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1.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674142

RESUMO

The gradual deterioration of articular cartilage was thought to be the central event in osteoarthritis (OA), but recent studies demonstrated the importance of low-grade synovitis in the progression of OA. The Syndecan (SDC) family of membrane proteoglycans is known to be involved in the regulation of inflammation, but there is limited evidence considering the role of syndecans in OA synovitis. Our study aimed to investigate the hip OA synovial membrane expression patterns of SDC1, SDC2 and SDC4, as well as exostosins and sulfotransferases (enzymes involved in the polymerisation and modification of syndecans' heparan sulphate chains). Synovial membrane samples of patients with OA (24) were divided into two groups according to their Krenn synovitis score severity. The immunohistochemical expressions of SDC1, SDC2, SDC4, EXT1, EXT2, NDST1 and NDST2 in synovial intima and subintima were then analysed and compared with the control group (patients with femoral neck fracture). According to our study, the immunoexpression of SDC1, NDST1 and EXT2 is significantly increased in the intimal cells of OA synovial membrane in patients with lower histological synovitis scores and SDC4 in patients with higher synovitis scores, in comparison with non-OA controls. The difference in the expression of SDC2 among the OA and non-OA groups was insignificant. SDC1, SDC4, NDST1 and EXT2 seem to be involved as inflammation moderators in low-grade OA synovitis and, therefore, should be further investigated as potential markers of disease progression and therapeutic goals.


Assuntos
Biomarcadores , Osteoartrite do Quadril , Sulfotransferases , Sindecanas , Sinovite , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inflamação/metabolismo , Inflamação/patologia , N-Acetilglucosaminiltransferases , Osteoartrite do Quadril/metabolismo , Osteoartrite do Quadril/patologia , Sulfotransferases/metabolismo , Sindecanas/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Sinovite/metabolismo , Sinovite/patologia , Biomarcadores/análise
2.
Kidney Blood Press Res ; 48(1): 505-514, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37307795

RESUMO

INTRODUCTION: Posttransplant anemia (PTA) is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of PTA with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. METHODS: We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our center. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis (AH), vascular fibrous intimal thickening (CV), interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. RESULTS: The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and PTA in both time points, independently from estimated glomerular filtration rate. AH and interstitial fibrosis were identified as independent risk factors for anemia 6 months after transplantation. CONCLUSION: Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA.


Assuntos
Anemia , Rim , Humanos , Estudos Retrospectivos , Rim/patologia , Fibrose , Sobrevivência de Enxerto , Biópsia , Anemia/etiologia , Atrofia
3.
Clin Transplant ; 36(4): e14572, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34967958

RESUMO

INTRODUCTION: Data on post-COVID-19 in renal transplant recipients (RTR) is scarce. We investigated the rate of hospitalizations, reasons for hospital admission, and mortality rate among RTR who survived acute COVID-19. METHODS: A multi-center retrospective observational cohort study measured hospital admission and death to 180 days after acute SARS-CoV-2 infection in 308 adult patients. RESULTS: The median age was 57 years, 64.9% were male. All patients had at least one comorbidity, and 26.3% had diabetes. Data on post-COVID-19 course was available for 267 patients, and 49 of them (15.9%) required hospital treatment after recovery from the acute infection. The most common indications included pneumonia (24.5%) and renal allograft dysfunction (22.4%), 7 (14.3%) had sepsis and 5 (10.2%) had thrombotic events. A median duration of the hospital stay was 12 days. Six patients (2.2%) died due to multiorgan failure, respiratory insufficiency or urosepsis. The strongest predictor for hospitalization after acute COVID-19 was hospitalization for acute SARS-CoV-2 infection, while better allograft function decreased the probability of hospitalization. CONCLUSION: Delayed consequences of acute COVID-19 are highly prevalent and the health care systems should be prepared to respond to the needs of RTR suffering from post-COVID-19 complications.


