Renal tolerance of targeted therapies (original) (raw)
Chemotherapy and renal toxicity
2008
Résumé. Les médicaments utilisés dans le traitement des cancers présentent des profils de tolérance rénale différents. Parmi les médicaments anticancéreux présentant une potentielle toxicité rénale, les dérivés du platine, le méthotrexate et la gemcitabine sont les mieux connus. Les mécanismes de leur toxicité rénale et les éventuelles méthodes de prévention sont présentés dans cet article. Les médicaments anti-angiogéniques, récemment commercialisés ou en cours de développement présentent également des interactions potentielles avec le rein. En règle, l'optimisation de la tolérance rénale des chimiothérapies anticancéreuses passe par une évaluation appropriée de la fonction rénale des patients, avant et au cours des traitements, à chaque cure en général. Cette évaluation de la fonction rénale doit être réalisée à l'aide des formules de Cockcroft-Gault et/ou aMDRD, la seule valeur de la créatininémie n'étant pas un indice fiable de la fonction rénale réelle. Lorsque la fonction rénale est anormale, une adaptation posologique doit être appliquée, améliorant ainsi la tolérance rénale, mais aussi extrarénale (hématologique par exemple), en réduisant le risque de surdosage médicamenteux chez des patients chez lesquels l'élimination des médicaments est altérée. ▲ Abstract. Antineoplastic drugs used in the treatment of cancers present with variable renal tolerance profiles. Among drugs with a potential for renal toxicity, platinum salts, methotrexate, and gemcitabine are well-known. The mechanisms of their renal toxicity and the means of its prevention are presented in this article. Anti-angiogenic drugs, recently marketed or still under clinical development, may also interact with the kidneys. In general, optimising the renal tolerance of anticancer drugs requires an appropriate evaluation of patients'renal function, before and during treatment, at each course. Serum creatinine alone is not a reliable index of renal function. Its evaluation must be performed with the use of Cockcroft-Gault or aMDRD formulae. In patients with abnormal renal function, dosage adjustment is often required to improve the renal tolerance, and also to limit the risk of extra-renal toxicities (such as haematological toxicities) induced by a drug overdosage, in those patients with reduced drug-elimination. ▲
2010
L'atteinte rénale consécutive à l'administration d'un médicament est une situation fréquente en pratique clinique. Il s'agit d'un évènement grave qui est associé à une morbidité et à une mortalité importantes. Du fait de sa riche vascularisation (25 % du débit cardiaque), le rein est en effet un organe particulièrement vulnérable à la toxicité des médicaments présents dans l'organisme. Par ailleurs, l'existence d'un gradient osmotique corticomédullaire favorise l'accumulation interstitielle des agents toxiques au niveau des papilles et de la zone médullaire. Le rôle fondamental du tubule rénal dans la réabsorption des solutés expose également le rein à une concentration particulièrement élevée de substances médicamenteuses tant dans la lumière tubulaire que dans la cellule tubulaire. Ainsi, l'atteinte rénale médicamenteuse peut concerner l'intégralité de la structure rénale : les glomérules, les tubules, le tissu interstitiel et les vaisseaux. Nous traitons de la néphrotoxicité des médicaments en nous arrêtant plus en détail sur la néphrotoxicité des traitements anti-infectieux (antibactériens, antifongiques, antipaludéens et antiviraux), la toxicité rénale des médicaments antalgiques (dont les anti-inflammatoires non stéroïdiens) et des médicaments anticancéreux étant déjà traités dans l'Encyclopédie médicochirurgicale. Nous mettons l'accent sur les mesures de prévention de la néphrotoxicité des médicaments qui consistent dans la détermination des populations à risque, la prise en compte ou l'élimination des facteurs favorisants et l'adaptation de la posologie des médicaments à la fonction rénale.
