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Acquired Gitelman syndrome (GS) associated with Sjögren syndrome (SS) is rare, and the test to determine the pathophysiological state of acquired GS in patients with primary SS has not been reported previously. A 47-year-old woman with sicca complex presented to our clinic with intermittent muscle cramping and weakness involving both lower extremities over several months. Laboratory findings showed hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria, which met the criteria for GS. Diagnostic evaluation identified primary SS as the cause of the acquired GS. Light microscopic examination of renal tissue from the patient showed mild tubulointerstitial nephritis. Immunohistochemical staining of renal tissue showed the absence of the sodium-chloride cotransporter (NCCT) in the distal convoluted tubules. Incubation of the patient's serum with normal mouse kidney tissue showed a pattern of NCCT in the distal convoluted tubules similar to that of incubation of normal mouse kidney with the rabbit polyclonal anti-NCCT antibody. This is a rare case of acquired GS associated with primary SS, and our findings suggest the presence of circulating autoantibodies to NCCT. [ABSTRACT FROM AUTHOR]

Keywords:antiphospholipid syndrome; papillary muscle rupture; systemic lupus erythematosus [ABSTRACT FROM PUBLISHER]

Background: The drug discovery and development pipeline is a long and arduous process that inevitably hampers rapid drug development. Therefore, strategies to improve the efficiency of drug development are urgently needed to enable effective drugs to enter the clinic. Precision medicine has demonstrated that genetic features of cancer cells can be used for predicting drug response, and emerging evidence suggest that gene-drug connections could be predicted more accurately by exploring the cumulative effects of many genes simultaneously., Results: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC 50 ) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC 50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control., Conclusions: DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development.

Magnetic nanoparticles and fluorescent quantum dots (QDs) can make many effective applications in biomedical system. Here, we demonstrated one way of synthetic method and its surface modification to use for biomedical applications. Fe3O4 nanoparticles are well known as magnetic materials and its magnetic property can be used in magnetic resonance imaging (MRI), cell detection. QDs as a fluorescent probes, make cell labeling and in vivo imaging possible. ZnS/AgInS2 QDs have a lower toxicity than other QDs (CdSe, CdTe, CdS). We combined two nanoparticles by hydrophobic interaction in their ligands. The prepared fluorescent magnetic composite particles were modified with CTAB-TEOS. The surface modified composite has a low cytotoxicity and these biocompatible particles will provide many possibilities in biomedical system.

Aim: Proteinuria is a primary factor requiring treatment in immunoglobulin (Ig)A nephropathy. The purpose of this study was to assess the relevance of treatment response and relapse of proteinuria with renal function decline., Methods: One hundred and twenty-five biopsy-proven primary IgA nephropathy patients who had more than 1.0 g/day proteinuria at the first assessment were studied. All patients underwent anti-proteinuric treatment, and the association of the rate of renal function decline with treatment responsiveness, clinical and laboratory data was investigated., Results: The treatment response of the patients was: 30.4% complete response (<0.3 g/day proteinuria), 32.8% partial response (0.3-1.0 g/day), 23.2% minimal response (decrement but not reduced to <1 g/day) and 13.6% no response (no decrement of proteinuria). The slope of renal function decline (-1.06 vs-1.24 mL/min per 1.73 m(2)/year, P = 0.580) was comparable between complete and partial response groups, but they were slower than those of minimal or non-response groups (P < 0.001). In multivariate analysis including other parameters, mean arterial pressure (MAP; beta = -0.240, P = 0.004) during follow up, minimal (beta = -0.393, P < 0.001) and non-response (beta = -0.403, P < 0.001) were significant predictors. In further investigation of complete and partial response groups, MAP (beta = -0.332, P = 0.001) and relapse of proteinuria (beta = -0.329, P = 0.001) were independently associated with slope of renal decline., Conclusion: Achievement of less than 1.0 g/day proteinuria and MAP were important for limiting the loss of renal function, and relapse of proteinuria should be closely monitored in proteinuric IgA nephropathy.

Background/aims: The antibody monitoring system (AMS) is a recently developed enzyme-linked immunosorbent assay (ELISA) crossmatch assay to detect donor-specific anti-HLA immunoglobulin G antibodies (DS-HLA Abs). This study was conducted to compare the AMS with the flow cytometric crossmatch (FCXM) test in renal transplant recipients with high panel-reactive antibody (PRA)., Methods: Thirty-two sera were obtained from 10 patients with panel reactivity above 50%. When anti-HLA Ab was detected by ELISA PRA and the matched donor had the corresponding HLA antigen, it was considered to indicate DS-HLA Ab. The results of the AMS assay and FCXM were compared with the DS-HLA Abs., Results: Twenty-three (71.9%) sera were positive for DS-HLA Abs by ELISA PRA. The AMS assay showed that the number of compatible sera with DS-HLA Abs was 27 (84.4%), and it was significantly concordant (kappa = 0.649, p < 0.0001). For FCXM, the number of compatible sera with DS-HLA Abs was 26 (81.3%), and it was also significantly concordant (kappa = 0.614, p < 0.0001). There was a significant degree of concordance between the AMS assay and FCXM in detection of DS-HLA Abs (kappa = 0.452, p = 0.010)., Conclusion: The AMS assay is comparable to FCXM in detecting DS-HLA Abs in high PRA recipients., (Copyright (c) 2009 S. Karger AG, Basel.)

Background/aims: The development of acute renal failure (ARF) is a very rare complication in patients with acute hepatitis A (AHA)., Methods: We retrospectively investigated the overall incidence, risk factors, and clinical outcomes of ARF associated with AHA. Diagnosis of AHA was made according to the typical hepatitis symptoms and positivity of immunoglobulin M anti-hepatitis A virus in 208 patients with AHA., Results: ARF was noted in 12 (5.7%) patients, and dialysis was required in 8 (66%) patients. The median duration of hospitalization for patients with ARF was 18 days (range, 6-50 days). The development of ARF was observed in older patients (p = 0.004) and in patients with diabetes (p = 0.001), excessive alcohol consumption (p = 0.01), prolonged international normalized ratio (p = 0.019), and elevated aspartate aminotransferase concentration (p = 0.034). Multivariate analysis revealed that old age (odds ratio, OR, 1.2), elevated aspartate aminotransferase concentration (OR, 1.05), and diabetes (OR, 18.5) were independent risk factors for ARF (each p < 0.001). The prognosis of patients with ARF was good, and renal function recovered completely., Conclusion: ARF associated with AHA is not rare, and the possibility of AHA should be considered in patients with ARF with hepatic dysfunction., (Copyright 2008 S. Karger AG, Basel.)

Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex (''hump''). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment.

Interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay is a powerful tool for measuring the frequency of alloantigen-specific T cells, reflecting cellular immunity. We correlated the pretransplant frequencies of donor-specific and third-party-specific IFN-gamma ELISPOT tests, with the posttransplant outcomes of 45 recipients of living donor renal transplantations. The mean frequency of pretransplant donor-specific ELISPOT was significantly greater among patients with acute rejection episodes (ARE) than those without ARE (18.0 [12 to 50] versus 8.8 [5 to 30.4]) spots per 200,000 peripheral blood lymphocytes (PBLs; P=.024). A cutoff level of 12 spots per 200,000 PBLs on the donor-specific ELISPOT identified an ARE-positive patient with a sensitivity of 81.8% and a specificity of 64.7%. The recipients with pretransplant donor-specific ELISPOT+showed higher serum creatinine levels and lower glomerular filtration rate (GFR) at 6 posttransplant months (P<.05). Although the pretransplant third-party-specific ELISPOT results correlated with the donor-specific ELISPOT results (r=.783; P<.001), there was no significant difference in the third-party ELISPOT results between the ARE-positive and ARE-negative recipients. In conclusion, an analysis of pretransplant donor-specific IFN-gamma ELISPOT may identify the posttransplant risk of developing ARE and displaying decreased GFR at 6 months.

Background: Knowledge of kidney size is important for clinical assessment of renal disease. However, there are few studies on methods of assessing kidney size. The purpose of this study was to determine the usefulness of body index and radiological measurements for prediction of kidney size., Methods: One hundred and twenty five donors were enrolled. The sizes of donor kidneys obtained after nephrectomies for kidney transplantations were documented and the correlation coefficient between kidney length and body index was calculated. Kidney length was estimated from the distance between the first and third lumbar vertebrae (L1-3), intravenous pyelograms (IVPs), abdominal ultrasonography (US), and abdominal computed tomography (CT)., Results: Normal adult kidneys were 11.08 +/- 0.96 cm long, 6.25 +/- 0.67 cm wide, 4.73 +/- 0.65 cm thick and weighed 196.3 +/- 41.0 g. Correlation coefficients between kidney length and body height, body weight, body surface area and total body water content were 0.29, 0.31, 0.26, and 0.32, respectively. The difference between actual and predicted kidney lengths was -0.6 cm for L1-3, +1.2 cm for IVPs, -0.7 cm for abdominal US, -0.8 cm for transverse CT section, and -0.5 cm for coronal CT section., Conclusions: Abdominal coronal CT section predicted kidney length more accurately than other radiological methods, but all radiological methods were associated with prediction errors. As kidney length was correlated with body index, it is suggested that body index is the most useful and simplest method of estimating kidney size as an adjunct to treatment decisions concerning renal disease.

Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone and is a new clinically available class of agents for improving of insulin resistance in both animals and humans with type 2 diabetes. These studies aimed to determine whether long-term treatment with a long-acting GLP-1 analog, exendin-4, delayed the progression of diabetes. Male db/db mice and db/m mice at 8 wk of age were treated with exendin-4 for 8 wk, whereas the control db/db mice received only vehicle. Urinary albumin excretion was significantly decreased in db/db mice that were treated with 1 nmol/kg exendin-4 compared with those in db/db mice that were treated with 0.5 nmol/kg exendin-4 and control db/db mice (P < 0.005). Intraperitoneal glucose tolerance test was improved in db/db mice that were treated with 1 nmol/kg exendin-4 compared with other groups (P < 0.05). Despite this, fasting blood glucose, glycated hemoglobin, and creatinine concentrations were not significantly different among db/db mice. Renal histology studies further demonstrated that glomerular hypertrophy, mesangial matrix expansion, TGF-beta1 expression, and type IV collagen accumulation and associated glomerular lipid accumulation were significantly decreased in db/db mice that were treated with 1 nmol/kg exendin-4. Furthermore, there were fewer infiltrating inflammatory cells and apoptotic cells in the glomeruli of db/db mice that were treated with 1 nmol/kg exendin-4 compared with those in the other groups accompanied by an increase in the renal immunoreactivity of peroxisome proliferator-activated receptor alpha and GLP-1 receptor-positive cells and a decrease in 24-h urinary 8-hydroxy-deoxyguanosine levels (P < 0.01, respectively) along with decreases in lipid content. Taken together, exendin-4 treatment seems to ameliorate diabetic nephropathy together with improvement of the metabolic anomalies. These results suggest that exendin-4 could provide a therapeutic role in diabetic nephropathy that results from type 2 diabetes.

The development of anuria after appendectomy is usually related to complications associated with appendicitis or with the surgical sequelae of appendectomy. We report an unusual case of anuria after appendectomy in a 20-year-old woman. The patient was transferred to our hospital due to a sudden cessation of urine output just after appendectomy. We initially suspected that the anuria was caused by a complication of surgery. However, a review of her medical history and an abdominal computed tomography (CT) scan revealed that a distal ureteral stone in a single kidney had caused the anuria. There are few cases in the literature regarding a distal ureteral stone in a single kidney. This case indicates the importance of radiological evaluation in the differential diagnosis of acute appendicitis, especially in patients with unilateral renal agenesis.

Background: The prognosis and outcome of patients with end-stage renal disease are related to the quality of predialysis care and the timing of referral. Late referral (LR) has been correlated with more frequent hospital admissions, malnutrition and cardiovascular mortality after hemodilaysis (HD) is started., Methods: We investigated the effects of LR on cardiac hypertrophy, uremia-related metabolic risk factors and mortality in patients on HD. A baseline echocardiography was performed in 119 patients on HD, 67 of whom were early referrals (ER, referred more than 3 months before the start of HD) and 52 were LR (referred less than 3 months before the start of HD; median (range): 22.5 (4-120) vs. 1.0 (0-3) months, respectively)., Results: The survival curves showed a higher mortality rate in the LR patients than in the ER patients (log rank, p = 0.004). More patients in the LR group died of cardiovascular disease compared to the ER patients (p = 0.04). The plasma levels of albumin were significantly lower (p < 0.05), and the intact parathyroid hormone (iPTH) and log C-reactive protein (log CRP) were significantly higher in the LR patients compared to the ER patients (p < 0.05 and p < 0.001, respectively). The LR patients, especially nonsurvivors, showed greater impairment of systolic cardiac function and more concentric left ventricular hypertrophy (LVH) than ER patients, as determined by interventricular septal thickness (p < 0.001), left ventricular posterior wall thickness (p < 0.001), relative wall thickness (p = 0.02), and the left ventricular mass index (LVMi, p < 0.001). Interestingly, the duration of the pre-HD treatment, after referral, was positively associated with the plasma albumin (r = 0.229; p = 0.01) and negatively associated with the log CRP (r = -0.350; p < 0.001), iPTH (r = -0.309; p = 0.001) and LVMi (r = -0.268; p = 0.004). Multiple linear regression analysis also demonstrated that the log CRP and iPTH as well as the LR were independently associated with LVMi in the HD patients (p < 0.05)., Conclusions: The results of this study demonstrated that the LR HD patients were at an increased risk for more cardiovascular related mortality, severe concentric LVH and systolic dysfunction accompanied by inflammatory and malnutrition indices, as well as with increased iPTH levels. In the LR patients, the more severe LVH associated with severe inflammatory indices, as well as the higher iPTH levels, may be one of the causes of LR-related mortality., ((c) 2007 S. Karger AG, Basel)

