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. glomerular filtration rate (GFR)], those of tubular functions are rarely evaluated. Urea, the most abundant urinary solute, is markedly concentrated in urine when compared with plasma. We explored the urine-to-plasma ratio of urea concentrations (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 ± 17 years) from the Swiss Kidney Project on Genes in Hypertension (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 and uric acid for comparison. RESULTS: In a transversal study at baseline, estimated GFR (eGFR) was positively associated with U/P-urea ratio [ßscaled = 0.08, 95% CI (0.04; 0.13)] but not with the U/P ratio of osmolarity. Considering separately participants with renal function >90 or ≤90 mL/min × 1.73 m2, 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 [ßscaled = 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.

BACKGROUND: 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.

Trajectories of glomerular filtration rate and progression to end stage kidney disease after kidney transplantation.

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

COVID-19-related medical research: a meta-research and critical appraisal.

BACKGROUND: Since the start of the COVID-19 outbreak, a large number of COVID-19-related papers have been published. However, concerns about the risk of expedited science have been raised. We aimed at reviewing and categorizing COVID-19-related medical research and to critically appraise peer-reviewed original articles. METHODS: The data sources were Pubmed, Cochrane COVID-19 register study, arXiv, medRxiv and bioRxiv, from 01/11/2019 to 01/05/2020. Peer-reviewed and preprints publications related to COVID-19 were included, written in English or Chinese. No limitations were placed on study design. Reviewers screened and categorized studies according to i) publication type, ii) country of publication, and iii) topics covered. Original articles were critically appraised using validated quality assessment tools. RESULTS: Among the 11,452 publications identified, 10,516 met the inclusion criteria, among which 7468 (71.0%) were peer-reviewed articles. Among these, 4190 publications (56.1%) did not include any data or analytics (comprising expert opinion pieces). Overall, the most represented topics were infectious disease (n = 2326, 22.1%), epidemiology (n = 1802, 17.1%), and global health (n = 1602, 15.2%). The top five publishing countries were China (25.8%), United States (22.3%), United Kingdom (8.8%), Italy (8.1%) and India (3.4%). The dynamic of publication showed that the exponential growth of COVID-19 peer-reviewed articles was mainly driven by publications without original data (mean 261.5 articles ± 51.1 per week) as compared with original articles (mean of 69.3 ± 22.3 articles per week). Original articles including patient data accounted for 713 (9.5%) of peer-reviewed studies. A total of 576 original articles (80.8%) showed intermediate to high risk of bias. Last, except for simulation studies that mainly used large-scale open data, the median number of patients enrolled was of 102 (IQR = 37-337). CONCLUSIONS: Since the beginning of the COVID-19 pandemic, the majority of research is composed by publications without original data. Peer-reviewed original articles with data showed a high risk of bias and included a limited number of patients. Together, these findings underscore the urgent need to strike a balance between the velocity and quality of research, and to cautiously consider medical information and clinical applicability in a pressing, pandemic context. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/5zjyx/.

Intragraft gene expression in native kidney BK virus nephropathy versus T cell-mediated rejection: Prospects for molecular diagnosis and risk prediction.

Novel tools are needed to improve diagnostic accuracy and risk prediction in BK virus nephropathy (BKVN). We assessed the utility of intragraft gene expression testing for these purposes. Eight hundred genes were measured in 110 archival samples, including a discovery cohort of native kidney BKVN (n = 5) vs pure T cell-mediated rejection (TCMR; n = 10). Five polyomavirus genes and seven immune-related genes (five associated with BKVN and two associated with TCMR) were significantly differentially expressed between these entities (FDR < 0.05). These three sets of genes were further evaluated in samples representing a spectrum of BK infection (n = 25), followed by a multicenter validation cohort of allograft BKVN (n = 60) vs TCMR (n = 10). Polyomavirus 5-gene set expression reliably distinguished BKVN from TCMR (validation cohort AUC = 0.992), but the immune gene sets demonstrated suboptimal diagnostic performance (AUC ≤ 0.720). Within the validation cohort, no significant differences in index biopsy gene expression were identified between BKVN patients demonstrating resolution (n = 35), persistent infection (n = 14) or de novo rejection (n = 11) 6 months following a standardized reduction in immunosuppression. These results suggest that, while intragraft polyomavirus gene expression may be useful as an ancillary diagnostic for BKVN, assessment for concurrent TCMR and prediction of clinical outcome may not be feasible with current molecular tools.

Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival.

