed lipoproteins, and albumin on cultured human mesangial cell proliferation using non-radioactive colorimetric method by MTS/PMS assay. Lipoproteins added were low density lipoprotein(LDL), high density lipoprotein(HDL), very low density lipoprotein(VLDL), oxidized LDL(oxidation with copper sulfate in vitro) and glycated LDL and we also used albumin, glycated albumin, and interleukin-1beta as a positive control. RESULTS: Interleukin-1beta promoted the proliferation of cultured human mesangial cells up to concentration 20 ng/mL. LDL induced the proliferation of mesangial cells in a concentration-dependent manner up to concentration 100 microgram/mL. HDL and VLDL had no significant proliferative effect. Oxidized LDL caused the proliferation of mesangial cells at low concentration up to concentration 25 microgram/mL. Addition of glycated LDL resulted in a concentration- dependent inhibition of mesangial cells. Albumin and glycated albumin inhibited the proliferation of mesangial cells at low concentration of 100 microgram/mL, but cell growth was increased at higher concentrations. CONCLUSION: We demonstrated the effects of the single and modified proteins on the proliferation of cultured human mesangial cell by relatively simple colorimetric method. Results were almostly identical to those of previous studies obtained by radioactive method or cell counting assay.

Clinical Course of Patients with IgA Nephropathy between Combined Treatment of Immunosuppressive Agents and ACE Inhibitor and ACE Inhibitor alone

BACKGROUND: It has not been clear whether immunosuppressive therapy favorably influences renal function and proteinuria in IgA nephropathy (IgAN). Angiotensin converting enzyme inhibitor (ACEi) has an anti-proteinuric effect in IgAN. A retrospective study was done to see whether the addition of immunosuppressive therapy to ACEi produces a more excellent anti-proteinuric effect and preserves better renal function than ACEi alone. METHODS: A total of 49 patients with proteinuria>1.0 g/day and serum creatinine concentrations<1.5 mg/dL were followed-up from at least 1 year to 9 years. Among them, 25 patients were treated with the combination of cyclophosphamide, prednisolone and ACEi while the other 24 were treated with ACEi alone. RESULTS: The combination therapy or ACEi alone both reduced proteinuria with significant value (the combination group: from 5.74+/-5.08 to 2.29+/-2.77 g/day, ACEi group: from 3.85+/-2.54 to 1.68+/-1.91 g/day), while no significant differences in reduction of proteinuria were noticed between the two groups. There was no significant elevation of serum creatinine in both groups during follow-up (the combination group: from 0.91+/-0.20 to 1.03+/-0.38 mg/dL, ACEi group: from 0.93+/-0.27 to 0.99+/-0.37 mg/dL). This study showed no significant differences in the change in slope of 1/serum creatinine levels during the follow-up period between the two groups. CONCLUSION: We conclude that immunosuppressive therapy may not be beneficial in patients with proteinuric IgAN. ACEi may be a valuable therapeutic agent avoiding serious side effects of immunosuppressive agents.

High Glucose Induces MCP-1 Expression in Cultured Human Mesangial Cells Partly Via Tyrosine Kinase-AP-1 Pathway / 대한신장학회잡지

Infiltration of circulating monocytes into glomeruli has been implicated in the pathogenesis of glomerular injury in many human and experimental forms of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1), a potent chemokine with considerable specificity for monocytes, can be up-regulated by various cytokines and growth factors in mesangial cells. Glomerular infiltration of monocytes has been reported in diabetic nephropathy as well. However, effect of high glucose on MCP-1 expression in human mesangial cells has not been known well. We investigated the effect of high glucose on MCP-1 expression and its signal transduction pathway. Human mesangial cells were conditioned with glucose(5-60 mM) or mannitol chronically for up to 5 days. Expression of MCP-1 mRNA and protein was measured by Northern blot analysis and ELISA respectively. To examine the role of transcription factor AP-1 or NF-KB, electrophoretic mobility shift assay(EMSA) was performed. Glucose induced MCP-1 mRNA expression in a time and dose dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. EMSA revealed that glucose increased the AP-1 binding activity in a time and dose dependent manner but not NF-B. Inhibitor of AP-1, curcumin(7.5- 15 muM) dose dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein(12.5-50 muM) and herbimycin A(0.1-1 muM) inhibited the high glucose-induced MCP-1 mRNA expression in a dose dependent manner and also suppressed the high glucose-induced AP-1 binding activity. In summary, high glucose induces mesangial MCP-1 expression partly via tyrosine kinase-AP-1 pathway.

