BACKGROUND: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti- N -glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. METHODS: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. RESULTS: CD3 + T cell depletion <100/mm 3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. CONCLUSIONS: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.
- MeSH
- antilymfocytární sérum * imunologie MeSH
- dospělí MeSH
- galaktosyltransferasy MeSH
- imunosupresiva aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocytární deplece metody MeSH
- prasata MeSH
- rejekce štěpu imunologie prevence a kontrola MeSH
- T-lymfocyty imunologie účinky léků MeSH
- transplantace ledvin * škodlivé účinky MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
OBJECTIVES: The aim of this study was to investigate the association of lower urinary tract dysfunctions with urinary leakage from ureterocystoneoanastomosis (UCNA) after kidney transplantation. BACKGROUND: The UCNA leakage after kidney transplantation can be associated with various conditions while severe lower urinary tract dysfunctions could be one of them. METHODS: The analysis included all men who underwent kidney transplantation between January 2009 and December 2014. The parameters of storage and voiding functions were evaluated. All patients were monitored during their post-transplantation period for the incidence of urinary leakage from UCNA. Urodynamic parameters were compared between men with and without a documented leakage. RESULTS: The study cohort included 127 male patients, while UCNA leakage was observed in 11 (8.7 %) patients. Significant differences between both groups of patients were found for storage parameters (patients with leakage had smaller volume at first and a normal desire to void, smaller maximal cystometric capacity, and lower detrusor compliance) and voiding parameters (patients with leakage had a lower maximal flow rate, higher detrusor pressure at maximal flow rate and higher bladder outlet obstruction index). CONCLUSION: This study shows an association between lower urinary tract dysfunction and UCNA leakage in men without previous urological history (Tab. 2, Fig. 2, Ref. 24).
The recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in 20-35% of patients. The main aim of this study is to evaluate risk factors affecting the course of IgAN after renal biopsy of native kidney and kidney transplant. We evaluated clinical parameters and histological findings at the time of biopsy of native kidney and after kidney transplantation in 313 patients with IgAN with a follow-up of up to 36 years. Using hierarchical clustering method, patients with graft failure (n=50) were divided into two groups based on the mean time from kidney transplant to graft failure (11.2 versus 6.1 years). The time-to-graft failure corresponded well to the time from the renal biopsy of native kidney to end-stage renal disease (5.9 versus 0.4 years). Body mass index, proteinuria, microscopic hematuria, histological evaluation of fibrosis, and crescents at the time of renal biopsy of native kidney were the main variables for the differentiation of the two groups. Higher age of kidney-transplant donor, histological recurrence of IgAN, antibody-mediated rejection, and the onset of microscopic hematuria and proteinuria within 1 year after kidney transplant were also associated with worse graft survival in multivariate Cox regression analysis.
- MeSH
- biopsie MeSH
- chronické selhání ledvin chirurgie MeSH
- dospělí MeSH
- IgA nefropatie diagnóza etiologie patologie MeSH
- ledviny patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- multivariační analýza MeSH
- přežívání štěpu fyziologie MeSH
- proporcionální rizikové modely MeSH
- proteinurie patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
PURPOSE: This work investigated the effects of diuresis, duration of dialysis and age on lower urinary tract function in urologically healthy males on the waiting list for kidney transplant. MATERIALS AND METHODS: The study included all men who had kidney transplants at our centre between January 2009 and December 2014 who had normal urological findings prior to inclusion on the list. Diuresis, the duration of haemodialysis, age, and parameters of function of the lower urinary tract as determined by filling and voiding cystometry were evaluated. RESULTS: The study included 127 men (median age, 59 years; median diuresis, 250 mL; median duration of dialysis, 469.5 days). We found that greater diuresis was accompanied by significantly higher FDV, FDV/Cmax, NDV,Cmax and compliance and by significantly lower Pdet.max, PdetQmax and BOOI. Longer duration of dialysis was accompanied by significantly lower FDV, NDV and Cmax, compliance and Qmax.p and with significantlyhigher Pdet.max, PdetQmax and BOOI. Older age was associated with significantly higher Pdet.max and with significantly lower compliance. Worsening of the basic parameters of the storage function of the lower urinary tract occurred when diuresis decreased to 500-750 mL, when the duration of dialysis was one year and when patients were older than 54 years. CONCLUSION: In healthy male patients on the waiting list for kidney transplant, there were connections between the occurrence of dysfunctions of the lower urinary tract and diuresis, duration of dialysis and age. Patients should be monitored for dysfunctions of the lower urinary tract before and after transplantation.
- MeSH
- časové faktory MeSH
- chronická renální insuficience patofyziologie terapie MeSH
- dialýza ledvin * MeSH
- diuréza * MeSH
- hladké svalstvo patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- moč MeSH
- močení MeSH
- močový měchýř patofyziologie MeSH
- plocha pod křivkou MeSH
- poddajnost MeSH
- ROC křivka MeSH
- senioři MeSH
- seznamy čekatelů MeSH
- svalová kontrakce MeSH
- transplantace ledvin MeSH
- urodynamika * MeSH
- věkové faktory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Malignant melanoma is considered to be an immunogenic tumor, which is expected to change its behaviour in the field of immunosuppression. Although the incidence of melanoma in organ transplant recipients is increased to a smaller degree than in non-melanoma skin cancer, its potential morbidity and mortality has to be considered in the posttransplant care. The aim of this review is to investigate the relationship between melanoma and immunosuppression and to discuss management strategies for different melanoma scenarios in pre-transplant as well as posttransplant period.
- MeSH
- časové faktory MeSH
- dárci tkání MeSH
- hodnocení rizik MeSH
- hostitel s imunodeficiencí MeSH
- imunosupresiva škodlivé účinky MeSH
- incidence MeSH
- lidé MeSH
- melanom diagnóza epidemiologie imunologie terapie MeSH
- nádory kůže diagnóza epidemiologie imunologie terapie MeSH
- příjemce transplantátu * MeSH
- rizikové faktory MeSH
- transplantace orgánů škodlivé účinky MeSH
- výběr dárců MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH