Biomedical subjects

O Viklický

Publications and source records attributed to O Viklický.

At least 19 recordsLinked to original sources

PubMed2006

Mycophenolate mofetil ameliorates accelerated progressive nephropathy in rat.

BACKGROUND: Renal ischemia and hypertension have been suggested to be involved in the progression of renal diseases. Recently, we developed a model of accelerated major histocompatibility complex-independent renal injury, where high-renin hypertension aggravates functional and morphological changes induced by ischemia/reperfusion (I/R). In this model, we evaluated the effect of immunosuppressant mycophenolate mofetil (MMF) to test its capability to slow the progression of accelerated nephropathy. METHODS: 34 anesthetized uninephrectomized hypertensive transgenic (mREN2)27 rats (TGR) received a clamp on the renal pedicle for 45 min. Animals were treated with MMF 10 mg/kg/day (n = 10), 20 mg/kg/day (n = 10) or placebo (n = 10) orally via gavage for 12 weeks. Four animals were sham operated and not treated. Proteinuria and blood pressure were evaluated throughout the experiment. At the end of the experiment, kidney function was evaluated and kidneys harvested for morphological analysis and immunohistochemistry (CD4+, CD8+ lymphocytes and specific rat monocyte/macrophage marker ED-1+ cells). RESULTS: At week 12, both MMF-treated groups had lower proteinuria as compared to the placebo group (MMF 10: 22.4 +/- 9.8, MMF 20: 20.9 +/- 5.6 vs. 126.7 +/- 35.8; p < 0.01; sham 28.1 +/- 1.4 mg/day) and reduced glomerulosclerosis (MMF 10: 11.4 +/- 7.8, MMF 20: 5.2 +/- 2.7 vs. 20.9 +/- 10.9; p < 0.05; sham 15.7 +/- 9.2%). There were no differences in systolic blood pressure among groups. MMF-treated rats had lower CD4+ (MMF 10: 61.2 +/- 46.4, MMF 20: 29.3 +/- 18.2 vs. 125.3 +/- 42.8; p < 0.01, sham 84.9 +/- 6.1 cells/field of view) and CD8+ (MMF 10: 13.7 +/- 10.2, MMF 20: 10.0 +/- 8.1 vs. 37.8 +/- 14.3; p < 0.01; sham: 31.8 +/- 7.6 cells/field of view) lymphocytes infiltration and ED-1 macrophages infiltration (MMF 10: 5.5 +/- 6.4, MMF 20: 2.5 +/- 2.8 vs. 16.7 +/- 4.1; p < 0.01; sham 12.2 +/- 4.6 cells/field of view) than placebo-treated rats. CONCLUSION: Our results thus support the hypothesis about the key role of immune mechanisms in progression of chronic nephropathies.

Animals↗

PubMed2006

Intrarenal gene expression of proinflammatory chemokines and cytokines in chronic proteinuric glomerulopathies.

Proteinuria has been recently shown to be an independent risk factor for the progression of chronic nephropathies, but the actual mechanisms by which urinary protein load damages renal tissue in humans remain unsolved. Using real-time RT-PCR method we evaluated intrarenal mRNA expression of various cytokines and chemokines in patients with biopsy-proven IgA nephropathy (IgAN, n=11), membranous nephropathy (MN, n=6) and focal and segmental glomerulosclerosis (FSGS, n=6) who exhibited proteinuria over 0.5 g/day. There was a significant positive correlation between the proteinuria extent and the intrarenal RANTES (regulated upon activation normal T cell expressed and secreted) mRNA expression in patients with IgAN, a similar trend was also observed in patients with MN and FSGS. There were no clear relationships between the proteinuria and intrarenal mRNA expression of tumor necrosis factor alpha, transforming growth factor beta1 and monocyte chemoattractant peptide-1. There were no differences in the pattern of cytokine mRNA expression between different glomerulopathies. In conclusion, our results support the hypothesis that lymphocytes, macrophages and their products provoke tissue injury in response to proteinuria independently of the nature of renal diseases in man.

Adult↗

PubMed2006

The influence of the endothelin-converting enzyme-1 gene polymorphism on the progression of autosomal dominant polycystic kidney disease.

