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1.
N Engl J Med ; 388(5): 418-426, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36724328

RESUMO

BACKGROUND: Therapeutic hypothermia in brain-dead organ donors has been shown to reduce delayed graft function in kidney recipients after transplantation. Data are needed on the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation. METHODS: At six organ-procurement facilities in the United States, we randomly assigned brain-dead kidney donors to undergo therapeutic hypothermia (hypothermia group), ex situ kidney hypothermic machine perfusion (machine-perfusion group), or both (combination-therapy group). The primary outcome was delayed graft function in the kidney transplant recipients (defined as the initiation of dialysis during the first 7 days after transplantation). We also evaluated whether hypothermia alone was noninferior to machine perfusion alone and whether the combination of both methods was superior to each of the individual therapies. Secondary outcomes included graft survival at 1 year after transplantation. RESULTS: From 725 enrolled donors, 1349 kidneys were transplanted: 359 kidneys in the hypothermia group, 511 in the machine-perfusion group, and 479 in the combined-therapy group. Delayed graft function occurred in 109 patients (30%) in the hypothermia group, in 99 patients (19%) in the machine-perfusion group, and in 103 patients (22%) in the combination-therapy group. Adjusted risk ratios for delayed graft function were 1.72 (95% confidence interval [CI], 1.35 to 2.17) for hypothermia as compared with machine perfusion, 1.57 (95% CI, 1.26 to 1.96) for hypothermia as compared with combination therapy, and 1.09 (95% CI, 0.85 to 1.40) for combination therapy as compared with machine perfusion. At 1 year, the frequency of graft survival was similar in the three groups. A total of 10 adverse events were reported, including cardiovascular instability in 9 donors and organ loss in 1 donor owing to perfusion malfunction. CONCLUSIONS: Among brain-dead organ donors, therapeutic hypothermia was inferior to machine perfusion of the kidney in reducing delayed graft function after transplantation. The combination of hypothermia and machine perfusion did not provide additional protection. (Funded by Arnold Ventures; ClinicalTrials.gov number, NCT02525510.).


Assuntos
Hipotermia Induzida , Hipotermia , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Função Retardada do Enxerto/etiologia , Preservação de Órgãos/métodos , Rim , Sobrevivência de Enxerto , Doadores de Tecidos , Hipotermia Induzida/efeitos adversos , Perfusão/métodos , Morte Encefálica
2.
Liver Transpl ; 29(2): 184-195, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36668691

RESUMO

The aim of this study was to investigate whether the combination of low-dose sirolimus (SRL) and low-dose extended-release tacrolimus (TAC) compared to normal-dose extended-release TAC results in a difference in the renal function and comparable rates of rejection, graft and patient survival at 36 months after transplantation. This study was an open-label, multicenter randomized, controlled trial. Patients were randomized to once-daily normal-dose extended-release TAC (control group) or once-daily combination therapy of SRL and low-dose extended-release TAC (interventional group). The primary endpoint was the cumulative incidence of chronic kidney disease (CKD) defined as grade ≥3 (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) at 36 months after transplantation. In total, 196 patients were included. CKD at 36 months was not different between the control and interventional group (50.8%, 95% CI: 39.7%-59.9%) vs. 43.7%, 95% CI: 32.8%-52.8%). Only at 6 months after transplantation, the eGFR was higher in the interventional group compared to the control group (mean eGFR 73.1±15 vs. 67.6±16 mL/min/1.73 m2, p=0.02) in the intention-to-treat population. No differences in the secondary endpoints and the number of serious adverse events were found between the groups. Once daily low-dose SRL combined with low-dose extended-release TAC does ultimately not provide less CKD grade ≥3 at 36 months compared to normal-dose extended-release TAC.


Assuntos
Transplante de Rim , Transplante de Fígado , Insuficiência Renal Crônica , Humanos , Tacrolimo/uso terapêutico , Sirolimo/efeitos adversos , Imunossupressores/uso terapêutico , Transplante de Fígado/efeitos adversos , Transplante de Rim/efeitos adversos , Rim/fisiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/induzido quimicamente , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto
3.
Ther Drug Monit ; 45(1): 102-109, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36624577

RESUMO

PURPOSE: Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence. METHODS: A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models. RESULTS: The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM (P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43-2.10, P < 0.001)]. CONCLUSION: This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.


