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The renal toxicity of anticancer drugs is a clinical challenge because of the intrinsic toxicity of some anticancer drugs and because the cancer itself. Indeed, cancer patients are exposed to all types of renal disorders (obstructive, functional, organic because of radiotherapy, paraneoplastic glomerulopathy, thrombotic microangiopathy…). The therapeutic index of anticancer drugs is often narrow and the doses used for optimal efficacy are high. Improving safety requires a better dose adjustment, which depends on the correct evaluation of the renal function. Prevention remains important as the mortality associated with acute renal failure is very high.

Updated clinical practice guidelines recommend the long-term use of low-molecular-weight heparins or direct oral anticoagulants as the preferred option for the treatment of cancer-associated thrombosis (CAT), using a personalized approach matching the right drug to the right patient. In most cases, the benefit of anticoagulant therapy outweighs the risk. However, the long-term use of anticoagulants is associated with a non-negligible risk of bleeding, which constitutes a rare but serious adverse effect. Bleeding complications have been reported to be overall 2 to 3 times more frequent in cancer patients with CAT receiving anticoagulation than in non-cancer patients, with a reported incidence of major bleeding ranging from 2.4 to 16.0% in randomized controlled trials (RCT). In the absence of validated risk assessment model to predict the risk of bleeding in these patients, a careful evaluation of each individual profile, with adequate selection of the most appropriate anticoagulant for each individual patient, is warranted for overcoming management challenges, taking in account the numerous factors which may potentiate the overall bleeding risk in these complex patients, such as advanced or metastatic disease, older age, anemia, thrombocytopenia, renal impairment, liver dysfunction, and concomitant anticancer therapies. The purpose of this review is to call for awareness on bleeding complications as a major safety issue of CAT treatment and to summarize data from recent RCT and real-world studies on the incidence and risk factors for bleeding in this unique and challenging population to further help clinicians in decision-making.

The renal toxicity of anticancer drugs is a clinical challenge because of the intrinsic toxicity of some anticancer drugs and because the cancer itself. Indeed, cancer patients are exposed to all types of renal disorders (obstructive, functional, organic because of radiotherapy, paraneoplastic glomerulopathy, thrombotic microangiopathy…). The therapeutic index of anticancer drugs is often narrow and the doses used for optimal efficacy are high. Improving safety requires a better dose adjustment, which depends on the correct evaluation of the renal function. Prevention remains important as the mortality associated with acute renal failure is very high.

International audience; Direct oral anticoagulants (DOAC) are now recommended for the treatment of cancer-associated thrombosis (CAT) based on the results of dedicated trials demonstrating that DOAC are non-inferior to low molecular weight heparins in preventing recurrent venous thromboembolism (VTE) in this population. The definition of "cancer patient" differs substantially among studies. Whether patients with active cancer and those with a history of cancer (HOC) carry the same risks of recurrent VTE and bleeding remains unclear. Few studies reported data on the efficacy and safety of anticoagulants according to active cancer or HOC categories. While in subgroup analyses of EINSTEIN and HOKUSAI the rates of recurrent VTE and bleeding did not differ between these categories, results from a subgroup analysis of AMPLIFY, from HOKUSAI-Cancer, and from the COMMAND cohort suggest that HOC patients might have a lower bleeding risk than active cancer patients. Whether the inclusion of HOC patients in CAT studies might introduce some bias by decreasing the rates of both recurrent VTE and bleeding remains an unanswered issue since no dedicated prospective study addressed this question. A strict definition of active cancer should be used in further trials.

The development of interventional radiology techniques regularly exposes patients to the potential renal toxocity of iodinated contrast media. Faced with this risk of nephrotoxicity, gadolinium-based contrast agents have long been considered as a safe alternative to iodinated contrast media, especially in sensitive or at risk patients. However, these gadolinium-based contrast agents are not devoid of nephrotoxicity and present another risk, a complication related to renal failure, the nephrogenic systemic fibrosis. European and US recommendations from health agencies have recently come closer, defining groups of patients at risk of nephrogenic systemic fibrosis according to their level of renal function and the type of gadolinium-based contrast agent used. What are the real renal risks for these products? How to evaluate the benefit-risk balance of the patient to choose a radiological examination in an informative, effective and safe way? This article focuses on the description of the risks of gadolinium-based contrast agents, reviews existing recommendations and best practices to guide the choice of clinicians.

