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1.
Artigo em Inglês | MEDLINE | ID: mdl-38794882

RESUMO

BACKGROUND AND HYPOTHESIS: Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation and is classically associated with a significant decrease in graft survival. A major risk factor is a prior history of FSGS recurrence on a previous graft. This analysis reports the impact of a prophylactic treatment of FSGS recurrence in very high-risk patients who experienced a recurrence on a previous graft. METHODS: We performed a retrospective multicentre observational study in 25 French transplantation centres. The inclusion criteria were patients aged more than 18 years who had undergone kidney transplant between December 31, 2004, and December 31, 2020, and who had a history of FSGS recurrence on a previous graft. RESULTS: We identified 66 patients: 40 received prophylactic treatment (PT+), including intravenous cyclosporine and/or rituximab and/or plasmapheresis, and 26 did not receive any prophylactic treatment (PT-). The time to progression to end-stage kidney disease was similar between groups. The PT + group was younger at FSGS diagnosis and at the time of kidney retransplantation and lost their previous graft faster. The overall recurrence rate was 72.7% (76.9% in the PT- group and 70.0% in the PT + group, P = 0.54). At least partial remission was achieved in 87.5% of patients. The 5-year graft survival was 67.7% (95% CI: 53.4 to 78.4%): 65.1% (95%CI: 48.7 to 77.4%) in patients with FSGS recurrence vs. 77.3% (95% CI: 43.8 to 92.3%) in patients without recurrence (P = 0.48). CONCLUSION: Our study suggests that prophylactic treatment should not be used routinely in patients receiving a second transplantation after recurrence of FSGS on a previous graft. The recurrence rate is high regardless of the use of prophylactic treatment. However, the 5-year graft survival remains satisfactory.

2.
Nephrol Dial Transplant ; 38(Supplement_2): ii11-ii18, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37816675

RESUMO

BACKGROUND: Complement alternative pathway (AP) activation is linked to immunoglobulin A nephropathy (IgAN) prognosis severity, but Bb fragment's role is unclear. We examined the relationship between serum Bb fragment concentration at IgAN diagnosis and disease activity and outcomes. METHODS: This retrospective study included 125 biopsy-proven IgAN patients [age 39.9 years, 75% male, estimated glomerular filtration rate (eGFR) 82 ml/min, proteinuria 0.5 g/day] enrolled from 1984 to 2010 and followed for a minimum of 18 months. Monitoring continued until the last follow-up, end-stage kidney disease (ESKD) or death. Serum Bb fragment was measured using an enzyme-linked immunosorbent assay at diagnosis. Oxford classification and global optical score (GOS) were utilized for pathology assessment. RESULTS: Patients were followed for a median of 16 years; 42% developed chronic kidney disease stage ≥3, 19% reached ESKD and 9% died. Serum Bb fragment concentration negatively correlated with eGFR values at the last follow-up and positively with vascular and tubular histopathological indices. In univariate Cox regression analyses, higher Bb fragment concentration was associated with ESKD alongside older age, increased body mass index, arterial hypertension, lower eGFR, higher proteinuria, E1, S1, T1-2, GOS and corticotherapy. Patients with Bb levels ≥14.3 µg/ml had shorter mean kidney survival time (19.5 versus 22.7 years, P = .07); after adjusting for progression risk factors, the association persisted [hazard ratio 4.76 (95% confidence interval 1.56-14.43)]. CONCLUSIONS: Serum Bb fragment concentration at diagnosis may predict long-term IgAN outcomes, potentially due to AP activation at the endothelial surface. Further research is needed to confirm these results and evaluate Bb fragment's role in IgAN management.


