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      Phasing out the pre-transplant cytotoxicity crossmatch: Are we missing something? Translated title: Exclusão da prova cruzada por citotoxicidade pré-transplante: estamos perdendo algo

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          Abstract

          Introduction:

          The anti-human globulin-enhanced complement-dependent cytotoxicity crossmatch (AHG-CDCXM) assay has been used to assess the presence of donor-specific antibodies (DSA) in recipient’s serum before kidney transplantation. The flow cytometric crossmatch (FCXM) assay was first introduced as an additional test. The aim of this study was to clinically validate the single use of the FCXM assay.

          Methods:

          This study compared the outcomes of a cohort of kidney transplant patients that underwent FCXM only (FCXM group) versus a cohort of kidney transplant patients that underwent AHG-CDCXM (control group).

          Results:

          Ninety-seven patients in the FCXM group and 98 controls were included. All crossmatches in the control group were negative. One patient in the FCXM group had a positive B cell crossmatch. One year after transplantation, there were no significant differences in patient survival (p = 0.591) and graft survival (p = 0.692) between the groups. Also, no significant difference was found in the incidence of Banff ≥ 1A acute cellular rejection episodes (p = 0.289). However, acute antibody-mediated rejections occurred in 3 controls (p = 0.028).

          Conclusion:

          The results showed that discontinuing the AHG-CDCXM assay does not modify the clinical outcomes in a 1-year follow-up.

          Resumo

          Introdução:

          O ensaio de prova cruzada por citotoxicidade dependente do complemento antiglobulina humana (AHG-CDCXM - do inglês anti-human globulin-enhanced complement-dependent cytotoxicity crossmatch) tem sido usado para avaliar a presença de anticorpos específicos contra o doador (DSA - do inglês donor-specific antibodies) no soro do receptor antes do transplante renal. O ensaio de prova cruzada por citometria de fluxo (CFXM) foi introduzido pela primeira vez como um teste adicional. O objetivo deste estudo foi validar clinicamente o uso único do ensaio CFXM.

          Métodos:

          Este estudo comparou os resultados de uma coorte de pacientes de transplante renal que foram submetidos apenas ao CFXM (grupo CFXM) contra uma coorte de pacientes de transplante renal submetidos ao AHG-CDCXM (grupo controle).

          Resultados:

          Foram incluídos noventa e sete pacientes no grupo CFXM e 98 controles. Todas as provas cruzadas no grupo controle foram negativas. Um paciente no grupo CFXM teve uma prova cruzada positiva para células B. Um ano após o transplante, não houve diferenças significativas na sobrevida do paciente (p = 0,591) e na sobrevida do enxerto (p = 0,692) entre os grupos. Também não foi encontrada diferença significativa na incidência de episódios de rejeição aguda celular (p = 0,289) segundo critério de Banff ≥ 1A. No entanto, rejeições agudas mediadas por anticorpos ocorreram em 3 controles (p = 0,028).

          Conclusão:

          Os resultados mostraram que a interrupção do ensaio AHG-CDCXM não modifica os desfechos clínicos em um acompanhamento de 1 ano.

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          Most cited references28

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.

            Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations. Comparison of estimated and measured GFR. 15 clinical centers participating in a randomized, controlled trial. 1628 patients with chronic kidney disease participating in the MDRD Study. Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate. Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater. The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample. The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.
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              New equations to estimate GFR in children with CKD.

              The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
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                Author and article information

                Journal
                J Bras Nefrol
                J Bras Nefrol
                jbn
                Jornal Brasileiro de Nefrologia
                Sociedade Brasileira de Nefrologia
                0101-2800
                2175-8239
                19 April 2021
                Jul-Sep 2021
                : 43
                : 3
                : 365-374
                Affiliations
                [1 ]Santa Casa de Misericórdia de Porto Alegre, Laboratório de Imunologia de Transplantes, Porto Alegre, RS, Brasil.
                [2 ]Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Medicina: Ciências Médicas, Porto Alegre, RS, Brasil.
                [3 ]Santa Casa de Misericórdia de Porto Alegre, Centro de Nefrologia e Transplante Renal, Porto Alegre, RS, Brasil.
                Author notes
                Correspondence to: Jamile Abud. E-mail: jamile.abud.genetica@ 123456gmail.com

                Author’s Contribution

                Conception and design: Jamile Abud, Jorge Neumann.

                Analysis and interpretation: Jamile Abud, Cynthia da Silva, Elizete Keitel, Valter Duro Garcia, Roberto Ceratti Manfro, Jorge Neumann.

                Data collection: Jamile Abud, Bruna Brasil Dal Pupo.

                Writing of the article: Jamile Abud, Valter Duro Garcia, Roberto Ceratti Manfro, Jorge Neumann.

                Critical revision of the article: Roberto Ceratti Manfro, Jorge Neumann.

                Final approval of the article: Jamile Abud, Bruna Brasil Dal Pupo, Cynthia da Silva, Elizete Keitel, Valter Duro Garcia, Roberto Ceratti Manfro, Jorge Neumann.

                Statistical analysis: Jamile Abud.

                Overall responsibility: Jamile Abud, Jorge Neumann.

                All authors have read and approved the final version of the article.

                Conflict of Interest The authors declare that there is no conflict of interest.

                Author information
                http://orcid.org/0000-0002-9176-0464
                http://orcid.org/0000-0002-4211-4845
                http://orcid.org/0000-0002-3778-4473
                http://orcid.org/0000-0002-5519-8224
                http://orcid.org/0000-0002-7394-1501
                http://orcid.org/0000-0001-8324-3734
                http://orcid.org/0000-0002-1923-8348
                Article
                10.1590/2175-8239-JBN-2019-0222
                8428636
                33899906
                41d81ed8-f84e-4698-890c-b5a9e365fa35

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 March 2020
                : 07 December 2020
                Categories
                Original Article

                flow cytometry,cytotoxicity tests, immunologic,graft rejection,transplante.,citometria de fluxo,testes imunológicos de citotoxicidade,rejeição de enxerto,transplantation.

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