BACKGROUND: Transplant glomerulopathy, a common glomerular lesion observed after kidney transplant that is associated with poor prognosis, is not a specific entity but rather the end stage of overlapping disease pathways. Its heterogeneity has not been precisely characterized to date. METHODS: Our study included consecutive kidney transplant recipients from three centers in France and one in Canada who presented with a diagnosis of transplant glomerulopathy (Banff cg score ≥1 by light microscopy), on the basis of biopsies performed from January of 2004 through December of 2014. We used an unsupervised archetype analysis of comprehensive pathology findings and clinical, immunologic, and outcome data to identify distinct groups of patients. RESULTS: Among the 8207 post-transplant allograft biopsies performed during the inclusion period, we identified 552 biopsy samples (from 385 patients) with transplant glomerulopathy (incidence of 6.7%). The median time from transplant to transplant glomerulopathy diagnosis was 33.18 months. Kidney allograft survival rates at 3, 5, 7, and 10 years after diagnosis were 69.4%, 57.1%, 43.3%, and 25.5%, respectively. An unsupervised learning method integrating clinical, functional, immunologic, and histologic parameters revealed five transplant glomerulopathy archetypes characterized by distinct functional, immunologic, and histologic features and associated causes and distinct allograft survival profiles. These archetypes showed significant differences in allograft outcomes, with allograft survival rates 5 years after diagnosis ranging from 88% to 22%. Based on those results, we built an online application, which can be used in clinical practice on the basis of real patients. CONCLUSIONS: A probabilistic data-driven archetype analysis approach applied in a large, well defined multicenter cohort refines the diagnostic and prognostic features associated with cases of transplant glomerulopathy. Reducing heterogeneity among such cases can improve disease characterization, enable patient-specific risk stratification, and open new avenues for archetype-based treatment strategies and clinical trials optimization.

Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients.

Anti-angiotensin II type 1 receptor (AT1R) antibodies have been associated with allograft rejection. We hypothesized that circulating AT1R antibodies might identify kidney transplant recipients at increased risk of allograft rejection and loss who are not identified by the HLA system. We prospectively enrolled 1845 kidney transplant recipients from two centers. Donor-specific HLA antibodies (DSAs) and AT1R antibodies were measured at the time of the first acute rejection episode or at 1 year post-transplant. Allograft biopsy was performed to evaluate the rejection phenotype and to assess for endothelial activation. Overall, 371 (20.1%) participants had AT1R antibodies, 334 (18.1%) had DSAs, and 133 (7.2%) had both. AT1R antibodies were associated with an increased risk of allograft loss (adjusted HR 1.49, 95% CI 1.07-2.06 for AT1R antibodies alone and 2.26, 95% CI 1.52-3.36 for AT1R antibodies and DSAs). Participants with AT1R antibodies had a higher incidence of antibody-mediated rejection (AMR) compared with participants without AT1R antibodies (25.0% vs. 12.9%). Among 77 participants with histological features of AMR but without DSAs, 51 (66.2%) had AT1R antibodies. Compared to participants with prototypical DSA-mediated rejection, those with AT1R antibody-associated rejection had a higher prevalence of hypertension, more vascular rejection with arterial inflammation, higher levels of endothelial-associated transcripts, and lack of complement deposition in allograft capillaries. Thus, AT1R antibodies may identify kidney transplant recipients at high risk of allograft rejection and loss, independent of the HLA system. Recognition of complement-independent AT1R antibody-mediated vascular rejection could lead to the development of new treatment strategies to improve allograft survival.

Response to treatment and long-term outcomes in kidney transplant recipients with acute T cell-mediated rejection.

The recent recognition of complex and chronic phenotypes of T cell-mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR-a condition previously considered to lack relevant consequences for allograft survival-to the standard of care. In a prospective cohort of kidney recipients (n = 256) with biopsy-proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3 months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR = 0.94; 95% CI = 0.92-0.96; P < .001), proteinuria (HR = 1.40; 95% CI = 1.10-1.79; P = .007), time since transplantation (HR = 1.02; 95% CI = 1.00-1.03; P = .016), peritubular capillaritis (HR = 2.27; 95% CI = 1.13-4.55; P = .022), interstitial inflammation in sclerotic cortical parenchyma (i-IF/TA) (HR = 1.87; 95% CI = 1.08-3.25; P = .025), and donor-specific anti-HLA antibodies (DSAs) (HR = 2.67; 95% CI = 1.46-4.88; P = .001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI = 0.68; 95% CI = 0.41-0.95; P < .001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i-IF/TA, and anti-HLA DSAs (cross-validated accuracy = 0.80). Compared with responders (n = 155, 60.5%), nonresponders (n = 101, 39.5%) had a higher incidence of de novo DSAs, antibody-mediated rejection, and allograft loss at 10 years (P < .001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes.

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis.