Assuntos
Glomerulonefrite por IGA , Falência Renal Crônica , Humanos , Masculino , Adulto , Feminino , Glomerulonefrite por IGA/patologia , Estudos Retrospectivos , Fator B do Complemento , Progressão da Doença , Prognóstico , Falência Renal Crônica/complicações , Proteinúria/complicações , Taxa de Filtração Glomerular
3.
Nephrol Dial Transplant ; 38(10): 2257-2265, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37316441

RESUMO

INTRODUCTION: The International IgA Nephropathy Network developed a tool (IINN-PT) for predicting the risk of end-stage renal disease (ESRD) or a 50% decline in the estimated glomerular filtration rate (eGFR). We aimed to validate this tool in a French cohort with longer follow-up than previously published validation studies. METHODS: The predicted survival of patients with biopsy-proven immunoglobulin A nephropathy (IgAN) from the Saint Etienne University Hospital cohort was computed with IINN-PT models with or without ethnicity. The primary outcome was the occurrence of either ESRD or a 50% decline in eGFR. The models' performances were evaluated through c-statistics, discrimination and calibration analysis. RESULTS: There were 473 patients with biopsy-proven IgAN, with a median follow-up of 12.4 years. Models with and without ethnicity showed areas under the curve (95% confidence interval) of 0.817 (0.765; 0.869) and 0.833 (0.791; 0.875) and R2D of 0.28 and 0.29, respectively, and an excellent discrimination of groups of increasing predicted risk (P < .001). The calibration analysis was good for both models up to 15 years after diagnosis. The model without ethnicity exhibited a mathematical issue of survival function after 15 years. DISCUSSION: The IINN-PT provided good performances even after 10 years post-biopsy as showed by our study based on a cohort with a longer follow-up than previous cohorts (12.4 versus <6 years). The model without ethnicity exhibited better performances up to 15 years but became aberrant beyond this point due to a mathematical issue affecting the survival function. Our study sheds light on the usefulness of integrating ethnicity as a covariable for prediction of IgAN course.


Assuntos
Glomerulonefrite por IGA , Falência Renal Crônica , Humanos , Progressão da Doença , Etnicidade , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/etnologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etnologia , Falência Renal Crônica/etiologia , Prognóstico , Estudos Retrospectivos
4.
J Infect Dis ; 223(5): 885-892, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32691827

RESUMO

BACKGROUND: Identifying people with HIV (PWH) at risk for chronic kidney disease, cardiovascular events, and death is crucial. We evaluated biomarkers to predict all-cause mortality and cardiovascular events, and measured glomerular filtration rate (mGFR) slope. METHODS: Biomarkers were measured at enrollment. Baseline and 5-year mGFR were measured by plasma iohexol clearance. Outcomes were a composite criterion of all-cause mortality and/or cardiovascular events, and mGFR slope. RESULTS: Of 168 subjects, 146 (87.4%) had undetectable HIV load. Median follow-up was 59.1 months (interquartile range, 56.2-62.1). At baseline, mean age was 49.5 years (± 9.8) and mean mGFR 98.9 mL/min/1.73m2 (± 20.6). Seventeen deaths and 10 cardiovascular events occurred during 5-year follow-up. Baseline mGFR was not associated with mortality/cardiovascular events. In multivariable analysis, cystatin C (hazard ratio [HR], 5.978; 95% confidence interval [CI], 2.774-12.88; P < .0001) and urine albumin to creatinine ratio (uACR) at inclusion (HR, 1.002; 95% CI, 1.001-1.004; P < .001) were associated with mortality/cardiovascular events. Area under receiver operating curve of cystatin C was 0.67 (95% CI, .55-.79) for mortality/cardiovascular event prediction. Biomarkers were not associated with GFR slope. CONCLUSIONS: uACR and cystatin C predict all-cause mortality and/or cardiovascular events in PWH independently of mGFR.


Assuntos
Doenças Cardiovasculares , Infecções por HIV , Insuficiência Renal Crônica , Adulto , Albuminas , Albuminúria , Biomarcadores , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/virologia , Creatinina/urina , Cistatina C/urina , Taxa de Filtração Glomerular , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Pessoa de Meia-Idade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/virologia
5.
Am J Transplant ; 21(9): 3021-3033, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33512779

RESUMO

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.


