Real life results of direct acting antiviral therapy for HCV infection in HIV-HCV-coinfected patients: Epi-Ter2 study.

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.

Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

A case report of osteomalacia unmasking primary biliary cirrhosis.

Osteomalacia, a metabolic bone disease characterized by the inability to mineralize new osteoid, can be caused by vitamin D deficiency. We report a patient with symptomatic, biochemical, and imaging evidence of osteomalacia due to vitamin D deficiency, who as a result of work up for bone disease was diagnosed with early primary biliary cirrhosis. Osteomalacia was treated with high-dose vitamin D and serial bone density scans showed evidence of increasing bone mineral density suggesting osteoid mineralization in response to treatment. The diagnosis of cholestatic liver disease should be considered in all patients presenting with osteomalacia due to vitamin D deficiency, particularly if other cholestatic liver enzymes are elevated in addition to alkaline phosphatase.

Influence of CYP2D6 and CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy volunteers.

PURPOSE: This is the first study that connects pharmacokinetics of tolperisone with genetic polymorphism of the enzymes involved in its metabolism in human. We aimed to identify the influence of polymorphism of two main enzymes (CYP2D6 and CYP2C19) on pharmacokinetic profile of parent drug. METHODS: In a single-dose study, 28 healthy Caucasian male volunteers received an oral dose of 150 mg of tolperisone. The subjects were genotyped with respect to CYP2D6 and CYP2C19 enzymes. Plasma was sampled for up to 12 h post dose, followed by quantification of tolperisone by a fully validated HPLC-tandem mass spectrometry (MS/MS) method. The pharmacokinetic parameters were estimated using a non-compartmental method and compared statistically at level p < 0.05 across the genotyped groups. RESULTS: High variability (exceeded 100%) of main bioavailability parameters (AUCt, AUC(inf), C(max)) was observed in the whole group of subjects. An essential difference in the pharmacokinetics of tolperisone of quick metabolizers whose genotype expressed wild homozygote CYP2D6 *1/*1 with respect to heterozygous *1/*4 and *1/*5 subjects was demonstrated. The mean AUC(inf) was 2.1- and 3.4-fold higher in *1/*4 and *1/*5, respectively, than in *1/*1 subjects. In case of Cmax, the differences were greater and reached maximally 3.8 times (mean values 54.00, 98.85, and 205.20 ng/mL for CYP2D6 *1/*1, *1/*4, and *1/*5, respectively). Values of the parameters for the one subject that expressed *4/*4 genotype were even 8.5 times higher than in subjects with extensive or intermediate phenotype. Although CYP2C19 *1/*2 subjects had higher AUCt, AUC(inf), and Cmax values than *1/*1, no statistically significant differences were observed. Oral clearance (CL/F) significantly decreased by 65.7% in heterozygous *1/*2 relative to homozygous *1/*1 extensive metabolizers. CONCLUSION: In this study, we first demonstrated the effect of CYP2D6 polymorphism on pharmacokinetics of tolperisone in Caucasian subjects. The contribution of CYP2C19 enzyme seems to be less important.

Clostridium difficile infection in children hospitalized due to diarrhea.

The frequency of Clostridium difficile infection (CDI)-related hospitalizations is increasing. The aim of this study was to determine the extent of CDI among children hospitalized with diarrhea, risk factors or predictors for severe CDI, the prevalence of NAP1, and to compare the course of CDI depending on bacteria toxicity profile. A retrospective analysis of case records of 64 children (age range 3 months-16 years, median age 2.12 years) with CDI as defined by diarrheal disease and positive polymerase chain reaction (PCR) test (Xpert C. difficile) was conducted. Modified national adult guidelines were used to assess the severity of CDI. CDIs represented 2.7 % of patients with diarrhea (13.5 cases per 1,000 admissions). Thirty-three CDIs (52 %) were community-associated. Antibacterial use preceded CDI in 61 patients (95 %). Seventeen cases (27 %) were binary toxin-positive (CDT+), 13 of which were NAP1 (20.5 %). Over 75 % of CDIs with NAP1 was hospital-acquired, and more often proceeded with generalized infection (p < 0.05). Risk factors for severe CDI (34 %) included NAP1 [odds ratio (OR), 4.85; 95 % confidence interval (Cl), 1.23, 21.86) and co-morbidities (OR, 4.25; 95 % Cl, 1.34, 14.38). Diarrhea ≥10 stools daily was associated with severe CDI (p = 0.01). Recurrence occurred in three patients (4.5 %). There was no mortality. C. difficile is an important factor of antibiotic-associated diarrhea in children. Co-morbidities and NAP1 predispose to severe CDI.

The relationship between IL-28B polymorphisms and the response to peginterferon alfa-2a monotherapy in anti-HBe-positive patients with chronic HBV infection.

The impact of interleukin 28B (IL-28B) on the results of interferon (IFN)-based therapy in patients chronically infected with hepatitis B virus (HBV) is poorly understood. The aim of this study was to evaluate the relationship between IL-28B markers and the response to IFN monotherapy in Polish patients with anti-hepatitis B e (HBe)-positive chronic hepatitis B (CHB). We determined three single-nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, and rs8099917) in 86 patients who were treated with pegylated interferon (PEG-IFN) for 48 weeks. The effectiveness of the therapy was evaluated based on the virological and biochemical response. The primary efficacy parameters were the HBV DNA viral load below 400 IU/ml and 2,000 IU/ml in combination with alanine aminotransferase (ALT) normalization (<40 IU/l), measured 24 weeks after the treatment. Viral load below 400 IU/ml or 2,000 IU/ml with ALT normalization was achieved by 37 % and 46 % of patients, respectively. It has been shown that the distribution of IL-28B genotypes in the dominant genetic model in patients with different therapeutic success differ significantly only for rs12979860. The IL-28B rs12979860 CC genotype was associated with lower treatment success [odds ratio (OR), 0.31; p = 0.025 and OR, 0.37; p = 0.044 for <400 IU/ml HBV DNA with <40 IU/l ALT, and <2,000 IU/ml HBV DNA with <40 IU/l ALT, respectively]. However, in the conditional logistic regression analysis adjusted by factors associated with combined response, rs12979860 was significantly associated only with <400 IU/ml HBV DNA with <40 IU/l ALT (OR, 0.24; p = 0.026). IL-28B polymorphisms have prognostic significance in assessing the treatment effectiveness based on the virological and biochemical response of patients with anti-HBe-positive CHB.

Impact of IL-28B polymorphisms on pegylated interferon plus ribavirin treatment response in children and adolescents infected with HCV genotypes 1 and 4.

IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR (p = 0.058). Only the distribution between CC and CT-TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT-TT patients (p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV.

HBV DNA suppression during entecavir treatment in previously treated children with chronic hepatitis B.

The aim of this study was to assess HBV DNA suppression after 24 weeks of treatment with entecavir in previously treated children with CHB. Thirty children aged 5-17 years (25 males and 5 females) with CHB were treated with entecavir 0.5 or 1 mg daily. Twenty-two children were HBeAg-positive, eight were HBeAg-negative, and in eight HBV polymerase mutations were detected. After 24 weeks of treatment, mean and median HBV DNA levels and ALT activity were lower versus baseline, overall and in both subgroups. The overall median HBV DNA level decreased from 1.2 x 10(7) IU/mL to 3.3 x 10(2) IU/mL (p < 0.000004), in HBeAg-positive from 7.8x10(7) IU/mL to 6.3x10(3) IU/mL (p < 0.00004), and in HBeAg-negative from 2.5x10(4) IU/mL to 5.01x10(1) IU/mL (p < 0.03). The serum HBV DNA disappearance was observed in 7/8 (88%) HBeAg-negative and in 5/22 (23%) HBeAg-positive patients. The overall mean ALT activity decreased from 164+ 290 U/L to 34.1+ 18.9 U/L (p < 0.000007), in HBeAg-positive from 214+326 U/L to 38.59+19.2 U/L (p < 0.000074), and in HBeAg-negative from 27+14 U/L to 20+8 U/L (p < 0.03). Twenty-four weeks of treatment with entecavir results in suppression of HBV DNA in a substantial proportion of children previously treated ineffectively with CHB.