UNLABELLED: BACKGROUND; A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD), the most common renal hereditary disease. Endothelin-1 (ET-1) has been suggested to be an important disease-promoting factor of the kidney. Endothelin-converting enzyme-1 (ECE-1) is the main protease responsible for ET-1 generation by cleavage of its functionally inactive precursor. We examined the influence of the ECE-1b C-338A polymorphism on the progression of ADPKD toward end-stage renal disease (ESRD). The A allele was suggested to be associated with higher plasma level of ET-1. METHODS: 200 ADPKD patients (107 males, 93 females) who had reached ESRD were analyzed. Patients were divided into three groups: (1) 47 patients (23 males, 24 females) with ESRD later than in 63 yr (slow progressors); (2) 71 patients (38 males, 33 females) with ESRD before 45 yr (rapid progressors); and (3) 82 patients (46 males, 36 females) with ESRD between 45-63 yr. Moreover, we analyzed 160 genetically unrelated healthy Czech subjects as the control group (82 males, 78 females, mean age 51.4 +/- 8.2 yr). DNA samples from collected blood were genotyped for ECE-1b C-338A polymorphism using described polymerase chain reaction (PCR) followed by restriction enzyme digestion. We compared the frequencies of different genotypes between the groups of slow and rapid progressors and the ages of ESRD with regard to different genotypes. RESULTS: The ECE-1b C-338A genotype distribution showed no differences among the groups of slow progressors, rapid progressors, ADPKD group with ESRD between 45-63 yr and control group. Comparing the ages of ESRD of all patients, we did not find significant differences in the ages with regard to different genotypes: CC (51.5 +/- 10.1 yr), AC (51.6 +/- 11.4 yr), AA (48.2 +/- 5.9 yr). There was a tendency to lower age of ESRD in AA homozygotes in comparison with other genotypes (t-test, p = 0.12). We found no influence of gender. CONCLUSION: We excluded the effect of ECE-1b C-338A polymorphism on the progression of ADPKD. We could observe a mild tendency toward faster decline of renal function in AA homozygous individuals.

Aspartic Acid Endopeptidases↗

PubMed2006

[Post-transplantation lymphoproliferation in patients with intensive immunosuppression].

Organ allograft recipients are at higher risk for malignancies development. This risk is known to be different in different types of tumours. Skin cancers and lymphoproliferative disorders have been described to be ones the most frequent (comprising 15-25% of all malignancies). Here, we present the case of expansive formation localized near the renal allograft in patient, whose native kidneys failed as a consequence of long-term cyclosporine A therapy after orthotopic heart transplantation. The maintenance immunosuppression consisted of combination of cyclosporine A, mycophenolate mofetil and steroids. The expansion offside of transplanted kidney was detected by routine ultrasound examination. After indifferent neurological symptoms, sepsis, and then multiorgan failure occured. Shortly after acute surgery patient died. Autopsy and histopathology showed lymphoproliferative disorder--mo- nomorphic type of posttransplant lymphoproliferative disorder (PTLD). Occurence of PTLD in organ transplantation is discussed.

Adult↗

PubMed2005

BK-virus nephropathy and simultaneous C4d positive staining in renal allografts.

The role of antibodies in rejection of transplanted kidneys was the subject of debate at the last two Banff meetings and in medical journals. Diffuse C4d positive staining of peritubular capillaries (PTCs) was recognized as a marker of antibody-mediated rejection and this morphological feature was included in the updated Banff schema. At the same time polyomavirus infection of the renal allografts has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. At the present time, BK-virus nephropathy (BKN) represents the most common viral disease affecting renal allografts. BKN was identified in 6 patients in 12 biopsies and 2 graft nephrectomy specimens of 1115 biopsies between September 2000 and December 2003. Definite virus identification was done by immunohistochemistry. The reason for graft nephrectomies was graft failure due to BKN in a recipient after kidney-pancreas transplantation with good function of his pancreas graft and the necessity of continuing immunosuppression. Detection of C4d deposits was performed by immunofluorescence or by immunohistochemistry. In graftectomy samples C4d detection was performed by immunohistochemistry and retrospectively in all cases of BKN. Focal C4d positive PTCs and BKN were found simultaneously in 9 of 12 needle biopsies and in both graft nephrectomy samples. Detection of C4d by immunohistochemistry disclosed focal C4d positive staining in kidney tissue but diffuse in the sites where BK-virus inclusions in tubular epithelial cells were found. The complement system is part of the host defense response and is crucial to our natural ability to ward off infection. In cases of BKN, virus likely gains access to the bloodstream through injured tubular walls and via PTCs. Vascular endothelium in the PTCs represents a potential target antigen for alloresponse, and simultaneously possibly represents an imprint of complement activation or complement production in the places with BK-virus infection.