Introduction In patients with hematological cancers, the high risk of bleeding raises serious concerns when anticoagulant therapy is initiated for treatment of acute venous thromboembolism (VTE). In the CATCH trial, we showed that tinzaparin is associated with a significantly lower risk of clinically relevant bleeding (CRB) and clinically relevant non-major bleeding (CRNMB) compared with warfarin therapy in patients with a solid tumor or hematological cancer. Hence, we performed a post-hoc analysis to assess the risk of recurrent VTE (rVTE) and bleeding in the hematological cancer patient subgroup. Risk factors associated with rVTE and bleeding were also explored. Methods CATCH (ClinicalTrials.govNCT01130025; Lee A et al. JAMA 2015) was a Phase III, multinational, randomized, active-controlled, open-label trial. Patients with solid tumors or hematological malignancies were randomized to receive therapeutic dosing of tinzaparin (175 IU/kg OD) vs warfarin (INR target 2.0 - 3.0) for treatment of acute VTE. Treatment was given for up to 6 months but was withheld during periods of severe thrombocytopenia (platelet count < 50 x 10 9/L). The primary efficacy outcome was the composite of symptomatic deep vein thrombosis (DVT), symptomatic nonfatal pulmonary embolism (PE), fatal PE, incidental proximal DVT and incidental proximal PE. All thrombosis and bleeding outcomes, including rPE, rDVT, major bleeding (MB), CRB, and CRNMB were objectively documented and centrally adjudicated in a treatment-blinded fashion. Patients with myeloma, lymphoma or leukemia were included in this sub-group analysis. Treatment effect was assessed by means of a cox-regression with time to first event as outcome and deaths not due to fatal PE as a competing risk factor. The cumulative incidence functions and the corresponding 95% CIs were estimated. Results 94 of 900 subjects (10.4%) in CATCH had a hematological cancer. Of these patients, 44 and 50 received tinzaparin and warfarin, respectively. The most common hematological cancer was lymphoma (59.6%), followed by myeloma (30.9%), chronic leukemia (5.3%) and acute leukemia (4.3%). rVTE occurred in fewer patients assigned to tinzaparin versus warfarin (2.4% vs 6.4%) but this difference was not statistically significant (HR 0.36; 95%CI 0.04-3.14). All recurrent thrombotic events were PE; no rDVT occurred. Also, trends for less bleeding with tinzaparin were noted for MB (tinzaparin 0.0% versus warfarin 5.0%), CRB (tinzaparin 10.4% vs warfarin 23.5%; HR 0.53; 95%CI 0.15-1.83) and CRNMB (tinzaparin 10.4% vs warfarin 19.5%; HR 0.69; 95%CI 0.19-2.51). 3 patients in each treatment arm had a fatal bleeding event and there was no difference in overall mortality (tinzaparin 22.7% vs warfarin 22.0%). There were no risk factors associated with rVTE identified. Factors associated with CRB in patients with hematological cancer included the use of antiplatelet agents (HR 7.63; 95%CI 1.17-49.6; p=0.033) and renal insufficiency (HR 12.4; 95%CI 2.15-72.0; p=0.005). Conclusion In this post-hoc subgroup analysis of patients with hematological cancers who received anticoagulation for acute VTE, tinzaparin may be a more effective and safer alternative to warfarin. Randomized controlled trials are warranted to test this hypothesis in this challenging population with a high risk of bleeding. Figure 1 Figure 1. Disclosures Lee: Leo Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Servier: Consultancy, Honoraria. Bauersachs: Bayer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; LEO Pharma: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Janus: LEO Pharma: Current Employment. Leeder: LEO Pharma: Current Employment. Thoning: LEO Pharma: Current Employment. Khorana: Anthos: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria.

The increased incidence of cancer in hemodialysis patients has been discussed since the mid-70s. Today, physicians regularly encounter situations where they must manage the prescription of anticancer drugs in hemodialysis patients. Areas covered: Hemodialysis patients are at risk of dose-related toxicities due to pharmacokinetic modifications. Hemodialysis patients are at risk of therapeutic drug removal during their hemodialysis session, which may result in a loss of efficacy. In the advent of novel immunotherapies, particularly tumor vaccines, there is an increased theoretical risk of pharmacodynamic modification. Indeed, pharmacodynamic modifications have already been reported for viral vaccines. Expert opinion: It is important to consider all of the potential pharmacokinetic/pharmacodynamic modifications before prescribing anticancer drugs in hemodialysis patients. However, pharmacokinetic/pharmacodynamic modification should not be considered a contraindication for anticancer drug use in hemodialysis patients, rather, clinicians should be aware of the need individualize treatment according to available recommendations.

Anticoagulant agents have been approved by international regulatory agencies to prevent and treat venous thromboembolism (VTE). However, chronic kidney disease (CKD) is: (1) highly frequent in VTE patients; (2) strongly linked to VTE; and (3) a risk factor for cardiovascular morbidity/mortality and fatal pulmonary embolism. Therefore, an increasing number of patients are presented with CKD and VTE and more and more physicians must face the questions of the management of these patients and that of the handling of anticoagulant agents in CKD patients because of the pharmacokinetic modifications of these drugs in this population. These modifications may lead to overdosage and dose-related side effects, such as bleeding. It is therefore necessary to screen VTE patients for CKD and to modify the doses of anticoagulants, if necessary.

During the last decade, inhibitors of the vascular endothelial growth factor (VEGF) were developed for the treatment of cancer. Many anti-VEGF are available but the issue is still the same: to inhibit the effect of the VEGF on their receptors. There are two main classes, depending on the mechanism of action by blocking the binding of the ligand on the receptor (VEGF trap or monoclonal antibody) or by affecting directly the receptor (tyrosine kinase inhibitor [TKI], monoclonal antibody directed against the VEGF receptor). These selective agents are safe. Nevertheless, side effects were described, in particular renal and vascular effects. In this article, we analyze the frequency of these renovascular complications, their clinical aspects and the interest of these indexes as a marker of treatment efficacy.

The aim of the LIDOanemia surveys was to assess how anemia in cancer patients is managed by oncologists and hematologists according to the key messages of the EORTC guidelines.LIDO 1 and LIDO 2 (Leaning upon International Directives for Optimization: Anemia) were declarative web-based surveys conducted in France. LIDO 1 specifically focused on clinical features triggering the decision to treat anemia, biological indicators of anemia, the hemoglobin (Hb) threshold for initiating treatment and blood transfusion, and the Hb treatment target. In LIDO 2, participants were presented the main messages of the EORTC guidelines and were asked four questions to assess the impact of the guideline's broadcast on their practice.A total of 133 and 319 physicians took part in the LIDO 1 and 2 surveys, respectively. The majority were oncologists (65 and 61 %, respectively). Responses from LIDO 1 showed practice habits that differed from those recommended in the EORTC guidelines. However, LIDO 2 showed that an average of 18 % of the participating physicians were willing to amend their clinical practice after receiving a summary of the EORTC recommendations for anemia management.These findings raise the questions of how often and how to most effectively disseminate key guideline messages. With the best interests of patients in mind, the ultimate objective is to improve the understanding of consensus recommendations and to close the gap between them and actual clinical practice.

Background Data still remain scanty on the potential impact of chronic kidney disease (CKD) on the mortality of breast cancer (BC) patients. The results of 3 clinical studies we conducted (IRMA-2, CANDY and MARS) were pooled. In all 3, the methodology was the same regarding CKD, allowing pooled analysis on the prevalence of CKD and on the potential association between RI and overall survival (OS), and to stratify the risk, if any, depending on the GFR. Material and methods The KDIGO definition and classification of CKD was used. GFR was estimated with the MDRD formula. RI was defined as GFR Results The total population included 5908 solid cancer patients, among them, 1716 were young BC patients. Median age: 53.0 years, median body mass index: 23.4 kg/m2, bone metastasis: 27.7%, visceral metastasis: 38.7%. 75.9% of these patients were alive at the end of the 1-year follow-up. In these young BC patients, prevalences of a GFR Conclusion: This pooled analysis reported that: 1) abnormal GFR was frequent in young BC patients, 2) reduced GFR was a statistically significant prognostic factor for reduced OS. 3) This reduced OS began at an early stage of CKD in young BC patients, for a GFR Table. Multivariate Cox model regressions in BC patientsGFRn, %HR [95% CI]; p-value as compared to GFR ≥ 90GFR0.05GFR0.05GFR Citation Format: Launay-Vacher V, Janus N, Ray-Coquard I, Thariat J, Deray G, Beuzeboc P. Decreased overall survival in "young" breast cancer patients with renal insufficiency. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-33.

INTRODUCTION AND AIMS: Anaemia is very common in cancer patients. However, the impact of anaemia in venous thromboembolic (VTE) patients on the risk of bleeding is not well-known. Consequently, the question of the impact of anaemia in cancer-associated-thrombosis (CAT) patients is important. METHODS: All the literature (PubMed) was reviewed about the potential links between cancer, CAT and anaemia. However, there were no dedicated studies on this topic. Furthermore, the WHO definition of anaemia was the one used in most of the publications RESULTS: Several studies investigated about all the risks of bleeding/VTE in atrial fibrillation and VTE patients, including anaemia. Most of them reported that anaemia exposed VTE patients to a higher risk of bleeding. The COMMANDER study, evaluated the influence of anaemia in VTE patients and reported that VTE patients with mild and moderate/severe anaemia had higher risk for major bleeding and that the risk for major bleeding increased according to the severity of anaemia. The RIETE (Registro Informatizado Enfermedad Tromboembólica) reported that anaemia was found in 57% of the patients with cancer and in 28% without cancer (odds ratio 3.46; 95% CI 3.33-3.60), exposing to a higher risk of major bleeding. The same registry reported also that in CAT patients, anaemia had a two-fold higher rate of major bleeding and fatal bleeding than CAT patients without anaemia. This link between anaemia and bleeding in cancer patients are multifactorial. Indeed, there are both quantitative and qualitative changes in red blood cells that could affect bleeding and thrombosis, as well as interactions of red blood cells with cellular and molecular components of the haemostatic system. Indeed, for example, low haematocrits are associated with bleeding. Finally, it is interesting to notice that there is a gap between the definition of anemia in CAT patients when compared to not CAT cancer patients. Indeed, WHO definition is quite common in VTE and CAT patients but EORTC/NCCN are used in cancer patients for several reasons. As a consequence, it could be important to align on this point. CONCLUSIONS: Anaemia, cancer and thrombosis are closely linked. It is important to screen and manage both anaemia in CAT patients because of the increased risk of bleeding. Consequently, it is important to consider this bleeding risk in CAT patients before initiating an anticoagulants treatment or prophylaxis in cancer patients. Disclosures Janus: Bayer:Honoraria, Research Funding;Pierre Fabre Oncology:Research Funding;Novartis:Honoraria;Gilead:Honoraria, Research Funding;Vifor Pharma:Honoraria, Research Funding;Fresenius Medical Care:Honoraria;Amgen:Honoraria, Research Funding;B-Braun:Honoraria;Guerbet:Research Funding;TEVA:Research Funding;IPSEN:Honoraria;Pfizer:Consultancy, Honoraria;Roche:Honoraria, Research Funding;Daichii-Sankyo:Honoraria, Research Funding;LEO Pharma A/S:Current Employment, Honoraria.

Introduction Anticancer treatments has been changing since decades, evolving from chemotherapy (platinum salts) to recent check-point inhibitors. Nausea, vomiting and diarrhoea are common adverse events of anticancer drugs, despites the fact that some supportive care drugs can manage these adverse events. Gastro-intestinal (GI) disorders/toxicities are also important. Such as gastric/duodenal ulcer, gastritis, stomatitis, colitis, esophagitis... Cancer-associated-thrombosis (CAT) patients were also reported to be exposed to such GI disorders/toxicities and several publications recommended to consider these GI disorders/toxicities when choosing an anticoagulant in CAT (Carrier M. Curr Oncol 2018; Moik F. ESMO Open 2020). However, little is known about the nature of the anticancer drugs that CAT patients are receiving. The aim of this work was to check all the anticancer's SmPCs (Summary of Product Characteristics) on the EMA website for GI disorders. Methods All SmPCs of anticancer drugs indicated for lung cancer were checked on the EMA website. All adverse events regarding GI disorders/toxicities were collected. The frequency of adverse events used was the following: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000). However, it was decided to mainly focus on very common and common ones. Old anticancer drugs SmPCs (platinium salts...) were checked on electronic medicines compendium (medicines.org.uk), because these old SmPCs are not always available on the EMA website. Generics, biosimilars and drugs without a licence were excluded. Results Twenty-eight anticancer drugs were identified with a mix of traditional chemotherapies (platinum salts...), tyrosine kinase inhibitors (nib) and monoclonal antibodies (mab). Among these 28 anticancer drugs, 26 had at least one very common/common GI disorders/toxicities. Obviously, vomiting (82.1%) and diarrhoea (89.3%) are very well-known, but it was interesting to see that many anticancer drugs were associated with other very common/common GI toxicities such as stomatitis (71.4%) and colitis (10.7%). Additionally, several drugs (35.7%) were exposing to GI bleeding and/or GI perforation but these last adverse events were less common. Unfortunately, the SmPCs did not include data about the GI profile of the patients during the trials. Conclusion Monreal M et al reported in 1991 that acute gastroduodenal lesion was found in 21% of patients with venous thromboembolism, but there are no dedicated study about the incidence of GI disorders in CAT patients. This work reported that GI disorders/toxicities were common in anticancer drug's SmPCs. Consequently, it is important to be aware of this before initiating an anticoagulant treatment. However, this work had limitations. Indeed, these adverse events were reported in the SmPCs, based mainly on cancer trials and not on CAT trials. Furthermore, clinical trials and SmPCs may not always reflect the real clinical setting. Finally, lung cancer patients are usually receiving anticancer regimens that include several anticancer drugs, so the potential impact of GI disorders/toxicities from 2 or 3 anticancer drugs on a single patients could be greater. Nevertheless, it sounds reasonable to check for GI disorders/toxicities risks in order to initiate an adequate anticoagulant treatment in CAT patients and during follow-up. Disclosures Janus: Guerbet:Research Funding;B-Braun:Honoraria;LEO Pharma A/S:Current Employment, Honoraria;Fresenius Medical Care:Honoraria;Amgen:Honoraria, Research Funding;TEVA:Research Funding;Daichii-Sankyo:Honoraria, Research Funding;Roche:Honoraria, Research Funding;Vifor Pharma:Honoraria, Research Funding;Gilead:Honoraria, Research Funding;Novartis:Honoraria;Pierre Fabre Oncology:Research Funding;Bayer:Honoraria, Research Funding;Pfizer:Consultancy, Honoraria;IPSEN:Honoraria.

