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2.
Obes Facts ; 17(1): 98-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38043514

RESUMO

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients.


Assuntos
Injúria Renal Aguda , Cirurgia Bariátrica , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Rim , Cirurgia Bariátrica/efeitos adversos , Obesidade/complicações , Injúria Renal Aguda/complicações
3.
Transpl Int ; 36: 11244, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448448

RESUMO

Imlifidase recently received early access authorization for highly sensitized adult kidney transplant candidates with a positive crossmatch against an ABO-compatible deceased donor. These French consensus guidelines have been generated by an expert working group, in order to homogenize patient selection, associated treatments and follow-up. This initiative is part of an international effort to analyze properly the benefits and tolerance of this new costly treatment in real-life. Eligible patients must meet the following screening criteria: cPRA ≥ 98%, ≤ 65-year of age, ≥ 3 years on the waiting list, and a low risk of biopsy-related complications. The final decision to use Imlifidase will be based on the two following criteria. First, the results of a virtual crossmatch on recent serum, which shall show a MFI for the immunodominant donor-specific antibodies (DSA) > 6,000 but the value of which does not exceed 5,000 after 1:10 dilution. Second, the post-Imlifidase complement-dependent cytotoxicity crossmatch must be negative. Patients treated with Imlifidase will receive an immunosuppressive regimen based on steroids, rATG, high dose IVIg, rituximab, tacrolimus and mycophenolic acid. Frequent post-transplant testing for DSA and systematic surveillance kidney biopsies are highly recommended to monitor post-transplant DSA rebound and subclinical rejection.


Assuntos
Transplante de Rim , Adulto , Humanos , Pré-Escolar , Transplante de Rim/métodos , Teste de Histocompatibilidade/métodos , Antígenos HLA , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Anticorpos , Isoanticorpos
4.
Nat Med ; 29(5): 1211-1220, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37142762

RESUMO

For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.05% male and 37.95% female) followed in 20 transplant referral centers in Europe and North America. In the adult kidney transplant population, the Banff Automation System reclassified 83 out of 279 (29.75%) antibody-mediated rejection cases and 57 out of 105 (54.29%) T cell-mediated rejection cases, whereas 237 out of 3,239 (7.32%) biopsies diagnosed as non-rejection by pathologists were reclassified as rejection. In the pediatric population, the reclassification rates were 8 out of 26 (30.77%) for antibody-mediated rejection and 12 out of 39 (30.77%) for T cell-mediated rejection. Finally, we found that reclassification of the initial diagnoses by the Banff Automation System was associated with an improved risk stratification of long-term allograft outcomes. This study demonstrates the potential of an automated histological classification to improve transplant patient care by correcting diagnostic errors and standardizing allograft rejection diagnoses.ClinicalTrials.gov registration: NCT05306795 .


Assuntos
Transplante de Rim , Rim , Adulto , Humanos , Masculino , Feminino , Criança , Estudos Prospectivos , Rim/patologia , Transplante de Rim/efeitos adversos , Transplante Homólogo , Aloenxertos , Rejeição de Enxerto/diagnóstico , Biópsia
6.
Kidney Int ; 103(6): 1167-1179, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36990211

RESUMO

We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA. From 441 patients with protocol biopsy, there was a significant decrease of the score of tolerance in 45 patients with biopsy-proven subclinical rejection (SCR), a major threat associated with pejorative allograft outcomes that prompted an SCR score refinement. This refinement used only two genes, AKR1C3 and TCL1A, and four clinical parameters (previous experience of rejection, previous transplantation, sex of recipient and tacrolimus uptake). This refined SCR score was able to identify patients unlikely to develop SCR with a C-statistic of 0.864 and a negative predictive value of 98.3%. The SCR score was validated in an external laboratory, with two methods (qPCR and NanoString), and on 447 patients from an independent and multicenter cohort. Moreover, this score allowed reclassifying patients with discrepancies between the DSA presence and the histological diagnosis of antibody mediated rejection unlike kidney function. Thus, our refined SCR score could improve detection of SCR for closer and noninvasive monitoring, allowing early treatment of SCR lesions notably for patients DSA-positive and during lowering of immunosuppressive treatment.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Imunossupressores/uso terapêutico , Anticorpos , Tacrolimo/uso terapêutico , Soro Antilinfocitário , Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/genética , Isoanticorpos , Estudos Retrospectivos
7.
Nephrol Dial Transplant ; 38(1): 106-118, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36002032

RESUMO

BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.