BACKGROUND: Anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients' access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations. METHODS AND FINDINGS: To address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus). A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55-3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05-6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection. CONCLUSIONS: In this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification. TRIAL REGISTRATION: National Clinical Trial protocol ID: NCT03438058.

Correction: Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1002572.].

Complement-binding anti-HLA antibodies are independent predictors of response to treatment in kidney recipients with antibody-mediated rejection.

A major hurdle to improving clinical care in the field of kidney transplantation is the lack of biomarkers of the response to antibody-mediated rejection (ABMR) treatment. To discover these we investigated the value of complement-binding donor-specific anti-HLA antibodies (DSAs) for evaluating the response to treatment. The study encompassed a prospective cohort of 139 kidney recipients with ABMR receiving the standard of care treatment, including plasma exchange, intravenous immunoglobulin and rituximab. Patients were systematically assessed at the time of diagnosis and three months after treatment initiation for clinical and allograft histological characteristics and anti-HLA DSAs, including their C1q-binding ability. After adjusting for clinical and histological parameters, post-treatment C1q-binding anti-HLA DSA was an independent and significant determinant of allograft loss (adjusted hazard ratio 2.57 (95% confidence interval 1.29-5.12). In 101 patients without post-treatment C1q-binding anti-HLA DSA there was a significantly improved glomerular filtration rate with significantly reduced glomerulitis, peritubular capillaritis, interstitial inflammation, tubulitis, C4d deposition, and endarteritis compared with 38 patients with posttreatment C1q-binding anti-HLA DSA. A conditional inference tree model identified five prognostic groups at the time of post-treatment evaluation based on glomerular filtration rate, presence of cg lesion and C1q-binding anti-HLA DSA (cross-validated accuracy: 0.77). Thus, circulating complement-binding anti-HLA DSAs are strong and independent predictors of allograft outcome after standard of care treatment in kidney recipients with ABMR.

Diagnostic accuracy of immunofluorescence versus immunoperoxidase staining to distinguish immune complex-mediated glomerulonephritis and C3 dominant glomerulopathy.

AIMS: The technique used for classification of membranoproliferative glomerulonephritis (MPGN) has been changed from an electron microscopy-based to an immunofluorescence (IF)-based semiquantitative technique with immunoperoxidase (IP) staining as a backup option when IF is not possible. Since data on that matter is lacking, our aims were to study the interobserver variability, the correlation and the reclassification of MPGN based on these two techniques. METHODS AND RESULTS: We retrospectively analysed cases of type 1 MPGN. We repeated IF staining and performed IP staining for IgG, kappa, lambda, C3c and C4d in 35 renal biopsies, among which 19 biopsies had matched IP and IF samples. We observed substantial to near-perfect agreement among the seven observers for both IF and IP (W coefficients from 0.66 for IF lambda to 0.89 for IF C4d). Of the 19 cases with matched IP and IF samples, five (26%) turned out to have different diagnoses on IF and on IP. Also, the ability of C4d to discriminate immune complex-mediated glomerulonephritis (ICGN) from C3 glomerulopathy (C3G) was poor, with areas under the curve of 0.44 [95% confidence interval (CI) 0.24-0.63] and 0.66 (95% CI 0.50-0.81) for the receiver operating characteristic curves of IF and IP respectively. Limitations include the fact that no clinical data regarding complement activation were available. CONCLUSION: The diagnosis of ICGN versus C3GN depends on the immunochemical technique used. Also, the use of C4d failed to discriminate ICGN from C3G in our study. Further validation studies are required to avoid misdiagnosis based on kidney biopsy.

Clinical and histological evolution after de novo donor-specific anti-human leukocyte antigen antibodies: a single centre retrospective study.

BACKGROUND: Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) can be preformed or de novo (dn). Strategies to manage preformed DSA are well described, but data on the management and outcomes of dnDSA are lacking. METHODS: We performed a retrospective analysis of data from a single centre of the management and outcomes of 22 patients in whom a dnDSA was identified with contemporary and follow up biopsies. RESULTS: Evolution from baseline to follow up revealed a statistically significant loss of kidney function (estimated glomerular filtration rate: 45.9 ± 16.7 versus 37.4 ± 13.8 ml/min/1.73 m2; p = 0.005) and increase in the proportion of patients with transplant glomerulopathy (percentage with cg lesion ≥1: 27.2% vs. 45.4%; p = 0.04). Nine patients were not treated at the time of dnDSA identification, and 13 patients received various drug combinations (e.g., corticosteroids, plasmapheresis, thymoglobulins and/or rituximab). No significant pathological changes were observed for the various treatment combinations. CONCLUSION: Our retrospective analysis of a small sample suggests that dnDSA should be considered a risk factor for the loss of kidney function independent of the baseline biopsy, and multidisciplinary evaluations of the transplant patient are a necessary requirement. Further confirmation in a multicentre prospective trial is required.

