LA CYSTATINE C (NOUVEAU MARQUEUR DES MOYENNES MOLECULES EN EPURATION EXTRA-RENALE ?)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Renal biopsies after 70 years of age: a retrospective longitudinal study from 2000 to 2007 on 150 patients in Western France.

International audienceThe elderly are more often referred to nephrologists and questions about indications for renal biopsy are increasing. The vascular lesions that appear with aging make the diagnosis of additional nephropathy more difficult. The purpose of our study is to investigate the characteristics of renal biopsies in the elderly in order to evaluate the indications and their use in guiding specific therapeutic interventions. Patients over 70 years who underwent a renal biopsy between 2000 and 2007 in Rennes University Hospital were retrospectively analyzed for biopsy complications, clinical features, diagnosis, therapy and its complications, evolution and mortality. Among the 150 renal-biopsied patients, 60% had a glomerulopathy and 30% had nephrotic syndrome. Biopsy complications occurred in 3.3%. 64% of nephrotic patients received immunosuppressive treatment and 62% of them developed drug-associated complications. In the treated group, there was more remission and survival at day 1000 was improved. Renal biopsy may be indicated in the elderly, because it often gives a therapeutically useful diagnosis and complications are rare if contra-indications are respected. Kidney biopsy revealed histological diagnoses that were not usually suspected by the clinical presentation. In addition, immunosuppressive therapy did not alter the mortality rate, but did increase survival at 3 years

FP148ATHEROSCLEROTIC RENAL STENOSIS REVASCULARISATION IN THE POST-ASTRAL ERA

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Warfarin-related nephropathy induced by three different vitamin K antagonists: analysis of 13 biopsy-proven cases

International audienceBackground: Acute kidney injury (AKI) with renal tubular obstruction by red blood cell casts (RBCC) has been described in patients treated with warfarin and is known as warfarin-related nephropathy (WRN). Methods: To determine whether other vitamin K antagonists (VKA) cause WRN, we retrospectively collected and analyzed the clinical and histological data of 13 patients treated with different VKA (seven with fluindione, four with warfarin and two with acenocoumarol) in seven French hospitals. Results: They all developed gross hematuria following overanticoagulation complicated by severe AKI (median serum creatinine concentration = 693 μmol/L). Histological analysis of the kidney biopsies highlighted the presence of intratubular RBCC and acute tubular necrosis in all patients and of an underlying kidney disease in 12 patients. WRN was suspected in patients treated with warfarin; however, the initial diagnosis was incorrect in six of the nine patients treated with other VKA. Nine patients progressed to chronic kidney disease, one fully recovered renal function, two died and one still needs dialysis. Conclusions: This is the first report of AKI caused by fluindione. In agreement with the recent publication on AKI in two patients treated with dabigatran, we suggest that the term 'anticoagulant-related nephropathy' is more appropriate than WRN. Gross hematuria in patients with an underlying kidney disease and treated with VKA requires rapid control of the international normalized ratio and renal function monitoring

Area under the curve of tacrolimus using microsampling devices: towards precision medicine in solid organ transplantation?

International audiencePurpose - Therapeutic drug monitoring of tacrolimus using trough concentration (C) is mandatory to ensure drug efficacy and safety in solid organ transplantation. However, C is just a proxy for the area under the curve of drug concentrations (AUC) which is the best pharmacokinetic parameter for exposure evaluation. Some studies suggest that patients may present discrepancies between these two parameters. AUC is now easily available through mini-invasive microsampling approach. The aim of this study is to evaluate the relationship between AUC and C in patients benefiting from a complete pharmacokinetic profile using a microsampling approach. Methods - Fifty-one transplant recipients benefited from a complete pharmacokinetic profile using a microsampling approach, and their 24-h AUC were calculated using the trapezoidal method. The correlation with C was then explored. In parallel, we estimated AUC using the sole C and regression equations according to the post-transplantation days and the galenic form. Results - Weak correlations were found between 24-h AUC observed and the corresponding C (R = 0.60) and between AUC observed and expected using the sole C (R = 0.62). Therapeutic drug monitoring of tacrolimus using C leads to over- or under-estimate drug exposure in 40.3% of patients. Conclusion - Tacrolimus C appears to be an imperfect reflection of drug exposure. Evaluating AUC using a microsampling approach offers a mini-invasive strategy to monitor tacrolimus treatment in transplant recipients

Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF-four-year results of the Postconcept study.

International audienceCalcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months. Renal function (Cockcroft and Gault) was significantly better at month 48 (M48) in the SRL group both in the intent-to-treat population (ITT): 62.6 mL/min/1.73 m(2) versus 57.1 mL/min/1.73 m(2) (p = 0.013) and in the on-treatment population (OT): 67.5 mL/min/1.73 m(2) versus 57.4 mL/min/1.73 m(2) (p = 0.002). Two biopsy proven acute rejection episodes occurred after M12 in each group. Graft and patient survival were comparable (graft survival: 97.4 vs. 100%; patient survival: 97.4 vs. 97.6%, respectively). The incidence of new-onset diabetes was numerically increased in the SRL group (7 vs. 2). In OT, three cancers occurred in the SRL group versus nine in the CsA group and mean proteinuria was increased in the SRL group (0.42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation

Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study

International audienceBackground: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking.Objectives: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻1, tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications.Methods: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻1 receiving prophylactic (4500 IU.d⁻1) or therapeutic (175 IU.kg⁻1.d⁻1) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates.Results: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻1, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications.Conclusion: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment

Diagnosis and Risk Factors for Intracranial Aneurysms in Autosomal Polycystic Kidney Disease: A cross-sectional study from the Genkyst Cohort

International audienceBACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyze the risk factors associated with the occurrence of IAs in ADPKD patients. METHODS: Cross-sectional study performed in 26 nephrology centers from the Western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes.RESULTS: Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9, 6.2 and 8.1% at 50, 60 and 70 y, respectively. While this risk appeared to be similar in male and female individuals <50 y, after that age, the risk continued to increase more markedly in female patients, reaching 10.8% vs 5.4% at 70 y. The diagnosis rate of IAs was more than twofold higher in PKD1 compared to PKD2 with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension <35 y, smoking and PKD1 genotype were associated with an increased risk for diagnosis of IAs.CONCLUSIONS: This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of estrogen

New clinical forms of hereditary apoA-I amyloidosis entail both glomerular and retinal amyloidosis

International audienceApolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs*47, and a novel p.Thr185Alafs*41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and visionsaving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis