[EMPA-KIDNEY: empagliflozin in chronic kidney disease]. / EMPA-KIDNEY : l'empagliflozine dans la maladie rénale chronique.

The inhibition of the renin-angiotensin system represents the first preventive treatment of the chronic kidney disease (CKD), especially in presence of albuminuria. Recently, sodium-glucose cotransporter type 2 inhibitors (SGLT2i, gliflozins) demonstrated a nephroprotective effect, first in patients with type 2 diabetes at cardiovascular risk, then in diabetic patients with CKD assessed by a reduction of the glomerular filtration rate (GFR) and albuminuria (CREDENCE with canagliflozin), and finally in patients with CKD and albuminuria, with or without diabetes (DAPA-CKD with dapagliflozin). EMPA-KIDNEY study compared the effects of empagliflozin 10 mg/day versus placebo in patients with CKD, with or without diabetes. In comparison with the two previous renal studies, this clinical trial randomised patients with a lower GFR (78 % of patients with GFR inferior to 45 mL/min/1.73 m²) and a lower level of albuminuria (20 % of patients without pathological albuminuria). EMPA-KIDNEY demonstrated a reduction by 28 % (p inferior to 0.001) of the primary composite outcome (progression of CKD or cardiovascular death) and of several renal endpoints, including the shift to terminal CKD (-33 %), independently of the presence of diabetes, and with a tolerance profile comparable to what is already known. EMPA-KIDNEY results reinforce the use of SGLT2is, in general, and of empagliflozin, in particular, in a broader population with CKD and, thus, the indication of this pharmacological class in nephrology in combination with inhibitors of the renin-angiotensin system.

L'inhibition du système rénine-angiotensine représente le premier traitement de prévention de la maladie rénale chronique (MRC), en particulier chez les patients avec albuminurie. Récemment, les inhibiteurs des cotransporteurs sodium-glucose de type 2 (iSGLT2, gliflozines) ont démontré une néphroprotection, d'abord chez les patients avec un diabète de type 2 à risque cardiovasculaire, puis chez des patients avec MRC avec diminution du débit de filtration glomérulaire (DFG) et albuminurie (CREDENCE avec la canagliflozine), puis chez des patients avec MRC albuminurique, avec ou sans diabète (DAPA-CKD avec la dapagliflozine). L'étude EMPA-KIDNEY a comparé les effets de l'empagliflozine 10 mg/jour à un placebo chez des patients avec MRC, avec ou sans diabète. Par comparaison aux deux études précédentes, cet essai a recruté des patients avec un DFG plus bas (78 % de patients avec un DFG inf�rieur a 45 mL/min/1,73 m²) et avec un niveau d'albuminurie plus faible (dont 20 % de patients sans albuminurie pathologique). EMPA-KIDNEY a démontré une réduction de 28 % (p inf�rieur a 0,001) du critère primaire composite (progression de la MRC ou mort cardiovasculaire) et de divers critères rénaux secondaires, dont l'évolution vers la MRC terminale (-33 %), indépendamment de la présence d'un diabète, et avec un profil de tolérance de l'empagliflozine comparable à celui déjà connu. EMPA-KIDNEY consolide l'utilisation des iSGLT2, en général, et de l'empagliflozine, en particulier, dans une population plus diversifiée en ce qui concerne la MRC et, donc, l'indication de cette classe pharmacologique en néphrologie en combinaison avec les inhibiteurs du système rénine-angiotensine.e.

[Diagnostic approach to chronic kidney disease]. / Vignette diagnostique de l'étudiant. Approche diagnostique de la maladie rénale chronique.

Chronic kidney disease (CKD) affects ~7 % of the general population and is burdened with significant morbidity and mortality, especially cardiovascular disease. At the terminal stage, CKD requires demanding and costly treatments for the patient and the society, such as dialysis or kidney transplantation. The symptomatology of CKD is poor and unspecific, which complicates the identification and early management of patients with CKD. Diagnostic criteria for CKD include (1) renal morphological abnormality; and/or (2) proteinuria superior to150 mg/g creatinine; and/or (3) glomerular filtration rate (GFR) inferior to 60 ml/min/ 1.73 m². The persistence of these abnormalities for more than 3 months indicates the chronicity of the renal damage. Starting from an exemplary clinical case, we detail the diagnostic steps when faced with a suspicion of CKD.

: La maladie rénale chronique (MRC) touche ~7 % de la population générale et est grevée d'une morbi-mortalité, notamment cardiovasculaire, significative. à son stade terminal, la MRC nécessite des traitements lourds et coûteux pour le patient et pour la société, tels que la dialyse ou la transplantation rénale. La symptomatologie de la MRC est frustre et aspécifique, ce qui complique l'identification et la prise en charge précoce des patients insuffisants rénaux chroniques. Les critères diagnostiques de la MRC incluent (1) une anomalie morphologique rénale, et/ou (2) une protéinurie sup�rieur a 150 mg/g créatininurie, et/ou (3) un débit de filtration glomérulaire (DFG) inf�rieur a 60 ml/min/1,73 m². La persistance de ces anomalies pendant plus de 3 mois signe la chronicité de l'atteinte rénale. Au départ d'une vignette clinique paradigmatique, nous détaillons les étapes diagnostiques face à une suspicion de MRC.

[From the discovery of phlorizin (a Belgian story) to SGLT2 inhibitors]. / De la découverte de la phlorizine (une histoire belge) aux inhibiteurs des SGLT2.

Most physicians do not know, or do not remember, the name of phlorizin. Hence this molecule has a major historical importance because it was the precursor of gliflozins, a new class of oral antidiabetic drugs with recent therapeutic perspectives beyond diabetes. This article recalls the history of phlorizin: its discovery in the 19th century by De Koninck and Stas, the demonstration of its ability to induce glucosuria and reduce hyperglycaemia by von Mering, its use to demonstrate the concept of glucose toxicity by the team of DeFronzo and finally the development of selective (phlorizin being not selective) sodium-glucose cotransporter type 2 inhibitors (gliflozins) which block glucose reabsorption in renal tubules. Gliflozins have increasing therapeutic indications, not only in type 2 diabetes, but also in cardiology and nephrology among non-diabetic people with heart failure or renal insufficiency.

La plupart des médecins ne connaissent pas, ou ne se souviennent plus, de la phlorizine. Pourtant, cette molécule a une grande importance historique car elle a été le précurseur des gliflozines, une nouvelle classe d'antidiabétiques oraux ouvrant maintenant de nouvelles perspectives thérapeutiques au-delà du diabète. Cet article retrace l'histoire de la phlorizine : sa découverte au 19ème siècle par De Koninck et Stas, la démonstration de l'induction d'une glucosurie abaissant la glycémie par von Mering, son utilisation pour conceptualiser la notion de glucotoxicité par l'équipe de DeFronzo et, enfin, le développement d'inhibiteurs sélectifs (la phlorizine étant non sélective) des cotransporteurs sodium-glucose de type 2 (SGLT2, gliflozines),dans les tubules rénaux, bloquant la réabsorption du glucose. Les gliflozines ont, maintenant, des indications thérapeutiques de plus en plus larges, non seulement dans le diabète de type 2, mais aussi en cardiologie et en néphrologie chez des personnes non diabétiques avec insuffisance cardiaque ou insuffisance rénale.

[SGLT2 inhibitors and RAAS blockers : similarities, differences and complementarity]. / Inhibiteurs des SGLT2 et bloqueurs du système rénine-angiotensine. Similitudes, différences et complémentarité.

Both renin-angiotensin-aldosterone system inhibitors (RAASi) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i, gliflozins) reduce the risk of heart failure and of progressing towards end-stage renal disease, especially in patients with type 2 diabetes (T2D). Positive results reported in patients with T2D have been confirmed in people without diabetes. These two pharmacological classes now occupy a privileged place in international guidelines, in diabetology, cardiology and nephrology. The present article describes similarities and differences between these two types of medications. It emphasizes the importance of combining both approaches in order to optimize the cardiovascular and renal prognosis, while maintaining a good safety profile.