The development of interventional radiology techniques regularly exposes patients to the potential renal toxocity of iodinated contrast media. Faced with this risk of nephrotoxicity, gadolinium-based contrast agents have long been considered as a safe alternative to iodinated contrast media, especially in sensitive or at risk patients. However, these gadolinium-based contrast agents are not devoid of nephrotoxicity and present another risk, a complication related to renal failure, the nephrogenic systemic fibrosis. European and US recommendations from health agencies have recently come closer, defining groups of patients at risk of nephrogenic systemic fibrosis according to their level of renal function and the type of gadolinium-based contrast agent used. What are the real renal risks for these products? How to evaluate the benefit-risk balance of the patient to choose a radiological examination in an informative, effective and safe way? This article focuses on the description of the risks of gadolinium-based contrast agents, reviews existing recommendations and best practices to guide the choice of clinicians.

Resume Introduction Les valeurs pronostiques de l’hypertension et de la proteinurie des anti-VEGF (facteur de croissance endothelial vasculaire) n’ont pas encore ete evaluees dans la pratique clinique de routine dans le cancer du sein (CS). Les objectifs de l’etude MARS etaient d’apprecier la prevalence/incidence de la proteinurie et de l’hypertension a l’inclusion et durant le traitement par anti-VEGF, et de rechercher un lien potentiel avec la survie globale. Methodes Les patients naifs de tout anti-VEGF et debutant un traitement par anti-VEGF ont ete inclus dans 8 centres entre 2009 et 2011 avec une periode de suivi de 1 an. Les resultats du groupe de patientes atteintes de CS et traitees par bevacizumab sont presentes. Resultats Quatre cent deux patientes atteintes de CS et traitees par bevacizumab ont ete incluses. A l’inclusion, 12,4 % des patientes presentaient une hypertension, 23,9 % une proteinurie. Lors du suivi, l’incidence d’evenements de novo , proteinurie et hypertension, etait respectivement de 61,7 % et 16,8 %. Parmi les patientes avec une proteinurie de novo , 62,2 % l’ont amelioree ou normalisee par la suite. Aucune microangiopathie thrombotique n’a ete rapportee. A l’inclusion ou de novo , les analyses univariees/multivariees ont demontre que la proteinurie et l’hypertension n’etaient pas associees a la survie globale. Discussion Ces resultats montrent que la prevalence de l’hypertension et de la proteinurie a l’inclusion etait elevee et que les patientes traitees par bevacizumab developpaient frequemment une hypertension et/ou une proteinurie de novo . Enfin, ni l’hypertension ni la proteinurie, a l’inclusion ou de novo , n’etaient associees a la survie globale dans notre cohorte.

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 limit disparities in dosage and drug exposure according to the formula. SmPCs however, are not the only source of information to obtain data on the use of drugs in the renal insufficient population. Some other information sources exist, reliable, updated and easily accessible.

Background: In 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session. Methods: The ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session. Results: In total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft-Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG

BACKGROUND Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time. METHODS This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment. RESULTS This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases. CONCLUSIONS Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158–2163. © 2014 American Cancer Society.

Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit. Results: 1124 cancer pts were included; 402 breast cancer (BC) pts received bevacizumab (1st line: 14.4%; median durations of treatment: months)). Median age at inclusion was 55 years (19-65). Visceral, bone and cerebral metastasis frequencies were 74.7, 5.1 and 2.5%, respectively. HTN prevalences: 12.4%. Baseline renal assessment retrieved: Pu 23.9%, Hu 16.2%, mean aMDRD 96.4 ml/min/1.73m2 and 14 pts with aMDRD Conclusion: These results on the renovascular safety of bevacizumab in BC pts showed that 1) TMA is rare, 2) Grade 3 Pu developed in 4.6% of pts, with no grade 4, 3) less than 17% developed HTN, and 4) aMDRD was stable. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. Renovascular effects in MARS breast cancer patients treated with bevacizumabRenovascular effectsPrevalence at inclusionIncidence during follow-up (de novo**)Pu* (All grades)23.9%61.7%Pu* (Grade 1)22.2%47.1%Pu* (Grade 2)1.7%10.0%Pu* (Grade 3)0.0%4.6%Pu* (Grade 4)0.0%0.0%Hypertension12.4%16.8%Hu* (All Hu)16.2%42.1%Hu* (Traces/+)11.7%33.2%Hu* (++)2.6%6.3%Hu* (+++)1.9%2.6%SCr increase* (All grades)-80.0%SCr increase* (Grade 1)-68.6%SCr increase* (Grade 2)-7.1%SCr increase* (Grade 3)-0.3%*NCI-CTC v4; **de novo = patients with no event at inclusion and who presented an event during follow-up. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-06.