Background/aims: Rosiglitazone (RGTZ) has a protective effect against various types of injury. We evaluated the effects of RGTZ on renal injury in a stroke-prone spontaneously hypertensive rat (SHRSP) model., Methods: Male SHRSP rats were observed with or without RGTZ treatment for 10 weeks. Age-matched male Wistar-Kyoto rats were used as controls. The effect of RGTZ on hypertensive nephropathy was evaluated by assessing renal function, pathology, pro-inflammatory cytokine (osteopontin), profibrotic cytokine (betaig-h3), apoptotic cell death (TUNEL staining and caspase 3 expression), marker of oxidative stress (8-OHdG) and endothelial damage (eNOS)., Results: RGTZ treatment improved renal function and histopathology compared with SHRSP rats without treatment (p < 0.05). Osteopontin and betaig-h3 were significantly increased in SHRSP rat kidneys, but RGTZ treatment decreased both mediators. Apoptotic cell death was increased in renal tubular cells in the injured area in SHRSP rat kidneys, but RGTZ treatment decreased apoptotic cell death and caspase 3 expression. Increased urinary 8-OHdG excretion and decreased eNOS in SHRSP rats was reversed with RGTZ treatment., Conclusions: RGTZ protects hypertensive nephropathy in SHRSP rats., (Copyright 2007 S. Karger AG, Basel.)

This study was performed to investigate the impact of intima-media thickness (IMT) of radial artery on early failure of radiocephalic arteriovenous fistula (AVF) in hemodialysis (HD) patients. Ninety uremic patients undergoing radiocephalic AVF operation were included in this study. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. And then AVF patency was followed up for 1 yr after the operation. Of the total 90 patients, 31 patients (34%) had AVF failure within 1 yr after the operation. Mean IMT was thicker in failed group (n=31) than in patent group (n=59) (486+/-130 micrometer vs. 398+/-130 micrometer, p=0.004). The AVF patency rate within 1 yr after the operation was lower in patients with IMT > or = 500 micrometer (n=26) than in patients with IMT <500 micrometer (n=64) (p=0.017). Age was an independent risk factor of IMT. Diabetes mellitus tended to be independent risk factor but not statistically significant. Our data suggest that increased radial artery IMT is closely associated with early failure of radiocephalic AVF in HD patients.

Background: Increased intima-media thickness (IMT) of the radial artery is associated with early failure of radiocephalic arteriovenous fistula (AVF) in haemodialysis patients. Therefore, non-invasive measurements of radial artery IMT before AVF operations are very important in predicting AVF patency. This study was designed to evaluate the accuracy of high-resolution ultrasonography in measuring radial artery IMT in pre-dialysis uraemic patients., Methods: This study enrolled 43 pre-dialysis uraemic patients awaiting radiocephalic AVF operations for the first time. In this study, 17 age- and sex-matched uncomplicated hypertensive patients and 15 healthy subjects were included as a control. We measured the internal diameter (ID) and IMT of the radial artery using high-resolution ultrasonography on the wrists of uraemic patients as well as the control group before the AVF operation. We obtained specimens of the radial artery during the AVF operation and directly measured the IMT by histological examination., Results: The radial artery IMT of the uraemic patients (0.41 +/- 0.09 mm) was significantly thicker, compared to both those of the hypertensive (0.33 +/- 0.05 mm, P < 0.001) and the healthy patients (0.25 +/- 0.04 mm, P = 0.002). In contrast, the radial artery ID in the uraemic patients (1.85 +/- 0.48 mm) was smaller than both that of the hypertensive patients (2.08 +/- 0.31 mm, P = 0.023) and the healthy persons (2.34 +/- 0.37 mm, P = 0.001). Radial artery IMT had a negative correlation with radial artery ID in a total of 73 subjects (r = -0.290, P = 0.012). The value of the radial arterial IMT measured by sonographic examination correlated significantly with that by histological examination in 43 uraemic patients (r = 0.786, P < 0.001) and it correlated significantly with early AVF failure (r = 0.358, P = 0.027)., Conclusion: Our data suggest that high-resolution ultrasonography is an effective tool in measuring radial artery IMT in uraemic patients before AVF operation.

Background: Sudden cardiac death is common in patients on hemodialysis (HD), and its rate is as high as 25% of all cardiac deaths associated with left ventricular hypertrophy (LVH) and secondary hyperparathyroidism. A prolonged QT interval on standard electrocardiography is related to an increase in sudden death in various patient groups. It is also well known that LVH has been noted in uremic patients with high parathyroid hormone levels., Methods: To evaluate the response of intravenous calcitriol treatment on the QT interval and LVH in HD patients with secondary hyperparathyroidism (intact parathyroid hormone, iPTH, > 450 ng/ml), echocardiographic, electrocardiographic (ECG), and biochemical assessments were performed over a 15-week period in 25 HD patients before and after intravenous calcitriol treatment. We also evaluated 25 age-, sex-, HD duration-, and BMI-matched HD control patients with secondary hyperparathyroidism., Results: In patients receiving intravenous calcitriol, a significant reduction in iPTH levels (p < 0.05) and alkaline phosphatase levels (p < 0.01) was found without changes in values of serum calcium and ionized Ca2+, phosphorus, Na+, K+, Mg2+, hematocrit, blood pressure, or other hemodynamic changes. Echocardiograms showed significant decreases in the thickness of the interventricular septum (p < 0.05), left posterior wall thickness (p < 0.05), and left ventricle mass index (LVMi, p < 0.01). In addition, sequential ECG measurement in patients with calcitriol treatment showed significant reductions in QTcmax (QTmax interval corrected for heart rates, p < 0.01) and QTc dispersion (QT dispersion corrected for heart rates, p < 0.01). However, in the control patients, biochemical, hemodynamic, and ECG changes, as well as myocardial structural and functional changes were not seen. Multiple regression analysis in all patients indicated that iPTH and LVMi levels were independent predictors of QTcmax while the LVMi level was the only independent predictor of QTc dispersion (p < 0.05)., Conclusions: Our study showed a significant correlation between LVMi and QT dispersion in HD patients with secondary hyperparathyroidism. Intravenous calcitriol treatment, to be used for the control of secondary hyperparathyroidism, was found to cause regression of myocardial hypertrophy and a reduction in the QTc interval and dispersion, without biochemical and hemodynamic changes. These findings suggest that an active vitamin D metabolite has a cardioprotective action in HD patients., (2006 S. Karger AG, Basel.)

Gingival hyperplasia is a frequent complication in transplant patients who receive cyclosporine or calcium channel blockers. We studied an unusual case involving a renal transplant recipient with post-transplant non-Hodgkin's lymphoma that manifested as gingival hyperplasia. We initially consider that it was a side effect of cyclosporine and nifedipine. The lesion did not respond to dose reductions or the withdrawal of cyclosporine and nifedipine, and the gingival hyperplasia progressed in a localized fashion, becoming ulcerated and bleeding easily. Histological examination revealed the presence of malignant lymphoma.

