Renal tolerance of targeted therapies (original) (raw)
Related papers
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%...