Resume Les effets renaux des medicaments se manifestent par divers mecanismes et peuvent potentiellement toucher toutes les parties du rein. Il existe six types d’atteintes renales induites par les medicaments: les atteintes prerenales ; les nephropathies tubulaires ; les nephropathies interstitielles ; les nephropathies glomerulaires ; les nephropathies vasculaires et les nephropathies obstructives, telles que les cristalluries, les insuffisances renales aigues secondaires a des rhabdomyolyses, etc. La nephrotoxicite des medicaments survient principalement chez des patients ayant des facteurs de risque sous-jacents, pouvant rendre le rein plus fragile aux effets iatrogenes. On distingue les facteurs de risque lies au patient (âges extremes, hypovolemie, insuffisance renale chronique preexistante…), ceux lies au rein et ceux lies au traitement (posologie non adaptee, nephrotoxicite cumulee, diuretiques, anti-inflammatoires non steroidiens…). La connaissance des facteurs de risque et des mecanismes de nephrotoxicite sont la base d’une meilleure prevention et egalement d’une meilleure prise en charge de ces patients.

Implantable central venous access port (portacath) is used to provide long-term venous access and to deliver chemotherapy in cancer patients. Intravenous iron complexes are frequently prescribed in this setting, and some physicians use a portacath for their administration. The aim of this survey was to assess the frequency of this practice and the reasons supporting it. This declarative survey was conducted in France; 497 oncologists/hematologists were contacted to answer a survey on their practices regarding the administration of intravenous iron via a portacath. A total of 141 recipients (29.5 %) completed the questionnaire. The intravenous iron complexes most frequently used were iron sucrose and ferric carboxymaltose, and 55.2 % of the responders reported using a portacath to administer intravenous iron complexes. The main reasons mentioned for this practice were ease of administration (27.9 %) and preservation of venous capital (27.6 %). The main reasons reported for not using a portacath to administer intravenous iron were a history of thrombosis (45.1 %) or potential drug interactions (17.7 %). Efficacy and safety were expected to be similar to those observed with peripheral administration. A 47.6 % of physicians declared that they usually did not observe adverse reactions after use of a portacath for iron administration. Intravenous iron administration was always planned after chemotherapy for 46.6 % of the responders and before chemotherapy for 38.2 %, whereas 15.3 % did not have any preference for either option. Intravenous iron complexes (mainly iron sucrose and ferric carboxymaltose) are commonly administered through a portacath in cancer patients in France. The choice for this route of administration is supported by clinical considerations, but further studies are needed to confirm the efficacy and safety of this practice.

Pulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease that is characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. PH has been reported to be highly prevalent in patients with chronic kidney disease, and especially among end-stage renal disease patients undergoing haemodialysis. However, only few data are available on drug dosage adjustment to renal function for those drugs that are commonly used in the treatment of PH. We reviewed the literature and gathered information, although sparse, to propose guidelines for using these drugs in renal insufficiency patients.

Background: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: The MARS study is a multicentric prospective observational study of the renovascular safety of AVD in AVD-naive patients. in 7 centres from 2009 to 2011. There was no intervention on the choice of the AVD. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and dipstick Pu. This sub-group analysis presents the intermediate results for the first 184 patients with breast cancer (BC) receiving bevacizumab who completed the 1-year follow-up (f/u) (out of 337 BC patients in total). Results: All these 184 patients received bevacizumab (mean and median durations of treatment: 7.8 and 8 months, respectively). Median age at inclusion was 60 years. Bone, visceral and cerebral metastasis frequencies were 75.0, 52.2 and 7.1%, respectively. Diabetes and HTN prevalences were 4.3% and 10.3%, respectively. Baseline renal assessment retrieved: Pu 13.0%, Hu 8.2%, mean aMDRD 98.8 ml/min/1.73m2 and 1.1% had aMDRD Conclusion: These results show that 1) No thrombotic micro-angiopathy remains rare, 2) Pu developed in 16.3% of patients, with no grade 3/4, 3) less than 13% developed HTN, and 4) renal function was only slightly impaired with transient elevations in SCr. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM et Al. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-04.

Renal insufficiency has been shown to be highly prevalent in patients with cancer. This renal insufficiency has been reported to be associated with reduced overall survival and increased cancer-related mortality. Therefore, it is important to screen patients with cancer for renal insufficiency, using an adequate and reliable method of estimation of the renal function. Renal insufficiency may influence 1 or several of the 4 pharmacokinetic phases (absorption, distribution, metabolism, elimination/excretion), potentially resulting in marked modifications of the pharmacokinetic profile of a drug in patients with renal insufficiency. Consequently, it is potentially necessary to adjust the dosage of anticancer drugs in case of renal insufficiency in order to avoid drug accumulation and in order to reduce overdosage-related side effects. This dosage adjustment of anticancer drugs should be performed according to the level of renal function and with an appropriate and validated method. It is not always easy to find clear information on anticancer drug handling in these patients. However, several guidelines, publications and handbooks are available on how to adjust anticancer drug dosages in patients with renal insufficiency and will help practitioners to manage anticancer drugs in such patients.

Pain is frequent in cancer patients. To date, there is a consequent therapeutic arsenal so to manage pain; the different treatment strategies are the subject of various recommendations. Patients with cancer also frequently suffer from renal insufficiency, and this comorbidity may disrupt or jeopardize the analgesic strategy by changing the risk-benefit ratio of treatment options. This article provides recommendations for the use of drugs used for pain treatment after pointing out: 1) etiological and pathophysiological elements of pain; 2) therapeutic strategies for pain management; 3) data regarding renal failure in cancer and; 4) a point on drugs pharmacokinetics.