BK Virus↗

PubMed2004

Angiogenesis and organ transplantation.

Angiogenesis is a vessel development process that maintains the vascular supply for organ function. Regulation of angiogenesis is provided by positive factors, such as vascular endothelial or basic fibroblast growth factors, and negative factors, such as thrombospondin and macrophage-derived inflammatory cytokines. While the role of angiogenesis in the wound healing, embryogenesis, tumor growth and proliferative diseases is clear, in organ transplantation it is not yet well established. Herein we discuss the potential role of angiogenesis in chronic renal disease and in transplant settings.

Angiopoietins↗

PubMed2004

Cyclosporine renal dysfunction.

Cyclosporine (CsA), introduced as an immunosuppressive agent in the 1980s, quickly become the first-line treatment in organ transplantation. However, these improvements were associated with an increased incidence of renal dysfunction. CsA causes histopathological changes in renal transplants that are often difficult to distinguish from other processes, especially chronic allograft nephropathy. Enhanced angiotensin II, transforming growth factor-beta, and vascular endothelial growth factor expression together with down-regulation of nitric oxide synthesis may play roles in chronic CsA nephropathy. Efforts have recently focused upon protocols that minimize the risk of CsA nephrotoxicity while preserving low rates of acute rejection. Four types of CsA-sparing studies have emerged from recent clinical experience: (1) conversion studies in which a nonnephrotoxic drug is substituted to allow CsA reduction, (2) minimal CsA exposure studies in which reduced CsA doses are combined with nonnephrotoxic drugs, (3) withdrawal studies in which CsA is completely discontinued at some time after transplantation, and (4) CsA-free studies in which the drug is completely avoided from the time of transplantation. Monitoring of CsA immunosuppression according to C2 blood levels, which better correlate with the area under the time-concentration curve than trough concentrations, should reduce the risk for toxicity; however, the most appropriate target range has not yet been clearly established. Because of interindividual differences in CsA absorption and susceptibility to renal dysfunction, the current therapeutic drug monitoring should be supplemented with pharmacogenetic information on genetic variability of relevant genes for pharmacokinetic parameters and therapeutic targets. This approach may guide choices for immunosuppressants for particular patients, with low toxicity. Thus, despite of 20 years of its history, CsA renal dysfunction remains an important clinical challenge.

Calcineurin Inhibitors↗

PubMed2004

The influence of G-protein beta3-subunit gene and endothelial nitric oxide synthase gene in exon 7 polymorphisms on progression of autosomal dominant polycystic kidney disease.

BACKGROUND: A significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). The variability cannot be fully explained by the genetic heterogeneity of the disease. We examined the influence of G-protein beta3-subunit C825T polymorphism and endothelial nitric oxide synthase Glu298Asp polymorphism on the progression of ADPKD towards end stage renal failure (ESRF). METHODS: 306 ADPKD patients (pts) were analyzed; 261 pts (136 males, 125 females) with ESRF, with subgroup of 73 pts (44 males, 29 females) with ESRF before 45 years (rapid progressors), 46 pts (20 males, 26 females) with ESRF later than in 63 years (slow progressors) and 45 ADPKD pts (17 males, 28 females) in mean age 51 years with serum creatinine under 110 micromol/L (slow progressors) and 100 genetically unrelated healthy Czech subjects. DNA samples from collected blood were genotyped for G-protein beta3-subunit C825T genotype in exon 10 and for endothelial nitric oxide synthase Glu298Asp genotype in exon 7. RESULTS: The G-protein beta3-subunit C825T genotype exhibited no significant differences among the groups of slow progressors (6.6% (6/91) TT, 54.9% (50/91) CT, 38.8% (35/91) CC), rapid progressors (9.6% (7/73) TT, 46.6% (34/73) CT, 43.8% (32/73) CC), ADPKD group with ESRF between 40-63 years (9.2% (13/142) TT, 50% (71/142) CT, 40.8% (58/142) CC) and control group (12% TT, 44% CT, 44% CC). When comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages: males TT--51.7+/-8.8 years, CT--51.9+/-10.3 years, CC--49.7+/-10.2 years and females TT--56+/-9.9 years, CT--53.2+/-8.5 years, CC--53.9+/-8.7 years. The endothelial nitric oxide synthase Glu298Asp and Asp29Asp genotypes were significantly more frequent in rapid progressors (9.6% (7/73) Asp/Asp, 39.7% (29/73) Asp/Glu, 50.7% (37/73) Glu/Glu) and in ADPKD group with ESRF between 40-63 years (11.3% (16/142) Asp/Asp, 41.5% (59/142) Asp/Glu, 47.2% (67/142) Glu/Glu) in comparison with slow progressors (8.8% (8/91) Asp/Asp, 24.2% (22/91) Asp/Glu, 67.0% (61/91) Glu/Glu) and with control group (8% Asp/Asp, 32% Asp/Glu, 60% Glu/Glu) (Chi-square test, p<0.05). Comparing the ages of ESRF of all patients with ESRF, we did not find significant differences in the ages in males with Asp/Asp--54.9+/-10.4 years, Asp/Glu--50.2+/-9.4 years, Glu/Glu--51.0+/-10.4 years. We found out in homozygous Asp/Asp females significantly earlier onset of ESRF (49.2+/-5.6 years) in comparison with heterozygous females (53.3+/-7.2 years) and with Glu/Glu homozygous females (54.8+/-9.7 years) (t-test, p<0.05). CONCLUSION: We excluded the significance of G-protein beta3-subunit C825T polymorphism on the progression of ADPKD. We established the negative prognostic value of the carriers of Asp variant of eNOS polymorphism. Finding of new modifiers could have in future clinical consequences for ADPKD patients.

