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Biomedical subjects

S Vítko

Publications and source records attributed to S Vítko.

At least 19 recordsLinked to original sources

[Pregnancy and labor after combined pancreas-kidney transplantation in Czech Republic].

OBJECTIVE: To inform about the first own experiences and to present opinion on leading pregnancy and delivery after a combined pancreas and kidney transplantation. DESIGN: Case report and review article. SETTING: Department of Obstetric and Gynecology, 1st Medical Faculty of the Charles University and General Faculty Hospital, Prague. RESULTS AND CONCLUSIONS: Pregnancies and deliveries after the transplantation of solid organs are not common. Mostly there are experiences with women after kidney transplantation, smaller or no experiences are with women after transplantation of other solid organs. About 25 pancreas transplantation per year are performed in the Czech republic. Two women after the combined kidney and pancreas transplantation were the first in Czech republic to get pregnant spontaneously and delivered by using a chronic immunosupressive. therapy (Prograf, Imuran, Prednison) in 2002 and 2003. These single pregnancies were led as a high-risk pregnancy in Regional Perinatology Center in collaboration with Transplant and Diabetic Center. Both pregnancies were termined from the obstetrical indication before the term by cesarean section. Both children were healthy. The pregnancy of both patients has not affected the function of the transplanted organs and development of both children has been normal.

Adult↗

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↗

[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↗

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↗

[The results of kidney transplantation from very young paediatric cadaveric donors to adult recipients in Czech Republic in the years 1994-2001 (retrospective study of the Czech transplant centres)].

The results of kidney transplantation from very young paediatric cadaveric donors up to five years, which were transplanted to adult recipients, are evaluated in the first retrospective study of all Czech transplantcentres. In general, 42 of these transplantations were carried out during 1994-2001. In 28 cases single kidney was transplanted, in 14 cases en bloc graft of both children kidneys was transplanted. The reasons of kidney failure by recipients are usual (in 42.9% glomerulonephritis). An average age of the donors was 34.7 months (median 39 months). An average age of the recipients during transplantation was 42.6 years (median 43.5 years). All the kidneys were placed into retroperitoneum. As long as only single kidney was transplanted, the rules, already propagated by Salvatiera in 1970, were respected. At the transplantation of en bloc graft, Kinne's method with possible vessels elongation of the graft and with uretero-uretero anastomoses (in so called Ostrava modification) was used. The higher occurrence of the primary graft non-function (as 50% losses of all grafts) was confirmed in the study. Its reason was an acute thrombosis of vessels or rotation of graft stem. One-, three- and five-years patients and grafts survival were 97.6-90.5-90.5% and 76.2-73.8-73.8% actually. Patients survival are very good while grafts survival are average, momentarily a bit worse than national data published by the Czech Transplant Society, which determines one-, three- and five-years grafts survival with 90.3-82.9-75.5% and 79.1-71.1-65% actually. The kidney transplantation from paediatric cadaveric donors to adult recipients is acceptable under present allocated criteria, in case that some principles are kept. The study confirms the international experiences about rather higher incidence of surgical complications and primary graft non-function. In conclusion, some general references for reduction of complications, as well as for improvement of these transplantation results are introduced.

Adult↗

[Urinary infections in patients with urologic complications after kidney transplantation].

BACKGROUND: Urinary tract infections (UTI) are the most frequent infectious complications after renal transplantation (Tx). We tried to analyse whether the urinary tract infection was one of the factors which participated in the lower allograft survival rates and in the reduced allograft function in urologically complicated (UC) patients. METHODS AND RESULTS: We observed 77 patients after Tx whom 42 had urinary fistula, 32 had urinary tract dilatation a 3 suffered from both complications. They were observed from January 1992 through December 1999. 100 patients without urological complications represented a control group (N). Obtained data was statistically evaluated using t-test, chi 2-test, correlation analysis. Graft and patient survival rates were assessed using the Kaplan-Meier method. We have found that UC patients after Tx had worse renal function compared with patients not suffering from this complications. Using Kaplan-Meier methods we have found that graft survival rate in patients with UC is significantly lower than that in the control group (5-year graft survival 0.6 vs 0.82, p < 0.01). On the other hand there were no differences in the 5-year patients survival rate between the followed groups of patients (0.74 vs 0.83). There was no significant correlation between predicted creatinine clearance and followed indicators of UTI--total time of positive urine bacterial cultivation, number of infectious periods and total time of antibiotic therapy. There were no significant differences in graft survival during 5 years between patients with UTI and control group. CONCLUSIONS: Our results suggest that patients with UC are at increased risk of urinary tract infection. Our findings are in keeping with the assumption that UTI in patients with UC do not significantly participate in the decreased level of graft function and in the shorter graft survival rates.