Assuntos
Insuficiência Renal Crônica , Feminino , Humanos , Masculino , África , Brasil , Creatinina , Europa (Continente) , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , População Branca , População Negra
8.
Kidney360 ; 3(11): 1924-1933, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36514413

RESUMO

Background: Fibrosis progression is a major prognosis factor in kidney transplantation. Its assessment requires an allograft biopsy, which remains an invasive procedure at risk of complications. Methods: We assessed renal stiffness by magnetic resonance elastography (MRE) as a surrogate marker of fibrosis in a prospective cohort of kidney transplant recipients compared with the histologic gold standard. Interstitial fibrosis was evaluated by three methods: the semi-quantitative Banff ci score, a visual quantitative evaluation by a pathologist, and a computer-assisted quantitative evaluation. MRE-derived stiffness was assessed at the superior, median, and inferior poles of the allograft. Results: We initially enrolled 73 patients, but only 55 had measurements of their allograft stiffness by MRE before an allograft biopsy. There was no significant correlation between MRE-derived stiffness at the biopsy site and the ci score (ρ=-0.25, P=0.06) or with the two quantitative assessments (pathologist: ρ=-0.25, P=0.07; computer assisted: ρ=-0.21, P=0.12). We observed negative correlations between the stiffness of both the biopsy site and the whole allograft, with either the glomerulosclerosis percentage (ρ=-0.32, P=0.02 and ρ=-0.31, P=0.02, respectively) and the overall nephron fibrosis percentage, defined as the mean of the percentages of glomerulosclerosis and interstitial fibrosis (ρ=-0.30, P=0.02 and ρ=-0.28, P=0.04, respectively). At patient level, mean MRE-derived stiffness was similar across the three poles of the allograft (±0.25 kPa). However, a high variability of mean stiffness was found between patients, suggesting a strong influence of confounding factors. Finally, no significant correlation was found between mean MRE-derived stiffness and the slope of eGFR (P=0.08). Conclusions: MRE-derived stiffness does not directly reflect the extent of fibrosis in kidney transplantation.


Assuntos
Técnicas de Imagem por Elasticidade , Transplante de Rim , Humanos , Técnicas de Imagem por Elasticidade/métodos , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Fibrose , Biomarcadores
9.
Transpl Infect Dis ; 24(6): e13977, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36271650

RESUMO

The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or hematopoietic stem cell transplantation. This review provides an overview of the presentations given by the expert faculty, supplemented with educational clinical cases. Topics discussed include CMV epidemiology and diagnosis, the burden of CMV infection and disease, CMV-specific immunity and management of CMV in transplant settings. Major advances in the prevention and treatment of CMV in the past decade and increased understanding of CMV immunity have led to improved patient outcomes. In the future, management algorithms may be individualized based on the transplant recipient's immune profile, which will mark the start of a new era for patients with CMV.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Transplante de Pulmão , Transplante de Órgãos , Humanos , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Transplante de Órgãos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais/uso terapêutico
10.
Sci Transl Med ; 14(663): eabg1046, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130013

RESUMO

The generation of antibodies against donor-specific major histocompatibility complex (MHC) antigens, a type of donor-specific antibodies (DSAs), after transplantation requires that recipient's allospecific B cells receive help from T cells. The current dogma holds that this help is exclusively provided by the recipient's CD4+ T cells that recognize complexes of recipient's MHC II molecules and peptides derived from donor-specific MHC alloantigens, a process called indirect allorecognition. Here, we demonstrated that, after allogeneic heart transplantation, CD3ε knockout recipient mice lacking T cells generate a rapid, transient wave of switched alloantibodies, predominantly directed against MHC I molecules. This is due to the presence of donor CD4+ T cells within the graft that recognize intact recipient's MHC II molecules expressed by B cell receptor-activated allospecific B cells. Indirect evidence suggests that this inverted direct pathway is also operant in patients after transplantation. Resident memory donor CD4+ T cells were observed in perfusion liquids of human renal and lung grafts and acquired B cell helper functions upon in vitro stimulation. Furthermore, T follicular helper cells, specialized in helping B cells, were abundant in mucosa-associated lymphoid tissue of lung and intestinal grafts. In the latter, more graft-derived passenger T cells correlated with the detection of donor T cells in recipient's circulation; this, in turn, was associated with an early transient anti-MHC I DSA response and worse transplantation outcomes. We conclude that this inverted direct allorecognition is a possible explanation for the early transient anti-MHC DSA responses frequently observed after lung or intestinal transplantations.