Adult↗

PubMed2004

[Initial experience with protocol biopsies in transplanted kidneys].

BACKGROUND: The aim of protocol biopsy after renal transplantation was to assess the prevalence of chronic allograft nephropathy (CTN) and to correlate the degree of CTN with clinical and laboratory data. METHODS AND RESULTS: In 105 patients with a stabilized graft function, a protocol biopsy was carried out at 1 year after transplantation. CAN was found in 75% of patients, and in 6% an acute subclinical rejection was revealed. Statistically significant correlation was confirmed between CAN and recipient's age, development of acute rejection in the first year posttransplant, serum creatinine, clearance of creatinine, and proteinuria. There was no significant difference in CAN degree distribution between patients treated with cyclosporine-A or with tacrolimus. Twelve months after the biopsy, there was no significant change in kidney graft function. In patients treated with tacrolimus, cholesterol and triglycerides levels were significantly lower than in cyclosporine treated patients Over the next year, these values significantly decreased in both subgroups. CONCLUSIONS: The CAN was found in the majority of protocol biopsies at 1 year after kidney transplantation; subclinical acute rejection was revealed rarely.

Biopsy, Needle↗

PubMed2004

New immunosuppressive agents in chronic progressive glomerulopathies: an update.

The etiology of chronic glomerulopathies is not yet clear, however the impairment of immune system is supposed to play a decisive role. Thus, immunosuppressants are often used to slow the activity and/or progression of the disease. Usually the patients are treated either by corticosteroids alone or by the combination of corticosteroids with other immunosuppressive agents. Recently, immunosuppressants successfully applied in the transplantation medicine have been also tested in the therapy of chronic glomerulopathies. Cyclosporine A, a potent calcineurin inhibitor, has been used as a second line therapy. The place of CsA in lupus nephritis and especially in IgA nephropathy is not defined so well as it is in idiopathic nephrotic syndrome. The newer calcineurin inhibitor tacrolimus is already widely used in the transplantation medicine while its effectiveness in clinical nephrology has to be tested. Mycophenolate mofetil in monotherapy or with concomitant low-dose steroids can be regarded as an alternative therapeutical approach in case of standard regimens' failure. Sirolimus just entered clinical transplant medicine and its role in slowing the progression of chronic glomerulopathies is not yet clear.

Animals↗

PubMed2003

Detection of HLA-G on human extravillous cytotrophoblast and skeletal muscle with a new monoclonal antibody MEM-G/1.

Using immunohistochemistry with the newly available monoclonal antibody MEM-G/1 the reaction patterns on frozen and formaldehyde-fixed paraffin-embedded sections on human placentas, lymph nodes, skeletal muscles, and kidney and liver allografts were compared. HLA-G (a nonclassical major histocompatibility complex class I molecule that is assumed to influence the immune response during pregnancy and some pathological conditions) was found within human extravillous cytotrophoblast but not within villous cytotrophoblast and placental mesenchymal tissue. No HLA-G expression on human lymph nodes, tonsils, and kidney and liver allografts was demonstrated. However, HLA-G expression was observed in all samples of skeletal muscle. The binding capacity of monoclonal antibody MEM-G/1 provides new possibilities to study physiological and pathophysiological roles of HLA-G in humans.