Resume Rationnel et objectif La prise en charge d’un cancer en cours de dialyse ou chez un transplante est complexe et pose la question des interactions entre maladie renale chronique et cancer. Materiel et methodes Nous avons cherche a preciser l’incidence des cancers dans la population des dialyses et des transplantes, leur profils et leurs causes a travers une revue de la litterature qui a ete realisee. Resultats Une importante prevalence de l’insuffisance renale a ete observee en cancerologie avec 60 % des patients presentant un debit de filtration glomerulaire anormale. Parallelement, l’incidence des cancers chez le patient dialyse apparait plus elevee que dans la population generale pour certains cancers. Ainsi, apres l’initiation de la dialyse, le risque de survenue d’un cancer et de l’ordre de 1,1 a 1,8 par rapport a la population generale. Chez le transplante renal, une augmentation de l’incidence de certains cancers de novo est egalement constatee avec un risque relatif de 2,5 a 3,9, selon le type de tumeur. Les causes sont multifactorielles (stress oxydant, traitements immunosuppresseurs, etc.) Conclusion Chez ces patients transplantes, le risque de cancer sous immunosuppresseur au long cours impose des precautions particulieres en termes d’indication de transplantation. Cela comporte une recherche d’antecedent de cancer chez le donneur, le receveur et un suivi oriente. Ainsi, les medecins sont confrontes a des decisions de don d’organe ou de greffe en prenant en compte le risque de cancer dans des populations a risque.

Resume Introduction L’augmentation croissante de l’incidence des cancers chez des patients en dialyse a ete etudiee depuis les annees 1970. Parallelement, l’emergence des therapies ciblees oblige les oncologues, nephrologues et les pharmaciens a s’interroger sur le maniement en dialyse de ces nouvelles classes de medicaments pour lesquels on dispose peu de donnees. Methode Cette revue de la litterature fait le point sur la pharmacocinetique, la tolerance et l’efficacite des principales therapies ciblees en France, les anticorps monoclonaux et les inhibiteurs de tyrosine kinase. Cette revue a ete realisee en utilisant sur Pubmed les mots cles : rein, dialyse, hemodialyse, insuffisance renale terminale ainsi que le nom de chaque medicament. Resultats De la meme facon que pour les medicaments cytotoxiques, il n’existe dans la litterature que des rapports de cas isoles ou des series de cas isoles. Il est cependant possible d’emettre quelques recommandations : il n’est pas necessaire de modifier la posologie des anticorps monoclonaux de par leur nature meme. En revanche, la pharmacocinetique des inhibiteurs de tyrosine kinase differe d’un medicament a l’autre et il n’est pas possible de faire de recommandations globales. Conclusion Le recours aux therapies ciblees est possible chez les patients dialyses. Cependant, plusieurs medicaments necessitent une attention particuliere en situation de dialyse. De plus, dans la mesure oU ces medicaments sont recents, il est important que les oncologues, nephrologues et les pharmaciens soient particulierement vigilants dans l’evolution de leurs pratiques d’utilisation. La publication de toute information d’utilisation dans cette situation doit etre encouragee.

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study, which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients, treated in 15 cancer centers. Among them, 7.2% had a SCR level ≥ 110 mmol/L. In the 1,898 patients with breast cancer, only 31 patients (1.63%) had a SCR level ≥ 110 mmol/L. Nevertheless, respectively 51.8 and 50.8% had a creatinine clearance estimated with the Cockcroft-Gault and aMDRD formulae, below 90 mL/min. Even if the most used medications (anthracyclins, taxanes, trastuzumab, hormone therapies) are not nephrotoxic, these results are important because bevacizumab modifies the need for renal management. In case of renal insufficiency, some other treatments such biphosphonates IV, capecitabin and platin salts need drug dosage adjustment or interruption.

Anticancer drug management is complicated especially in renal insufficiency patients, a frequent situation in oncology. Several aspects need to be taken into account: first, the dosage. In this population, the kidney fails to eliminate drugs. Consequently, dosage adjustment can be necessary for drugs with pharmacokinetic profile altered by renal insufficiency in order to avoid dose-related side effects due to accumulation of the drug. Secondly, renal tolerance is an important aspect of anticancer drug management as renal insufficiency is a risk factor for developing renal side effects. Prevention of renal side effects is essential and means to limit this toxicity should be used, especially with hydration. Finally, it is essential to consider all the treatments prescribed in renal insufficiency patients in order to avoid accumulation of nephrotoxic drugs.

Resume L’utilisation des therapies ciblees est croissante dans le traitement du cancer. Les anticorps monoclonaux et les inhibiteurs de tyrosines kinases sont les plus couramment utilises, mais d’autres classes comme les inhibiteurs de mTOR sont egalement de plus en plus prescrits. Ces traitements sont volontiers donnes au long cours en phase metastatique et en traitement de maintenance. Il est donc important de surveiller l’occurrence de toxicites immediates, mais egalement de toxicites plus tardives et cumulatives. Les toxicites renales des therapies ciblees correspondent le plus souvent a des dommages structurels du nephron. Ainsi, les agents anti-epidermal growth factor receptor (EGFR) et anti-vascular endothelial growth factor receptor (VEGFR) ont des effets secondaires renaux car ces recepteurs de facteurs de croissance sont exprimes au niveau du rein. Les toxicites de molecules comme le bortezomib, l’erlotinib et le lapatinib sont moins connues. L’approbation par la US Food and Drugs Administration (FDA) et l’Agence europeenne du medicament (EMA) du sorafenib, du sunitinib et du temsirolimus a ete basee sur des etudes de moins 3 000 patients. Dans ce contexte, il y a assez peu de donnees sur leurs toxicites aigues et chroniques, notamment au niveau renal. Cette breve mise au point se propose de revenir sur les hypotheses physiopathogeniques, le diagnostic precoce et la prise en charge des toxicites renales des principales therapies ciblees disponibles en 2011.

Resume Introduction L’augmentation croissante de l’incidence des cancers en dialyse a ete etudiee depuis les annees 1970. Ainsi, les oncologues, les nephrologues et les pharmaciens sont de plus en plus confrontes a la problematique de l’utilisation des cytotoxiques chez les patients hemodialyses qui representent un million de patients a travers le monde et environ 36 000 patients en France. Chez les patients hemodialyses, les questions sont de deux ordres. D’une part, les patients hemodialyses n’ont plus de fonction renale fonctionnelle, exposant ainsi ces patients a un risque de surdosage et a des effets indesirables en cas de non-adaptation posologique. D’autre part, la possible dialysance des medicaments doit etre prise en compte afin de planifier au mieux l’administration des medicaments par rapport aux seances de dialyse et d’eviter une epuration trop precoce des medicaments par la dialyse et donc une inefficacite. Methode Cette revue de la litterature fait le point sur la pharmacocinetique, la tolerance et l’efficacite des traitements anticancereux chez le patient hemodialyse en utilisant sur Pubmed les mots cles : rein, dialyse, hemodialyse, insuffisance renale terminale ainsi que le nom de chaque medicament. Resultats Il n’existe sur ce sujet que des cas isoles ou de courtes series de cas dans la litterature. Une adaptation posologique en hemodialyse est necessaire pour 57,1 % des medicaments et 64,3 % doivent etre administres apres les seances de dialyse. Conclusion Les traitements anticancereux sont faisables en dialyse. Un grand nombre de medicaments necessitent une adaptation posologique et/ou une chronologie d’administration ajustee par rapport aux seances de dialyse tenant compte de leur dialysance. Des scores de fragilite, tels que ceux proposes en geriatrie, sont probablement necessaires pour guider la decision therapeutique.

Nous avons lu avec grand interet l’article de Mullier et al. [1] recemment publie dans les Annales de Biologie Clinique. Nous souhaiterions discuter des conclusions des auteurs et apporter deux complements d’information importants.Les auteurs precisent l’ensemble des parametres pharmacocinetiques des 3 anticoagulants oraux directs (AOD) actuellement disponibles en France. Cependant, il faut souligner que la part de l’elimination renale ne doit pas etre interpretee seule. En effet, [...]

Les chelates de gadolinium (Gd) sont des produits de contraste utilises au cours d’examen d’imagerie par resonance magnetique (IRM). A l’origine, ces medicaments etaient presentes comme des produits bien toleres tant sur le plan renal qu’extrarenal. Toutefois, plusieurs etudes ont rapporte des cas de nephrotoxicites induites par des produits de contraste a base de chelates de Gd. Dans la majorite des cas, l’atteinte renale etait observee apres une administration intra-arterielle de ces produits, a des doses superieures a 0,2 mmol/kg et chez des patients ayant une insuffisance renale preexistante. Le mecanisme responsable de cette nephrotoxicite n’a pas ete clairement decrit. De plus, plusieurs chelates de Gd semblent etre responsables d’un effet indesirable rare et severe, chez les patients insuffisants renaux chroniques, la fibrose nephrogenique systemique (FNS). Cet effet indesirable semble lie a l’utilisation de chelates de Gd de type lineaire, qui, dans certaines conditions, deviendraient instables et libereraient le Gd de son chelate, provoquant ainsi la FNS. Les facteurs de risque de cette maladie ne sont pas encore connus, a l’exception de l’insuffisance renale et de l’utilisation de ces produits. Cette revue de la litterature a pour but de faire la synthese des possibles effets renaux des produits de contraste a base de chelate de Gd, ainsi que de faire le point sur la FNS.

Background The Renal Insufficiency and Anticancer Medications (IRMA) study reported a renal insufficiency (RI) prevalence of 50%–60% in a population of almost 5000 patients with solid tumors, 80% of whom were being treated with anticancer drugs that either necessitated dosage adjustment or were potentially nephrotoxic drugs. A national multicenter study from 15 cancer centers in France analyzed IRMA data on patients with prostate cancer. Patients and Methods Data on patients with prostate cancer from the IRMA study were analyzed. Renal function was calculated using Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas to estimate the prevalence of RI. Anticancer drugs' potential renal toxicity and need for dosage adjustment were detailed. Results Of the 222 IRMA patients with prostate cancer, 14.9% had a serum creatinine (SCr) level of > 110 μmol/L. When using Cockcroft-Gault and aMDRD formulas, 62.6% and 55.9%, respectively, of the patients had RI. Of the 228 anticancer drug prescriptions, 82.9% required dose adjustments for RI or were drugs with no available data on their administration in patients with RI. Of the patients treated, 86.9% received ≤ 1 such drug, but only 29.1% received nephrotoxic drugs. Conclusion The prevalence of RI in patients with prostate cancer was very high in spite of a normal SCr level in most cases. Some anticancer drugs, particularly some bisphosphonates and platinum salts, might be nephrotoxic and/or need dosage adjustment. However, other important drugs in prostate cancer, such as docetaxel, neither require dose reduction nor present with potential nephrotoxicity. Both issues were significantly more important in the patients with bone metastases compared with those with nonmetastatic disease.

The prevalence of renal insufficiency before and at 1, 12, and 60 months after liver transplantation (LTx; primary endpoint) and the changes in the glomerular filtration rate (GFR) at same time points according to the immunosuppressive regimen (coprimary endpoint) were investigated. The primary outcome was determined for the entire cohort, whereas the coprimary endpoint was determined only for 2 groups of patients: those who started and remained on a calcineurin inhibitor (CNI) alone, that is, the CNI-alone group (n = 624), and those who started and remained on a CNI in combination with mycophenolate mofetil (MMF), that is, the MMF group (n = 117). GFR was

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study which demonstrated the high prevalence of abnormal renal function in a population of 4684 solid tumor patients. Among them, 50-60% had decreased renal function, and 80% were treated with anticancer drugs that either necessitated dosage adjustment in case of renal insufficiency (RI) or were potentially nephrotoxic drugs. Since elderly patients are well-known to have reduced renal function, either due to physiological aging or their disease/medication history, a subgroup analysis of this particular population of patients was performed. In 1553 IRMA patients whose age was > or =65 years, the prevalence of RI was very high in spite of normal serum creatinine values in most cases. Anticancer drugs used may be nephrotoxic or need dosage adjustment in a high number of cases.