[Nephrology]. / Néphrologie.

New antidiabetic drugs which slow effectively the course of diabetic nephropathy are now available. There is no benefit of prophylactic hydratation to prevent contrast nephropathy in patients with moderate chronic kidney disease. In elderly hemodialysis patients, hemodiafiltration seems better tolerated than conventional hemodialysis, although there is a similar dialysis-induced myocardial stress with both methods. Role of de novo donor-specific antibodies is better characterized, which may subsequently lead to new treatments of graft rejection.

La prise en charge de la néphropathie diabétique a connu une avancée majeure avec de nouvelles classes thérapeutiques aux propriétés néphro- et cardioprotectrices importantes. L'hydratation prophylactique n'apporte pas de bénéfice avéré lors d'administration de produit de contraste chez des patients avec insuffisance rénale chronique modérée. En hémodialyse chonique, l'hémodiafiltration semble mieux tolérée chez les personnes âgées que l'hémodialyse traditionnelle, bien qu'elle engendre durant la séance de dialyse le même stress myocardique. En transplantation, le rôle des anticorps dirigés contre le donneur est mieux précisé et laisse espérer à l'avenir des traitements mieux ciblés pour éviter le rejet.

A population-based approach to assess the heritability and distribution of renal handling of electrolytes.

The handling of electrolytes by the kidney is essential for homeostasis. However, the heritability of these processes, the first step in gene discovery, is poorly known. To help clarify this, we estimated the heritability of serum concentration, urinary excretion, renal clearance, and fractional excretion of sodium, potassium, magnesium, calcium, phosphate, and chloride in a population-based study. Nuclear families were randomly selected from the general population in Lausanne, Geneva, and Bern, Switzerland, and urine collected over 24-hour periods. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including sex, age, body mass index, and study center as covariates in the model. The 1128 participants, from 273 families, had a mean age of 47 years, body mass index of 25.0 kg/m2, and an estimated glomerular filtration rate (CKD-EPI) of 98 mL/min/1.73 m2. The heritability of serum concentration was highest for calcium, 37% and lowest for sodium, 13%. The heritability of 24-hour urine clearances, excretions, and fractional excretions ranged from 15%, 10%, and 16%, respectively, for potassium to 45%, 44%, and 51%, respectively, for calcium. All probability values were significant. The heritability for phosphate-related phenotypes was lower than that for calcium. Thus, the serum and urine concentrations as well as urinary excretion and renal handling of electrolytes are heritable in the general adult population. The phenotypic variance attributable to additive genetic factors was variable and was higher for calcium. These results pave the way for identifying genetic variants involved in electrolyte homeostasis in the general population.

Nephrotic Syndrome in Small Cell Lung Cancer and Induction of C-Mip in Podocytes.

Paraneoplastic nephrotic syndrome is often a complication in patients with cancer, and various histologic lesions have been described in the kidney. We report the case of a 76-year-old woman who presented with a podocytopathy that was found to be associated with a small cell lung carcinoma (SCLC). One cycle of carboplatin-etoposide combination therapy led to resolution of nephrotic syndrome and remission of the lung carcinoma. C-Maf-inducing protein (C-Mip) was overexpressed in both podocytes and cancer cells, but was not found in control kidney and lung tissue samples. C-Mip also was absent in SCLC cells from 30 patients without nephrotic syndrome. Exposing cultured podocytes to a sample of our patient's serum that was collected prior to chemotherapy led to disorganization of the podocyte cytoskeleton and induction of C-Mip expression, which was not observed with control serum or our patient's serum sampled after chemotherapy. These observations suggest that C-Mip may play an important role in SCLC-related podocytopathy and that a circulating factor likely induces its expression in the kidney.

[Biopsy transcriptome in kidney transplantation : ready for primetime ?] / 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 diagnostique.

[Genetic kidney diseases: new perspectives on diagnosis]. / 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.

[Nephrology: news in renal transplantation]. / Néphrologie. Actualités 2014 en transplantation rénale.

The selection of potential living donors will have to consider the latest data on risk factors for morbidity and mortality when a first degree relationship exists with a recipient in end-stage renal disease of unknown, and for women of childbearing age. Renal transplant patients with active hepatitis C of unknow origin will benefit from new antivirals without the risk of acute rejection. Preemptive CYP3A5 genotyping and extended-release tacrolimus formulations should allow the prescription of a suitable dose of tacrolimus immediately and avoid overexposure as a source of nephrotoxicity. The place of everolimus and belatacept in the panel of immunosuppressive treatments is being defined, based on infectious and immunologic risk factors.