Animals↗

PubMed2003

Influence of the alpha-adducin and ACE gene polymorphism on the progression of autosomal-dominant polycystic kidney disease.

Adult↗

PubMed2003

[An unusual manifestation of tuberculosis in a female patient after kidney transplantation. Case report].

Organ transplant recipients are at the increased risk of infection complications. Herein, we present a case of unusual localisation of tuberculosis in renal allograft recipient treated by combination of cyclosporine A, mycophenolate mofetil and steroids. After the non specific prodromes, surgery due to ileus discovered ileocaecal tumour. Microscopically tuberculosis inflammatory process with ulcerations of the intestinal mucosa and classification of the lymphatic nodes, instead of the expected lymphoma was proved to be present. We are discussing the incidence of tuberculosis in relation to immunosuppressive therapy as well as possible pathways of tuberculosis transmission.

Diagnosis, Differential↗

PubMed2003

TGF-beta1 expression and chronic allograft nephropathy in protocol kidney graft biopsy.

Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF-beta1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF-beta1 plasma levels, cyclosporine levels, plasma lipids, HLA-mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF-beta1 tissue expression is linked with chronic vasculopathy.

Adult↗

PubMed2002

[The kidneys, ageing and transplantation].

The discrepancy between the increasing number of patients listed for kidney transplantation and limited cadaver donor sources has led the transplant community towards indication of elderly people as potential kidney donors. Based on clinical data, the kidney grafts explanted from aged donors have limited survival rates compared with younger ones. The donor age has been also implicated as the important alloantigen-independent risk factor for later onset of chronic allograft neprohopathy called chronic rejection. In this review we focused on some pathophysiological aspects of kidney aging and on the fate of transplanted kidney removed from elderly donors.

Aged↗

PubMed2002

Effect of sirolimus on ischemia/reperfusion injury in transgenic hypertensive rat.

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Animals↗

PubMed2002

[Transforming growth factor (TGF-beta) and kidney transplantation].

Transformation growth factor (TGF-beta) is a cytokine, which takes part in many clinical conditions linked to different chronic disease states. Its production is regulated by genes and polymorphism of TGF-beta gene individually predetermines levels of its production. TGF-beta is produced by a number of normal, predominately haemopoietic and tissue cells. Moreover, it controls cell proliferation and differentiation, and namely it stimulates fibrogenesis. Profibrogenic efficacy plays a physiological role in wound healing and it is implicated in a spectrum of disease states, such as diabetic nephropathy, chronic glomerulonepthritis, lung fibrosis, or postirradiation fibrosis. In kidney transplant recipients. TGF-beta has been suggested to be involved in the chronic rejection pathogenesis by enhancing fibrogenesis.

Fibrosis↗

PubMed2002

[Increased sP-selectin and other cardiovascular risk factors: fibrinogen, tissue plasminogen activator (t-PA Ag) and acute phase proteins after kidney transplantation].

BACKGROUND: Our study was designed to monitor the presence of the "coronary artery disease (CAD) risk factors" after kidney transplantation. METHODS: 26 kidneys transplant recipients with well-functioning (creatinine clearance > 0.8 mL/s) renal allografts receiving cyclosporine A (CsA) as the basic component of immunosuppressive therapy and 60 healthy age-matched controls were included into the study. As "CAD risk factors" were determined the levels of fibrinogen, acute phase proteins orosomucoid and C-reactive protein, t-PA Ag, PAI-1 Ag and soluble adhesion molecules E-selectin, P-selectin and ICAM-1 in the peripheral blood serum or plasma. RESULTS: Renal transplant recipients showed higher BMI (p < 0.001) and levels of fibrinogen (p < 0.001), t-PA Ag (p = 0.007) and PAI-1 Ag (p < 0.001), acute phase protein orosomucoid (p < 0.001) and higher level of soluble P-selectin (p = 0.038). The levels of sICAM-1 and sE-selectin did not differ statistically significantly from those in controls. CONCLUSION: Our study has demonstrated renal graft recipients with good kidney function already show significantly raised levels of "CAD risk factors" fibrinogen, acute phase reactant orosomucoid, t-PA Ag, PAI-1 Ag and sP-selectin.

Acute-Phase Proteins↗