The Urine-to-Plasma Urea Concentration Ratio is associated with eGFR and eGFR decline over time in a population cohort.

BACKGROUND Evaluation of renal function and of factors associated with its decline are important public health issues. Besides markers of glomerular function (e.g., GFR), those of tubular functions are rarely evaluated. Urea, the most abundant urinary solute, is markedly concentrated in urine when compared to plasma. We explored the urine-to-plasma ratio of urea concentrateions (U/P-urea-ratio) as a marker of tubular functions. METHODS We evaluated the relationship of the U/P-urea-ratio with eGFR at baseline in 1043 participants (48±17y) from the SKIPOGH population-based cohort, using mixed regression. In 898 participants, we assessed the relation between U/P-urea-ratio and renal function decline between two study waves 3 years apart. We studied U/P ratios for osmolarity, Na, K, uric acid for comparison. RESULTS In a transversal study at baseline, eGFR was positively associated with U/P-urea-ratio (βscaled = 0.08, 95%CI[0.04;0.13]) but not with the U/P ratio of osmolarity. Considering separately participants with renal function > or ≤ 90 ml/minx1.73m2, this association was observed only in those with reduced renal function. In the longitudinal study, eGFR declined at a mean rate of 1.2 ml/min per year. A significant association was observed between baseline U/P-urea-ratio and eGFR decline (βscaled = 0.08, 95%CI[0.01;0.15]). A lower baseline U/P-urea-ratio was associated with a greater eGFR decline. CONCLUSION This study provides evidence that the U/P-urea-ratio is an early marker of kidney function decline in the general adult population. Urea is easy to measure with well-standardized techniques and at low cost. Thus, the U/P-urea-ratio could become an easily available tubular marker for evaluating renal function decline

Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes.

peer reviewedBACKGROUND: Many kidneys donated for transplant in the United States are discarded because of abnormal histology. Whether histology adds incremental value beyond usual donor attributes in assessing allograft quality is unknown. METHODS: This population-based study included patients who received a deceased donor kidney that had been biopsied before implantation according to a prespecified protocol in France and Belgium, where preimplantation biopsy findings are generally not used for decision making in the allocation process. We also studied kidneys that had been acquired from deceased United States donors for transplantation that were biopsied during allocation and discarded because of low organ quality. Using donor and recipient characteristics, we fit multivariable Cox models for death-censored graft failure and examined whether predictive accuracy (C index) improved after adding donor histology. We matched the discarded United States kidneys to similar kidneys transplanted in Europe and calculated predicted allograft survival. RESULTS: In the development cohort of 1629 kidney recipients at two French centers, adding donor histology to the model did not significantly improve prediction of long-term allograft failure. Analyses using an external validation cohort from two Belgian centers confirmed the lack of improved accuracy from adding histology. About 45% of 1103 United States kidneys discarded because of histologic findings could be accurately matched to very similar kidneys that had been transplanted in France; these discarded kidneys would be expected to have allograft survival of 93.1% at 1 year, 80.7% at 5 years, and 68.9% at 10 years. CONCLUSIONS: In this multicenter study, donor kidney histology assessment during allocation did not provide substantial incremental value in ascertaining organ quality. Many kidneys discarded on the basis of biopsy findings would likely benefit United States patients who are wait listed

Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial

BACKGROUND: The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown. METHODS: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization. RESULTS: This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m2 vs 45.0 mL/min per 1.73 m2, P = 0.408). There were also no significant differences in the secondary endpoints of death (1.0% vs 1.5%; P = 0.737), primary nonfunction (4.1% vs 1.5%, P = 0.159), graft failure (3.1% vs 1.5%, P = 0.370), rejection (18.6% vs 13.6%, P = 0.289), and discontinuation of study medication (19.6% vs 12.6%, P = 0.348). Treatment failure, defined as a composite endpoint of these individual secondary endpoints, was more common in the early steroid withdrawal group (P = 0.027), but this group had fewer serious adverse events and a more favorable cardiovascular risk profile. CONCLUSIONS: Based on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis

Influence de la maladie rénale chronique terminale sur la disposition et le métabolisme extra rénal des médicaments : exemple des inhibiteurs du récepteur P2Y12 à l'ADP