Dilatation, Pathologic↗

ACE gene polymorphism and long-term renal graft function.

OBJECTIVES: The long-term outcome of transplanted kidneys has not changed substantially and only a minority of grafts survives more than 15 yr. The aim of this study was to determine the influence of ACE gene polymorphism on long-term outcome after renal transplantation. DESIGN AND METHODS: Using PCR, we evaluated ACE I/D gene polymorphism in a group of patients with long-term graft function (LTF) over 15 yr and compared it with control groups of transplant recipients and population sample. RESULTS: The distribution of genotypes in the LTF group differed from transplant controls (p < 0.05). Moreover, DD homozygotes in the LTF group had better creatinine clearance (DD: 1.1 +/- 0.3, ID: 0.96 +/- 0.3, II: 0.76 +/- 0.3 mL/s; p < 0.05). There were no differences in genotype distribution between transplant and population samples. CONCLUSIONS: Results of our study have demonstrated a possible connection between the DD variant of ACE I/D gene polymorphism and excellent long-term graft function.

Adult↗

Angiotensin II-induced hypertension in bradykinin B2 receptor knockout mice.

The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)-induced hypertension in mice. BK B2receptor knockout (B2R-/-) and wild-type (B2R+/+) mice (22to 26 g) were infused with either saline (SAL) or Ang II (40ng/min) via an osmotic minipump implanted intraperitoneally. On day 12after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B2R+/+ and SAL/B2R-/- mice(128+/-5 versus 133+/-6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B2R-/- than in Ang II/B2R+/+ mice (173+/-6versus 156+/-5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP)was also higher in anesthetized Ang II/B2R-/- mice than in Ang II/B2R+/+mice (139+/-3 versus 124+/-3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45ng/min) caused equivalent increases in SBP in B2R+/+ and B2R-/- mice measured on day 12 after implantation (151+/-4 versus 149+/-5 mm Hg, n=9and 8). MAP also did not differ on day 13 after implantation between NE/B2R+/+ and NE/B2R-/- mice (120+/-6 versus 122+/-4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B2R-/- mice than in Ang II/B2R+/+ mice (2.34+/-0.06 versus 4.33+/-0.19 mL x min-1 x g-1; P<0.05). Acute inhibition of NO synthase (NOS)with nitro-L-arginine-methyl ester (0.5 microg x g-1 x min-1) in SAL/B2+/+ and SAL/B2-/- mice caused equal increases in MAP (142+/-1 versus 145+/-1 mmHg) and decreases in RPF (2.06+/-0.06 versus 2.12+/-0.15 mL x min-1 x g-1).However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B2R+/+ mice than of Ang II/B2R-/- mice, such that MAP after NOS inhibition in Ang II/B2R+/+ approached that of Ang II/B2R-/- mice (156+/-2versus 159+/-2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B2R+/+ mice to values similar to those of Ang II/B2R-/- mice before NOS inhibition (2.12+/-0.09 versus 2.34+/-0.06 mL x min-1 x g-1). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B2R-/- mice to Ang II-induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.

Angiotensin II↗

[The urinary tract in graft recipients and urologic complications after kidney transplantation].