2006
Reçu le xxx Accepté le xxx s Summary Statins in patients with kidney failure Efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplants Background > Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipidlowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients. Methods > We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population. Results > The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is simi-s Résumé tome 35 > n°2 > février 2006 > cahier 1 Karie S, Launay-Vacher V, Deray G, Isnard-Bagnis C lar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment. Conclusion > Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed. Karie S, Launay-Vacher V, Deray G, Isnard-Bagnis C. Prescription des statines en cas d'insuffisance rénale. Efficacité, tolérance et maniement chez le patient insuffisant rénal et chez le patient transplanté rénal.
La Presse Médicale
Reçu le xxx Accepté le xxx s Summary Statins in patients with kidney failure Efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplants Background > Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipidlowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients. Methods > We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population. Results > The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is simi-s Résumé tome 35 > n°2 > février 2006 > cahier 1 Karie S, Launay-Vacher V, Deray G, Isnard-Bagnis C lar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment. Conclusion > Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed. Karie S, Launay-Vacher V, Deray G, Isnard-Bagnis C. Prescription des statines en cas d'insuffisance rénale. Efficacité, tolérance et maniement chez le patient insuffisant rénal et chez le patient transplanté rénal.
Pharmacokinetics of antibiotics and continuous extra renal therapy
2005
The effect of continuous extrarenal therapy on the pharmacokinetics of antibiotics is closely related on the purification technique used and on the characteristics of the molecule concerned. The antibiotics highly bound to plasmatic proteins as those with a high volume of distribution are poorly eliminated by the continuous hemofiltration technique. The estimate of the “filter clearance” of an antibiotic can be calculated as the product of the ultrafiltration rate by the percentage of the unbound form of the molecule. The initial load necessary for obtaining a desired concentration is never affected by the technique of purification. A dose adaptation is necessary only if the clearance induced by the purification technique takes part in more than 20% of the total body clearance of the antibiotic. The calculation of the dose adaptation can be done, either while referring to the published data, or by estimating the filter clearance. The reference to pharmacokinetic data published imper...
Annales de cardiologie et d'angéiologie, 2015
Chronic kidney disease is a progressive disease which has become a real public health issue. In patients with renal disease, drugs pharmacokinetics may be altered. The handling of drugs requires a special attention in these patients. Indeed, there is a risk of accumulation and drug overdose if dosage is not adjusted to the stage of renal insufficiency. Thus, to achieve a dosage adjustment knowing how to evaluate renal function is absolutely necessary. Different formulae are available including the Cockcroft and Gault formula aMDRD and CKD-EPI. In patients with cardiac issues, it appears that the CKD-EPI formula is that of choice in terms of clinical risk stratification. However, some summaries of product characteristics (SmPC) of drugs used in cardiology, such as Dabigatran(®), mention the need to use the Cockcroft-Gault, less accurate than aMDRD and CKD-EPI, in order to adjust the dose in patients with impaired renal function. Standardization of recommendations is necessary to limi...
[How to adjust the dose of drugs in chronic kidney disease?]
La Revue du praticien
Renal insufficiency is a common disease, in the general population as well as in some specific diseases such as HIV infection or cancer. The vast majority of medicines require a dosage adjustment in case of renal dysfunction, it is thus of a crucial importance to know how to evaluate appropriately renal function, on one hand, but also to have access to reliable information sources on how to handle the drugs in such cases. Most often, the Summary of Drug Characteristics (SmPC) only provides partial information, which may even be false in some cases as compared to the most recent data from the literature. However, some information sources exist, reliable, updated, and easily accessible.
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2013
To evaluate the outcomes following targeted therapies in the management of metastatic renal cell carcinoma (mRCC), through the study of overall survival (OS) and progression-free (PFS). We retrospectively included 78 patients treated with targeted therapies for mRCC at the Paul Papin Cancer Institute from 2004 to 2009. Overall survival (OS), progression free survival (PFS), response to treatment, occurrence of grade III and IV side effects, were analyzed following first and second line treatments. Median follow-up was 33 months [5-236], and 41 patients died (52.6%). Median OS was 36 months [95% CI 29-43]. The median PFS was 14 months [95% CI 6.71-21.29] for sunitinib, 38 months [95% CI 11.41-64.59] for bevacizumab with interferon (IFN), and 8 months [95% CI 0-17.03] for IFN alone. A partial reduction, stabilization or increase in tumor size was observed for 19.2%, 47.4% and 25.6% of cases. A second line treatment was given for 53 patients. They received either sunitinib (n=20, 37.8%...