Background: Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy., Methods: Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.5 mg/kg), or both CsA and FTY720 (0.125 mg/kg). The effects of FTY720 on CsA-induced renal injury were evaluated using renal function tests and histopathology, and the expression of mediators of CsA-induced renal injury (osteopontin, transforming growth factor-beta1 [TGF-beta1], betaig-h3, and angiotensin II)., Results: FTY720 treatment significantly decreased T-lymphocyte accumulation in kidneys compared with CsA treatment alone. FTY720 treatment improved not only CsA-induced renal dysfunction but also renal histopathology, demonstrated by decreased macrophage infiltration and interstitial fibrosis. Increased osteopontin, TGF-beta1, betaig-h3, and angiotensin II expression in CsA-treated rat kidneys were decreased with FTY720 treatment., Conclusions: FTY720 treatment prevents CsA-induced renal injury.

Peroxisome proliferator activated receptor gamma (PPARgamma) agonist has not only antidiabetic effect but also a protective effect against various types of injury of the kidney. The protective effects of PPARgamma agonists are observed in diabetic nephropathy and non-diabetic renal diseases such as 5/6 ablation model of renal failure, experimental glomerulonephritis, ischemia-reperfusion injury, hypertensive nephropathy and cyclosporin-induced renal injury. The mechanism of renoprotection by PPARgamma agonist is multifactorial. Anti-fibrotic and anti-inflammatory effects, suppression of renin-angiotensin system, vascular protective effect and antiapoptotic effect were proposed.

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.

Background: C-reactive protein (CRP), which reflects chronic inflammation, is a strong predictor of cardiovascular mortality in hemodialysis patients. We investigated whether persistent elevation of CRP is associated with cardiac function and morphology in patients maintained on hemodialysis., Methods: Predialysis high-sensitivity CRP (hs-CRP) was measured twice at an interval of 3 weeks in 52 stable hemodialysis patients, and echocardiographic studies were performed., Results: 25 patients showed persistent elevation of predialysis hs-CRP (>3 mg/l, high CRP group). Patients in the high CRP group had a lower dialysis dose (p < 0.01), higher troponin T (p < 0.01), and higher fibrinogen (p < 0.01). Echocardiographic studies showed that left atrial diameter (LA, p < 0.05), interventricular septal thickness (IVST, p < 0.05), left ventricular end-diastolic volume (LVEDV, p < 0.05), and left ventricular mass index (LVMI, p < 0.05) were higher in the high CRP group. However the ejection fraction (EF) was lower in the high CRP group (p < 0.05), which also contained more patients with low EF (<40%) (p < 0.01). There was no difference in diabetes mellitus, acute infection and type of vascular access between the groups. hs-CRP level was positively correlated with troponin T (r = 0.416, p < 0.01) and fibrinogen (r = 0.560, p < 0.001), and IVST with hs-CRP level (r = 0.291, p < 0.05), whereas the EF was negatively correlated with hs-CRP (r = -0.301, p < 0.05). In addition, the high CRP group correlated positively with IVST (r = 0.281, p < 0.05), LVEDV (r = 0.322, p < 0.05), and LVMI (r = 0.312, p < 0.05) and negatively with EF (r = -0.311, p < 0.05). On multivariate analysis, the high CRP group (beta = -0.312, beta = 0.238, and beta = 0.318, respectively) was a significant predictor of EF (R = 0.62, p = 0.025), LVMI (R = 0.928, p = 0.02) and IVST (R = 0.64, p = 0.01)., Conclusions: Persistent elevation of CRP, which is an independent risk factor for EF, LVMI and IVST, may predict cardiac hypertrophy and dysfunction in patients maintained on hemodialysis.

The combination of idiopathic thrombocytopenic purpura (ITP) and chronic renal failure (CRF) is uncommon. This report highlights a case of renal transplantation in a patient with ITP. A 35-year-old man with ITP was admitted with uremic symptoms. A renal transplant and splenectomy was simultaneously performed. A prophylactic pneumococcous vaccination was performed and intravenous immunoglobulin (1 g/kg) was administered before and after the operation. The patient's platelet count increased gradually after the splenectomy. During a two-year follow up period, the graft function was well maintained. Renal transplantation in a patient with ITP is recommended with a well-designed strategy to prevent potential complications.

Background: Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury., Methods: CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death., Results: Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3)., Conclusion: rHuEPO has a renoprotective effect against chronic CsA-induced renal injury., (Copyright 2005 S. Karger AG, Basel.)

Background: We recently demonstrated that upregulation of the transforming growth factor (TGF)-beta1 inducible gene-h3 (betaig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between betaig-h3 expression and TIF during losartan treatment in this model., Methods: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on betaig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-beta1 and intrarenal angiotensin II were compared across treatment groups., Results: Concurrent administration of losartan significantly attenuated betaig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 +/- 5 vs. 39 +/- 5%, p < 0.01 vs. CsA) and the expression of TGF-beta1 mRNA (336 +/- 49 vs. 685 +/- 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 +/- 5 vs. 38 +/- 6, p < 0.05 vs. CsA)., Conclusion: Losartan is capable of abrogating the upregulation of TGF-beta1 and betaig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity., (Copyright (c) 2005 S. Karger AG, Basel.)

Background/aim: Induction of heat shock protein 70 (HSP70) is important in the tolerance of subsequent ischemia-reperfusion (I/R) injury. The aim of this study was to evaluate the effect of HSP70 induction by 1,25-dihydroxyvitamin D3 (VD3) on subsequent I/R injury in rats., Methods: HSP70 was induced in Sprague-Dawley rats by VD3 treatment for 7 days, and the effect of VD3 pretreatment on subsequent I/R injury was evaluated in terms of renal function, tubular necrosis score, tumor necrosis factor alpha mRNA expression, mitogen-activated protein kinase expression, and proliferating cell nuclear antigen expression., Results: VD3 treatment increased HSP70 expression which was localized to renal tubular cells in the outer medulla. Pretreatment with VD3 before I/R injury resulted in (1) decreased blood urea nitrogen and serum creatinine levels; (2) decreased tubular cell necrosis; (3) increased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; (4) decreased tumor necrosis factor alpha mRNA expression, and (5) increased extracellular signal regulated protein kinase and decreased c-Jun N-terminal kinase expression., Conclusion: Our study demonstrates that VD3 is a nontoxic inducer of HSP70 and exerts a protective effect against subsequent I/R injury.

Background: Nitric oxide (NO) is related to the pathogenesis of renal hemodynamics in diabetes mellitus. Endothelial nitric oxide synthase (eNOS) gene polymorphism is considered the deterioration factor for progressive renal disease. It has been reported that an interaction of angiotensin II (Ang II) and NO is involved in the control of glomerular hemodynamics. This study aimed to elucidate the roles of eNOS and the angiotensin-converting enzyme (ACE) gene polymorphism for the progression of type 2 diabetic nephropathy (DN)., Methods: Korean type 2 diabetic patients (n = 177) were studied. eNOS and ACE genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. They were divided into three groups: group 1 consisted of patients with normoalbuminruia (n = 59), group 2 had microalbuminuria (n = 35) and group 3 had overt nephropathy (n = 83)., Results: Group 3 had a higher frequency of eNOS(GT) than groups 1 and 2. Patients with eNOS(GT) genotype showed more rapid deterioration in renal function, higher incidence of overt nephropathy and lower renal survival than those with eNOS(GG) genotype. However, there was no significant association between the ACE genotypes and DN, and no interaction between eNOS and ACE gene polymorphism., Conclusion: These results imply that eNOS(GT) genotype is associated with the progression of type 2 DN in Korean patients.