Assuntos
Glomerulosclerose Segmentar e Focal , Transplante de Rim , Adulto , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Humanos , Transplante de Rim/efeitos adversos , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
6.
Retina ; 41(11): 2332-2341, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33840791

RESUMO

PURPOSE: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome. METHODS: Retrospective case series of patients presenting with catastrophic antiphospholipid syndrome and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at catastrophic antiphospholipid syndrome diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best-corrected visual acuity. RESULTS: This study included 23 patients (11 cases treated by the authors and 12 published case reports); 21 (91%) of them female. Their median age at diagnosis was 28 years (range, 16-79 years). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n = 11, 48%), or retinal vasculitis (n = 1, 4%). Final best-corrected visual acuity was not significantly worse than the best-corrected visual acuity at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months (range, 2-132 months), nearly half the patients (n = 11, 48%) had permanent vision loss including best-corrected visual acuity of <20/400 for 4 patients. CONCLUSION: Posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.


Assuntos
Síndrome Antifosfolipídica/complicações , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/etiologia , Acuidade Visual , Adolescente , Adulto , Idoso , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Transtornos da Visão/diagnóstico , Adulto Jovem
7.
Nephrol Dial Transplant ; 35(7): 1179-1186, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445530

RESUMO

BACKGROUND: The prognosis of IgA nephropathy (IgAN) is very heterogeneous. Predicting the nature and the rate of the disease progression is crucial for refining patient treatment. The aim of this study was to evaluate the prognostic impact of an Oxford classification-based repeat kidney tissue evaluation to predict end-stage renal disease (ESRD). METHODS: Patients with biopsy-proven primary IgAN who underwent two renal biopsies at our centre were analyzed retrospectively. Renal biopsies were scored by two pathologists blinded to the clinical data and according to the updated Oxford classification. Cox models were generated to evaluate the prognostic impact considering the Oxford classification elementary lesions from the first (Model 1) or the second (Model 2) biopsy, adjusted on clinical data at time of reevaluation. The prognostic impacts of the dynamic evolution of each elementary lesion between biopsies were also assessed through univariate and multivariate evaluation. RESULTS: A total of 168 adult patients were included, with a median follow-up duration of 18 (range 11-24) years. The second biopsy was performed either systematically (n = 112) of for-cause (n = 56), after a median time of 5.4 years. The prognostic performances of Model 2 (second biopsy) were significantly better than Model 1 (first biopsy, analysis of deviance P < 0.0001). The dynamic changes of C and T lesions were significantly associated with the progression toward ESRD after adjustment on variables from Model 2. CONCLUSION: Both static and dynamic Oxford-based histological evaluation offered by a repeat biopsy improves the prediction of ESRD in patients with IgAN.


Assuntos
Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/patologia , Falência Renal Crônica/complicações , Adulto , Biópsia , Progressão da Doença , Feminino , Glomerulonefrite por IGA/etiologia , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação , Estudos Retrospectivos
8.
PLoS Genet ; 13(2): e1006609, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28187132

RESUMO

Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known. We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8). These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1. We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians. Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians. Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1. By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells. Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.


Assuntos
Galactosiltransferases/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Glomerulonefrite por IGA/genética , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Alelos , Povo Asiático/genética , Linhagem Celular , Estudos de Coortes , Galactose/deficiência , Regulação da Expressão Gênica , Frequência do Gene , Redes Reguladoras de Genes , Predisposição Genética para Doença/etnologia , Genótipo , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/etnologia , Glicosilação , Humanos , Imunoglobulina A/sangue , Modelos Genéticos , Proteínas do Tecido Nervoso/genética , Fenótipo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Ubiquitina-Proteína Ligases/genética , População Branca/genética
9.
Kidney Int ; 95(4): 896-904, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30819555

RESUMO

While direct measurements of glomerular filtration rate (GFR) provide the most accurate evaluation of pre-donation kidney function, guidelines do not systematically require the use of a reference method. We evaluated whether and to what extent relying upon creatinine-based estimating equations (eGFR) rather than direct measurement of GFR (mGFR) alters the selection of potential living donors. We compared the impact of 4 equations (the MDRD study equation, the CKD-EPI equation, the revised Lund-Malmö equation, and the full age spectrum [FAS] equation) on the evaluation of 2733 potential donors with GFR measured by reference methods. We also considered the impact of using either absolute or age-adapted GFR thresholds. The CKD-EPI and FAS equations had the best performances (P10 of 50.6% and 47.8%; P30 of 94.4% and 93.1%, respectively) and led to the lowest proportion of improperly evaluated candidates. Misclassification was more frequent when GFR adequacy was defined as an absolute threshold of 90 ml/min/1.73m2 as compared to an age-adapted definition (26% and 5%, respectively). Interpretation of eGFR according to an absolute threshold of 90 ml/min/1.73m2 identified 1804 candidates eligible to donate, compared to 2648 when mGFR was interpreted with age-adapted thresholds. We conclude that creatinine-based estimates cannot substitute for direct GFR measurement to evaluate candidates for kidney donation. When reference methods for direct GFR measurement are not available, our data suggest that a strategy based on age-adapted eGFR values estimated with either the CKD-EPI or FAS equation should be preferred.


Assuntos
Seleção do Doador/métodos , Taxa de Filtração Glomerular , Transplante de Rim , Rim/fisiopatologia , Doadores Vivos , Adulto , Fatores Etários , Creatinina/sangue , Seleção do Doador/normas , Feminino , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
10.
Br J Clin Pharmacol ; 85(6): 1215-1226, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30768726

RESUMO

AIM: Previous pharmacokinetic (PK) studies have proposed various dosing regimens for vancomycin in intensive care unit (ICU) patients undergoing renal replacement therapy (RRT), but all are restricted to specific RRT modalities. To be useful in practice, a population PK model would need to predict vancomycin clearance during any RRT modality. Development of such a model is feasible using meta-analysis of published summarized estimates of vancomycin PK parameters. Our aims were: (i) to develop and validate a population PK model for vancomycin that takes into account any RRT modalities, and (ii) to predict vancomycin dosing for RRT patients in ICU. METHODS: Vancomycin pharmacokinetics were assumed to be two-compartmental, total body clearance being the sum of non-RRT clearance and RRT-induced clearance. Drug disposition and non-RRT clearance parameters were estimated by systematic review and meta-analysis of previously published parameter estimates. The relationship between RRT-induced clearance and RRT flowrate settings was assessed using a model-based meta-analysis. Prediction performances of the PK model were assessed using external data. RESULTS: The meta-analyses of disposition parameters, non-RRT clearance and RRT-induced clearance included 11, 6 and 38 studies (84 RRT clearance measurements) respectively. The model performed well in predicting external individual PK data. Individual vancomycin concentrations during RRT were accurately predicted using Bayesian estimation based solely on pre-RRT measurements. CONCLUSIONS: The PK model allowed accurate prediction of the vancomycin pharmacokinetics during RRT in ICU patients. Based on the model of RRT-induced clearance, an appropriate adjustment of the vancomycin dosing regimen could be proposed for any kind of flowrate settings.


Assuntos
Antibacterianos/administração & dosagem , Cálculos da Dosagem de Medicamento , Unidades de Terapia Intensiva , Modelos Biológicos , Terapia de Substituição Renal , Vancomicina/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Humanos , Terapia de Substituição Renal/efeitos adversos , Vancomicina/efeitos adversos , Vancomicina/farmacocinética
11.
Eur J Clin Microbiol Infect Dis ; 38(10): 1811-1819, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273646