Assuntos
Diabetes Mellitus , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Tacrolimo/efeitos adversos , Imunossupressores/efeitos adversos , Diabetes Mellitus/induzido quimicamente
4.
Sci Rep ; 13(1): 861, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650247

RESUMO

Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00-2.77) and 1.20 (0.60-2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.


Assuntos
Ferro , Transplante de Rim , Humanos , Estudos de Coortes , Transplante de Rim/efeitos adversos , Transferrina/análise , Ferritinas , Rim/química
5.
Kidney Int ; 103(2): 256-258, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36681454

RESUMO

Youth with chronic kidney disease are known to have impaired health-related quality of life (HRQOL), particularly as the disorder increases in severity. Few prospective, longitudinal investigations of HRQOL within the context of pediatric chronic kidney disease exist. In the current issue, Guha et al. provide a longitudinal assessment of HRQOL for a cohort of youth with chronic kidney disease. Their findings suggest that children may experience meaningful improvement in HRQOL when they transition from dialysis to transplant.


Assuntos
Transplante de Rim , Insuficiência Renal Crônica , Humanos , Adolescente , Criança , Qualidade de Vida , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Insuficiência Renal Crônica/cirurgia , Diálise Renal
6.
Ren Fail ; 45(1): 2161395, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36688793

RESUMO

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.


Assuntos
Transplante de Rim , Tromboembolia Venosa , Trombose Venosa , Adulto , Humanos , Tromboembolia Venosa/epidemiologia , Estudos de Casos e Controles , Prevalência , Transplante de Rim/efeitos adversos , Trombose Venosa/etiologia , Fatores de Risco , Estudos Retrospectivos
7.
World J Surg Oncol ; 21(1): 18, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691019

RESUMO

One of the main causes of post-transplant-associated morbidity and mortality is cancer. The aims of the project were to study the neoplastic risk within the kidney transplant population and identify the determinants of this risk. A cohort of 462 renal transplant patients from 2010 to 2020 was considered. The expected incidence rates of post-transplant cancer development in the referenced population, the standardized incidence ratios (SIR) taking the Italian population as a comparison, and the absolute risk and the attributable fraction were extrapolated from these cohorts of patients. Kidney transplant recipients had an overall cancer risk of approximately three times that of the local population (SIR 2.8). A significantly increased number of cases were observed for Kaposi's sarcoma (KS) (SIR 195) and hematological cancers (SIR 6.8). In the first 3 years post-transplant, the risk to develop either KS or hematological cancers was four times higher than in the following years; in all cases of KS, the diagnosis was within 2 years from the transplant. Post-transplant immunosuppression represents the cause of 99% of cases of KS and 85% of cases of lymphomas, while only 39% is represented by solid tumors. Data related to the incidence, the percentages attributable to post-transplant immunosuppression, and the time of onset of neoplasms, particularly for KS and hematological tumors could help improve the management for the follow-up in these patients.


Assuntos
Neoplasias Hematológicas , Transplante de Rim , Neoplasias , Sarcoma de Kaposi , Humanos , Transplante de Rim/efeitos adversos , Neoplasias/epidemiologia , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/epidemiologia , Incidência , Fatores de Risco
8.
BMC Infect Dis ; 23(1): 50, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694138

RESUMO

BACKGROUND: Nannizziopsis is a genus of fungi with several known cases in reptiles of pyogranulomatous infections at cutaneous and musculoskeletal level, of rapid and fatal evolution. There are few cases of this genus described in humans, mainly skin affection but also with visceral abcesses, typically in immunosuppressed patients, with a recent visit to Africa. CASE PRESENTATION: A 45-year-old woman immunosuppressed after renal transplantation and with a recent visit to Nigeria presented with a painless breast abcess, ulceration to the skin and bleeding, and non hematic telorrhea. The mammogram, also completed with an ultrasound scan, showed a polylobulated nodule, BI-RADS 4C. Due to the suspicion of breast cancer, a core needle biopsy was performed and the pathology study showed abundant presence of fungal spores and hyphae. It was identified by genomic amplification of the internal transcription spacer region-2 and a percentage of similarity with sequences of Nannizziopsis obscura from GenBank of 98% was obtained. An empiric treatment with anidulafungin was initiated, and after the surgical resection, it was replaced by isavuconazole, with a total time of treatment of one month. CONCLUSIONS: This is the first case report of a successful treatment of Nannizziopsis obscura with isavuconazole, with the shortest time of treatment published for this fungi. We highlighted the importance of referring difficult to diagnose species to reference centers, as well as achieving the most complete resection in order to shorten the antibiotic therapy.


Assuntos
Transplante de Rim , Feminino , Humanos , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Nigéria , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Fungos , Hospedeiro Imunocomprometido
9.
BMC Nephrol ; 24(1): 19, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694123

RESUMO

INTRODUCTION: Immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0-incompatible living donor kidney transplantation. CASE PRESENTATION: A 34-year-old unvaccinated patient is diagnosed with SARS-CoV-2 infection four months after kidney transplantation. With only mild symptoms and an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m2, therapy with molnupiravir was initially given. Within the next eight weeks, transplant biopsies were performed for acute graft failure. These showed acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB), and borderline rejection (BANFF cat. 3). A therapy with prednisolone and intravenous immunoglobulins was performed twice. With unchanged graft failure, the third biopsy also formally showed BANFF cat. 4 IB. However, fluorescence in situ hybridization detected SARS-CoV-2 viruses in large portions of the distal tubules. After nine weeks of persistent COVID-19 disease neither anti-SARS-CoV-2 IgG nor a SARS-CoV-2-specific cellular immune response could be detected, leading to the administration of sotrovimab and remdesivir. Among them, SARS-CoV-2 clearance, detection of IgG, and improvement of graft function were achieved. CONCLUSION: Lack of viral clearance can lead to complications of SARS-CoV-2 infection with atypical manifestations. In kidney transplant patients, before initiating therapy, the differential diagnoses of "rejection" and "virus infection" should be weighed against each other in an interdisciplinary team of nephrologists, infectious diseases specialists and pathologists.


Assuntos
COVID-19 , Nefropatias , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , Hibridização in Situ Fluorescente , COVID-19/complicações , SARS-CoV-2 , Rejeição de Enxerto , Nefropatias/etiologia , Imunoglobulina G
11.
Clin J Am Soc Nephrol ; 18(1): 91-98, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36719161

RESUMO

BACKGROUND: Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS: We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS: Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS: Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.


Assuntos
Transplante de Rim , Medicare Part D , Adulto , Humanos , Idoso , Estados Unidos/epidemiologia , Gabapentina/uso terapêutico , Analgésicos Opioides/uso terapêutico , Benzodiazepinas/uso terapêutico , Transplante de Rim/efeitos adversos , Prescrições de Medicamentos , Estudos Retrospectivos
12.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649519

RESUMO

BACKGROUND: Levels of zonulin, a surrogate marker of intestinal permeability, are elevated in various disorders including insulin resistance, obesity, celiac disease, and inflammatory bowel disease. We aimed to elucidate the association of zonulin levels and metabolic syndrome (MS) in renal transplant recipients. METHODS: Seventy-nine renal transplant recipients were enrolled. Diagnosis of MS was established employing the Adult Treatment Panel III (ATP III) criteria. Serum zonulin level was determined using the double antibody sandwich ELISA method. RESULTS: MS was encountered in 37 (41.6%) of the 79 patients. Serum zonulin level was significantly higher in patients with MS compared to those without MS (p < 0.001). Serum zonulin level correlated with presence of MS (r: 739, p < 0.001), abdominal obesity (r: 514, p < 0.001), fasting glucose level (r: 361, p: 0.001), presence of fasting glucose/diabetes criterion of MS (r: 316, p: 0.005), presence of low HDL criterion of MS (r: 266, p: 0.018), and BMI (r: 527, p < 0.001). CONCLUSIONS: A Zonulin-mediated increase in intestinal permeability may play a role in the pathogenesis of metabolic syndrome. We propose that zonulin may be a suitable surrogate marker of MS in renal transplant recipients.