Assuntos
COVID-19 , Transplante de Rim , Sepse , Adulto , COVID-19/epidemiologia , Comorbidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Transplantados
4.
Kidney Int ; 99(1): 186-197, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781106

RESUMO

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.


Assuntos
Falência Renal Crônica , Transplante de Rim , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Estudos Prospectivos
5.
Clin Transplant ; 35(12): e14486, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34532893

RESUMO

Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.


Assuntos
Injúria Renal Aguda , COVID-19 , Transplante de Rim , Aloenxertos , Biópsia , Rejeição de Enxerto/etiologia , Humanos , Rim , Transplante de Rim/efeitos adversos , Nefrectomia , SARS-CoV-2
6.
Acta Clin Croat ; 60(Suppl 3): 39-44, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36404998

RESUMO

Epilepsy is one of the most prevalent chronic neurological diseases, affecting about 70 million people worldwide. Patients with epilepsy often encounter cognitive dysfunction, which is influenced by different factors including age at the onset of epilepsy, etiology of epilepsy, type of seizures, seizure frequency and duration, psychiatric comorbidity, and antiepileptic drug (AED) therapy. Event-related potentials are useful, noninvasive, objective clinical and research instrument for evaluation of cognitive functions in patients. The aim of this study was to investigate and determine the effect of AED monotherapy and polytherapy on cognitive changes in patients with epilepsy, detected with P300 event-related potentials and compared with age- and gender-matched healthy individuals. The study was conducted in 82 patients with generalized and focal epilepsy and 82 healthy individuals aged 18-65 years. Cognitive evoked P300 potentials were recorded in all study subjects using auditory 'oddball' paradigm. The results showed the patients taking AED polytherapy to have a significantly longer P300 latency and significantly lower N200-P300 amplitude. These results indicate that AED polytherapy might worsen cognitive impairment in patients with epilepsy.


Assuntos
Anticonvulsivantes , Epilepsia , Humanos , Anticonvulsivantes/efeitos adversos , Potenciais Evocados P300/fisiologia , Epilepsia/tratamento farmacológico , Cognição/fisiologia
7.
Transpl Infect Dis ; 22(4): e13341, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32453874

RESUMO

BACKGROUND: The aim of this study is to determine the incidence, etiology, clinical characteristics, and outcomes of renal transplant recipients diagnosed and treated for central nervous system (CNS) infection at our institution. METHODS: We analyzed data from all renal transplant recipients between January 2007 and December 2019 that were diagnosed and treated for CNS infections at our institution. RESULTS: Of 1374 patients who received renal allografts, 13 were diagnosed with CNS infections (9 males), with a mean age of 53.5 years. Patients were diagnosed with CNS infections between 2 months and 11 years after the transplantation. Causative agents included JC virus, Streptococcus pneumoniae, Cryptococcus neoformans, Herpes zoster virus, Mycobacterium tuberculosis, Listeria monocytogenes, and West Nile virus. One patient had concomitant Nocardia and Neisseria infection. Immunosuppression was reduced in all patients. The patient with JC encephalitis and the patient with concomitant Neisseria and Nocardia meningitis died. One patient was returned to dialysis. Other patients recovered with differing levels of neurologic sequelae. CONCLUSION: Central nervous system infections in renal transplant recipients are rare. However, they are associated with significant morbidity and mortality. A high level of awareness is needed: neurological symptoms may be nonspecific and caused by non-infectious conditions related to the underlying disease, or side-effects of immunosuppressive drugs.