Aim: To examine whether the reversibility of chronic cyclosporine A (CsA) nephrotoxicity is associated with apoptotic cell death and its regulatory factors., Methods: Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg, sc) for 5 weeks, and then withdrawing it for 5 or 10 weeks. The effect of CsA withdrawal on apoptotic cell death was evaluated by an in situ TdT-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and the expression of pro-apoptotic [transforming growth factor-beta 1 (TGF-beta 1) and Fas] and anti-apoptotic [epidermal growth factors (EGF) and Bcl-2] factors., Results: Discontinuation of CsA induced significant decreases in TUNEL-positive cells in a time-dependent manner and the reduction in TUNEL-positive cells was correlated with the tubulointerstitial fibrosis score (r=0.919, P<0.01). Upregulation of TGF-beta and Fas expression in CsA-treated rat kidneys was decreased significantly after withdrawal of CsA. In contrast, downregulated EGF and Bcl-2 expression returned to normal or supernormal levels., Conclusion: CsA withdrawal is associated with a decrease in apoptotic cell death and with changes in the expression of pro-apoptotic and anti-apoptotic molecules involved in renal wound repair. This may constitute one of the mechanisms underlying the reversibility of chronic CsA nephrotoxicity.

Up-regulation of transforming growth factor-beta (TGF-beta) is known to play an important role in the tubulointerstitial injury of chronic cyclosporin A (CsA) nephropathy, but the expression of the TGF-beta-inducible gene-h3 (betaig-h3) is undetermined. In this study we examined betaig-h3 expression and its relationship to tubulointerstitial injury in a rat model of chronic CsA nephropathy. Sprague-Dawley rats kept on a low-salt diet (0.05% sodium) were treated daily for 4 weeks with subcutaneous injections of vehicle (olive oil, 1 mL/kg) or CsA (15 mg/kg). The expression of betaig-h3 messenger RNA (mRNA) and protein was evaluated with the use of in situ hybridization, immunohistochemical methods, and immunoblotting. We also compared renal function, histologic findings (tubulointerstitial fibrosis), and expression of TGF-beta1 among treatment groups. In vehicle-treated kidney, betaig-h3 mRNA and protein were constitutively expressed in the outer medulla and cortex, which was confined to the terminal portion of afferent arterioles, the S3 segment of the proximal tubules, and distal convoluted tubules. CsA treatment significantly up-regulated betaig-h3 expression in the interstitium, especially in expanded and fibrotic areas. Quantitative analysis revealed that CsA induced a significant (twofold) increase in betaig-h3 mRNA and protein, and this increase was correlated with up-regulation of TGF-beta1 expression (r =.943, P <.001) and the tubulointerstitial fibrosis score (r =.746, P =.05). Our observations indicate that an increase in betaig-h3 expression, along with TGF-beta1 up-regulation, is closely associated with tubulointerstitial fibrosis in a rat model of chronic CsA nephropathy.

We investigated the effects of pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on interstitial inflammation and fibrosis, using an animal model of chronic cyclosporine A (CsA)-induced nephropathy. Sprague-Dawley rats were maintained on a low-salt diet (0.05% sodium) and treated daily for 1 or 4 wk with vehicle (olive oil; 1 ml/kg sc), CsA (15 mg/kg sc), or both CsA and pravastatin (5 or 20 mg/kg in the drinking water). Anti-inflammatory and antifibrotic effects of pravastatin were studied by evaluating the concentrations of the inflammatory mediators osteopontin (OPN) and C-reactive protein (CRP), of fibrotic cytokine-transforming growth factor (TGF)-beta1, and the presence of ED-1-positive cells (macrophages). In addition, renal function, serum lipid levels, histopathology (arteriolopathy and tubulointerstitial fibrosis), and the expression of the vasoactive factors endothelial nitric oxide synthase (eNOS) and renin protein were also compared for different treatment groups. Pravastatin induced dose-dependent decreases in the expression of OPN, intrarenal CRP, and TGF-beta1, and in the numbers of ED-1-positive cells at 1 and 4 wk. These were accompanied by a significant attenuation of tubulointerstitial fibrosis at 4 wk. The downregulation of eNOS protein expression in CsA-treated rat kidney was markedly upregulated by pravastatin treatment, although intrarenal renin expression was unaffected. Renal dysfunction induced by CsA significantly improved with administration of pravastatin at a dose of 20 mg/kg. Neither CsA nor pravastatin influenced serum lipid or high-sensitivity CRP levels in the treatment groups. Thus in chronic CsA nephropathy, pravastatin effectively abrogates the progression of tubulointerstitial inflammation and fibrosis. This may support the clinical use of pravastatin.

Although ultrasonography is regarded as the gold standard in the diagnosis of obstructive nephropathy, dilatation is sometimes not observed by ultrasonography. We report upon a case of minimally dilated obstructive nephropathy due to an ureter stone in a kidney donor with volume depletion. A 54-year-old man was admitted due to anuria and abdominal pain of 2 days duration. Ten years previously, his right kidney was donated for transplantation, and one month before admission, he abstained from all food except water and salt, for 30 days for religious reasons. He had lost 8 kg of body weight. On admission, he had clinical signs of volume depletion, i.e., a dehydrated tongue and decreased skin turgor. Laboratory data confirmed severe renal failure, his blood urea nitrogen level was 107.3 mg/dL, and his serum creatinine 16.5 mg/dL. The plain X-ray was unremarkable and ultrasonography showed only minimal dilatation of the renal collecting system. On follow-up ultrasonography, performed on the 5th hospital day, the dilatation of the collecting system had slightly progressed and a small stone was found at ureter orifice by cystoscopy. Removal of stone initiated dramatic diuresis with a rapid return of renal function to normal by the third day.

Hypoalbuminemia frequently occurs in Hemorrhagic Fever with Renal Syndrome (HFRS), but clinical significance of hypoalbuminemia is not well known. This study was designed to evaluate hypoalbuminemia as a marker of severity of disease in patients with HFRS. We evaluated the relationship between the level of serum albumin and clinical parameters representing the severity of disease in 144 patients with HFRS. The patients were divided into three groups based on the level of serum albumin; Group I (normal serum albumin), Group II (serum albumin <3.5 g/dL and >/=3.0 g/dL), and Group III (serum albumin <3.0 g/dL). Of the total of 144 patients, 42 patients (29.2%) were categorized as Group I, 39 patients (27.1%) as Group II, and 63 patients (43.8%) as Group III. Group III had a higher rate of incidence in episode of hypotension, pulmonary edema than did Group I and Group II. The lowest level of serum albumin was positively correlated with platelet count (r=0.505, p<0.001) and was negatively correlated with leukocyte count (r=-0.329, p<0.001), BUN (r=-0.484, p<0.001), serum creatinine (r=-0.394, p<0.001), and AST (r=-0.251, p=0.002). Our data suggest that hypoalbuminemia frequently occurs in the acute stage of HFRS, and level of serum albumin is associated with the disease severity of HFRS.

