Comparison of different equations for renal function evaluation as proxies for antibiotic drug clearance: the examples of amoxicillin and cloxacillin

International audienceThe most appropriate renal function estimation equation to predict drug clearance is a matter of debate. In this study, we compare the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) and the Cockroft-Gault (CG) equations to predict amoxicillin and cloxacillin clearance among hospitalized patients receiving high doses of these antibiotic treatments. This study aimed to compare different equations used to predict amoxicillin and cloxacillin clearance among hospitalized patients receiving amoxicillin or cloxacillin treatments outside the intensive care unit. Data from 128 patients contributing 268 plasma samples was analyzed, and correlations between the equations and the amoxicillin and cloxacillin antibiotic clearance rates were calculated. We found a correlation between antibiotic clearance and all the renal function estimation equations, CG being the best, with a R(2) of 0.35 for amoxicillin and 0.29 for cloxacillin (compared to 0.26 and 0.21 for MDRD and 0.12 and 0.24 for CKD-EPI). CG should be preferentially used as a proxy for amoxicillin and cloxacillin drug clearance, but the use of completely different tools such as therapeutic drug monitoring could help individualize antibiotic dosage

A pharmacist-led intervention to improve kidney transplant recipient outcomes and identify patients at risk of highly variable trough tacrolimus levels: a cohort study

International audienceObjectivesGiven the positive impact of appropriate medication management on graft outcome and therefore of patient survival and graft function, the pharmacist's role in the kidney transplantation team has evolved over recent decades. The primary objective of this study was to determine whether pharmacist-led intervention after kidney transplantation is associated with a lower graft rejection rate and intra-patient variation in tacrolimus trough concentrations (C-min). The study's secondary objective was to develop a questionnaire to identify patients at risk for highly variable C-min. MethodsWe retrospectively analysed kidney transplant recipients at Rennes University Hospital (France) between January 2013 and December 2020. Patients who received pharmacist-led education (intervention group, n=139) were compared with patients who did not (control group, n=131), according to graft survival at 1 year post-transplant, coefficient of variation (%CV) for the tacrolimus C-min, age, sex, length of hospital stay post-transplantation, body mass index, and Charlson Comorbidity Index. In the intervention group, a questionnaire assessing patient knowledge was introduced to compare scores with the %CV. ResultsIn the intervention group, 1 year post-transplant graft survival was higher (95.7% vs 88.5%, p=0.0289) and patients had fewer variabilities in C-min. The %CV was correlated with questionnaire scores (r=-0.9758, p<0.0001). ConclusionsPharmacist-led interventions may have contributed to improved graft survival and patient management of immunosuppressants. Because %CV correlates with the patient questionnaire score, its introduction could be useful in identifying kidney transplant patients who would benefit most from a pharmacist-led patient education

HEMATURIA AND ABSENCE OF RETINOPATHY ARE NOT INDICATIVE OF NON -TYPE 2 DIABETES ASSOCIATED RENAL DISEASE IN PATIENTS WITH OTHERWISE TYPICAL DIABETIC KIDNEY DISEASE

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Modulation of the microbiota by oral antibiotics treats immunoglobulin A nephropathy in humanized mice

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgA is mainly produced by the gut-associated lymphoid tissue (GALT). Both experimental and clinical data suggest a role of the gut microbiota in this disease. We aimed to determine if an intervention targeting the gut microbiota could impact the development of disease in a humanized mouse model of IgAN, the α1KI-CD89Tg mice

The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN. Kidney International (2012) 82, 1284-1296; doi:10.1038/ki.2012.192; published online 5 September 2012Agence Nationale pour la Recherche (ANR JCJC)Agence Nationale pour la Recherche (ANR JCJC)Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale (FRM) [ING20080914226]ARC [SFI20111204013]ARCAAP du Programme National de Recherche en Nephrologie Urologie (PNR)AAP du Programme National de Recherche en Nephrologie Urologie (PNR)FAPESP-INSERMFAPESPINSERMCNPqINSERMCNPq-INSERMUSP/COFECUBUSP/COFECUBSocietede NephrologieSocietede NephrologieNIHNIH [DK061525, DK078244, DK082753, DK083663, DK075868, GM098539]Ministry of Education, Youth and Sport, Czech RepublicMinistry of Education, Youth and Sport, Czech Republic [MSM 6198959205, MSM 6198959216

Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study

International audienceKidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which producedextended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causingM/ME in the general population were infrequent (2%, forStreptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%–70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and theprobabilistic treatment of M/ME in SOTRs

Risk of Perforated Colonic Diverticulitis in Patients With Chronic Kidney Disease Requiring Sodium Polystyrene Sulfonate

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