Nejvíce citovaný článek - PubMed ID 20973913
The aim of this narrative review is to summarize recent knowledge about the diagnostic significance of immunobiological detection of C3d with a focus on renal and skin tissue biopsies. We completed the present narrative review with our own experiences with preparation and practical use of monoclonal C3d antibodies at a small national level.
- MeSH
- kůže MeSH
- ledviny * patologie MeSH
- monoklonální protilátky MeSH
- transplantace ledvin * MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- monoklonální protilátky MeSH
Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.
- Klíčová slova
- interleukins, kidney transplantation, long-term graft survival, polymorphisms,
- MeSH
- alografty MeSH
- interleukin-10 * genetika MeSH
- interleukin-6 * genetika MeSH
- ledviny MeSH
- lidé MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- interleukin-10 * MeSH
- interleukin-6 * MeSH
BACKGROUND This post hoc analysis of data from the prospective OSAKA study evaluated the efficacy and safety of prolonged- and immediate-release tacrolimus in patients who received kidneys from extended-criteria (ECD) and standard-criteria (SCD) donors. MATERIAL AND METHODS Within the ECD and SCD groups, patients were randomized to one of 4 tacrolimus-based regimens (initial dose): Arm 1, immediate-release tacrolimus (0.2 mg/kg/day); Arm 2, prolonged-release tacrolimus (0.2 mg/kg/day); Arm 3, prolonged-release tacrolimus (0.3 mg/kg/day); Arm 4, prolonged-release tacrolimus (0.2 mg/kg/day) plus basiliximab. All patients received mycophenolate mofetil and bolus corticosteroids; Arms 1-3 also received tapered corticosteroids. ECDs met the definition: living/deceased donors aged ≥60 years, or 50-60 years with ≥1 other risk factor, and donation after circulatory death. Primary composite endpoint: graft loss, biopsy-confirmed acute rejection or renal dysfunction by Day 168. Outcomes were compared across treatment arms with the chi-squared or Fisher's exact test. RESULTS A total of 1198 patients were included in the analysis (ECD: n=620 [51.8%], SCD: n=578 [48.2%]). Patients with kidneys from ECDs were older versus SCDs (mean age, 55.7 vs. 44.5 years, p<0.0001). A higher proportion of patients with kidneys from ECDs versus SCDs met the primary composite endpoint (56.8% vs. 32.4%, p<0.0001). However, no statistically significant differences in clinical outcomes or the incidence of treatment-emergent adverse events were seen between treatment arms within each donor group. CONCLUSIONS Worse outcomes were experienced in patients who received kidneys from ECDs versus SCDs. Prolonged-release tacrolimus provided similar graft survival to the immediate-release formulation, with a manageable tolerability profile.
- MeSH
- chronické selhání ledvin chirurgie MeSH
- dospělí MeSH
- imunosupresiva aplikace a dávkování MeSH
- imunosupresivní léčba MeSH
- léky s prodlouženým účinkem MeSH
- lidé středního věku MeSH
- lidé MeSH
- přežívání štěpu MeSH
- prospektivní studie MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- takrolimus aplikace a dávkování MeSH
- transplantace ledvin * MeSH
- výběr dárců MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- imunosupresiva MeSH
- léky s prodlouženým účinkem MeSH
- takrolimus MeSH