Les inhibiteurs du système rénine-angiotensine-aldostérone (iSRAA) et les inhibiteurs des cotransporteurs sodium-glucose de type 2 (iSGLT2, gliflozines) réduisent le risque d'insuffisance cardiaque et de progression vers l'insuffisance rénale terminale, notamment chez les patients avec un diabète de type 2 (DT2). Les effets positifs rapportés chez les patients DT2 ont été confirmés chez les personnes non diabétiques. Ces deux classes pharmacologiques occupent maintenant une place de choix dans les recommandations internationales, en diabétologie, en cardiologie et en néphrologie. Cet article fait le point sur les similitudes et les différences entre ces deux familles médicamenteuses. Il insiste sur l'importance de les combiner pour optimiser le pronostic cardiovasculaire et rénal, tout en maintenant un bon niveau de sécurité.

[SGLT2 inhibitors in patients with chronic kidney disease : from clinical trials to guidelines and new prospects for clinical practice]. / Inhibiteurs des SGLT2 chez les patients avec insuffisance rénale chronique : des essais contrôlés aux recommandations internationales et perspectives en pratique clinique.

Sodium-glucose cotransporter type 2 inhibitors (iSGLT2 or gliflozins) exert their antidiabetic action through a specific renal mechanism, by inhibiting tubular glucose reabsorption. These agents have proven their efficacy to reduce major cardiovascular events and hospitalisation for heart failure, but also the progression of chronic kidney disease (CKD), in patients with type 2 diabetes (T2DM) at high risk, independently of glucose control. While the glucose-lowering effect of iSGLT2 is decreasing with the decline of estimated glomerular filtration rate (eGFR), both cardiovascular and renal protections remain present until an eGFR as low as 30 ml/min/1,73 m². These effects were demonstrated in several meta-analyses and in two trials specifically dedicated to renal outcomes in patients with CKD and macroalbuminuria : CREDENCE with canagliflozin and Dapa-CKD with dapagliflozin. In addition, Dapa-CKD showed similar positive results whatever the presence or absence of T2DM. Safety profile of SGLT2is among patients with CKD is good and similar to that of patients with normal renal function. These favourable findings led to a privileged place of SGLT2i in recent international guidelines promoted by diabetologists, cardiologists and nephrologists. Current restrictive criteria for the prescription and reimbursement of SGLT2i in Belgium according to eGFR level (initiation only if eGFR superior to 60 and interruption if eGFR inferior to 45 ml/min/1.73 m²) should be enlarged very soon owing to convincing results of published controlled trials.

Les gliflozines (inhibiteurs des cotransporteurs sodium-glucose de type 2 ou iSGLT2) ont un mécanisme d'action antidiabétique spécifiquement rénal, en inhibant la réabsorption tubulaire du glucose. Indépendamment du contrôle glycémique, ces médicaments ont prouvé leur efficacité pour réduire les événements cardiovasculaires majeurs et les hospitalisations pour insuffisance cardiaque, mais aussi la progression vers l'insuffisance rénale chronique (IRC) terminale chez des patients diabétiques de type 2 (DT2) à haut risque. Si l'effet anti-hyperglycémiant des iSGLT2 diminue avec le déclin du débit de filtration glomérulaire (DFG), les effets protecteurs cardiovasculaires et rénaux persistent au moins jusqu'à un DFG de 30 ml/min/1,73 m². Ces effets ont été démontrés dans plusieurs méta-analyses des essais cardiovasculaires et dans deux essais spécifiquement à visée rénale chez des patients avec IRC et macroalbuminurie, CREDENCE avec la canagliflozine et Dapa-CKD avec la dapagliflozine. En outre, Dapa-CKD a montré les mêmes effets positifs en cas d'IRC non diabétique. Par ailleurs, le profil de sécurité des gliflozines chez les patients avec IRC est bon et comparable à celui des patients avec fonction rénale normale. Ces résultats favorables ont donné aux iSGLT2 une place privilégiée dans les dernières recommandations internationales diabétologiques, cardiologiques et néphrologiques. Les critères restrictifs actuels de prescription et de remboursement en Belgique des iSGLT2 en fonction du niveau de DFG (instauration si DFG sup�rieur a 60 et interruption si DFG inf�rieur a 45 ml/min/1,73 m²) devraient être élargis prochainement au vu des résultats convaincants des essais cliniques disponibles.