BACKGROUND: Urological complications after renal transplantation condition reduce graft survival and function. It may be assumed that an important part, in addition to technical factors during removal and implantation of the organ may be played also by factors of the recipient. The authors investigated whether in the development of some urological complications (urinary fistulae and urinary tract dilatation) also pathological changes of the urinary tract of the recipient, kidney diseases leading to renal failure or the development of urinary flow rate during the first days after transplantation of the kidney participate. METHODS AND RESULTS: The authors investigated 77 patients after renal transplantation where during the period from Jan. 1992 till Dec. 1996 a urinary fistula developed (42 cases), dilatation of the urinary tract (32) or both complications (3). The control group was formed by 100 patients without urological complications who did not differ as to demographic data, basic immunosuppressive treatment and who had transplantations during the same period and by the same surgical techniques. The assembled data were evaluated statistically, the two groups being compared by means of t-test, chi 2 test and the non-parametric Mann-Whitney test resp. The authors investigated factors which might participate in the quality of the recipient urinary tract, in particular the recipient's age. In the group of urologically complicated cases there were significantly (p < 0.05) more patients above 55 years. There were also more males (67.5% vs. 32.5%, p < 0.05). In further factors such as the ratio of BMI ratio or the underlying kidney disease leading to renal failure and the presence of diabetes mellitus the authors did not record significant differences. The residual urinary flow rate, duration of dialysis treatment before transplantation and the number of transplantations did not differ significantly. The authors tried to evaluate the possible influence of urinary flow rate on the development of urological complications after transplantation of the kidney. CONCLUSIONS: The assembled findings support the idea that the development of a urinary fistula or dilatation of the urinary tract were not significantly influenced by changes in the urinary tract of the recipient conditioned by the period of the reduced function, as may be assumed on the basis of the time of dialysis treatment. The development of the investigated urological complications was not significantly influenced by the presence of underlying kidney diseases nor by increased urinary flow rate during the first days after transplantation. The authors did not confirm the risk of re-transplantation. An significant effect on the development of urological complications could be exerted by male sex and age above 55 years.

Adult↗

TGF-beta I gene polymorphism in heart transplant recipients--effect on renal function.

Renal dysfunction is a severe late complication of heart transplantation (HTx). Transforming growth factor beta I (TGF beta I) is a potent multifunctional cytokine with profibrogeneic effect. TGF beta I gene polymorphism correlates with cytokine production. In the present study, we looked for a predictor of renal insufficiency after HTx. In 175 HTx pts and 268 controls, polymorphism in the signal peptide of the TGF beta gene, substitution of leucine-proline at codon 10 and arginine-proline at codon 25, was evaluated by PCR. Renal function was followed after HTx and was compared with the TGF beta I genotypes. There were no differences in the frequencies of alleles and genotypes of TGF beta I gene in the healthy population and HTx recipients; TGF beta I genotype distribution in recipients with ischemic heart disease and dilated cardiomyopathy was almost identical. Renal function was decreasing in most HTx recipients with time. Progression of renal insufficiency (RI) was worse in patients with Leu at codon 10 (LeuLeu vs. LeuPro p < 0.01, LeuLeu vs. ProPro; p < 0.01). RI progression was also more pronounced in individuals homozygous at codon 25 (ArgArg vs. ArgPro; p < 0.01). In individuals heterozygous at codon 10 (LeuPro), the genotype at codon 25 determined the progression of RI (LeuPro/ArgArg vs. LeuPro/ArgPro; p < 0.05). In our study, we have demonstrated the prognostic significance of TGF beta I gene polymorphism for renal insufficiency in heart transplant recipients.

Amino Acid Substitution↗

Characterization of patient antibodies after kidney transplantation.

OBJECTIVE: The aim of this study was to characterize patient antibodies before and after cadaver and/or living-donor kidney transplantation and to correlate these data with the clinical course after transplantation. METHODS: Sera from 69 cadaver, 9 living-related and 2 patients waiting for living-donor kidney transplantation were analyzed by the complement dependent cytotoxicity (CDC) test, flow cytometry (FCXM) and ELISA. RESULTS: FCXM revealed that 15.0% of patients before transplantation and 16.7% after transplantation had antibodies to donor cells. 10.3% patients were positive before and after transplantation (+/+), while 6.8% developed antibodies early after transplantation (-/+). Analysis of the specificity of those antibodies by ELISA showed that it was directed to: 1) mismatched donor HLA antigens 2) antigens belonging to the same cross-reacting group (CREG) as the mismatched donor antigens 3) HLA antigens not expressed by donor cells or, probably, to non-HLA antigens. CONCLUSION: Anti-HLA antibodies were detected in patients before and after transplantation and in most cases their anti-HLA specificity could be determined. Fast and precise characterization of antibodies in patients before and after transplantation can be performed by both sensitive methods--FCXM and ELISA--which may help predict the onset of immunological complications and, consequently, improve the prognosis after organ transplantation.