Assuntos
Infecções Bacterianas do Sistema Nervoso Central/epidemiologia , Infecções do Sistema Nervoso Central/epidemiologia , Viroses do Sistema Nervoso Central/epidemiologia , Transplante de Rim/efeitos adversos , Transplantados/estatística & dados numéricos , Adulto , Idoso , Infecções Bacterianas do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/diagnóstico , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
9.
World J Clin Cases ; 12(6): 1104-1110, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38464928

RESUMO

BACKGROUND: Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. AIM: To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. METHODS: A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. RESULTS: Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. CONCLUSION: Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

10.
J Chemother ; : 1-5, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741515

RESUMO

Two Enterobacter hormaechei isolates harbouring three carbapenemase genes each, were isolated from two patients from different ICUs at University Hospital Centre Zagreb, Croatia, which is to our knowledge, the first report of triple carbapenemase (blaVIM-2, blaNDM-1, and blaOXA-48) co-existence in E. hormachei strains and also among Enterobacterales members in Croatia. Antimicrobial susceptibility testing showed susceptibility only to colistin and amikacin. The production of carbapenemases was phenotypically tested by immunochromatographic assay and confirmed by PCR. Detailed analysis by Whole Genome Sequencing (WGS) of short reads by Illumina and long reads by Oxford Nanopore Technologies (ONT) was additionally performed and showed that both isolates belonged to ST200. They were separated by 98 Single Nucleotide Polymorphisms (SNPs) having variations in the number of blaVIM-2 genes on the chromosome, the number of blaNDM-1 genes on the plasmid, non-identical blaNDM-1 plasmids, different plasmid content in general, and only one isolate carried a 94 kb prophage.

11.
J Clin Med ; 13(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38673655

RESUMO

Background/Objectives: The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to cause an unusual immunological dysregulation triggering alloimmunity and leading to graft rejection. Methods: This prospective observational cohort study assessed 321 kidney transplant recipients who had COVID-19 infection. After the infection, patients' sera were tested for the presence of anti-HLA de novo DSA and non-DSA specificities. Logistic regression analysis and a stepwise multivariable logistic regression analysis were used to analyze the independent risk factors associated with the development of antibodies, adjusting for known confounders. The variables evaluated were acute COVID-19 characteristics (i.e., presentation, and need for hospitalization), demographic characteristics (i.e., age, gender, and primary renal disease), clinical characteristics (i.e., various comorbidities), and post-COVID-19 sequelae. Results: Anti-HLA de novo DSA developed in 18.7% of patients, while anti-HLA class I and class II non-DSA antibodies developed de novo in 84 (26.3%) and 83 (25.9%) patients, respectively. The development of DSA, HLA-DQ, and HLA-DR antibodies was predicted by the history of graft rejection. Obesity appeared to be protective against the emergence of de novo DSA. De novo DSA and HLA-DR antibody formation was positively linked with intravenous immunoglobulin use, CMV-hyperimmune globulin use, and decreased doses of immunosuppression during acute infection. Better allograft function during the acute disease was a protective factor against the formation of HLA-DQ and HLA-DR antibodies. Positive predictors of de novo DSA development were graft biopsy and the reactivation of EBV after infection. Conclusions: These findings suggest that the SARS-CoV-2 virus has an immunomodulatory effect and may be associated with an increased mortality in this population.

12.
J Clin Med ; 13(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38929894

RESUMO

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.

13.
Nat Commun ; 15(1): 554, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228634

RESUMO

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.


Assuntos
Nefropatias , Transplante de Rim , Humanos , Rim/patologia , Transplante Homólogo , Nefropatias/patologia , Biópsia
14.
Kidney Blood Press Res ; 37(1): 9-14, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23445870

RESUMO

Primary cardiac hemangioma is a very rare benign vascular tumor, with valvular hemangiomas being even less frequent as valves are generally avascular structures. We present the first case of mitral valve hemangioma in a renal transplant recipient. Patient presented with progressive dyspnea. Transesophageal echocardiogram (TEE) demonstrated a 0.8x0.9-cm pedunculated tumor mass on the posterior leaflet of the mitral valve. Coronary angiography identified a small artery which filled from the circumflex artery and fed the tumor. The tumor was surgically removed. Histopathological examination revealed a hemangioma. The postoperative course was uneventful with stable graft function.