Stability of cefepime in aqueous eye drops.

The aim of the studies was to determine HPLC the stability of cefepime in 1% and 5% buffered eye drops of developed formulary composition, which were stored for 30 days at the temperature of 4 degrees C and 20 degrees C, protected from light. Separation was performed on RP18 Gemini octadecylsilane column (250 mm x 4.6 mm, 5.0 microm) at a temperature of 25 degrees C. The mobile phase consisted of 0.015 M solution of sodium salt of pentane sulphonic acid brought to pH 4.0 with glacial acetic acid and 45% KOH solution and acetonitrile 94:6 w/w, with detection of 254 nm. The method was linear in the range of 12.6-125 microg/ml (R2 = 0.9996). The limit of detection (LOD) was 3 microg/ml and limit of quantification (LOQ) was 10 microg/ml. 10% degradation of cefepime in 1% and 5% buffered eye drops stored at the temperature of 4 degrees C, depending on the composition of the eye drops, occurred after 21-27 days in 1% eye drops and 18-21 days in 5% eye drops. In the eye drops, which were stored at the temperature of 20 degrees C, 10% degradation of cefepime took place on the third day of storage regardless of formulary composition of 1% and 5% drops. Cefepime stability lasting a couple of weeks in 1% and 5% solution allows extemporaneous preparation of buffered eye drops containing cefepime.

Paraoxonase 1: The Lectin-Like Oxidized LDL Receptor Type I and Oxidative Stress in the Blood of Men with Type II Obesity.

OBJECTIVES: Obesity has serious consequences such as the onset of metabolic syndrome, type 2 diabetes, atherosclerosis, or cardiovascular complications. The aim of this study was to evaluate the levels of paraoxonase 1 (PON1), lectin-like oxidized LDL receptor-1 (LOX-1), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and lipid peroxidation processes in the course of obesity. METHODS: 28 men took part in the experiment. Fourteen of them were obese; the control group consisted of 14 physically active men without obesity features. The concentrations of malondialdehyde (MDA), PON1, LOX-1, and tumor necrosis factor α (TNFα) as well as the activities of erythrocytic SOD, CAT, and GPx were determined in the study. RESULTS: Statistically significant higher MDA, LOX-1, and TNFα levels were observed in obese subjects. Conversely, lower concentrations of PON1 in obese men were found. CONCLUSIONS: An imbalance in oxidation-reduction processes accompanies obesity. Moreover, inflammatory cytokines and atherosclerotic complications are involved in the obesity process. The obtained results suggest that the studied parameters may be independent prognostic markers preceding the development of cardiovascular and metabolic complications in people afflicted with type II obesity.

Early hyperglycemia after allogenic kidney transplantation.

BACKGROUND: The aim of the study was to establish the impact of early hyperglycemia on development of diabetes mellitus (DM) in patients after kidney transplantation and to evaluate possible risk factors for post-transplantation DM. We also sought to assess the impact of early hyperglycemia and DM on the renal graft function in the long term (3 year follow-up). MATERIAL/METHODS: 1200 transplant patients from one center, were followed up for 3 years. The rate of chronic rejection, CMV infection, hypertension and dyslipidemia were analyzed. The renal allograft function was examined and pancreatic function peptide C concentration was determined. RESULTS: Early hyperglycemia (within first week after transplantation) was detected in 76 out of 1131 patients (6.7%). In this group within three years observation posttransplantation diabetes mellitus (PTDM) was observed in 57 patients (relative risk 75%). In comparison, transplanted patients with good early glucose control had 8% risk of developing DM within the same period after transplantation. In addition early hyperglycemia predisposed to worse renal graft function and higher proteinuria. The incidence of hypertension as well as the rate of CMV infection was comparable in the DM group and in non-DM patients. PTDM patients had higher values of serum peptide C concentration (p < 0.05), additionally hyperinsulinemia was observed. The kidney allograft function assessed as serum creatinine level was significantly impaired after 3 years in PTDM group compared to non-DM patients. CONCLUSIONS: Our date show the importance of normal glucose concentration in early period after transplantation as predictive factor for diabetes mellitus development and worsening of transplanted organs.