Antibody-Dependent Cell Cytotoxicity↗

Atherogenesis markers in patients with chronic rejection of renal allografts.

Patients with renal insufficiency are thought to be at the higher risk of atherosclerosis complications. In the present study we evaluated some atherogenesis risk factors in patients with biopsy proven chronic vascular rejection of transplanted kidney and compared them with matched groups of transplant recipients. Patients with chronic rejection had higher plasma levels of alfa-I-acid glycoprotein and fibrinogen as well as soluble P-selectin level. Surprisingly we found no differences in other adhesion molecules. In conclusion, patients with chronic renal graft rejection are at the higher risk of atherosclerosis development.

Acute-Phase Proteins↗

Urinary tract infection in patients with urological complications after renal transplantation with respect to long-term function and allograft survival.

Urological complications after renal transplantation (urinary fistula, urinary tract dilatation) are frequently associated with urinary tract infections (UTI). We tried to analyse whether urinary tract infection was one of the factors which participated in the lower allograft survival rates and reduced allograft function in urologically complicated (UC) patients. We observed 77 patients after renal transplantation (Tx) of whom 42 had urinary fistula, 32 had urinary tract dilatation a 3 had both complications (I/1992-XII/1996). 100 patients without urological complications represented a control group (N). Obtained data was statistically evaluated using t-test, chi 2-test, correlation analysis. Graft and patient survival rates were assessed using the Kaplan-Meier method. We have found that UC patients after Tx had a worse renal function compared with patients not suffering from this complication. Using Kaplan-Meier methods we have found that graft survival rate in patients with UC is significantly lower than that in the control group (5-year graft survival 0.6 vs 0.82, p < 0.01). On the other hand there were no differences in the 5-year patients survival rate between the followed groups of patients (0.74 vs 0.83). There was no significant correlation between predicted creatinine clearance and followed indicators of UTI--total time of positive urine bacterial cultivation, number of infectious periods and total time of antibiotic therapy. There were no significant differences in graft survival during 5 years between patients with UTI and without UTI. Our results suggest that patients with UC are at increased risk of urinary tract infection. Our findings are in keeping with the assumption that UTI in patients with UC do not significantly participate in the decreased level of graft function and the shorter graft survival rates.

Creatinine↗

Hyperlipidemia and obesity after renal transplantation.

Obesity is very frequently found after renal transplantation (Tx). It may represent risk factor for development of atherosclerosis and chronic allograft nephropathy. In a prospective randomized metabolic study we monitored for a period of 12 months a total of 427 patients (pts) (M 228/F 199) aged 20-70 yrs after Tx. All patients were treated with cyclosporin A and prednisone at standard doses. We compared the findings of 118 pts with a body mass index (BMI) > or = 30 (kg/m2, Group I) with data obtained from 309 pts with BMI < 30 (Group II) one year after Tx. The mean values of the analysed parameters were as follows (Gr I vs Gr II): total cholesterol (TC): 7.2 +/- 2.4 vs 6.1 +/- 2.0, triglycerides (TG) 3.8 +/- 1.6 vs 2.6 +/- 0.6; LDL-cholesterol 4.1 +/- 1.2 vs 3.0 +/- 0.7; fasting glycemia 8.0 +/- 3.2 vs 5.2 +/- 2.0 (all mmol/L, all p < 0.01); HDL-cholesterol/TG 0.28 +/- 0.07 vs 0.38 + 0.06, p < 0.025). The mean values of corrected Ccr, cyclosporine level, Lp(a) and proteinuria did not differ significantly. There were also no statistical differences in apo E isoforms. In conclusion, our data suggest hyperlipidemia-associated obesity should be treated effectively as a high-risk factor after Tx.

Adult↗

The role of ERCP in management of biliary complications after liver transplantation.

Biliary complications remain to pose a serious problem in patients after liver transplantation. In the past, they occurred in as many as 50% of patients, and were associated with a height mortality. This has changed and at present the incidence of this complications is lower. The authors present their own series and discuss the role of ERCP in the management of complications.

Biliary Tract Diseases↗