Assuntos
Dispneia/diagnóstico , Neoplasias Cardíacas/diagnóstico , Hemangioma/diagnóstico , Transplante de Rim/efeitos adversos , Valva Mitral/patologia , Complicações Pós-Operatórias/diagnóstico , Progressão da Doença , Dispneia/etiologia , Feminino , Neoplasias Cardíacas/complicações , Hemangioma/complicações , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
15.
Transplant Proc ; 55(2): 342-345, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36822885

RESUMO

BACKGROUND: The aim of this case study was to explore the possible link between viral infections and collapsing focal segmental glomerulosclerosis (cFSGS) in patients who underwent kidney transplantation. METHODS: This case study included 3 case reports of patients who underwent kidney transplantation. The case reports were presented clinically and pathohistologically with cFsGS as a possible consequence of viral infections. RESULTS: The first patient developed cFSGS after polymerase chain reaction for SARS-CoV2 was positive twice. He gradually developed terminal stage chronic kidney disease. The second patient developed cFSGS with high range proteinuria after cytomegalovirus infection, which has been treated with 3 lines of antiviral medicaments. The third patient developed cFSGS as a possible consequence of hepatitis B virus infection. CONCLUSIONS: This case study highlighted the importance of viral etiology in the pathway of cFSGS. Pathogenic links between viral infections and concomitant glomerulopathies are challenging, especially in immunocompromised transplanted patients.


Assuntos
COVID-19 , Glomerulosclerose Segmentar e Focal , Transplante de Rim , Masculino , Humanos , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/patologia , Transplante de Rim/efeitos adversos , RNA Viral , COVID-19/complicações , SARS-CoV-2 , Proteinúria/etiologia
16.
Ther Apher Dial ; 27(5): 882-889, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37217275

RESUMO

OBJECTIVES: In this study, we investigated whether SARS-CoV-2 stimulates autoantibody production. METHODS: The study included 91 patients hospitalized due to COVID 19, with no previous history of immunological diseases. Immunofluorescence assays were performed to detect antinuclear antibodies (ANAs) and antineutrophil cytoplasmic antibodies (ANCAs), along with tests for specific autoantibodies. RESULTS: The median age (57% male) was 74 years (range 38-95 years). Autoantibodies were positive in 67 (74%), ANA in 65 (71%), and ANCA in 11 (12%) patients. Female gender (p = 0.01), age (p = 0.005), and Charlson comorbidity index (p = 0.004) were significant predictors for the development of ANA/ANCA antibodies (p = 0.004). Nuclear mitotic apparatus (NuMA)-like, positivity was the strongest predictor of acute kidney injury (AKI), together with noninvasive ventilation and eGFR (χ2 = 49.01, P < 0.001). CONCLUSION: Positive autoantibodies in a large proportion of patients suggest a role of autoimmunity in the pathophysiology of acute COVID-19 disease. NuMA was the strongest predictor of AKI.


Assuntos
Injúria Renal Aguda , COVID-19 , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos , Anticorpos Anticitoplasma de Neutrófilos , SARS-CoV-2
17.
BMJ Open Ophthalmol ; 8(Suppl 2): A13, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37604564