[Physical principles of renal replacement therapy applied to end stage renal disease patients]
Néphrologie & thérapeutique, 2009
Le terme « hémodialyse » englobe l'ensemble des modalités d'épuration extrarénale capables de restaurer périodiquement le « milieu intérieur » de patients insuffisants rénaux chroniques résultant de la défaillance de leurs fonctions excrétrices. Il fait appel à différentes modalités techniques (hémodialyse, hémofiltration, hémodiafiltration) qui font intervenir des principes physiques élémentaires (diffusion, convection, adsorption). La capacité d'épuration dépend de la méthode utilisée, de la toxine urémique considérée, des caractéristiques spécifiques du patient et des conditions d'application (durée du traitement, fréquence, débits utilisés). La clairance instantanée des solutés de référence traduit la performance d'un dialyseur utilisé dans des conditions cliniques optimales mais ne reflète en rien la clairance corporelle du patient. La clairance corporelle effective des toxines urémiques est beaucoup plus difficile à évaluer en pratique dans la mesure où elle fait intervenir la durée du traitement, la complexité du milieu intérieur et l'interaction du système patient/hémodialyse. La notion de « dose de dialyse », volontiers utilisée pour qualifier l'efficacité du programme de dialyse, ne doit pas se résumer à celle d'une mesure périodique de la « clairance fractionnelle » de l'urée, plus connue sous le nom de Kt/V. Elle doit faire appel à un ensemble de marqueurs clinicobiologiques couvrant le spectre des anomalies de l'insuffisance rénale chronique. La bonne connaissance des principes physiques régissant les échanges de solutés en dialyse est indispensable à tout néphrologue soucieux d'améliorer la qualité du traitement et la survie de ses patients.
Journal de Pharmacie Clinique, 2023
Objective. The aim of this study was to evaluate the dosage adjustment of drugs prescribed to patients with a GFR < 60 mL/min/1,73 m2 admitted to the nephrology department of our hospital. Method. This was a prospective study conducted in the nephrology department of our hospital over a one-month period. The study was conducted by a resident and a pharmacy intern assigned to the nephrology department. Results. We determined that 50% of patients had end-stage renal failure, 19.2% had severe renal failure and 30.8% had moderate renal failure. Among the cases studied, 19.3% of prescribed dosages did not take into account the patient’s renal function, hence the need for pharmaceutical interventions, of which 35.5% were accepted. Conclusion. In order to improve drug management for patients with chronic kidney disease in our hospital, it is important to draw up a practical guide to adapting drug dosage to renal function, specific to our establishment.
[Renal failure and cystic kidney diseases]
Journal de radiologie, 2011
Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50-60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficu...
Adaptation des thérapeutiques médicamenteuses en cas d’insuffisance hépatocellulaire
Réanimation, 2007
nistration. Since algorithms are still missing for drugs adaptation in patients with liver failure, it is strongly recommended to look after drugs pharmacokinetics in critically ill patients with liver dysfunction. In patients with liver failure, evaluation of liver toxicity has to be done before any prescription. It can be done thanks to the French liver toxicity network called Hepatox ® and has to be completed by drugs residues screening tests.