Assuntos
Formação de Anticorpos , Isoanticorpos , Animais , Rejeição de Enxerto , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , Humanos , Isoantígenos , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos , Receptores de Antígenos de Linfócitos B
11.
Nephrol Ther ; 18(3): 195-201, 2022 Jun.
Artigo em Francês | MEDLINE | ID: mdl-35241379

RESUMO

INTRODUCTION: Iron deficiency is common and associated with worse outcomes in patients with non-dialysis chronic kidney disease. We performed a national, multicentre, observational and transversal study to assess the prevalence of iron deficiency as well as current iron deficiency screening practices in this population. PATIENTS AND METHODS: A total of 25 nephrology centres in France participated in the study. All adult non-dialysis chronic kidney disease patients who met the inclusion (GFR>15mL/min/1.73m2) and exclusion criteria and provided consent were systematically recruited over a 4-week inclusion period. Investigators were asked to perform a blood test (hemoglobin concentration, serum iron, serum ferritin and transferrin saturation) and to complete a questionnaire about their iron status monitoring practices. The primary objective was to assess the prevalence of iron deficiency (serum ferritin<100µg/L and/or transferrin saturation<20%). Secondary objectives were to evaluate the prevalence of absolute iron deficiency (serum ferritin<100µg/L and transferrin saturation<20%) and functional iron deficiency (serum ferritin≥100µg/L and transferrin saturation<20%), the prevalence of iron deficiency according to haemoglobin concentration and chronic kidney disease stage, the proportion of centres that perform routine evaluation of iron status and the number of patients receiving iron supplementation. RESULTS: A total of 1211 patients with non-dialysis chronic kidney disease were included in the analysis. The overall prevalence of iron deficiency was 47.1%. The rates of absolute iron deficiency and functional iron deficiency and anaemia were 13.4% and 17.1%, respectively. Among the 25 participating centres, 12 reported routine assessment of iron status in non-dialysis chronic kidney disease patients. CONCLUSION: In this observational study, a high prevalence of iron deficiency was observed among non-dialysis chronic kidney disease patients. Less than half of participating centres reported routine assessment of iron status.


Assuntos
Anemia Ferropriva , Deficiências de Ferro , Insuficiência Renal Crônica , Adulto , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/etiologia , Ferritinas , Humanos , Ferro , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Transferrinas
12.
Am J Transplant ; 22(3): 865-875, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34863025

RESUMO

The pathogenicity of de novo donor-specific antibodies (dnDSA) varies according to their characteristics. While their MFI, complement-fixing ability, and IgG3 subclass are associated with ABMR occurrence and graft loss, they are not fully predictive of outcomes. We investigated the role of the Fc glycosylation of IgG3 dnDSA in ABMR occurrence using mass spectrometry after isolation by single HLA antigen beads. Between 2014 and 2018, we enrolled 54 patients who developed dnDSA (ABMR- n = 24; ABMR+ n = 30) in two French transplant centers. Fucosylation, galactosylation, GlcNAc bisection, and sialylation of IgG3 dnDSA were compared between ABMR+ and ABMR- patients. IgG3 dnDSA from ABMR+ patients exhibited significantly lower sialylation (7.5% vs. 10.5%, p < .001) and higher GlcNAc bisection (20.6% vs. 17.4%, p = .008). Fucosylation and galactosylation were similar in both groups. DSA glycosylation was not correlated with DSA MFI. In a multivariate analysis, low IgG3 sialylation, high IgG3%, time from transplantation to kidney biopsy, and tacrolimus-free regimen were independent predictive factors of ABMR. We conclude that a proinflammatory glycosylation profile of IgG3 dnDSA is associated with a risk of ABMR occurrence. Further studies are needed to confirm the clinical interest of DSA glycosylation and to clarify its role in determining the risk of ABMR and graft survival.


Assuntos
Transplante de Rim , Glicosilação , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Imunoglobulina G , Isoanticorpos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
13.
Clin Chem Lab Med ; 60(3): 401-407, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-34670031

RESUMO

OBJECTIVES: Most data on glomerular filtration rate (GFR) originate from subjects <65 years old, complicating decision-making in elderly living kidney donors. In this retrospective multi-center study, we calculated percentiles of measured GFR (mGFR) in donors <65 years old and extrapolated these to donors ≥65 years old. METHODS: mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors <65 years (n=1,983), using quantiles modeled as cubic splines (two linear parts joining at 40 years). Percentiles were extrapolated and validated in an internal cohort of donors ≥65 years (n=147, France) and external cohort of donors and healthy subjects ≥65 years (n=329, Germany, Sweden, Norway, France, The Netherlands) by calculating percentages within the extrapolated 5th-95th percentile (P5-P95). RESULTS: Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5-P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5-P95. CONCLUSIONS: We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.


