Service de Nephrologie Immunologie Clinique

Joué-lés-Tours, France

Service de Nephrologie Immunologie Clinique

Joué-lés-Tours, France

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Shabir S.,Queen Elizabeth Hospital | Halimi J.-M.,Service de Nephrologie Immunologie Clinique | Cherukuri A.,University of Leeds | Ball S.,Queen Elizabeth Hospital | And 8 more authors.
American Journal of Kidney Diseases | Year: 2014

Background Accurate prediction of kidney transplant failure remains imperfect. The objective of this study was to develop and validate risk scores predicting 5-year transplant failure, based on data available 12 months posttransplantation. Study Design Development and then independent multicenter validation of risk scores predicting death-censored and overall transplant failure. Setting & Participants Outcomes of kidney transplant recipients (n = 651) alive with transplant function 12 months posttransplantation in Birmingham, United Kingdom, were used to develop models predicting transplant failure risk 5 years posttransplantation. The resulting risk scores were evaluated for prognostic utility (discrimination, calibration, and risk reclassification) in independent cohorts from Tours, France (n = 736); Leeds, United Kingdom (n = 787); and Halifax, Canada (n = 475). Predictors Weighted regression coefficients for baseline and 12-month demographic and clinical predictor characteristics. Outcomes Death-censored and overall transplant failure 5 years posttransplantation. Measurements Baseline data and time to transplant failure. Results Following model development, variables included in separate scores for death-censored and overall transplant failure included recipient age, sex, and race; acute rejection; transplant function; serum albumin level; and proteinuria. In the validation cohorts, these scores showed good to excellent discrimination for death-censored transplant failure (C statistics, 0.78-0.90) and moderate to good discrimination for overall transplant failure (C statistics, 0.75-0.81). Both scores demonstrated good calibration (Hosmer-Lemeshow P > 0.05 in all cohorts). Compared with estimated glomerular filtration rate in isolation, application of the scores resulted in statistically significant and clinically relevant risk reclassification for death-censored transplant failure (net reclassification improvement [NRI], 36.1%-83.0%; all P < 0.001) and overall transplant failure (NRI, 38.7%-53.5%; all P < 0.001). Compared with the previously described US Renal Data System-based risk calculator, significant and relevant risk reclassification for overall transplant failure was seen (NRI, 30.0%; P < 0.001). Limitations Validation is required in further populations. Conclusions These validated risk scores may be of prognostic utility in kidney transplantation, accurately identifying at-risk transplants, and informing clinicians and patients. © 2014 by the National Kidney Foundation, Inc.


PubMed | Queen Elizabeth Hospital, University of Leeds, Service de Nephrologie Immunologie clinique, Dalhousie University and University of Birmingham
Type: Journal Article | Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation | Year: 2014

Accurate prediction of kidney transplant failure remains imperfect. The objective of this study was to develop and validate risk scores predicting 5-year transplant failure, based on data available 12 months posttransplantation.Development and then independent multicenter validation of risk scores predicting death-censored and overall transplant failure.Outcomes of kidney transplant recipients (n=651) alive with transplant function 12 months posttransplantation in Birmingham, United Kingdom, were used to develop models predicting transplant failure risk 5 years posttransplantation. The resulting risk scores were evaluated for prognostic utility (discrimination, calibration, and risk reclassification) in independent cohorts from Tours, France (n=736); Leeds, United Kingdom (n=787); and Halifax, Canada (n=475).Weighted regression coefficients for baseline and 12-month demographic and clinical predictor characteristics.Death-censored and overall transplant failure 5 years posttransplantation.Baseline data and time to transplant failure.Following model development, variables included in separate scores for death-censored and overall transplant failure included recipient age, sex, and race; acute rejection; transplant function; serum albumin level; and proteinuria. In the validation cohorts, these scores showed good to excellent discrimination for death-censored transplant failure (C statistics, 0.78-0.90) and moderate to good discrimination for overall transplant failure (C statistics, 0.75-0.81). Both scores demonstrated good calibration (Hosmer-Lemeshow P>0.05 in all cohorts). Compared with estimated glomerular filtration rate in isolation, application of the scores resulted in statistically significant and clinically relevant risk reclassification for death-censored transplant failure (net reclassification improvement [NRI], 36.1%-83.0%; all P<0.001) and overall transplant failure (NRI, 38.7%-53.5%; all P<0.001). Compared with the previously described US Renal Data System-based risk calculator, significant and relevant risk reclassification for overall transplant failure was seen (NRI, 30.0%; P<0.001).Validation is required in further populations.These validated risk scores may be of prognostic utility in kidney transplantation, accurately identifying at-risk transplants, and informing clinicians and patients.