[Kidney injury in COVID-19]. / Atteintes rénales de la COVID-19.

The SARS-CoV-2 virus causes a respiratory distress syndrome, the main symptom of COVID-19 (for "COronaVIrus Disease 2019"). This infectious disease has been causing a major health and socio-economic pandemic since December 2019. The pulmonary alveolus is regarded as the main target of SARS-CoV-2. However, this coronavirus is capable of directly or indirectly affecting other organs, including the kidneys. Here, we summarize the presumed pathophysiology of COVID-19 renal disease. The incidence of acute kidney injury ranges from 0,5 to 22 % of all patients infected with SARS-CoV-2. The need for renal replacement therapy is reported in 5-9 % of patients in intensive care. Histological analysis of renal biopsies mainly shows acute tubular necrosis of varying severity, as well as the congestion of glomerular and peri-tubular capillaries. Endothelitis has been described in few cases. Evidence for a factual inflammation of the glomerulus remains controversial. The medium/long term consequences of COVID-19 nephropathy are unknown and will deserve a tight follow-up.

Le virus SARS-CoV-2 provoque un syndrome de détresse respiratoire aiguë, le symptôme principal de l'infection COVID-19 (pour «COronaVIrus Disease 2019¼). Cette maladie infectieuse provoque une pandémie de gravité sanitaire et socio-économique majeure depuis décembre 2019. La cible principale du SARS-CoV-2 serait l'alvéole pulmonaire. Néanmoins, ce coronavirus est capable d'affecter directement ou indirectement d'autres organes, y compris les reins. Nous résumons ici la physiopathologie présumée de l'atteinte rénale de la COVID-19. L'incidence de l'insuffisance rénale aiguë varie entre 0,5 à 22 % de tous les patients infectés par le SARS-CoV-2. La nécessité d'une épuration extra-rénale est rapportée chez 5-9 % des patients pris en charge aux soins intensifs. L'analyse histologique de biopsies rénales montre, principalement, une nécrose tubulaire aiguë de sévérité variable, ainsi qu'une congestion des capillaires glomérulaires et péri-tubulaires. Une endothélite a parfois été décrite. L'atteinte inflammatoire du glomérule reste débattue. Les conséquences à moyen/long termes de la néphropathie COVID-19 sont inconnues et mériteront un suivi étroit.

[Therapeutic innovation in nephrology : 10 years of progress]. / Nouveautés thérapeutiques en néphrologie : 10 ans d'avancées.

Chronic kidney disease (CKD) impairs the quality of life and increases the risk for cardiovascular morbimortality. Intensive research is conducted in order to slow down CKD development and progression. During the past decade, a better understanding of the pathophysiological mechanisms of glomerular diseases has highlighted the benefits of rituximab. Progresses have also been made in the understanding of the mechanisms of autosomal polycystic kidney disease, the most frequent inherited kidney disease. These observations led to the discovery and validation of tolvaptan, a blocker of the V2 receptor of the antidiuretic hormone as an innovative treatment. Type 2 diabetic disease is the leading cause worldwide of endstage kidney disease and dialysis. The development of new drugs, such as the gliflozins (inhibiting the sodium glucose reabsorption in the proximal tubule), has contributed to an improvement in the management of the cardiovascular and renal risks especially reducing congestive heart failure rate. Another important progress in nephrology since the beginning of the new century concerns a more precise estimation of the kidney function, which allows to better evaluate the slope of CKD progression and test the influence of different therapeutic approaches aiming at correcting anemia, hyperkalemia, metabolic acidosis and disturbances of calcium and phosphate. The present review summarizes all of these major advances in the field of CKD diagnosis and treatment, and envisions the future of nephrology for the next decade.