Assuntos
Transplante de Rim , Síndrome Metabólica , Adulto , Humanos , Síndrome Metabólica/diagnóstico , Transplante de Rim/efeitos adversos , Obesidade , Haptoglobinas , Glucose , Biomarcadores , Permeabilidade
13.
Life Sci Alliance ; 6(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36717250

RESUMO

The BK polyomavirus (BKPyV) is an opportunistic pathogen, which is only pathogenic in immunosuppressed individuals, such as kidney transplant recipients, in whom BKPyV can cause significant morbidity. To identify broadly neutralizing antibodies against this virus, we used fluorescence-labeled BKPyV virus-like particles to sort BKPyV-specific B cells from the PBMC of KTx recipients, then single-cell RNAseq to obtain paired heavy- and light-chain antibody sequences from 2,106 sorted B cells. The BKPyV-specific repertoire was highly diverse in terms of both V-gene usage and clonotype diversity and included most of the IgM B cells, including many with extensive somatic hypermutation. In two patients where sufficient data were available, IgM B cells in the BKPyV-specific dataset had significant differences in V-gene usage compared with IgG B cells from the same patient. CDR3 sequence-based clustering allowed us to identify and characterize three broadly neutralizing "41F17-like" clonotypes that were predominantly IgG, suggesting that some specific BKPyV capsid epitopes are preferentially targeted by IgG.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Transplante de Rim/efeitos adversos , Leucócitos Mononucleares , Infecções por Polyomavirus/etiologia , Imunoglobulina G , Imunoglobulina M
14.
Pediatr Transplant ; 27 Suppl 1: e14423, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36650661

RESUMO

Living donors are the main source of transplanted kidneys for children and young people in many countries, but there still remains a significant need for deceased donor kidney transplantation. Given the waiting times associated with deceased donor kidney transplantation and the morbidity or mortality that can occur in those on the waiting list, it is essential that the utilization of kidneys from deceased donors is optimized. The use of organs from deceased donors at increased risk of transmitting human immunodeficiency virus, hepatitis B virus, or hepatitis C virus is relatively common in adults, but far less so in children. The risks and benefits of the use of kidneys from increased infectious risk donors (IIRD) are discussed. The variation of definitions of IIRD between countries is explored as is the need for pediatric nephrologists and transplant surgeons to have an understanding of the prevalence of viral diseases within the country in which they work. The role of screening tests such as nucleic acid tests is examined, along with the concept of residual risk. Finally, considerations in acquiring informed consent in the use of kidneys from IIRDs in children and young people are discussed.


Assuntos
Hepatite C , Falência Renal Crônica , Transplante de Rim , Adulto , Humanos , Criança , Adolescente , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Rim , Doadores Vivos , Falência Renal Crônica/etiologia
17.
Curr Opin Nephrol Hypertens ; 32(2): 204-211, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36633323

RESUMO

PURPOSE OF REVIEW: To summarize the current state of evidence related to the outcomes of older adults who need and receive kidney transplants, and strategies to facilitate appropriate transplant access in this at-risk group. RECENT FINDINGS: Older adults are a rapidly growing subgroup of the kidney transplant waitlist. Compared to younger adults, older kidney transplant recipients have increased mortality after kidney transplant and lower death-censored graft survival. In determining suitability for transplantation in older patients, clinicians must balance procedural and immunosuppression-related risk with incremental survival when compared with dialysis. To appropriately increase access to transplantation in this population, clinicians and policy makers consider candidates' chronological age and frailty, as well as the quality of and waiting time for a donated allograft. Given risk of deterioration prior to transplant, candidates should be rapidly evaluated, listed, and transplanted using living donor and or less than ideal deceased donor organs when available. SUMMARY: Access to transplantation for older adults can be increased through targeted interventions to address frailty and reduce waiting times through optimized organ use. Focused study and educational interventions for patients and providers are needed to improve the outcomes of this vulnerable group.