RESUMO

The aim of this study was to investigate the relationship between nasal and rectal Staphylococcus aureus carriage in intensive care unit (ICU) patients and the occurrence of ICU-acquired infections related to S. aureus carriage. Three hundred and ninety-five patients admitted in ICU were screened for S. aureus nasal and rectal carriages and followed to record S. aureus infections during their stay. S. aureus strains were genotyped by arbitrarily primed PCR, spa-typing, microarray and whole genome sequencing. At ICU admission, 112 of 363 (30.9%) patients carried S. aureus including 61 (16.8%) exclusive nasal carriers, 40 (11.0%) combined nasal and rectal carriers and 11 (3.0%) exclusive rectal carriers. The 152 S. aureus isolates from nasal and rectal swabs belonged to 19 clonal complexes (CCs). Patients colonized in both nose and rectum harboured different strains in at least 40% of cases according to arbitrarily primed PCR data. Nasal carriers of CC5 S. aureus had an increased risk of rectal carriage (RR = 1.85, P < .05). S. aureus nasal and rectal carriage was a risk factor of S. aureus ICU-acquired infection (RR = 4.04; 95%CI [1.38-11.76]). Incidence rates of endogenous ICU-acquired infections in exclusive nasal carriers, exclusive rectal carriers and in both nasal and rectal carriers were 0.08 (5/61), 0.09 (1/11) and 0.03 (1/40), respectively (p = 0.47). Rectal swabbing increased the detection of S. aureus carriage and revealed an important diversity of S. aureus strains in ICU patients. Further studies are needed to understand how S. aureus rectal carriage increases the risk of endogenous ICU-acquired infections.


Assuntos
Portador Sadio/epidemiologia , Estado Terminal , Unidades de Terapia Intensiva , Mucosa Nasal/microbiologia , Reto/microbiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Estudos Prospectivos , Staphylococcus aureus/classificação , Staphylococcus aureus/genética
12.
Transfus Apher Sci ; 58(3): 262-265, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31029612

RESUMO

Plasma exchange had been proposed to treat many kidney diseases. A few controlled studies, observational studies, and mechanistic evidence have specified the better indications, which are thrombotic microangiopathies, kidney transplantation and ANCA-associated vasculitides. Plasma removal can be realized by filtration, centrifugation, or immunoadsorption, with differences in efficacy, but these also impact on volume load and anticoagulation in patients with renal failure.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Nefropatias/terapia , Troca Plasmática , Microangiopatias Trombóticas/terapia , Humanos
13.
J Am Soc Nephrol ; 29(2): 661-669, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29114042

RESUMO

Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40.1 years; median follow-up, 132 months). We determined the number of CFHR3 and CFHR1 gene copies by quantitative PCR and collected clinical and biologic data by reviewing the patients' medical records. In all, 30.5% of the patients were heterozygous and 4% were homozygous for CFHR3,1Δ We did not detect an association between CFHR3,1Δ and age, eGFR, urinary protein excretion rate, or the presence of hypertension or hematuria at the time of diagnosis. The mean intensities of immune IgA, IgG, and C3 deposits were lower in the group with heterozygous or homozygous gene deletions than in those with no deletion. However, CFHR3,1Δ did not associate with progression to stage 3 CKD or renal death. In conclusion, the CFHR3,1Δ genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits.


Assuntos
Proteínas Sanguíneas/genética , Proteínas Inativadoras do Complemento C3b/genética , Mesângio Glomerular/metabolismo , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/imunologia , Adulto , Idoso , Progressão da Doença , Feminino , Dosagem de Genes , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/fisiopatologia , Heterozigoto , Homozigoto , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Deleção de Sequência , População Branca , Adulto Jovem
14.
Kidney Int ; 94(3): 616-624, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30143068

RESUMO

Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m2. While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m2). Three groups of donors were defined according to baseline mGFR: below 80, 80-89.9 and 90 mL/min/1.73 m2 or more. Thirty-two percent of donors were selected despite an mGFR below 90 mL/min/1.73 m2. Donors with the lowest mGFR were significantly older (60 ± 9 vs. 47 ± 11 years) and this applied to both male and female donors. The lifetime-standardized renal reserve, defined as the pre-donation mGFR value divided by the expected number of remaining years of life, was similar irrespective of baseline mGFR groups. Similar results were obtained when eGFR was used instead of mGFR. Finally, in a subgroup of 132 donors with repeated mGFR five years after donation, the magnitude of mGFR decrease was similar in all groups (-34.3%, -33.9%, and -34.9% respectively). Thus, the decision to accept individuals with mGFR lower than 90 mL/min/1.73 m2 for kidney donation is highly dependent on the age of the candidate. Hence, threshold values lower than 90 mL/min/1.73 m2 are reasonable for older donors. Age-calibrated mGFR may improve efficiency of the selection process.