RESUMO

PURPOSE: Possible transmission of SARS-CoV-2 from donors to recipients via cornea grafts is still a concern of the transplantation community. Current recommendations are to avoid corneal transplants from donors with ongoing SARS-CoV-2 infection or those recently exposed to it. During pandemic period in Croatia 21/1113; (1,9%) corneas were procured from donors positive for SARS-CoV-2 by postmortem nasopharyngeal swab tests. That tissue was discarded. Due to the lack of knowledge about the infectivity of such corneas, we started prospective study of SARS-CoV-2 presence in cornea tissue. Here we show our first results. METHODS: In the study period we had four corneas procured from two post-mortem SARS-CoV-2 positive donors. For the presence of SARS-CoV-2, analysis is performed on donor serum, hypothermic storage medium and cornea tissue lysate. Corneas were stored in hypothermic condition for 8 to 10 days, after which tissue was macerated and washed with PBS. The intracellular content was released by incubation with lysis buffer, followed by centrifugation. Next, tissue lysate, serum and hypothermic storage medium were in parallel subjected to fully automated nucleic acid isolation and RNA expression was analyzed by qRT-PCR. During isolation, RNasaP was used as internal control for successful nucleic acids isolation. RESULTS: No SARS-CoV-2 RNA was detected in the donors serum, storage medium and cornea tissue from donors who were SARS-CoV-2-positive upon tissue procurement. In nasopharyngeal swabs of post mortem positive donors cycle threshold values of viral copies were high (CT>34), indicating that there was small number of viral particles in infected donors that could have impact on negative results in tested tissue. CONCLUSION: Our data suggested that corneas may not be SARS-CoV-2 permissive if the donor was postmortem positive. Further research is required to gain more coherent insight into SARS-CoV-2 transmission via corneal transplantation.


Assuntos
COVID-19 , Vacinas Anticâncer , Humanos , SARS-CoV-2/genética , Reação em Cadeia da Polimerase em Tempo Real , COVID-19/diagnóstico , Estudos Prospectivos , Córnea , Teste para COVID-19
18.
Int Urol Nephrol ; 55(2): 477-482, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36030358

RESUMO

PURPOSE: The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease. METHODS: This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods. RESULTS: This study enrolled 48 patients with a median age of 32.3 years (range, 18-46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis-83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (p-0.033 and 0.03, respectively). CONCLUSION: Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.


Assuntos
Angiomiolipoma , Hamartoma , Falência Renal Crônica , Insuficiência Renal Crônica , Dermatopatias , Esclerose Tuberosa , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Esclerose Tuberosa/complicações , Esclerose Tuberosa/epidemiologia , Inibidores de MTOR , Estudos Retrospectivos , Hamartoma/complicações , Falência Renal Crônica/etiologia , Falência Renal Crônica/complicações , Angiomiolipoma/complicações , Angiomiolipoma/patologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia
19.
BMJ ; 381: e073654, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37257905

RESUMO

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.


Assuntos
Transplante de Rim , Insuficiência Renal Crônica , Adulto , Humanos , Taxa de Filtração Glomerular , Creatinina , Rim , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/cirurgia , Insuficiência Renal Crônica/epidemiologia
20.
Acta Med Croatica ; 66 Suppl 2: 22-36, 2012 Oct.
Artigo em Servo-Croata (Latino) | MEDLINE | ID: mdl-23513413

RESUMO

The balance and quality of different renal replacement treatment modalities used in the elderly with end-stage renal disease vary between countries depending on economic resources, distribution of renal units, number of specialists, and patterns of reimbursement of both hospitals and physicians. Elderly patients with end-stage renal disease need detailed assessment of medical, psychological, motor, and social factors in order to choose an appropriate renal replacement treatment option. Presence or absence of significant comorbidity is much more important than the chronological age. The choice between hemodialysis and continuous ambulatory peritoneal dialysis is largely dependant on preferences of the local team and the patient. Patients with adequate cardiovascular systems are generally considered to be more suitable for hemodialysis. Hemoglobin should be optimized (Hb between 100 and 120 g/L) in all patients. Poor cardiac status and/or angina will require assessment, medical treatment, and, if necessary, surgical treatment or angioplasty. Transplantation should be considered in all reasonably fit and carefully selected patients older than 65 or even 70 years. Only the permanent shortage of suitable kidneys limits our ability to treat all those who could benefit from this type of treatment. Renal transplant recipients may benefit in terms of both survival and quality of life even if older than 70 years and beyond. Immunosuppressive therapy in elderly patients should be moderate.


Assuntos
Falência Renal Crônica/terapia , Idoso , Humanos , Terapia de Substituição Renal
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