Exercise-induced Acute Renal Failure in a Patient with Renal Hypouricemia / 대한신장학회잡지

We report a case of exercise-induced acute renal failure associated with renal hypouricemia in a 35- year-old man who complained of oliguria and back pain after swimming. Laboratory tests revealed that serum blood urea nitrogen and creatinine level were elevated, the serum uric acid concentration was subnormal(2.1 mg/dL). After conservative treatment, renal function was recovered. But, uric acid level decreased to 0.4 mg/dL. In addition, there was no supression of urate clearance to creatinine clearnace ratio(CUA/CCr) following the administration of pyrazinamide, and no increase of CUA/CCr after benzbromarone. Therefore, we think the cause of renal hypouricemia in this patient may be the subtotal defect in the urate transport.

The effects of high glucose concentration, angiotensin II and its blockers on the production of IL-6 and fibronectin in cultured human mesangial cells / 대한내과학회지

BACKGROUND: Diabetic nephropathy is a leading cause of end-stage renal disease and is charaterized by activation of some growth factors (e.g., angiotensin II, endotelin-1, IL-8, and TGF-beta) and deposition of extracellular matrix proteins. Both ACE inhibitors and AT1 receptor blockers partially prevent renal hypertrophy in diabetes. Recently, IL-6 is thought to act as an autocrine growth factor for the mesangial cells. Angiotensin II (Ang II) is one of the noninflammatory stimulators of IL-6 release from mesangial cells. IL-6 have been implicated in glomerulonephritis, including mesangioproliferative glomerulonephritis. IL-6 may be associated with renal damage, especially mesangioproliferative diabetic nephropathy. However, little is known about the pathogenetic relations between IL-6 and diabetic nephropathy. METHODS: To evaluate the effects of high glucose concentration, Ang II and its blockers on IL-6 and fibronectin production, human mesangial cells were cultured in various conditions. Normal concentration (100 mg/dL) and high concentration of D-glucose (450 mg/dL), Ang II (10(-7)M), high glucose with Ang II, captopril (10(-6)M), and losartan (10(-6)M) were added. After 48 hours, IL-6 and fibronectin concentration in the supernatant were measured by ELISA method. RESULTS: The effects of various conditions on the production of IL-6 and fibronectin in cultured human mesangial cells were as follows: 1. The concentration of IL-6 in the supernatant was significantly low in high glucose group (9.9+/-0.2 pg/mL) compared to that in control group (18.0+/-6.2 pg/mL) (p<0.05), and there was no difference in the supernatant concentration of fibronectin between the groups of high glucose and control. 2. The concentration of IL-6 in the supernatant of Ang II group (28.0+/-5.0 pg/mL) was significantly higher than that in control group (18.0+/-6.2 pg/mL) (p<0.05), and there was no difference in the supernatant concentration of fibronectin between the groups of Ang II and control. 3. In the supernatant of high glucose with Ang II group, the concentration of IL-6 (20.0+/-4.0 pg/mL) was significantly higher than that of high glucose group (9.9+/-0.2 pg/mL) (p<0.05), and the concentration of fibronectin (3,100+/-50 pg/mL) was significantly higher than that of control group (2,840+/-290 pg/mL) (p<0.05). 4. The concentration of IL-6 in the supernatant was significantly lowered after the addition of captopril (10.7+/-1.8 pg/mL) and losartan (9.3+/-2.4 pg/mL) in high glucose with Ang II group (20.0+/-4.0 pg/mL) (p<0.05). 5. The concentration of fibronectin was significantly lowered after the addition of captopril (2,640+/-30 pg/mL) and losartan (2,440+/-230 pg/mL) in high glucose with Ang II group (3,100+/-50 pg/mL) (p<0.05). 6. There was no difference in the concentration of supernatant IL-6 and fibronectin between the groups of captopril and losartan. CONCLUSION: High glucose concentration decreases and Ang II increases the production of IL-6 by cultured human mesangial cells. Captopril and losartan decrease the production of IL-6 and fibronectin which have been stimulated by high glucose concentration and Ang II. These drugs may be useful in the treatment of renal disease, especially diabetic nephropathy, in which Ang II and high blood glucose are cooperative in the progression of nephropathy.