Acute respiratory failure in kidney transplant recipients: a multicenter study

International audienceINTRODUCTION: Data on pulmonary complications in renal transplant recipients are scarce. The aim of this study was to evaluate acute respiratory failure (ARF) in renal transplant recipients. METHODS: We conducted a retrospective observational study in nine transplant centers of consecutive kidney transplant recipients admitted to the intensive care unit (ICU) for ARF from 2000 to 2008. RESULTS: Of 6,819 kidney transplant recipients, 452 (6.6%) required ICU admission, including 200 admitted for ARF. Fifteen (7.5%) of these patients had combined kidney-pancreas transplantations. The most common causes of ARF were bacterial pneumonia (35.5%), cardiogenic pulmonary edema (24.5%) and extrapulmonary acute respiratory distress syndrome (ARDS) (15.5%). Pneumocystis pneumonia occurred in 11.5% of patients. Mechanical ventilation was used in 93 patients (46.5%), vasopressors were used in 82 patients (41%) and dialysis was administered in 104 patients (52%). Both the in-hospital and 90-day mortality rates were 22.5%. Among the 155 day 90 survivors, 115 patients (74.2%) were dialysis-free, including 75 patients (65.2%) who recovered prior renal function. Factors independently associated with in-hospital mortality were shock at admission (odds ratio (OR) 8.70, 95% confidence interval (95% CI) 3.25 to 23.29), opportunistic fungal infection (OR 7.08, 95% CI 2.32 to 21.60) and bacterial infection (OR 2.53, 95% CI 1.07 to 5.96). Five factors were independently associated with day 90 dialysis-free survival: renal Sequential Organ Failure Assessment (SOFA) score on day 1 (OR 0.68/SOFA point, 95% CI 0.52 to 0.88), bacterial infection (OR 0.43, 95% CI 0.21 to 0.90), three or four quadrants involved on chest X-ray (OR 0.44, 95% CI 0.21 to 0.91), time from hospital to ICU admission (OR 0.98/day, 95% CI 0.95 to 0.99) and oxygen flow at admission (OR 0.93/liter, 95% CI 0.86 to 0.99). CONCLUSIONS: In kidney transplant recipients, ARF is associated with high mortality and graft loss rates. Increased Pneumocystis and bacterial prophylaxis might improve these outcomes. Early ICU admission might prevent graft loss

Age-adapted percentiles of measured glomerular filtration in healthy individuals:extrapolation to living kidney donors over 65 years

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 m(2)) 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

Anticorps impliqués dans la positivité du crossmatch lymphocytaire B en transplantation rénale (caractérisation et implications fonctionnelles des anticorps anti-hla et anti-cellules endothéliales)

Nous avons analysé, chez 62 patients, des anticorps impliqués dans le crossmatch lymphocytaire B positif (CMB+) en transplantation rénale. Dans 39% des cas la positivité est due à des auto-anticorps ou des anticorps anti-HLA cl II spécifiques du greffon. Dans 61% des cas, ces anticorps sont non identifiables. La survie des greffons suivant la cible des anticorps montre que le CMB+ n'est pas toujours une contre-indication à la greffe. La réactivité des sérums de 57 patients a été testée sur des cellules endothéliales (AECA). La présence d'AECA, notée chez 33% des patients, est corrélée à leur immunisation anti-HLA mais indépendante du CMB+. Ces AECA induisent in vitro l'apoptose de cellules endothéliales. Dans une 3ème partie, nous avons montré que les anticorps anti-HLA cl II, connus pour induire l'apoptose de cellules présentatrices d'antigènes (CPA) professionnelles, n'ont pas d'effet sur les cellules endothéliales, qui en allo-transplantation peuvent devenir des CPA.We have identified, in 62 patients, antibodies involved in postive B cell crossmatch (+BCM) in kidney transplantation. In 39% the positivity was due to auto-antibodies and donor specific anti-HLA cl II antibodies. In 61% of cases, these antibodies remain unidentified. Graft survival according to antibody targets show that +BCM is not toujours a contre-indication of tran splantation. Detection of anti-endothelial ceil antibodies (AECA) was performed on sera of 57 patients was tested with endothelial cells. AECA, found in 33% of patients, was correled with anti-HLA immunization but independent of +BCM. However, these AECA induce in vitro endothelial cell apoptosis. In a third part, we have shown that anti-HLA cl II antibodies, known to induce antigen presentating cell (APC) apoptosis, have no effects on endothelial cells, wich can become APC in allo-transplantation.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Caractérisation des anticorps allo-immuns et anti-HLA en transplantation rénale (étude de leur rôle sur le devenir du greffon)

Malgré les progrès des immunothérapies, le rejet chronique est un problème majeur de la transplantation rénale. Les causes les plus fréquentes sont la Glomérulopathie du Transplant (GT) et la fibrose interstitielle et atrophie tubulaire (FIAT). La GT est définie par des lésions chroniques associées à des anticorps anti-HLA donneur-spécifiques (DSA) et un dépôt de C4d. La FIAT est une lésion non humorale. Les anticorps anti-HLA de classe II corrèlent avec le rejet chronique. Cependant les isotypes d'IgG diffèrent dans leur capacité à fixer le complément, donc à engendrer du C4d, et ceci a très peu été étudié en transplantation rénale. De plus, des études ont montré que le développement de DSA anti-HLA corrélait avec un développement d'anticorps non HLA. Le but de notre projet était d'étudier les anticorps de patients greffés afin de trouver des profils d'isotypes d IgG et d'anticorps non HLA spécifiques de quatre statuts, dont la GT, la FIAT, les patients transplantés ayant un greffon stable (STA) et les patients dialysés (DIA). Les sérums des patients ont été analysés par la technique Luminex Single Antigen Bead, adaptée afin de détecter les isotypes d'IgG anti-HLA DSA. D'autre part, les sérums ont été criblés sur des puces contenant 8000 protéines humaines et comparés entre eux afin d'obtenir des listes de biomarqueurs uniques et spécifiques de chaque statut du greffon. Aucun isotype d IgG ne distingue les IFTA des TG, bien que les TG développent plus de DSA à des MFI plus élevées. Cependant, les puces à protéines ont permis de définir des listes de biomarqueurs pour chaque statut du greffon. Ces données pourraient donc aider au diagnostic précoce du statut du greffon.Although huge improvements have been made in immunotherapies, chronic rejection remains a major problem in the field of kidney transplantation. The leading causes are Transplant Glomerulopathy (TG) and Interstitial Fibrosis and Tubular Atrophy (IFTA). TG is defined by chronic lesions associated with anti-HLA donor-specific antibodies (DSA) and C4d deposits on the graft. IFTA is a non-immune injury. Anti-HLA class II antibodies are correlated to chronic rejection. However, IgG isotypes differ in their ability to bind the complement, thus producing C4d, and this has not been extensively studied. Furthermore, studies have shown that anti-HLA DSA development was correlated with non-HLA antibodies development. Our project aimed at studying antibodies developed by transplanted patients to define IgG anti-HLA isotypes and non-HLA antibodies profiles specific of each of four kidney status including TG, IFTA, transplanted patients with a stable function (STA) and dialysis patients (DIA). Sera of all patients have been analyzed on single antigen bead with the modified luminex technology to detect anti-HLA DSA isotypes. Sera have also been screened on protein arrays to obtain unique biomarkers specific of each kidney status. No IgG isotype differentiates IFTA from TG patients, though the last develop more DSA at higher MFI values. However, protein arrays led us to obtain lists of biomarkers for each kidney status. These data could help getting an early diagnosis of kidney status.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF