• MeSH
• akutní nemoc MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• homologní transplantace MeSH
• lidé MeSH
• rejekce štěpu * MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The adverse impact of cytomegalovirus (CMV) infection after solid organ transplantion is currently believed to be mediated primarily by its immunomodulatory effects. There is a large body of evidence showing that both CMV disease and asymptomatic viremia are independent risk factors for the development of allograft rejection. The aim of this article is to summarize mechanisms whereby CMV is involved in the development and progression of allograft rejection, with particular emphasis on renal transplant recipients. The article will also address the potential of anti-CMV preventive protocols designed to favorably affect the incidence of allograft rejection.

• MeSH
• antivirové látky terapeutické užití   MeSH
• chemoprofylaxe MeSH
• cytomegalovirové infekce imunologie   prevence a kontrola   virologie   MeSH
• Cytomegalovirus účinky léků   MeSH
• homologní transplantace škodlivé účinky   MeSH
• lidé MeSH
• rejekce štěpu epidemiologie   imunologie   prevence a kontrola   virologie   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antivirové látky MeSH

• MeSH
• dospělí MeSH
• homologní transplantace MeSH
• imunoglobulin D analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• rejekce štěpu * MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin D MeSH

PURPOSE: A clinically manifested acute rejection is associated with graft dysfunction and with some ultrasound findings. The aim of our study was to determine the potential of ultrasound evaluation in the detection of subclinical acute rejective changes diagnosed in stable grafts by protocol biopsy. METHODS: Gray-scale evaluation, color Doppler imaging (CDI) and power Doppler imaging (PDI) was performed before each of 184 protocol graft biopsies in 77 patients in the third week, third month and first year after transplantation. The group was divided into four subgroups-normal histological finding, borderline changes, subclinical acute rejection of IA grade, and a clinically manifested acute rejection of IA grade. The sonographic findings were compared with individual groups. RESULTS: Detection of parenchymal edema using gray-scale imaging significantly differentiated borderline changes and subclinical acute rejection of IA grade from normal histological findings in the third week and in the third month (P=0.013, P=0.002 and P=0.024, P<0.001), respectively. A similar finding could be recorded in the latter group in the first year after transplantation (P=0.024). The presence of edema and reduced peripheral parenchymal perfusion in PDI significantly more often indicated a clinically manifested acute IA rejection (P=0.019, P=0.004, P=0.044). Parenchymal CDI hyperperfusion had a high specificity (89.5%) but a low sensitivity (60%) in the detection of the subclinical form of acute IA rejection. CONCLUSION: A composite gray-scale, PDI and CDI evaluation provide a significant differentiation of groups with borderline changes and subclinical acute rejection and groups with normal histological finding and clinically manifested acute rejection.

• MeSH
• akutní nemoc MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neúspěšná terapie MeSH
• rejekce štěpu diagnostické zobrazování   etiologie   MeSH
• senioři MeSH
• transplantace ledvin škodlivé účinky   diagnostické zobrazování   MeSH
• ultrasonografie dopplerovská metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Renal allograft biopsies remain the best diagnostic tool to investigate the type and degree of graft injury, provide therapeutic and prognostic information and to assess the extent of irreversible chronic organ damage - if done right. This review highlights pertinent aspects relevant not only for collecting optimal tissue samples but also for rendering diagnoses. Pathologists and clinicians are provided with "take home messages" and practical tips what to do, what to avoid and what to keep in mind.

• Klíčová slova
• kidney allograft - kidney allograft biopsy - diagnostic approach.,
• MeSH
• alografty MeSH
• jehlová biopsie metody   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• prognóza MeSH
• rejekce štěpu diagnóza   MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The view on the role of donor-specific antibodies in organ transplantation has been changed during the last several decades. Today, it is considered that the majority of cases of the late renal allograft dysfunction and loss are caused by the presence of donor-specific antibodies to HLA antigens. The real breakthrough in the diagnosis of antibody-mediated rejection was represented by the discovery of C4d, which enabled the determination of the diagnostic criteria of acute and later chronic antibody-mediated rejection. Although detection of C4d has been the cornerstone in the diagnosis of antibody-mediated rejection for over 10 years, it has become clear that some cases with similar morphological and clinical features do not have detectable C4d. Outcomes of key studies concerning presence of donor specific antibodies and morphological features in the graft biopsy samples resulted in the modification of Banff classification of 2013, which includes integrating C4d negative antibody-mediated rejection and also that acute vascular rejection (v1, v2) can be a part of the antibody-mediated rejection.

• Klíčová slova
• kidney allograft - antibody-mediated rejection - T-cell mediated rejection.,
• MeSH
• dárci tkání MeSH
• HLA antigeny MeSH
• komplement C4b imunologie   MeSH
• ledviny imunologie   patologie   MeSH
• lidé MeSH
• rejekce štěpu diagnóza   imunologie   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HLA antigeny MeSH
• komplement C4b MeSH

BACKGROUND: Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation. METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy. RESULTS: No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively. CONCLUSIONS: Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.

• MeSH
• acyklovir škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• analýza přežití MeSH
• antivirové látky terapeutické užití   MeSH
• časové faktory MeSH
• cytomegalovirové infekce prevence a kontrola   MeSH
• dospělí MeSH
• ganciklovir škodlivé účinky   terapeutické užití   MeSH
• homologní transplantace MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci ledvin klasifikace   chirurgie   MeSH
• rejekce štěpu epidemiologie   prevence a kontrola   MeSH
• reoperace MeSH
• rizikové faktory MeSH
• testování histokompatibility MeSH
• transplantace ledvin mortalita   fyziologie   MeSH
• valaciclovir MeSH
• valin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• ganciklovir MeSH
• imunosupresiva MeSH
• valaciclovir MeSH
• valin MeSH

BACKGROUND: Cytomegalovirus (CMV) disease is a risk factor for allograft rejection in renal transplant (RTx) recipients. However, the role of asymptomatic CMV infection remains controversial. OBJECTIVES: To determine the impact of CMV disease and asymptomatic infection on biopsy-proven acute rejection (BPAR) during 12 months post-RTx. STUDY DESIGN: A total of 106 consecutive RTx recipients at risk for CMV (donor and/or recipient CMV seropositive) were followed prospectively for 12 months post-RTx. CMV activity was monitored using nested PCR from whole blood. Three-month prophylaxis with valacyclovir or ganciclovir was given to 94 patients. BPAR episodes were classified according to the Banff 97 criteria. Multivariate Cox proportional hazards model was used to estimate the effect of CMV disease, asymptomatic infection, and other covariates on BPAR. RESULTS: Asymptomatic CMV infection occurred in 23% of the patients and 10% developed CMV disease. The incidence of BPAR was 29%. CMV disease was an independent risk factor for BPAR (HR=3.0, P=0.014), while asymptomatic CMV infection was not (P=0.987). In addition to CMV disease, expanded criteria donor and donor age were independent predictors for BPAR. In univariate analysis, valacyclovir (HR=0.26, P=0.008) decreased the risk of BPAR. A similar trend was observed with ganciclovir (HR=0.42, P=0.058). Only valacyclovir remained significant in multivariate analysis (HR=0.18, P=0.044). CONCLUSIONS: CMV disease, but not asymptomatic infection, is an independent risk factor for BPAR during the first 12 months post-RTx.