Assuntos
Seleção do Doador/métodos , Taxa de Filtração Glomerular , Transplante de Rim/normas , Doadores Vivos , Adulto , Fatores Etários , Idoso , Seleção do Doador/normas , Feminino , França , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
J Am Soc Nephrol ; 28(6): 1943-1950, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28255003

RESUMO

A prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years) on calcineurin inhibitor-based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy-proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1-specific IgG and IgA autoantibodies in serum obtained at time of transplant or native-kidney IgAN diagnosis (30 patients only). Overall, 13 patients died, 34 kidneys failed (17 due to CPR), and 34 patients developed CPR after a mean interval of 5.8 years. Compared with healthy controls (n=30), patients had significantly elevated serum Gd-IgA1 levels at diagnosis and transplant, but levels did not associate with any outcome. Patients also had significantly elevated levels of normalized (but not total) serum Gd-IgA1-specific IgG autoantibodies at diagnosis and transplant, and the level at transplant associated with higher risk of CPR (relative risk, 2.68; 95% confidence interval, 1.26 to 5.71; P=0.01; area under the receiver operating characteristic curve, 0.62; 95% confidence interval, 0.51 to 0.74; P=0.05). Normalized Gd-IgA1-specific IgG autoantibody level remained an independent risk factor for CPR in multivariate analysis. Serum Gd-IgA1-specific IgA autoantibody level did not change between diagnosis and transplant or predict outcome. This study emphasizes post-transplant prognostic value of normalized serum IgG antiglycan autoantibody level in patients with IgAN.


Assuntos
Autoanticorpos/sangue , Autoimunidade , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/cirurgia , Transplante de Rim , Biomarcadores/sangue , Feminino , Glomerulonefrite por IGA/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva
17.
Pediatr Nephrol ; 32(10): 1935-1940, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28429121

RESUMO

BACKGROUND: This study describes the long-term results of renal autotransplantation for renovascular hypertension performed in children who are now 21 years of age or older. METHODS: Sixteen children (4 boys, 12 girls) with a mean age of 11.2 years at the time of the procedure underwent ex-vivo surgery at the university hospital of Saint-Etienne between 1992 and 2008. Acetylsalicylic acid was used for antiplatelet therapy in the postoperative period, without routine anticoagulation. The mean follow-up period was 15 years. The clinical course of these patients was retrospectively reviewed in adulthood and the results analyzed. RESULTS: The children were treated with a mean of 2.37 drugs per patient, and the mean preoperative blood pressure of the entire patient population was 151/89 mmHg. Mean preoperative creatinine clearance was 80 ml/min/1.73 m2. There was no postoperative death. One patient experienced a thrombosis immediately after the surgery, leading to a redo surgery. In this patient diuresis was restarted, but without efficient concentration and filtration, ultimately leading the patient to have a renal transplant after 1 year. At the end of the follow-up period, eight of the 16 patients (50%) were cured and the others were improved. At the last follow-up the mean blood pressure was 127/70 mmHg, and the mean number of drugs per patient was 0.68. The mean creatinine clearance at last follow-up was 104.3 ml/min/1.73 m2. Three patients had secondary procedures, with two undergoing percutaneous angioplasty (at postoperative months 9 and 12, respectively) and one having an hepatorenal bypass at postoperative year 4. Primary patency was 12/16 (75%); primary assisted patency was 15/16 (94%); secondary patency was 16/16 (100%). CONCLUSION: This study shows that renal autotransplantation has good and stable long-term results and is an effective conservative strategy for treating renovascular hypertension in children, thus avoiding nephrectomy.