Medecine Et Hygiene, 2001
Les diurétiques sont fréquemment utilisés dans le traitement des états oedémateux. Ils inhibent la réabsorption du sodium au niveau du tubule rénal, provoquant ainsi une excrétion accrue de sodium et d'eau. On distingue trois catégories de diurétiques, en fonction de leur site d'action : les diurétiques proximaux, les diurétiques de l'anse et les diurétiques distaux. Leur posologie doit être adaptée chez les patients souffrant d'insuffisance rénale aiguë et chronique ou d'un syndrome néphrotique.Le but des diurétiques dans l'insuffisance rénale aiguë est essentiellement de maintenir une diurèse, afin d'éviter le recours à une épuration extrarénale. La perfusion continue des diurétiques de l'anse et l'adjonction de diurétiques distaux sont souvent nécessaires. Dans l'insuffisance rénale chronique, les diurétiques sont indispensables dans le traitement de l'hypertension artérielle associée et des oedèmes. Les diurétiques de l'anse doivent être employés en premier lieu avec une adaptation de leur posologie. La combinaison avec des diurétiques distaux peut s'avérer utile. Enfin, la prise en charge du syndrome néphrotique nécessite le plus souvent d'augmenter les doses de diurétiques et leur fréquence d'administration.
La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne, 2008
We report a case of acute renal insufficiency in a 77 year-old patient who took flurbiprofen as antiplatelet therapy. This is an important observation because it illustrates the potential risk of acute renal insufficiency, when using flurbiprofen before invasive medical examination or surgery in patients receiving long-term treatment with angiotensin converting enzyme inhibitors or angiotensin II inhibitors. This risk is probably underestimated in usual clinical practice.
La prise en charge thérapeutique du patient transplanté rénal est le plus souvent complexe et expose à un risque d'évènements iatrogènes médicamenteux. Les patients sont confrontés, d'une part, à des médica-ments à marge thérapeutique étroite avec notamment les immunosuppresseurs et, d'autre part, à de nombreuses comorbidités associées. Celles-ci favorisent une polymédication, générant ainsi des interactions médicamenteuses et augmentant le risque d'apparition d'effets indésirables. Des comportements à risques tels que la mauvaise adhé-sion au traitement sont également à prendre en compte. Ce travail présenté sous la forme d'une synthèse de la littérature médicale, abordera le profil physiopathologique et thérapeutique du patient transplanté rénal ainsi que les problèmes reliés à la pharmacothérapie générés par les thérapeutiques immunosuppressives. Pour définir la place du pharmacien clinicien et l'intégration des soins pharmaceutiques, nous présenterons une revue de la littérature médicale sur les missions potentielles du pharmacien clinicien visant à optimiser la prise en charge thérapeutique du patient transplanté rénal. Abstract. The therapeutic management of renal transplant patient is often complex and exposed to a risk of occurrence of iatrogenic drug events. Patients are treated by drugs with a narrow therapeutic range including immunosuppressants, and have many comorbidities. These promote polymedication, generating drug interactions and increasing the risk of developing side effects. Risk behaviours such as poor adherence to treatment are also taken into account. This medical literature review discusses the pathophysiology and therapeutic profiles of renal transplant patients as well as drug-related problems generated by immunosuppressive therapy. To define the role of the clinical pharmacist and the integration of pharmaceutical care, we present a review of the potential missions of clinical pharmacist to optimize the therapeutic management of renal transplant patients.
[Moderate impairment of renal function and cardiovascular risk]
La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne, 2009
The objective of this review is to analyze the relationship between moderate decrease in renal function and cardiovascular (CV) risk and to discuss the potential mechanisms of this association. Prevalence of chronic kidney disease (CKD) is increasing in developed countries. Several studies have shown that a moderate fall in glomerular filtration (GFR) or the presence of microalbuminuria is associated with an increase in CV risk, independently of the traditional CV risk factors. Mechanisms are probably multiple and could include anemia, calcium/phosphate metabolism, inflammation, but also large arteries function. In order to achieve primary or secondary prevention of CV risk, DFG should be estimated from serum creatinine and microalbuminuria should be assessed in every high risk subject. The finding of CKD implies optimal management of all traditional CV risk factors. Future studies are needed in order to evaluate the efficacy and safety of specific therapeutic approach to reduce CV ...