The status of dialytic therapy in Korea at the end of 2001 was reported by the end-stage renal disease (ESRD) registry committee of Korean Society of Nephrology, where data were collected through an internet on-line registry program. The number of dialysis centres was 335 and the number of haemodialysis machines was 5529. The total number of patients with dialysis was 23,057 (haemodialysis 17,568, peritoneal dialysis 5489). Prevalence and incidence of dialysis patients were 477.5 and 96.4 patients per million population. The most common primary cause of end-stage renal diseases was diabetic nephropathy (41.5%), hypertensive nephrosclerosis (15.4%), and chronic glomerulonephritis (13.6%). Eighty-six percent of haemodialysis patients were on dialysis therapy three times a week, the mean urea reduction ratio was 66.7 +/- 8.68% and mean Kt/V was 1.250 +/- 0.292 in male patients; 1.526 +/- 0.361 in female patients. The technical survival of haemodialysis in 5 years was 30.2% and peritoneal dialysis was 13.8%. The common complication of haemodialysis patients was hypertension (43.3%), gastrointestinal disease other than peptic ulcer (8.0%), congestive heart failure (7.6%), and of peritoneal dialysis patients were also hypertension (28.8%), congestive heart failure (5.0%), and peritonitis (4.8%). The most common causes of death were cardiac diseases (26.9%), vascular diseases, including cerebrovascular accidents (22.7%), and infection (17.8%).

Improving the ability of the kidney to tolerate ischemic injury has important implications. We investigated the effect of recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) injury and evaluated the role of heat shock protein (HSP) 70 in rHuEPO-induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, and rats were killed at 24, 48, and 72 h after I/R injury. Pretreatment of rHuEPO resulted in the following: i) decreased serum creatinine level; ii) decreased tubular cell apoptosis and necrosis, measured by DNA fragmentation analysis and TUNEL staining and histomorphological criteria; iii) decreased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; iv) increased bcl-2 protein and decreased caspase 3 activity; and v) decreased JNK expression. rHuEPO treatment increased HSP70 expression in a dose-dependent manner in normal rat kidneys, and inhibition of HSP70 expression by quercetin eliminated the renoprotective effect of rHuEPO in ischemic kidneys. Our study demonstrates that rHuEPO has a protective effect on subsequent I/R injury and that this effect is associated with induction of HSP70. Our study provides a new avenue for therapy to prevent renal damage after I/R injury.

Bone morphogenetic protein-7 (BMP-7), which belongs to the TGF-beta superfamily, has been shown to reduce macrophage infiltration and tissue injury in animal models of inflammatory renal disease. To explore the mechanism involved in the anti-inflammatory effect, we investigated the effect of BMP-7 on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells. BMP- 7 significantly inhibited constitutive and IL-1 beta-induced MCP-1 protein production and MCP-1 mRNA expression by mesangial cells in a time- and concentration-dependent manner. BMP-7 also inhibited IL-1 beta-induced monocyte chemotactic activity released from the mesangial cells. We examined the role of transcription factors NF-kappa B and AP-1 in BMP-7 inhibition of IL-1 beta-induced MCP-1 expression. IL-1 beta increased NF-kappa B and AP-1 activity and both transcription factors mediated IL-1 beta-induced MCP-1 expression in mesangial cells. BMP-7 inhibited IL-1 beta-induced AP-1 activity in a concentration-dependent manner. In contrast, IL-1 beta-induced NF-kappa B activity and I kappa B alpha degradation were not affected by BMP-7. Furthermore, IL-1 beta-induced phosphorylation of c-Jun N-terminal kinase was inhibited by BMP-7. These data suggest that BMP-7 inhibits constitutive and IL-1 beta-induced MCP-1 expression in human mesangial cells partly by inhibiting c-Jun N-terminal kinase activity and subsequent AP-1 activity, and provide new insight into the therapeutic potential of BMP-7 in the inflammatory renal diseases.

Background: Combined treatments of mycophenolate mofetil (MMF) and losartan (LSRT) have synergistic effects on various renal diseases through their hemodynamic and anti-inflammatory effects. This study investigated whether MMF treatment is effective in inhibiting inflammatory processes in chronic cyclosporine A (CsA) nephrotoxicity, and whether combined treatment using MMF and LSRT affords superior protection compared with the respective monotherapies., Methods: Rats on a low-salt diet were given vehicle (VH group, olive oil, 1 mg/kg per day), CsA (15 mg/kg per day), CsA and LSRT (CsA+LSRT group, 100 mg/L per day), CsA and MMF (CsA+MMF group; 40 mg/kg per day), or CsA, LSRT and MMF (CsA+LSRT MMF group). Control groups received each drug without CsA treatment. Renal function, histologic parameters (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and mediators of CsA-induced nephrotoxicity (angiotensin-II, osteopontin, and transforming growth factor [TGF]-beta1) were studied., Results: The CsA-treated rats showed decreased renal function and increased histologic parameters compared with the VH-treated rats. The CsA+MMF treatment significantly improved renal function and histopathologic parameters compared with the CsA group, and combined treatment with MMF and LSRT further improved those parameters compared with the CsA+LSRT and CsA+MMF groups. At a molecular level, increased expression of angiotensin II protein, osteopontin, and TGF-beta1 mRNAs in the CsA group were significantly decreased with MMF, and further decrease was observed with the combined treatment using MMF and LSRT., Conclusions: MMF treatment decreases CsA-induced nephrotoxicity, and combined treatment with LSRT has a synergistic effect in preventing chronic CsA nephrotoxicity.

Background: Osteopontin (OPN) mediates progressive renal injury in various renal diseases by attracting macrophages, and its expression is regulated by the renin-angiotensin system (RAS). We studied the association between OPN expression and tubulointerstitial injury, and investigated the effect of ramipril on OPN expression in an animal model of non-insulin-dependent diabetes mellitus (NIDDM): Otsuka Long-Evans Tokushima Fatty (OLETF) rats., Methods: Control (Long-Evans Tokushima Otsuka, LETO) and diabetic (OLETF) rats were treated with ramipril (3 mg/kg in drinking water) or vehicle for nine months, starting at 20 weeks of age. Systolic blood pressure, body weight, urinary protein excretion and oral glucose tolerance tests (OGTT) were monitored periodically. Renal function, histology (glomerulosclerosis, tubulointerstitial fibrosis, and ED-1-positive cells as a measure of macrophage infiltration), and expressions of OPN and transforming growth factor-beta1 (TGF-beta1) were evaluated at the end of the study., Results: Compared with the LETO rats, OLETF rats showed declines in creatinine clearance rate, increases in urinary protein excretion and systolic blood pressure, and development of glomerulosclerosis, tubulointerstitial fibrosis, and inflammatory cell infiltration (all P < 0.05). Blocking angiotensin II with ramipril significantly improved all of these parameters (all P < 0.01). At the molecular level, expressions of OPN and TGF-beta1 were up-regulated in the OLETF rats, and were markedly suppressed following ramipril treatment. The sites of strong OPN mRNA and protein expressions were localized to areas of renal injury. Of note, the expression of OPN mRNA was strongly correlated with the number of ED-1-positive cells (r = 0.560, P = 0.01) and the tubulointerstitial fibrosis score (r = 0.500, P < 0.05)., Conclusions: Up-regulation of OPN expression may play a role in tubulointerstitial injury associated with diabetic nephropathy, and blockade of the RAS by ramipril may confer renoprotection by decreasing OPN expression in non-insulin-dependent diabetic nephropathy.

Background: The radiocephalic arteriovenous fistula (AVF), which provides the best vascular access for hemodialysis, continues to have a high incidence of early failure. Intimal hyperplasia (IH) of the radial artery is observed commonly in uremic patients before hemodialysis, but the impact of this preexisting IH on the early failure of radiocephalic AVFs has not been reported yet. Therefore, we designed this study to: (1) investigate clinical risk factors for IH, and (2) determine whether preexisting IH of the radial artery is associated with early failure of a radiocephalic AVF., Methods: Specimens from the radial artery were obtained during the radiocephalic AVF operation. IH was measured with trichrome staining, and AVF patency was prospectively followed up for 12 months after the operation., Results: Of the 59 patients, 45 patients had evidence of IH in their radial artery (76.2%). Patients with IH (n = 45) were older than those without IH (n = 14; 58 +/- 12 versus 44 +/- 17 years; P = 0.003). The incidence of diabetes mellitus in patients with IH was greater than that in patients without IH (60.0% versus 28.6%; P = 0.004). Of the 57 patients, except for 2 patients who died before the end point of the study with patent AVFs, fistula failure was observed only in patients with IH (22 of 44 patients; 50% versus 0%; P < 0.001). The intima was thicker in the failed-AVF group than the patent-AVF group (93.1 +/- 37.5 versus 45.6 +/- 17.4 micrometer P < 0.001)., Conclusion: This study suggests that early failure of radiocephalic AVFs in hemodialysis patients is closely associated with preexisting IH of the radial artery., (Copyright 2003 by the National Kidney Foundation, Inc.)

Renal interstitial inflammation is an important factor in the pathogenesis of chronic cyclosporin A (CsA) nephropathy. We studied the expression of the chemoattractant osteopontin (OPN) and the relationship between OPN expression and tubulointerstitial injury in a rat model of chronic CsA nephropathy. Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15 mg/kg sc) for 5 wk and then withdrawing it for 5 or 10 wk. Renal function, histopathology (arteriolopathy, ED-1-positive cells, and tubulointerstitial fibrosis), renin-angiotensin system (RAS) activity, and OPN expression were observed during the follow-up period. Renal function deteriorated in CsA-treated rats, with the development of typical histopathology and activation of RAS. After CsA withdrawal, these parameters were significantly reversed (all P < 0.05). The upregulation of OPN mRNA and protein expression seen in CsA-treated rat kidneys was decreased 5 wk after CsA withdrawal and was further decreased after 10 wk. Of note, OPN mRNA expression correlated with the number of infiltrating macrophage (r = 0.651, P < 0.01) and tubulointerstitial fibrosis (r = 0.729, P < 0.01). These findings suggest that OPN expression and macrophage infiltration decrease after long-term CsA withdrawal in rats with established chronic CsA nephropathy, and this is closely associated with recovery from renal injury.

Renal tubular acidosis in renal transplant recipients usually is asymptomatic and subclinical. The authors report a case of severe renal tubular acidosis manifested as muscle weakness in a renal transplant recipient. The patient received a renal transplant 30 months ago and had a history of successive episodes of acute rejection during the past 2 months. On admission, arterial blood (arterial blood pH, 7.11; pco(2), 12.8 mm Hg; and bicarbonate, 4 mEq/L [4 mmol/L]) and urine gas analysis were compatible with distal renal tubular acidosis. The graft biopsy findings showed superimposed acute rejection on chronic allograft nephropathy, and immunohistochemical staining and electron microscopic findings showed the reduced immunoactivity of H(+)ATPase pump and anion exchanger 1. The patient was treated successfully with intravenous bicarbonate and oral steroid pulse therapy. This finding suggests that rejection-related renal tubular acidosis should be considered a cause of severely affected metabolic acidosis in renal transplant recipients.

Background: The signaling pathways of mitogen-activated protein kinases (MAPKs) are important molecular components responsible for ischemia/reperfusion (I/R) injury in the kidneys. Preconditioning with cyclosporine A (CsA) or FK506 reduces subsequent I/R injury. We studied the effect of preconditioning with CsA or FK506 on MAPK expression in ischemic rat kidneys., Methods: Two separate studies were performed using Sprague-Dawley rats. First, MAPK (extracellular signal-regulated kinase [ERK], jun N-terminal kinase [JNK], p38) expressions were observed at 0, 10, 20, 30, 60, 120, and 1,440 min after I/R injury. Second, the effects of preconditioning with CsA or FK506 on MAPK expressions were observed in rat kidneys with I/R injury. I/R injury was induced by clamping both renal arteries for 45 min. Rats were pretreated with intravenous (IV) CsA (3 mg/kg) or IV FK506 (0.3 mg/kg) 6 hr before I/R injury and killed 30 min later. Expression of MAPK was measured using immunoblot and immunohistochemistry., Results: MAPK (ERK, JNK, p38) expressions were significantly increased in kidneys with I/R injury compared with sham-operated controls, and immunohistochemistry revealed increased MAPK immunoreactivity in renal tubules of the outer medulla. Kidneys preconditioned with low-dose CsA or FK506 showed significantly increased ERK expression compared with kidneys with I/R injury alone (CsA, 9.5- vs. 4.5-fold; FK506 10.4- vs. 4.5-fold: P<0.05) but showed decreased JNK (CsA, 3.8- vs. 5.3-fold; FK506, 3.4- vs. 5.3-fold: P<0.05) and p38 expression (CsA, 2.5- vs. 3.7-fold; FK506, 2.1- vs. 3.7-fold: P<0.05)., Conclusions: Preconditioning with CsA or FK506 differentially regulates the expression of MAPK in rat kidneys with I/R injury, and this may explain the remarkable protective effects of these agents.

Human polyomavirus (PV) interstitial nephritis has recently been recognized as a cause of severe renal allograft dysfunction. It occurs in immunosuppressed patients after reactivation of the latent virus PV type BK (BK virus) in the renal epithelium. BK disease is defined as a morphologically manifest renal infection with cytopathic signs accompanied by varying degrees of interstitial inflammatory cell infiltrates and functional impairment. It is also identified by the presence of cells containing viral inclusion bodies (decoy cells) in the urine. The authors report a case of BK PV interstitial nephritis in a 36-year-old renal allograft recipient. Under light microscopy the chief diagnostic indicator was detection of intranuclear viral inclusions, which were found exclusively in tubular epithelial cells. Cells with viral changes were often enlarged with nuclear atypia and chromatin basophilia. Widespread interstitial plasma cell infiltrates associated with tubulitis were present. Intranuclear paracrystalline arrays of virus particles 35-38 nm in diameter were present as characteristic ultrastructural indicators. Urine samples revealed decoy cells with ground-glass-type intranuclear inclusions positive for BK virus by electron microscopy.

Background: Chronic inflammation characterized by increased C-reactive protein (CRP) levels strongly predicts cardiovascular death in both nonrenal and renal patients. We investigated the role of hemodialysis-induced elevated CRP levels on cardiac hypertrophy in hemodialysis patients., Methods: We grouped 118 stable patients as responders and nonresponders according to the response of CRP (>4 mg/L) after a single hemodialysis session., Results: Predialysis CRP and interleukin-6 (IL-6) concentrations were significantly greater in responders compared with nonresponders (6.4 versus 2.0 mg/L and 8.7 versus 4.8 ng/L, respectively; P < 0.01). Postdialysis CRP concentrations in responders (8.8 mg/L; P < 0.05) and IL-6 concentrations in responders and nonresponders (10.0 versus 5.4 ng/L; P < 0.05) further increased. Intact parathyroid hormone, fibrinogen, total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) [Lp(a)] levels (P < 0.05), as well as interventricular septal thickness (IVST; P < 0.005), left ventricular posterior wall thickness (LVPWT; P < 0.05), and left ventricular mass index (LVMi; P < 0.05) were significantly greater in responders compared with nonresponders. Predialysis and postdialysis CRP levels correlated positively with Lp(a) (P < 0.01, P < 0,05, respectively), fibrinogen, and predialysis and postdialysis IL-6 levels (P < 0.001) and negatively with albumin level (P < 0.05, P < 0.01, respectively). LVMi, as well as IVST and LVPWT, correlated not only with predialysis and postdialysis CRP levels, but also IL-6 levels (P < 0.05). The interval changes in postdialysis to predialysis CRP levels correlated significantly with IVST, PWT (r = 0.500; r = 0.458; P < 0.001, respectively), and LVMi (r = 0.252; P < 0.05). On multivariate analysis, the responder was the only predictor of IVST, LVPWT, and LVMi (P < 0.001, P < 0.001, and P < 0.01, respectively)., Conclusion: Elevated CRP concentrations associated with hemodialysis may be useful for the prediction of proatherogenic reactivity and cardiac hypertrophy., (Copyright 2002 by the National Kidney Foundation, Inc.)

Background: Epidermal growth factor (EGF) plays an important role in tubular regeneration in kidneys with ischemia/reperfusion (I/R) injury. This study was undertaken to evaluate the influence of cyclosporine A (CsA) or FK506 on mature EGF expression and tubular regeneration in rat kidneys with I/R injury., Methods: Two separate studies were performed. First, the expression of EGF and tubular regeneration was observed in rat kidneys with I/R injury on days 1, 2, 3, 5, and 7. Second, the dose-dependent response of EGF expression and tubular regeneration to CsA (5, 10, and 20 mg/kg) or FK506 (0.25, 0.5, and 1.0 mg/kg) was observed in rat kidneys with I/R injury. I/R injury was induced by clamping both renal arteries for 45 min, and CsA or FK506 was injected just after release of vascular clamps. Rats were sacrificed on day 1 for evaluation of EGF expression, and on day 2 for evaluation of BudU-positive cells. Renal function, tubular injury score, EGF expression assessed by immunoblotting, levels of CsA and FK506 in whole blood, and immunostaining for BrdU was studied., Results: EGF expression was maximal on day 1 (cortex, 29-fold; medulla, 31-fold compared with sham-operated controls), and renal tubular regeneration measured with the number of BrdU-positive cells was maximal on days 2 and 3 in kidney with I/R injury, and thereafter the level of EGF and the number of BrdU-positive cells decreased progressively. CsA or FK506 treatment to ischemic rat kidneys reduced the expression of EGF and the number of BrdU-positive cells in a dose-dependent manner., Conclusions: CsA or FK506 treatment delays recovery from acute tubular necrosis, and this may be associated with decreased EGF expression by CsA or FK506., (Copyright 2002 S. Karger AG, Basel)

Background: Colchicine (Col) is beneficial to renal injury because of its anti-inflammatory effect, but its mechanism has yet to be elucidated. The present study was designed to evaluate the inhibitory effects of colchicine on osteopontin (OPN) expression and the macrophage accumulation in chronic cyclosporine (CsA) nephrotoxicity in rats., Methods: Male adult Sprague-Dawley rats on a low salt diet (LSD, 0.05% sodium) were treated daily with Col (30 microg/kg), CsA (15 mg/kg), and both CsA and colchicine or vehicle (olive oil 1 ml/kg) for 4 weeks. The effects of colchicine on chronic CsA nephrotoxicity were evaluated by examining renal function, histopathology, and ED-1 positive cells. The expressions of OPN mRNA and protein were estimated respectively by Northern blot and immunohistochemistry., Results: Compared with vehicle-treated rats, CsA-treated rats showed an increase in serum creatinine, a decline in creatinine clearance rate, and tubulointerstitial fibrosis (all p < 0.01). Concomitant administration of colchicine reversed all of the above parameters (all p < 0.01). Of note, the upregulated expression of osteopontin mRNA and protein seen in CsA-treated rats was significantly decreased after colchicine treatment. Furthermore, the expression of osteopontin mRNA was strongly correlated with the number of ED-1 positive cells (r = 0.712, p < 0.001) and the tubulointerstitial fibrosis score (r = 0.586, p = 0.007)., Conclusion: Colchicine is capable of abrogating the upregulation of chemotactic OPN expression and macrophage influx, and this is associated with improved renal tubulointerstitial fibrosis in chronic CsA nephrotoxicity., (Copyright 2002 S. Karger AG, Basel)

Superior mesenteric artery (SMA) syndrome is a rare disease in which the third portion of the duodenum is compressed by SMA. There are many causes leading to the SMA syndrome, however it's extremely rare that aortic aneurysm causes a SMA syndrome. We report a case of a successfully treated SMA syndrome due to an abdominal aortic aneurysm in a renal transplant recipient. The patient was a 52-yr-old woman with a thin stature (weight 40 kg, height 164 cm). She received a renal transplant 8 yr before, and had hypertension and abdominal aortic aneurysm. Her SMA syndrome developed in a prolonged supine position for the accidental rib fractures and was diagnosed by clinical and radiological findings. After a surgical correction (resection of an aneurysm and aortobiiliac bypass with an inverted Y graft), her symptoms relieved without deterioration of the graft function.