Dieme B.,French Institute of Health and Medical Research | Halimi J.M.,Service de Nephrologie immunologie Clinique | Halimi J.M.,University of Tours | Emond P.,French Institute of Health and Medical Research | And 9 more authors.
Transplantation | Year: 2014

BACKGROUND: Biomarkers that can predict graft function and/or renal side effects of calcineurin inhibitors (CNI) at each stage of treatment in kidney transplantation are still lacking. We report the first untargeted GC-MS-based metabolomic study on urines of renal transplant patients. This approach would bring insight in biomarkers useable for graft function monitoring. METHODS: All consecutive patients receiving a kidney allograft in our transplantation department over a 6-month period were prospectively included and followed up for 12 months. We collected urine samples on the seventh day (D7) after transplantation, then at month 3 (M3) and month 12 (M12), and obtained mass-spectrometry-based urinary metabolic profiles. Multivariate analyses were conducted to compare metabolic profiles at the 3 different periods and to assess potential differences between cyclosporine and tacrolimus. Differences in metabolic signatures were also assessed according to graft function at D7 and renal function at M3 and M12. RESULTS: The urinary metabolic patterns varied over time in cyclosporine- and tacrolimus-treated patients and were somewhat different at D7, M3, and M12 between the 2 treatment groups. Principal metabolites that differed, regardless of the treatment used, were mainly sugars, inositol, and hippuric acid. Interestingly, among tacrolimus-treated patients, different metabolic signatures were found between patients with immediate or delayed graft function at D7. CONCLUSION: Urinary metabolomics represents a noninvasive way of monitoring immunosuppressive therapy in renal transplant patients. Although it is too early to consider it as a biomarker of CNI-induced injury or graft function, metabolomics appears a promising evaluation tool in this area. Copyright © 2014 by Lippincott Williams & Wilkins.


PubMed | Service de Nephrologie Immunologie Clinique, French Institute of Health and Medical Research and Laboratoire Of Biochimie Et Biologie Moleculaire
Type: Journal Article | Journal: Journal of nephrology | Year: 2015

Late recognition plays an important role in prognosis associated with kidney disease; thus, information transfer at hospital discharge regarding kidney disease is crucial. Whether it is notified in patients hospital discharge summary (HDS) is presently largely unknown.Cross-sectional.The prevalence of kidney dysfunction [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and its reporting to primary-care physicians from 26 units [11 surgery, 11 medical, 4 intensive care units (ICUs)] of a university hospital were analyzed in 14,000 hospitalizations.eGFR.Notification of kidney dysfunction in HDS.GFR was estimated from serum creatinine using the Modification of Diet in Renal Disease formula.Kidney dysfunction was frequent (27.2 %) but infrequently notified in the main-body of the HDS (overall 25.3 %, medical 25 %, surgical 16.3 %, ICU 48.4 %) even when severe (eGFR 15-29.9 ml/min/1.73 m(2) was notified in 68.8, 38.5, and 79.8 % of HDSs in medical, surgical and ICUs, respectively). Notification in the HDS conclusion was rare (overall 11.4 %, medical 9.8 %, surgical 8.4 %, ICU 27.5 %). Reporting remained low when eGFR remained abnormal at discharge (medical 35.8 %, surgical 22.5 %, ICU 62.2 %) but was worse for acute kidney injury (16.0, 17.1, and 37.7 %, respectively). The optimal eGFR cut-off for reporting was 39 ml/min/1.73 m(2). Longer durations of hospitalization, greater numbers of creatinine measurements and of abnormal eGFR were associated with notification, regardless of the type of unit.Lack of data to define acute or chronic kidney injury with precision.Kidney dysfunction is frequent in hospitalized patients but is usually not notified, even when severe or still present at discharge, suggesting that it is not considered important to disclose to primary-care physicians. This lack of information may decrease physicians awareness, and may affect continuity of care in patients with kidney dysfunction.