Assuntos
Hipertensão Renovascular/cirurgia , Complicações Pós-Operatórias/epidemiologia , Artéria Renal/transplante , Trombose/epidemiologia , Enxerto Vascular/efeitos adversos , Adolescente , Adulto , Criança , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Rim/irrigação sanguínea , Rim/fisiopatologia , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Trombose/etiologia , Trombose/prevenção & controle , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Resultado do Tratamento , Enxerto Vascular/métodos , Grau de Desobstrução Vascular , Adulto Jovem
18.
Ann Vasc Surg ; 44: 245-252, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28479451

RESUMO

BACKGROUND: Kidney recipients are increasingly older with arterial disease and extended arterial calcifications. In a kidney transplantation population, the prognosis value of aortic and iliac calcifications remains poorly explored. We aimed to assess the impact of pretransplantation aortoiliac vascular calcifications on patients, grafts survival, and cardiovascular events. METHODS: This retrospective study included kidney transplantation patients from 2006 to 2012 for whom we had available presurgery abdominal computed tomography results (n = 100). We designed a score to quantify aortoiliac calcifications. Primary end points were patient and graft survival. Secondary end points were renal function and cardiovascular morbidity. Predictive performances of calcification score were assessed using area under receiver-operating characteristic curves. Patients were classified in quartiles depending on global calcium score value. RESULTS: The cumulated rate of death and graft loss was 13% with no significant differences for survival between quartiles. No significant difference was observed in renal function (P = 0.4). Seventeen cardiovascular events were registered with a significant correlation between calcium score elevation and need of cardiovascular surgery during the follow-up (P = 0.01). Global calcium score had a predictive value of 74.5% (95% confidence interval 0.62-0.87) with 71% sensitivity and 73% specificity. CONCLUSIONS: Aortoiliac calcifications do not decrease patient and graft survival. High calcium score predict cardiovascular events and procedures during the follow-up.


Assuntos
Doenças da Aorta/complicações , Artéria Ilíaca , Transplante de Rim , Calcificação Vascular/complicações , Idoso , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/mortalidade , Área Sob a Curva , Angiografia por Tomografia Computadorizada , Feminino , Sobrevivência de Enxerto , Humanos , Artéria Ilíaca/diagnóstico por imagem , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/mortalidade
19.
J Am Soc Nephrol ; 26(7): 1503-12, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25694468

RESUMO

Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan-binding lectin-associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome-wide association studies identified deletion of complement factor H-related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1-containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease.


Assuntos
Proteínas do Sistema Complemento/genética , Predisposição Genética para Doença , Glomerulonefrite por IGA/genética , Imunoglobulina A/genética , Ativação do Complemento/genética , Compreensão , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Glomerulonefrite por IGA/fisiopatologia , Humanos , Imunoglobulina A/metabolismo , Masculino , Prognóstico , Fatores de Risco , Papel (figurativo) , Sensibilidade e Especificidade , Índice de Gravidade de Doença
20.
Blood Purif ; 40(2): 167-72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26278703

RESUMO

We retrospectively evaluated the ability of protein-A immunoadsorption (IA) as compared to that of conventional plasma exchanges (PE) in reducing the mean fluorescence intensity (MFI) of anti-HLA antibodies assessed by the single antigen assay in sensitized renal transplant recipients. Change in MFI of 441 anti-HLA antibodies was measured after 1 single session of IA or after 3 consecutive daily PE sessions. While both strategies were able to significantly lower the amount of anti-HLA antibodies, the relative reduction in MFI was higher after IA as compared to PE (-69 vs. -58%, respectively, p = 0.003). This better efficacy of IA was observed despite a lower total volume of treated plasma (105 ± 6 vs. 160 ± 16 ml/kg after IA and after PE, respectively). Our data suggest a higher efficiency of IA over conventional PE sessions to remove anti-HLA antibodies and call for a larger evaluation of IA to confirm its potential added value in desensitization protocols.


Assuntos
Anticorpos/isolamento & purificação , Técnicas de Imunoadsorção , Troca Plasmática/métodos , Insuficiência Renal Crônica/terapia , Proteína Estafilocócica A/química , Anticorpos/sangue , Antígenos HLA/sangue , Antígenos HLA/imunologia , Humanos , Transplante de Rim , Troca Plasmática/instrumentação , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/cirurgia , Estudos Retrospectivos
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