BACKGROUND: The process of kidney transplantation remains the optimal treatment for end-stage renal disease, offering improved quality of life and increased survival rates compared to long-term dialysis. However, despite advances in surgical techniques, immunosuppression regimens, and post-operative care, there are still significant challenges in predicting the organ's status and long-term outcomes of transplantation. Among the many factors that influence graft survival, the quality of the donated organ plays a fundamental role. There is an ongoing need for accurate and reliable biomarkers. Syndecan-1 is found in the endothelial glycocalyx and shed at a higher rate into the blood during systemic pathological conditions. The aim of this study is to evaluate the potential of serum syndecan-1 levels as a biomarker for assessing donor kidney quality and to investigate its correlation with donor characteristics and short-term outcomes in kidney recipients. MATERIAL AND METHODS: We investigated serum syndecan-1 levels in 80 deceased donors and correlated them with donor characteristics and short-term outcomes (defined as delayed graft function - defined as the need for dialysis within the first week post-transplantation and renal function at 3 months post-transplantation - assessed using serum creatinine levels) in 104 corresponding kidney recipients. This single-center retrospective observational cohort study was conducted from April to December 2021. RESULTS: The donor pool consisted of 65% males with a median age of 53 years. Of these, 45 donors (56%) were classified as extended criteria donors. Higher syndecan-1 levels correlated with the last creatinine levels before organ procurement (R = 0.32, p = 0.01) and were marginally higher in donors with acute kidney injury (p = 0.07). However, syndecan-1 levels were not associated with short-term outcomes in kidney recipients (renal function at 3 months). CONCLUSIONS: The data suggests syndecan-1 could be a potential biomarker for assessing donor kidney quality, although its implications on recipient outcomes require further study. This pilot investigation underscores the importance of syndecan-1 in evaluating organ quality but highlights the necessity for more extensive research to validate these findings and explore their implications in transplant success.
- MeSH
- biologické markery * krev MeSH
- chronické selhání ledvin chirurgie krev terapie MeSH
- dárci tkání * MeSH
- dospělí MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- opožděný nástup funkce štěpu krev MeSH
- přežívání štěpu MeSH
- retrospektivní studie MeSH
- syndekan-1 * krev MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- biologické markery * MeSH
- SDC1 protein, human MeSH Prohlížeč
- syndekan-1 * MeSH
Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.
- Klíčová slova
- Antibodies, COVID-19, Kidney transplantation, SARS-CoV-2, Vaccination,
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- glykoprotein S, koronavirus imunologie MeSH
- humorální imunita MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutralizující protilátky * krev imunologie MeSH
- příjemce transplantátu * MeSH
- protilátky virové * krev imunologie MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 imunologie aplikace a dávkování MeSH
- vakcíny proti COVID-19 imunologie aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glykoprotein S, koronavirus MeSH
- neutralizující protilátky * MeSH
- protilátky virové * MeSH
- spike protein, SARS-CoV-2 MeSH Prohlížeč
- vakcína BNT162 MeSH
- vakcíny proti COVID-19 MeSH
Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.
- Klíčová slova
- ABMR, TCMR, biopsy, gene expression, gradients, kidney transplant, microarray, transplant rejection,
- MeSH
- biopsie MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- isoprotilátky imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- přežívání štěpu imunologie MeSH
- prognóza MeSH
- rejekce štěpu * patologie imunologie etiologie MeSH
- rizikové faktory MeSH
- T-lymfocyty imunologie MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- isoprotilátky MeSH
BACKGROUND: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies. METHODS: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA+) who had received desensitization and did not develop active/probable AMR by histology (R-) was compared with biopsies showing active/probable AMR (R+/DSA+). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R-/DSA-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30). RESULTS: The transcriptome of R-/DSA+ was similar to R+/DSA+ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA+ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA+ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R-/DSA+ samples as AMR and found no differences in AMR molecular scores between R+ and R- DSA+ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time. CONCLUSIONS: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.
- Publikační typ
- časopisecké články MeSH
The aim of this prospective study was to assess the duration of culture-viable SARS-CoV-2 and to monitor the emergence of mutations in a cohort of 23 kidney transplant recipients (KTRs) from June 2022 to June 2023. Combined nares/oropharyngeal swabs were collected weekly starting as soon as possible after symptom onset. The time from symptom onset to a negative culture was 11 days (interquartile range, 8-14), while the time to negative reverse transcriptase quantitative polymerase chain reaction was 18 days (interquartile range, 15-30). Beyond the first swab, 21.7% had a positive culture, and 8.7% replicated viable virus for longer than 30 days. T cell depletion (rate ratio, 2.5; 95% confidence interval [95% CI], 1.9-3.3; P < .001) and time from transplantation (rate ratio, 0.93; 95% CI, 0.90-0.97; P = .006) were associated with the time of viable virus shedding. A cycle threshold value of 24.2 demonstrated a 91.3% negative predictive value of viability (95% credible interval [95% CrI], 76-100). The odds of viability decreased by 69% per week of infection (odds ratio, 0.31; 95% CrI, 0.12-0.76). Overall, ribonucleic acid sequencing did not show accelerated molecular evolution though mutation rate could be increased in molnupiravir-treated KTRs. In conclusion, viable SARS-CoV-2 is eliminated rapidly, the risk of virus evolution is low, and prolonged self-isolation is generally unnecessary for most KTRs.
- Klíčová slova
- SARS-CoV-2, immunodeficiency, immunosuppression, infectiousness, kidney transplantation, public health, virus evolution, virus viability,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.