Halimi J.-M.,Service de Nephrologie Immunologie Clinique
Transplantation | Year: 2013

Nephrotic-range proteinuria has been known for years to be associated with poor renal outcome. Newer evidence indicates that early (1-3 months after transplantation) low-grade proteinuria and microalbuminuria (1) provide information on the graft in terms of donor characteristics and ischemia/reperfusion injury, (2) may occur before the development of donor-specific antibodies, (3) predict the development of diabetes and cardiovascular events, and (4) are associated with reduced long-term graft and patient survivals.Low-grade proteinuria and microalbuminuria are also predictive of diabetes, cardiovascular morbidity, and death in nontransplanted populations, which may help us to understand the pathophysiology of low-grade proteinuria or microalbuminuria in renal transplantation. The impact of immunosuppressive medications, including mammalian target of rapamycin inhibitors, on graft survival is still discussed, and the effect on proteinuria is crucial to the debate. The fact that chronic allograft rejection may exist as early as 3 months after renal transplantation indicates that optimal management of low-grade proteinuria or microalbuminuria should occur very early after transplantation to improve long-term renal function and the overall outcome of renal transplant recipients. The presence of low-grade proteinuria or microalbuminuria early after transplantation must be taken into account to choose adequate immunosuppressive and antihypertensive medications. Limited information exists regarding the benefit of therapeutic interventions to reduce low-grade proteinuria or microalbuminuria. Whether renin angiotensin blockade results in optimal nephroprotection in patients with low-grade proteinuria or microalbuminuria is not proven, especially in the absence of chronic allograft nephropathy. Observational studies and randomized clinical trials yield conflicting results. Finally, randomized clinical trials are urgently needed. Copyright © 2013 by Lippincott Williams & Wilkins.


Badin J.,Service de Reanimation Medicale | Longuet H.,Service de Nephrologie immunologie Clinique | Guillon A.,Service de Reanimation Medicale | Barbet C.,Service de Nephrologie immunologie Clinique | And 4 more authors.
Transplantation Proceedings | Year: 2012

Kidney transplantation is the favored method to treat end-stage renal disease. Some recipients develop severe diseases requiring admission to an intensive care unit (ICU). Acute kidney injury (AKI) is a common complication among critically ill patients but few data are available among renal transplant recipients. The aim of this monocenter retrospective study was to describe renal function in kidney transplant recipients admitted to an ICU and to evaluate their renal functional recovery after this stay. We identified all renal transplant recipients admitted to our medical ICU from January 1, 2001, to December 31, 2010: namely, 79 stays by 62 patients. We used the glomerular filtration rate criteria of the RIFLE classification to evaluate AKI during the ICU stay. During the ICU stay, 56 patients (70.9%) were classified as "no AKI" according to the RIFLE classification; 11 (13.9%) belonged to class R, 10 (12.7%) to class I, and 2 (2.5%) to class F. Overall, 24% of the patients needed dialysis during the ICU stay. Mortality rate at 3 months after the ICU stay was 25.3%. Among the patients who survived, 40 (68%) recovered to their baseline renal function at 3 months, most of them being classified as no AKI during the ICU stay. We have herein reported the evolution of renal function among kidney graft recipients after an ICU stay. © 2012 Elsevier Inc.


Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a new family of hypoglycemic agents. Their hypoglycemic action is due to the glycosuria they induce: they inhibit the reabsorption of glucose and sodium in the renal proximal tubule. The efficacy of SGLT2 inhibitors depends on initial glycemia (as all hypoglycemic agents) and glomerular filtration rate (GFR) (poor efficacy in patients with GFR <45ml/min/m2). They also reduce arterial pressure by-4 (systolic) and-2 (diastolic) mmHg, and body weight by 2-3kg. Short-term tolerance is a key issue since they can provoke acute kidney dysfunction and hypotension requiring surveillance and adequate management. There is presently no data suggesting that they can be nephrotoxic over the long term; in contrast, some studies suggests that they could be afford some degree of renal protection in some patients, especially those with glomerular hyperfiltration which can be corrected by SGLT2 inhibitors. © 2015 - Elsevier Masson SAS - Tous droits réservés.