Increased mRNA expression of transforming growth factor beta in the arterial wall of chronically rejected renal allografts in humans.

INTRODUCTION: Transforming growth factor beta (TGF-beta) has an established role in interstitial damage of renal transplants during chronic rejection (CR). However, its involvement in transplant vasculopathy is not clear. The aim of the study was to assess TGF-beta gene expression in the walls of large-caliber arteries within chronically rejecting renal allografts. We evaluated associations between gene expression of this factor and intimal thickness or clinical data. MATERIAL AND METHODS: Renal artery samples of kidney allografts were obtained from 20 hemodialysis patients with end-stage renal graft disease due to CR, who were undergoing graftectomy. The control group included 32 hemodialysis patients with end-stage renal disease, undergoing nephrectomy due to autosomal dominant polycystic kidney disease (n = 12), chronic pyelonephritis (n = 13), or kidney limited tumor (n = 7). Gene expression of TGF-beta was measured using real-time PCR. RESULTS: TGF-beta mRNA expression was 3.25-fold higher in CR than in control patients (P < .001). Expression of mRNA for this cytokine was not influenced by the following factors: intimal thickness; age; serum cholesterol, triglycerides and glucose; BMI; graft survival; time of dialysis before transplantation; total ischemic time; immunosuppressive regimen; incidence of acute rejection episode; panel reactive antibodies; and period of dialysis before graftectomy. TGF-beta is involved in neointimal formation in CR.

Problems in the diagnosis of profound trichophytosis barbae.

Zoophilic species of human dermatophytoses, such as Trichophyton mentagrophytes are significantly rare. We present a case of a 42-year-old male who for 2 months had been unsuccessfully treated and then referred to hospital with suspected actinomycosis. Lesions on the skin on his neck, submandibular area, cheeks and groins were consistent with extremely painful, merging inflammatory tumours and infiltrations with the presence of numerous pustules in hair follicles that poured purulent contents forming into yellow crusts after compression. The treatment with terbinafine was successful. The final identification of the Trichopyton mentagrophytes var. granulosum strain was performed based on a microscopic assessment of the culture, and the result of species identification was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.

BACKGROUND: Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVE: This study compared hypericum and the SSRI sertraline in the treatment of depression. METHODS: In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks. RESULTS: The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size. CONCLUSION: The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.

Sensitive enantiomeric separation of aliphatic and aromatic amines using aromatic anhydrides as nonchiral derivatizing agents.

New pre-column derivatizing reagents: phthalic anhydride, 3-nitrophthalic anhydride, diphenic anhydride, 1,8-naphthalic anhydride and diphenylmaleic anhydride have been developed for resolving chiral compounds having amine groups. Although all of these agents produce derivatives with high molar absorptivities, the later two also fluoresce. Upon derivatization, aromatic analytes containing free carboxylic groups are produced. Both of these moieties enhance chiral recognition on cyclodextrin-based columns. The derivatization reaction is carried out at room temperature by shaking a buffered aqueous solution of a sample with an acetonitrile solution of the reagent. The reaction is fast and proceeds without any detectable racemization. The labeled compounds have favorable chromatographic properties which are demonstrated by resolution of a number of chiral compounds on cyclodextrin-bonded phases operated with non-aqueous polar organic eluents. The selectivity and good efficiency of this system contributes to its high sensitivity and in its applicability for detecting low levels of enantiomeric impurities. The detection limit is in the picomole range and less than 0.1% enantiomeric impurities can be determined in some cases.

Influence of Uro-Vaxom on sIgA level in urine in children with recurrent urinary tract infections.

We have examined the influence of Uro-Vaxom on secretory IgA (sIgA) level in urine of children with recurrent urinary tract infections. In the group of children treated with antibiotics and Uro-Vaxom, a significant increase of sIgA in the urine was found which persisted for at least 3 months. During this period no infection appeared in 92% examined children.

Hepatitis C virus (HCV) serotype in the asymptomatic HCV-infected patients from selected groups.

In asymptomatic hepatitis C virus (HCV)-infected blood donors and persons from high risk groups (intravenous drug users and hemodialyzed patients) HCV serotypes 1, 2, 3, 4 and 6 have been detected. The most frequent was serotype 1. In the group of intravenous drug users (IDU) a coexistence of different serotypes was observed.

Proteolytic enzymes activities in patients after myocardial infarction correlate with serum concentration of TGF-beta.

Myocardial infarction (MI) is caused by occlusion of coronary artery and insufficient oxygen supply to a certain area of myocardium. Its necrosis appears as a result of MI. The process of tissue repair after MI is very complicated and it is influenced by numerous factors, including growth factors and proteolytic enzymes. The aim of the study was to determine serum transforming growth factor beta (TGF-beta) concentration on day 2 and 7 after MI and to asses the relationship of this growth factor with serum proteolytic activity of collagenase and elastase. In addition, the effect of fibrynolytic treatment on these factors was evaluated. About 100 patients with MI were enrolled to the study. The control group consisted of 50 healthy individuals. We observed that TGF-beta1 concentration correlated positively with collagenase activity on the second day after MI and that it also correlated positively with elastase activity on day 2 and 7 after MI. Moreover, treatment with streptokinase (SK) caused a significant increase of TGF-beta serum concentration. Our data indicate that TGF-beta1 may be one of the factors involved in tissue repair process after MI. Its effect seems to be mediated by collagenase and elastase and may change with the time that elapsed after MI.

New concepts in organ transplantation.

Major progress has been made in clinical transplantation over recent years due to close cooperation between clinical specialists and academic investigators. High success rates are evident by longer patient and graft survivals. Treatment procedures have been integrated into fixed protocols utilizing new chemical immunosuppressive reagents that have improved the management of transplanted patients. Further developments in organ transplantation through better surgical techniques have allowed grafts of pancreas, lungs, and intestine. Current transplant medicine has, however, its limitations, especially in the context of the donor organ shortage, the toxicity of immunosuppressive drugs, the chronic rejection activity, and the inability to produce a state of immunologic tolerance. This paper sought to review new concepts in organ transplantation, especially concerning immunologic tolerance and the organ donor shortage.

Extracellular matrix proteins, proteolytic enzymes, and TGF-beta1 in the renal arterial wall of chronically rejected renal allografts.

Chronic rejection (CR) is the leading cause of long-term failure of transplanted kidneys. The vascular hallmark is intimal hyperplasia, accompanied by macrophage, foam cell, and T-cell infiltration. Intimal thickening results from the migration and proliferation of smooth muscle cells and increased deposits of extracellular matrix (ECM) proteins, due to release of growth factors and cytokines as well as altered ECM protein turnover. We assessed the content of fibronectin (FN) and transforming growth factor-beta1 (TGF-beta1) as well as the activities of collagenase and cathepsin B and L in renal artery walls of chronically rejected human renal allografts. We investigated renal artery samples from 8 patients with CR undergoing graftectomy, 12 patients undergoing nephrectomy, and 7 organ donors. The results were related to the DNA content of homogenates. Cathepsin B and L activities were significantly higher among those with compared with donors (P =.022). There was a trend toward higher collagenase activity in CR compared with donors and the nephrectomy group. TGF-beta1 was significantly enhanced in CR compared with donors (P =.010), and showed a trend toward higher concentrations in CR compared with the nephrectomy group. The trend was toward lower FN concentrations in CR compared with the nephrectomy group and toward higher concentrations compared with donors. Summarizing, renal CR is accompanied by enhanced proteinase activity, alterations of ECM proteins, and increased TGF-beta1 in the renal artery wall. We conclude that ECM turnover and cytokines play an important role in neointimal formation and CR pathogenesis.