L'insuffisance rénale chronique (IRC) altère la qualité de vie, expose à une morbi-mortalité cardiovasculaire majorée, et peut conduire à la dialyse chronique et/ ou la transplantation rénale. Tout progrès qui freinerait le développement et la progression de cette IRC est le bienvenu. Au cours de ces dernières années, une meilleure compréhension des mécanismes physiopathologiques de certaines maladies glomérulaires a permis l'utilisation d'un traitement plus ciblé, le rituximab, qui apporte une nouvelle option dans des situations difficiles. Des progrès ont également été faits dans la compréhension des mécanismes expliquant la perte de fonction rénale chez le patient atteint de polykystose rénale autosomique dominante, la maladie rénale génétique la plus fréquente. Les études cliniques ont permis de démontrer la néphro-protection du tolvaptan, un antagoniste des récepteurs V2 de l'hormone antidiurétique. Dans le domaine du diabète de type 2, première cause mondiale de prise en charge en dialyse, l'avènement des gliflozines (inhibiteurs de la réabsorption tubulaire rénale de glucose et de sodium) a été une réelle révolution thérapeutique pour freiner l'évolution de l'insuffisance rénale chronique et limiter le risque cardiovasculaire (surtout la décompensation cardiaque) de ces patients. Enfin, une meilleure estimation de la fonction rénale a permis de mieux situer le patient dans sa vitesse de progression à travers les différents stades de l'IRC. Ce faisant, la gestion des anomalies métaboliques rencontrées au cours de celle-ci, telles qu'anémie, hyperkaliémie, acidose, troubles du métabolisme phosphocalcique, s'est améliorée. Cette revue fait état des avancées majeures dans le domaine du diagnostic de l'IRC et de ses traitements et envisage le futur de la néphrologie dans les 10 prochaines années.

[How I explore a proteinuria]. / Comment j'explore une protéinurie.

The measurement of proteinuria is a very simple tool to screen and manage kidney diseases. Its predictive role is also relevant from a cardiovascular point of view. However, the interpretation of the results is not always easy. Indeed, there are several different methods to detect or measure proteinuria (or albuminuria), varying from the measurement on a 24-hour urine collection to the simplest detection with dipsticks or measurement on a random urine sample. Some methods are measuring total proteins, whereas others are measuring more specifically albuminuria. For all methods, pitfalls exist and will be discussed. A positive result must be confirmed by a quantitative measurement on 24-hour collection or on a first morning sample (this last one can only be interpreted as a ratio to urinary creatinine excretion). Lastly, we will briefly discuss the management of a patient with a new diagnosis of proteinuria (or albuminuria).

La recherche d'une protéinurie est un outil simple de dépistage et de suivi de la maladie rénale. Elle a aussi un rôle prédictif important, que ce soit au niveau néphrologique ou cardiovasculaire. Son interprétation n'est cependant pas toujours simple. Il existe, en effet, différentes méthodes pour évaluer la protéinurie (ou l'albuminurie) qui vont d'une mesure sur la récolte de 24h à l'utilisation simple de la bandelette réactive (« tigette ¼) sur un échantillon urinaire. Certaines méthodes permettent la recherche et/ou la quantification de la protéinurie dite totale, alors que d'autres mesurent plus exclusivement l'albuminurie. Pour toutes les méthodes et pour tous les dosages, des pièges diagnostiques existent et seront discutés. Un résultat positif doit systématiquement être confirmé quantitativement sur un second échantillon soit à partir d'urine de 24h, soit sur un échantillon du matin (la mesure sur échantillon n'étant interprétable que si elle est rapportée à l'excrétion urinaire de créatinine). Enfin, nous tracerons les grandes lignes de la prise en charge d'un patient chez qui une protéinurie (ou une albuminurie) est découverte.

Renal outcomes with dipeptidyl peptidase-4 inhibitors.

Dipeptidyl peptidase-4 inhibitors (DPP-4is) are increasingly being used in the management of type 2 diabetes (T2D). The present review summarizes the current knowledge of the effects of DPP-4is on renal outcomes by analyzing the experimental preclinical data, the effects of DPP-4is on urinary albumin-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) from observational studies and clinical trials, and renal events (including kidney failure requiring renal replacement therapy) in recent large prospective cardiovascular outcome trials. Renal protection has been demonstrated in various animal models that have implicated different underlying mechanisms independent of glucose control, whereas prevention of new onset microalbuminuria and/or progression of albuminuria has been reported in some clinical studies, but with no significant effects on eGFR in most of them. The long-term clinical effects of DPP-4is on renal outcomes and the development of end-stage renal disease remain largely unknown and, thus, demand further investigations in prospective trials and long-term observational studies. In conclusion, despite promising results in animal models, data on surrogate biological markers of renal function and clinical renal outcomes remain rather scanty in patients with T2D, and mostly demonstrate the safety rather than true efficacy of DPP-4is.

CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing in HIV-infected patients.

OBJECTIVES: To evaluate concordance between glomerular filtration rate (GFR) estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic kidney disease epidemiology study group equations) for drug dosing in HIV-infected patients. PATIENTS AND METHODS: We performed a monocentric study. GFR was measured using the gold standard method (plasma clearance of iohexol) in 230 HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR) and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90 mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and without indexation to body surface area (BSA). RESULTS: Mean age was 48±10 years, mean mGFR was 101±26 mL/min. Concordance between mGFR and eGFR estimated with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as the breakpoint value, all equations had similar concordance rates with mGFR (with or without indexation to BSA). CONCLUSION: CKD-EPI equation has the same concordance with GFR and with CG when used for drug dosing.

Osteoporosis in Frail Patients: A Consensus Paper of the Belgian Bone Club.

In this consensus paper, the Belgian Bone Club aims to provide a state of the art on the epidemiology, diagnosis, and management of osteoporosis in frail individuals, including patients with anorexia nervosa, patients on dialysis, cancer patients, persons with sarcopenia, and the oldest old. All these conditions may indeed induce bone loss that is superimposed on physiological bone loss and often remains under-recognized and under-treated. This is of particular concern because of the major burden of osteoporotic fractures in terms of morbidity, mortality, and economic cost. Therefore, there is an urgent need to appreciate bone loss associated with these conditions, as this may improve diagnosis and management of bone loss and fracture risk in clinical practice.

Effects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial.

The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

[Rituximab (MabThera): a new therapy for ANCA vasculitis]. / Le médicament du mois. Rituximab (MabThera): nouveau médicament dans les vascularites associées á ANCA.

Three recently published randomized studies have demonstrated the efficacy of rituximab in the induction and maintenance therapy of ANCA vasculitis. This is a major advance since these types of vasculitis entail a high morbity and mortality.

KDIGO Guidelines and Kidney Transplantation: Is the Cystatin-C Based Recommendation Relevant?

The KDIGO guidelines propose a new approach to diagnose chronic kidney disease (CKD) based on estimated glomerular filtration rate (GFR). In patients with a GFR value comprised between 45 and 59 mL/min/1.73 m(2) as estimated by the CKD-EPI creatinine equation (eGFRcreat ), it is suggested to confirm the diagnosis with a second estimation using the CKD-EPI cystatin C-based equations (eGFRcys /eGFRcreat-cys) . We sought to determine whether this new diagnostic strategy might extend to kidney transplant recipients (KTR) and help to identify those with decreased GFR. In 670 KTR for whom a measured GFR was available, we simulated the detection of CKD using the two-steps approach recommended by the guidelines in comparison to the conventional approach relying on creatinine equation. One hundred forty-five patients with no albuminuria had eGFRcreat between 45 and 59 mL/min/1.73 m(2) . Among them, 23% had inulin clearance over 60 mL/min/1.73 m(2) and were thus incorrectly classified as CKD patients. When applying the Kidney Disease: Improving Global Outcomes (KDIGO) strategy, 138 patients were confirmed as having a GFR below 60 mL/min with eGFRcreat-cys . However, 21% of them were misclassified in reference to measured GFR. Our data do no not support the use of cystatin C as a confirmatory test of stage 3 A CKD in KTR.

[How to manage chronic kidney disease in the elderly?]. / Altération de la fonction rénale chez le patient âgé: comment la gérer?