La maladie coronarienne est l'une des principales causes de morbi-mortalité parmi les patients atteints d'une insuffisance rénale terminale (IRT). Le rôle de l'urémie comme facteur de risque indépendant de morbimortalité cardiovasculaire est incomplètement compris et pourrait impliquer une calcification des vaisseaux plus importante. Il semble également que les antiagrégants plaquettaires inhibant le récepteur P2Y12 à l'ADP comme le clopidogrel ou le prasugrel soient moins efficaces dans leur capacité à inhiber l'agrégation plaquettaire selon le degré d'insuffisance rénale chronique. Le cas d'un patient dialysé avec maladie coronarienne ayant présenté deux resténoses sur stent malgré un traitement de clopidogrel nous a conduit à une réflexion sur son efficacité dans ces conditions et à une revue de la littérature sur le niveau de preuve dans la prescription des antiagrégants plaquettaires lors de l'IRT. Les propriétés pharmacocinétiques de ces traitements sont potentiellement perturbées à différents niveaux (absorption, distribution, et métabolisme) pouvant conduire à une efficacité moindre qui a été décrite dans la littérature pour le clopidogrel et le prasugrel. Le ticagrélor semble donc être le traitement de choix dans cette indication chez le patient en IRT et sa prescription pourrait, à l'avenir, être quantifiée grâce au profil métabolomique des cytochromes P450 avant de débuter le traitement

Transcriptome de la biopsie et transplantation rénale : prêt pour la transition clinique ?

Kidney graft biopsy is the main diagnostic tool used in kidney transplantation to classify disease processes. Graft biopsies are performed at a predetermined time (protocol) or by indication. However, they bear limitations including the interobserver variability. Intragraft transcriptomics has taken the center stage in the field of biomarkers research in kidney transplantation as it might improve disease stratification. Although already included in the international Banff classification, clinical transition has yet to be confirmed in external validation studies. Also transcriptomics performance could benefit from association with other omics data. La biopsie du greffon rénal est l’un des principaux outils diagnostiques pour la classification des processus pathologiques en transplantation rénale. Les biopsies du greffon sont effectuées à temps fixe (biopsie de protocole) ou sur indication. Toutefois, elles ont plusieurs limitations dont la variabilité interobservateur. La transcriptomique intragreffon a pris une place prépondérante dans la recherche sur les biomarqueurs en transplantation rénale visant à une meilleure stratification des maladies. Bien que déjà incluse dans la classification internationale de Banff, la transition clinique doit être encore confirmée par des études de validation externe. Enfin, l’association à d’autres plateformes omics pourrait permettre une meilleure résolution de cet outil diagnostiqu

Recipient rs1045642 Polymorphism Is Associated With Office Blood Pressure at 1-Year Post Kidney Transplantation: A Single Center Pharmacogenetic Cohort Pilot Study

Background: Corticosteroids are associated with reduced bone mineral density (BMD), as well as water and salt retention, leading to hypertension. They are substrates for P-glycoprotein, a protein coded by the highly polymorphic ABCB1 gene. We hypothesized that one ABCB1 polymorphism, rs1045642, is associated with blood pressure and BMD parameters at 1-year post kidney transplantation (KT).Methods: Rs1045642 was genotyped using pyrosequencing in 40 KT recipients. Both dominant (CC vs. CT + TT) and codominant (CC vs. CT vs. TT) genetic models (analysis of variance from linear regressions) were adjusted for confounding variables (age, sex, type of nephropathy, glomerular filtration rate, and corticosteroid use at 1 year).Results: Rs1045642 genotypes were significantly associated with systolic (SBP) and diastolic (DBP) blood pressure 1-year post-transplantation, independent of the genetic model used (adjusted codominant model: SBP p-value = 0.015, DBP p-value = 0.038; adjusted dominant model: SBP p-value = 0.003, DBP p-value = 0.011). A non-statistically significant trend was observed for an association between rs1045642 and BMD change at 1-year post-KT.Conclusions: Rs1045642 is significantly associated with higher BP 1 year after KT. Further investigations are necessary to confirm the role of rs1045642 in corticosteroid-related adverse effects

Letter by Bouatou et al Regarding Article, "Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation"

Letter to the Editor

Maladies génétiques rénales : perspectives diagnostiques

Suspected renal inherited disorders are regularly evaluated in nephrology consultations both in adults and children. A positive family history and/or a typical phenotype should lead to genetic investigations. A confirmatory diagnosis integrated in a multidisciplinary genetic counseling approach gives patient guidance for further pregnancy. It also allows physician to better stratify disease risk and indicates treatment in some cases. The time to diagnosis and costs have been dramatically reduced thanks to next generation sequencing in several cases of complex inherited nephrologic syndromes