PubMed | Service de nephrologie immunologie clinique
Type: Comparative Study | Journal: Annales de cardiologie et d'angeiologie | Year: 2013

Abnormal albuminuria ( 30 mg/g) and low estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m(2)) not only are renal risk factors, but also cardiovascular and coronarian risk factors. Though, the relation between coronary risk and renal risk, and its interaction with insufficiently controlled brachial pressure (BP) is poorly described in the literature.We realised a cross-sectional study on subjects 40 and older, having attended a medical exam in 11 IRSA centers between 2006 and 2010. Every subject filled a questionnaire, underwent biological analysis, and a clinical examination. eGFR and albuminuria were measured, and the 10-year risk of coronarian event was calculated (Lauriers equation)We analysed 118,314 subjects, amongst whom 96,400 had no personal cardiovascular history. Amongst those, 9.1% had a 10-year coronary risk over 10%. There was a continuous relationship between coronary risk and renal risk: subjects with a risk above 15% had a significative risk of pathological albuminuria (OR: 6.87 [5.58-8.44]), and of low eGFR (2.26 [1.82-2.78]) compared to those with a risk under 5%. There was a continuous relationship between BP and renal risk, with a significative risk of pathological albuminuria (OR=7.75 [6.69-8.96]) and of low eGFR (OR: 1.33 [1.09-1.60]) in subjects with BP greater than or equal to 180/110 mmHg, compared to those with normal BP.In the French population, 9.1% of subjects have a 10-year coronary risk above 10%. This risk is associated to abnormalities of the renal function. The relation between coronary risk and renal risk is continuous and dose-dependent, as is the relation between BP and renal risk.


PubMed | Service de Nephrologie Immunologie Clinique
Type: Journal Article | Journal: Transplantation | Year: 2011

The predictive value of doubling of serum creatinine (DSC) has never been assessed in renal transplantation. We evaluated it in terms of its use for clinical trials, cost-effectiveness studies, and individual patients.Retrospective longitudinal study in 896 renal transplant recipients.Death-censored graft loss occurred in 133 patients, during follow-up (up to 21 years). DSC was a risk factor for graft loss; however, the relative risk was different in patients with glomerular filtration rate less than 40 vs. more than or equal to 40 mL/min (hazard ratio: 14.5 [95% confidence interval: 7.4-28.4] vs. 47.8 [28.4-80.6], P=0.0051). Parameters influencing creatinine value (weight, age, sex) did not modify DSCs predictive value. The use of the composite endpoint DSC or death-censored graft loss instead of death-censored graft loss alone in clinical trials would reduce sample size by 7.1% to 9.0%. The annual probability of DSC to graft loss transition decreased from 76% (follow-up <1 year) to 5% (follow-up 10 years). Median graft half-life after DSC was 10 months [95% confidence interval: 6-18] but varied with increasing time to DSC (<1 year: 1 month [0.5-6]; 3-4.9 years: 15 months 5/67) and reference creatinine (<130 mol/L: 3 months 2/6); 130 mol/L: 25 months 15/37).DSC may be adequately used to refine the risk of death-censored graft loss for individual patients. However, the use of DSC as an endpoint in clinical trials marginally affects sample size, and the probability of DSC to graft loss transition is not constant, which limits the use of DSC in cost-effectiveness analyses of renal transplantation.


PubMed | Service de Nephrologie Immunologie Clinique
Type: Journal Article | Journal: Transplant international : official journal of the European Society for Organ Transplantation | Year: 2012

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09), P<0.0001]. RI >0.75 (vs. 00.75) was a potent a predictor of NODAT [HR: 3.29 (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001] and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High RI early after renal transplantation is a long-term risk factor for NODAT, and could be used to refine the individual risk of NODAT.

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