From age 30 onwards, kidney function physiologically decreases although this deterioration cannot yet be called chronic kidney disease. The latter appears in those exposed to cardiovascular risk factors associated with inflammation and oxidative stress. A diffuse atherosclerosis then develops Patients with a decreased glomerular filtration rate, especially below the threshold of 45 ml/min, are characterised by a poor physical heath and by cognitive disorders, leading to frailty. In these conditions, a management strategy to reduce the increased risk of acute kidney injury should be outlined and the need for renal replacement therapy be considered. One must try to maintain the best possible quality of life, promoting in some situations a conservative approach.

[Estimation of the glomerular filtration rate in 2014 by tests and equations: strengths and weaknesses]. / L'estimation de la filtration glomérulaire en 2014: intérêts et limites des tests et formules.

The accurate estimation of the glomerular filtration rate (GFR) is a goal of multiple interests regarding clinical, research and public health aspects. The strong relationship between progressive loss of renal function and mortality underlines the need for early diagnosis and close follow-up of renal diseases. Creatinine is the commonest biomarker of GFR in use. By reason of non-renal determinants of GFR, it is required to integrate creatinine values within equations that take in account its most important determinants (i.e., age, sex). The CKD-EPI 2009 equation is now recommended as the first line equation to estimate GFR within the general population. In this indication, it should replace MDRD that tends to overestimate the prevalence of stage 3 chronic kidney disease with GFR around 60 ml/min. However, many questions remain about the accuracy of GFR equations in specific situations such as extremes of age or body weight. The identification of new biomarkers, less determined by non-renal determinants, is of importance. Among these biomarkers, cystatin-C is more accurate to estimate GFR when it is combined to creatinine (i.e., equation CKD-EPI 2012). However the indica. tions for using cystatin-C instead of creatinine alone are still unclear and its use remains limited in routine practice. In conclusion, neither biomarker nor equation gives an accurate estimation for the whole range of GFR and for all patient populations. Limits of prediction are relying on both biomarker's properties and the range of GFR that is concerned, but also rely on the measurement methods. Therefore, it is crucial to interpret the estimated GFR according to the strengths and weaknesses of the equation in use.

[Evaluation of glomerular filtration rate in 2014]. / Estimation du débit de filtration glomérulaire en 2014.

Chronic kidney disease (CKD) is a frequent affection, most often detected by evaluation of the glomerular filtration rate (GFR). Measuring GFR by a reference method is not possible for every single patient, even if these methods are probably underused. However, serum creatinine has several limitations of which clinicians should be aware. Knowing these limitations, creatinine and creatinine-based equations (including other parameters like age, gender and ethnicity) still represent the most used and easiest way to detect and assess CKD.

[Medication of the month. Febuxostat (Adenuric)]. / Le médicament du mois. Fébuxostat (Adenuric).

Gout is a rheumatologic disease due to the deposition of urate (the catabolite of purines) crystals within joints. Prevalence of the disease is high. Potential articular and nephrological complications are numerous. Therefore, a chronic, preventive and effective therapy is required in specific patients. Dietary changes are frequently insufficient and urate-lowering therapy is thus necessary, like uricosuric or xanthine oxydase inhibitors. The objective of these therapies is to lower serum urate levels below 6 mg/dL. The xanthine oxydase inhibitor allopurinol is still the most used in the context of gout prevention. However, allopurinol tolerance and efficacy are far from optimal. Now, a new therapy is available in Belgium, the febuxostat. Febuxostat is a new xanthine oxidase inhibitor.Tolerance and therapeutic effect seem better compared to allopurinol. In this article, we review pharmacological data about this new treatment. We also review the most important clinical trials underlining strengths and limitations of febuxostat.

[Hypophosphatemia and tumor-induced osteomalacia]. / Hypophosphatémie et ostéomalacie oncogénique.

In this article, we will discuss about hypophosphatemia due to tumor-induced osteomalacia. This disease is characterized by severe muscular and articular tenderness inducing profound walking limitation. Clinical chemistry results show severe hypophosphatemia due to hyperphosphaturia. Fibroblast growth factor 23 (FGF-23) is abnormally high. Physiological role of FGF-23 is examined. We also consider the pathophysiology of tumor induced osteomalacia, the use of different investigations to localize the tumor and therapies available to treat this rare disease.