Assuntos
Fragilidade , Transplante de Rim , Humanos , Idoso , Transplante de Rim/efeitos adversos , Fragilidade/diagnóstico , Diálise Renal , Rim , Transplante Homólogo , Sobrevivência de Enxerto , Doadores de Tecidos
18.
BMC Med Genomics ; 16(1): 11, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658573

RESUMO

BACKGROUND: T cell-mediated rejection is an important factor affecting early transplant kidney survival. Ferroptosis has been shown to play a pathogenic role in a variety of diseases, which was not reported in TCMR. Here we developed a model for assessing activation of ferroptosis-related genes in TCMR to find a better screening method and explore the contribution of ferroptosis in TCMR. METHODS: We performed unsupervised consensus clustering according to expression of ferroptosis-related genes based on RNA-seq data from kidney transplant biopsies, and developed an assessment model characterized by ferroptosis gene expression through PCA, which was evaluated in multiple external datasets as well as blood and urine samples. Pathway enrichment and immune cell infiltration analysis were used to explore the possible targets and pathways involved in ferroptosis and TCMR. RESULTS: A ferroptosis gene expression scoring model was established. The diagnostic specificity and sensitivity of TCMR in renal biopsy samples were both over 80%, AUC = 0.843, and AUC was around 0.8 in multi-dataset validation, and was also close to 0.7 in blood and urine samples, while in predicting of graft survival at 3 years, scoring model had a good prognostic effect as well. Pathway enrichment and PPI network speculated that TLR4, CD44, IFNG, etc. may be the key genes of ferroptosis in TCMR. CONCLUSIONS: Ferroptosis scoring model could better diagnose TCMR and predict graft loss, and could be used as a potential screening method in blood and urine samples. We speculate that ferroptosis plays an important role in TCMR.


Assuntos
Ferroptose , Rejeição de Enxerto , Transplante de Rim , Biópsia , Ferroptose/genética , Rejeição de Enxerto/genética , Rim/patologia , Transplante de Rim/efeitos adversos , Linfócitos T/metabolismo
19.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674540

RESUMO

This study addresses a joint nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy approach to provide a platform for dynamic assessment of kidney viability and metabolism. On porcine kidney models, ROS production, oxidative damage kinetics, and metabolic changes occurring both during the period between organ retrieval and implantation and after kidney graft were examined. The 1H-NMR metabolic profile-valine, alanine, acetate, trimetylamine-N-oxide, glutathione, lactate, and the EPR oxidative stress-resulting from ischemia/reperfusion injury after preservation (8 h) by static cold storage (SCS) and ex vivo machine perfusion (HMP) methods were monitored. The functional recovery after transplantation (14 days) was evaluated by serum creatinine (SCr), oxidative stress (ROS), and damage (thiobarbituric-acid-reactive substances and protein carbonyl enzymatic) assessments. At 8 h of preservation storage, a significantly (p < 0.0001) higher ROS production was measured in the SCS vs. HMP group. Significantly higher concentration data (p < 0.05-0.0001) in HMP vs. SCS for all the monitored metabolites were found as well. The HMP group showed a better function recovery. The comparison of the areas under the SCr curves (AUC) returned a significantly smaller (-12.5 %) AUC in the HMP vs. SCS. EPR-ROS concentration (µmol·g-1) from bioptic kidney tissue samples were significantly lower in HMP vs. SCS. The same result was found for the NMR monitored metabolites: lactate: -59.76%, alanine: -43.17%; valine: -58.56%; and TMAO: -77.96%. No changes were observed in either group under light microscopy. In conclusion, a better and more rapid normalization of oxidative stress and functional recovery after transplantation were observed by HMP utilization.


Assuntos
Transplante de Rim , Animais , Suínos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Espécies Reativas de Oxigênio/metabolismo , Perfusão/métodos , Rim/metabolismo , Estresse Oxidativo , Lactatos/metabolismo , Metaboloma , Alanina/metabolismo
20.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674775

RESUMO

The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.


Assuntos
Microbioma Gastrointestinal , Transplante de Rim , Viroses , Humanos , Rim , Transplante de Rim/efeitos adversos , Imunossupressores , Bactérias
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