Assuntos
Transplante de Rim , Idoso , Creatinina , Taxa de Filtração Glomerular , Humanos , Rim , Doadores Vivos , Estudos Retrospectivos
14.
Br J Clin Pharmacol ; 88(5): 2118-2127, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34709683

RESUMO

AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages. RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR <60 mL/min and at BMI 18.5-25 kg/m2 , all equations performed similarly, and for BMI < 18.5 kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2 ). The four more recent equations also classified mGFR stages better than CG. CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.


Assuntos
Insuficiência Renal Crônica , Índice de Massa Corporal , Creatinina , Estudos Transversais , Taxa de Filtração Glomerular , Humanos
15.
Nat Rev Nephrol ; 17(12): 795-813, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34446934

RESUMO

Unconventional T cells are a diverse and underappreciated group of relatively rare lymphocytes that are distinct from conventional CD4+ and CD8+ T cells, and that mainly recognize antigens in the absence of classical restriction through the major histocompatibility complex (MHC). These non-MHC-restricted T cells include mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, γδ T cells and other, often poorly defined, subsets. Depending on the physiological context, unconventional T cells may assume either protective or pathogenic roles in a range of inflammatory and autoimmune responses in the kidney. Accordingly, experimental models and clinical studies have revealed that certain unconventional T cells are potential therapeutic targets, as well as prognostic and diagnostic biomarkers. The responsiveness of human Vγ9Vδ2 T cells and MAIT cells to many microbial pathogens, for example, has implications for early diagnosis, risk stratification and targeted treatment of peritoneal dialysis-related peritonitis. The expansion of non-Vγ9Vδ2 γδ T cells during cytomegalovirus infection and their contribution to viral clearance suggest that these cells can be harnessed for immune monitoring and adoptive immunotherapy in kidney transplant recipients. In addition, populations of NKT, MAIT or γδ T cells are involved in the immunopathology of IgA nephropathy and in models of glomerulonephritis, ischaemia-reperfusion injury and kidney transplantation.


Assuntos
Nefropatias , Células T Invariantes Associadas à Mucosa , Células T Matadoras Naturais , Linfócitos T CD8-Positivos , Humanos
16.
Sci Immunol ; 6(61)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330813

RESUMO

Human γδ T cells contribute to tissue homeostasis and participate in epithelial stress surveillance through mechanisms that are not well understood. Here, we identified ephrin type-A receptor 2 (EphA2) as a stress antigen recognized by a human Vγ9Vδ1 TCR. EphA2 is recognized coordinately by ephrin A to enable γδ TCR activation. We identified a putative TCR binding site on the ligand-binding domain of EphA2 that was distinct from the ephrin A binding site. Expression of EphA2 was up-regulated upon AMP-activated protein kinase (AMPK)-dependent metabolic reprogramming of cancer cells, and coexpression of EphA2 and active AMPK in tumors was associated with higher CD3 T cell infiltration in human colorectal cancer tissue. These results highlight the potential of the human γδ TCR to cooperate with a co-receptor to recognize non-MHC-encoded proteins as signals of cellular dysregulation, potentially allowing γδ T cells to sense metabolic energy changes associated with either viral infection or cancer.


Assuntos
Proteínas Quinases Ativadas por AMP/imunologia , Antígenos/imunologia , Linfócitos Intraepiteliais/imunologia , Neoplasias/imunologia , Receptor EphA2/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Proteínas Quinases Ativadas por AMP/genética , Animais , Anticorpos Monoclonais/imunologia , Linhagem Celular , Humanos , Camundongos Knockout , Receptores de Antígenos de Linfócitos T gama-delta/genética
17.
Pediatr Nephrol ; 36(10): 3159-3168, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33895898