- Klíčová slova
- antimicrobial stewardship, kidney transplantation, questionnaire, urinary tract infection,
- MeSH
- antibakteriální látky * terapeutické užití MeSH
- beta-laktamasy MeSH
- cefalosporiny terapeutické užití MeSH
- dospělí MeSH
- kombinace léků piperacilin a tazobactam terapeutické užití MeSH
- lékařská praxe - způsoby provádění statistika a číselné údaje MeSH
- lidé středního věku MeSH
- lidé MeSH
- příjemce transplantátu statistika a číselné údaje MeSH
- průzkumy a dotazníky MeSH
- Pseudomonas aeruginosa účinky léků izolace a purifikace MeSH
- pyelonefritida * farmakoterapie mikrobiologie MeSH
- transplantace ledvin * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky * MeSH
- beta-laktamasy MeSH
- cefalosporiny MeSH
- kombinace léků piperacilin a tazobactam MeSH
BACKGROUND: Acute kidney injury in deceased donors (D-AKI) is one of the common causes of donor kidney discard. The risk factors for D-AKI and its impact on kidney transplantation outcomes are not yet fully understood. METHODS: This single-center, retrospective cohort study included 388 donors referred between June 2021 and December 2022. D-AKI was defined and staged according to kidney disease: Improving global outcomes criteria, and donor clinical variables were analyzed to identify risk factors for D-AKI. Delayed graft function and estimated glomerular filtration rate (eGFR) at 6 mo were evaluated in 369 kidney grafts transplanted from donors with and without D-AKI. RESULTS: AKI was present in 171 deceased donors (44.1%), with 117 (30.2%) classified as AKI stage 1 and 54 (14%) as AKI stages 2 or 3. Donor history of hypertension (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.21-3.10; P = 0.005), history of diabetes (OR 2.2; 95% CI, 1.21-3.98; P = 0.008), and anoxia as the cause of death (OR 2.61; 95% CI, 1.5-4.61; P < 0.001) were independently associated with an increased risk of D-AKI. Multivariable mixed models identified donor age (β -0.49; 95% CI, -0.71 to -0.28; P < 0.001) as the only independent risk factor for lower eGFR at 6 mo. D-AKI was not associated with delayed graft function or lower eGFR at 6 mo. CONCLUSIONS: Hypertension, diabetes, and anoxia as the cause of death were identified as risk factors for AKI in deceased donors. D-AKI should not be used as the sole criterion to assess the risk of poor graft outcomes. A broader range of donor variables should be considered when evaluating graft viability.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: We would like to present an unusual case of simultaneous stenosis of renal graft artery and vein diagnosed four months after transplantation. both treated by stent placement. Our aim is to point at the fact that renal graft venous stenosis is very rarely reported in the literature and - as it is not easy to diagnose by routine US - it could be overlooked. If early detected it can be treated by stent placement. CASE PRESENTATION: We present a case of 36-old-male with renal failure who received a kidney graft from deceased donor. The patient experienced delayed graft function. No rejection was found in the biopsy. Four months after transplantation the kidney function deteriorated to sCr 280 µmol/l. Graft artery stenosis together with graft vein stenosis was revealed. Both lesions were dilated with stent placement, the graft function returned to 230 µmol/l and became stable for 10 years. Ten years after stent placement graft function deteriorated to 300 µmol/l. An in stent restenosis of arterial stent was detected. It was successfully dilated by the balloon, the graft function returned to 230 µmol/l and stays stable for another 5 years. CONCLUSIONS: An unusual simultaneous transplanted kidney artery and vein stenosis treated by stent placement is presented. The patient had stable graft function for 15 years after the procedure with one re-intervention on arterial stent.
- Klíčová slova
- Arterial stenting, Transplanted kidney, Venous stenting,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Live donor kidney transplantation is considered the optimal choice for renal replacement therapy, providing established benefits, such as superior patient survival and improved quality of life. However, immunological challenges, including ABO blood group incompatibility and, particularly, donor-specific HLA antibodies, may impact long-term outcomes considerably or even prevent safe direct transplantation with the intended donor. METHODS: In this review, the authors discuss kidney paired donation (KPD) as a viable strategy to overcome immunological barriers to living donation through organ exchanges. We thereby lay special focus on the Czech-Austrian transnational KPD program. RESULTS: While the benefits of KPD programs are well established for adult recipients, recent data suggest that this may hold true also for pediatric patients. Complex algorithms, considering factors like the intricate patterns of HLA sensitization, play a pivotal role in predicting suitable matches, but for pediatric patients also non-immunological factors including age and weight match may play a role. As pool size proves crucial for program efficacy, several countries in Europe have now initiated transnational collaborations to maximize match rates. Among those, the Czech-Austrian transnational joint program, established in 2015 and now expanded to a cooperation with the Israel transplant program to further increase transplant rates, represents a successful example. CONCLUSION: KPD programs, with their innovative approaches and international partnerships, hold promise for enhancing outcomes and addressing the increasing demand for kidney transplantation.
- Klíčová slova
- ABO incompatibility, HLA incompatibility, kidney paired donation, kidney transplantation,
- MeSH
- dítě MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- lidé MeSH
- transplantace ledvin * MeSH
- žijící dárci * MeSH
- získávání tkání a orgánů * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
- Názvy látek
- HLA antigeny MeSH
- Klíčová slova
- complement, complement genetics, de novo thrombotic microangiopathy, kidney transplantation,
- MeSH
- imunosupresiva škodlivé účinky MeSH
- inhibitory kalcineurinu * škodlivé účinky MeSH
- lidé MeSH
- prognóza MeSH
- takrolimus škodlivé účinky MeSH
- transplantace ledvin škodlivé účinky MeSH
- trombotické mikroangiopatie * etiologie chemicky indukované patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- úvodníky MeSH
- Názvy látek
- imunosupresiva MeSH
- inhibitory kalcineurinu * MeSH
- takrolimus MeSH