• MeSH
• acyklovir analogy a deriváty   terapeutické užití   MeSH
• akutní nemoc MeSH
• antivirové látky terapeutické užití   MeSH
• cytomegalovirové infekce komplikace   prevence a kontrola   virologie   MeSH
• Cytomegalovirus genetika   izolace a purifikace   MeSH
• ganciklovir terapeutické užití   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• pooperační komplikace * prevence a kontrola   MeSH
• přenašečství MeSH
• prospektivní studie MeSH
• rejekce štěpu epidemiologie   etiologie   MeSH
• rizikové faktory MeSH
• transplantace ledvin škodlivé účinky   MeSH
• valaciclovir MeSH
• valin analogy a deriváty   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• ganciklovir MeSH
• valaciclovir MeSH
• valin MeSH

Antibody-mediated rejection (ABMR) is a major obstacle to the long-term success in kidney transplantation. Diagnosis of ABMR is determined according to the internationally recognized Banff criteria. However, a significant proportion of patients does not meet all the defined criteria, and the outcome of such cases remains poorly understood. The histology of ABMR frequently lacks sensitivity and specificity. More importantly, mixed forms of ABMR and T cell-mediated rejection as well as findings of nonspecific injury are common in clinical settings. Donor-specific anti-HLA antibodies (DSA) are detectable only in half of the ABMR cases by histology. Prognostic role of non-HLA antibodies against various endothelial proteins has been discussed. Antibody independent NK cell activation reflecting killer-cells' inhibitory receptor incompatibility is suggested in microvascular inflammation in DSA negative patients. Molecular assessment of ABMR has been prioritized to overcome high interobserver variability and improve diagnostics in mixed forms of rejections and in DSA negative cases. Finally, donor-derived cell-free DNA detected in a recipient's peripheral blood sample has been proposed as a noninvasive marker for diagnosis of graft rejection, and thus might serve as a liquid biopsy in the near future. Despite all achievements, diagnosing ABMR in kidney allografts remains to be a challenge in a significant number of cases.

• MeSH
• alografty MeSH
• isoprotilátky MeSH
• ledviny patologie   MeSH
• lidé MeSH
• rejekce štěpu diagnóza   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• isoprotilátky MeSH

BACKGROUND: Bioavailability of tacrolimus (Tac) and cyclosporine is determined by cytochrome P450IIIA and by P-glycoprotein encoded by the CYP3A4/CYP3A5 and ABCB1 genes. Polymorphisms in these genes have been suggested to influence acute rejection and pharmacokinetics in renal transplantation. We aimed to validate these findings in a haplotype analysis. METHODS: A total of 832 renal transplant recipients were genotyped for the CYP3A4 -288A>G, CYP3A5 +6986G>A, ABCB1 +1236C>T, +2677G>T>A, and +3435C>T polymorphisms. Their association with acute rejection and with pharmacokinetic parameters was analyzed in haplotype models. RESULTS: Apart from human leukocyte antigen-DR mismatches, delayed graft function and age at renal transplantation, acute rejection was also predicted by the [ABCB1 +1236C; +2677G; +3435T] haplotype. Allograft survival was determined by donor age, age at renal transplantation, delayed graft function, cold ischemia, and history of more than two acute rejections. Homozygotes for the [CYP3A4 -288A; CYP3A5 +6986G] haplotype achieved earlier therapeutic concentrations of Tac and a higher concentration to dose ratio at week 1. ABCB1 haplotypes did not influence pharmacokinetic parameters. CONCLUSIONS: ABCB1 haplotypes modify the risk of acute rejection, suggesting that ABCB1 allelic arrangement is a stronger regulator of P-glycoprotein activity than single polymorphisms. The risk of acute rejection determined by ABCB1 is independent of pharmacokinetic parameters. CYP3A haplotypes control the bioavailability of Tac, but do not modify the risk of acute rejection.

• MeSH
• alely MeSH
• dítě MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• homologní transplantace MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• P-glykoprotein genetika   metabolismus   MeSH
• P-glykoproteiny MeSH
• předškolní dítě MeSH
• přežívání štěpu genetika   MeSH
• rejekce štěpu genetika   metabolismus   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• transplantace ledvin * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABCB1 protein, human MeSH Prohlížeč
• P-glykoprotein MeSH
• P-glykoproteiny MeSH