RESUMO

BACKGROUND: A precise assessment of glomerular filtration rate is key to delineate the care of children with a solitary functioning kidney (SFK). Data regarding measured GFR (mGFR) in this population is restricted to a single study of 77 individuals, which suggested that a GFR estimation (eGFR) method based on creatinine and cystatin C (eGFR-CKiD2) performed better than Schwartz's equation (eGFR-Schwartz). METHODS: We measured GFR in 210 consecutive adolescents (7 to 22 years old) with an SFK referred to our institution between 2014 and 2019 and in 43 young candidates for kidney donation (18 to 25 years old). We compared the distribution of mGFR in both groups and determined the factors associated with reduced mGFR in adolescents with an SFK. We further compared different eGFR formulas with mGFR and assessed the association of mGFR and eGFRs with PTH and FGF23, two early indicators of GFR reduction. RESULTS: While adolescents with an SFK had a similar median mGFR to healthy controls (103 ± 24ml/min/1.73m2 vs. 107 ± 12 ml/min/1.73m2), the fraction of individuals with an mGFR below 90 ml/min/1.73m2 was higher in patients with SFK (23% vs. 5% in controls; P = 0.005). Multiple linear regression identified older age, ipsilateral abnormalities of the urinary tract, lack of compensatory hypertrophy, and treated hypertension as independent factors associated with reduced mGFR. A smaller bias using eGFR-Schwartz (95% confidence interval (95%CI): 3 to 7) was revealed when compared to other eGFR. Compared to eGFR-Schwartz, mGFR showed a stronger correlation with PTH (r = 0.04 vs. r = 0.1) and FGF23 (r = 0.03 vs. r = 0.05). CONCLUSION: SFK is not a benign condition, since 20% of the patients display altered kidney function. Our results raise caution regarding the use of the cystatin-based equation. mGFR shows a better ability than eGFR-Schwartz to differentiate patients showing early homeostatic adaptation to GFR reduction.


Assuntos
Rim/fisiologia , Rim Único , Adolescente , Adulto , Idoso , Criança , Creatinina , Receptores ErbB , Taxa de Filtração Glomerular , Humanos , Adulto Jovem
18.
Transpl Int ; 34(6): 1123-1133, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33774875

RESUMO

Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is <90 ml/min/1.73 m2 (KDIGO guidelines) or 80 ml/min/1.73 m2 (most US centres). However, age-related GFR decline results in a lower eGFR for older candidates. That may limit the number of older kidney donors. Yet, continuing the screening with a GFR measure increases the number of eligible donors. We hypothesized that in-depth screening should be proposed to all candidates with a normal eGFR for age. We compared the evolution of eGFR after donation between three groups of predonation eGFR: normal for age (Sage ) higher than 90 or 80 ml/min/1.73 m2 (S90 and S80, respectively); across three age groups (<45, 45-55, >55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.


Assuntos
Falência Renal Crônica , Transplante de Rim , Taxa de Filtração Glomerular , Humanos , Rim , Falência Renal Crônica/cirurgia , Doadores Vivos , Pessoa de Meia-Idade , Nefrectomia
19.
Clin Transplant ; 35(3): e14207, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33369772

RESUMO

After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non-melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post-transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen.


Assuntos
Transplante de Rim , Neoplasias Cutâneas , Inibidores de Calcineurina , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Ácido Micofenólico , Projetos Piloto , Estudos Retrospectivos , Prevenção Secundária , Sirolimo/uso terapêutico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Serina-Treonina Quinases TOR
20.
Clin Transplant ; 35(2): e14171, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33247459

RESUMO

BACKGROUND: Rituximab has been proposed as induction therapy in kidney transplant recipients (KTRs) with preformed donor-specific antibodies (DSA) or a positive flow cross-match. We here evaluated whether adding rituximab was associated with a higher incidence of post-transplant malignancies (PTM) due to greater immunosuppression. PATIENTS AND METHODS: Forty-eight HLA-sensitized KTRs received induction therapy with anti-thymocyte globulin (ATG) and rituximab because of preformed DSA or a positive flow cross-match (RTX group). They were compared with a control group of 154 patients receiving ATG alone. RESULTS: Thirty-nine of 202 (19.3%) patients developed PTM; the rate was similar in the RTX and no-RTX groups (14.6% vs. 20.8%, respectively, P = .3). The distributions of the types of cancer were similar between the two groups, with the majority being non-melanoma skin cancer (NMSC, n = 24). The risk factors for PTM were male gender, age, history of cancer, and azathioprine. CONCLUSION: Our data do not indicate a higher rate of post-transplantation de novo malignancies after kidney transplantation in high-immunological risk patients who received induction therapy based on ATG and rituximab.


Assuntos
Transplante de Rim , Neoplasias , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Antígenos HLA , Humanos , Imunossupressores/efeitos adversos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Neoplasias/epidemiologia , Neoplasias/etiologia , Estudos Retrospectivos , Rituximab/efeitos adversos , Transplantados
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