Resume Introduction Les effets dermatologiques sont les evenements indesirables les plus frequents de l’erlotinib (Tarceva®). Toutefois, il n’existe a ce jour aucune recommandation precise sur la prise en charge preventive ou curative de ces effets chez les patients traites par erlotinib. L’etude « Prise en charge des effets dermatologiques sous erlotinib » (PRECEDE) avait pour objectif de decrire la prise en charge actuelle des effets dermatologiques induits par erlotinib (erlotinib-related skin effects [ERSE]) en France. Patients et methodes L’etude PRECEDE est un observatoire national retrospectif qui a inclus tous les patients atteints de cancer du poumon non a petites cellules ayant ete traites par erlotinib de janvier 2005 a decembre 2007 dans l’un des sept centres participants. Toutes les donnees relatives aux traitements preventifs et curatifs ont ete relevees dans le dossier medical des patients. Resultats Deux cent trente-quatre patients ont ete inclus dans l’etude ; 48,7 % d’entre eux ont recu une information sur la possible survenue d’un effet dermatologique induit par erlotinib, 15,8 % se sont vus prescrire une ordonnance de medicament a prendre en cas d’effet dermatologique induit par erlotinib et 65,0 % des patients ont eu un tel effet qui, dans la majorite des cas (86,2 %), a ete reversible avec ou sans traitement. Chez les 85 patients traites avec succes, 178 prescriptions composees de 35 medicaments differents ont ete denombrees. Conclusion Les effets dermatologiques induits par erlotinib sont frequents, mais regressent dans la plupart des cas avec ou sans traitement. Toutefois, il existe une grande diversite de medicaments utilisee pour traiter ces evenements indesirables, demontrant ainsi que des recommandations plus precises sur la prise en charge de ces evenements sont necessaires afin de les prevenir et de les traiter efficacement.

Objectives. The prevalence of kidney disease (KD) indicators together with the profile of RA drugs prescribed in RA patients was investigated in the MATRIX study (MeThotreXate And Renal Insufficiency). Methods. Renal function (RF) was assessed using Cockcroft–Gault (CG) and abbreviated Modification of Diet in Renal Disease (aMDRD) study formulae. Results. Serum creatinine (SCr) was normal in 81.4% of the 129 patients included. According to the National Kidney Foundation (NKF) classification, the distribution by stage of KD was, using the aMDRD and CG formulae, as follows: stage 1: 11.3% and 11.4%; stage 2: 20.0% and 20.3%; stage 3: 15.0% and 24.1%; stage 4: 0% and 1.3%; stage 5: 0%. Proteinuria, haematuria and leucocyturia were observed in 16%, 17% and 20% of the patients, respectively. Using the aMDRD and CG formulae, 36% and 38% of the prescriptions made in patients with glomerular filtration rate (GFR)

The increased incidence of malignancies in patients with chronic kidney patients and especially in end-stage kidney disease (ESKD) patients has been discussed since the mid-1970s. Consequently, oncologists, nephrologists, and pharmacists are increasingly facing challenging situations of cytotoxic drug handling in dialysis patients because of pharmacokinetic modifications. In these patients, two main issues must be considered. First, the absence of renal function in hemodialysis (HD) patients may necessitate drug dosage reduction. Therefore, drug prescription must be cautiously checked before administration with appropriate dosage adjustment whenever necessary to ensure efficacy while avoiding overdosage and related side effects. Second, drug clearance by dialysis session must be taken into account for appropriate chemotherapy timing administration to avoid drug removal, which may result in a loss of efficacy. These two main considerations must not be considered as a contra-indication to chemotherapy in ESKD patients, but more as a need for an individualized prescription according to available recommendations.

Purpose Side effects of antiangiogenic agents are moderate compared with other therapies. The most frequent adverse events are of a renovascular origin and manifest as hypertension (HTN) and thrombotic microangiopathy. To date, data are scanty on the renal tolerance of such drugs regarding renal function as itself, i.e., glomerular filtration rate (GFR). We report on the evolution of GFR in patients receiving antiangiogenic therapy after unilateral nephrectomy for kidney cancer. Patients and methods Data from 73 patients followed in our oncology department for kidney cancer, who had undergone unilateral nephrectomy, and received any antiangiogenic therapy were reviewed. Their GFR was calculated using the aMDRD formula. Results All patients showed a declining renal function over time (−1.23 and −2.51 mL/min/1.73 m 2 using the slope of the curve or the difference between GFR at baseline and that at the end of treatment, respectively). Among them, patients who were recorded as having HTN before initiation of antiangiogenic therapy showed a higher decrease in their GFR of −13.28 and −12.06 mL/min/1.73 m 2 . Conclusion We recommend that blood pressure should be measured closely in those patients before initiation of antiangiogenic therapy. When HTN is diagnosed, it should be treated and renal function should be monitored since those patients may be at risk for rapidly decreasing renal function under therapy.

Hepatitis C virus (HCV) is a major public health issue because infection may lead to liver failure, cirrhosis and hepatocellular carcinoma. In patients with renal dysfunction, hepatitis C can also worsen the underlying renal disease. Treating HCV infection is thus mandatory in this population. New therapies for hepatitis C have recently been developed, and some have been launched. Most of them are used in combination with the current standard of care, ribavirin and pegylated interferon alfa. Some of them can be used in regimens without ribavirin and/or pegylated interferon. However, few data are available on dosage adjustment for renal function in patients receiving these very new drugs. We reviewed the literature on this subject and gathered information, although scarce, to propose guidelines for using these drugs in patients with chronic kidney disease.

Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time.This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment.This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases.Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158-2163. © 2014 American Cancer Society.

Nephrogenic systemic fibrosis (NSF) has been related to the use of gadolinium-based contrast agents (GBCAs) in patients undergoing dialysis. The Prospective Fibrose Nephrogénique Systémique study, a French prospective study supported by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament) and the French Societies of Nephrology, Dermatology, and Radiology, aimed at determining the incidence of NSF in patients undergoing long-term dialysis.Adult patients undergoing long-term dialysis receiving a magnetic resonance imaging (MRI) examination prescribed between January 15, 2009 and May 31, 2011, with or without GBCA were included. The methodology was based on a patient form intended to detect any dermatological event (DE) that may occur within 4 months after the examination. Further investigations were planned with their physicians if a DE was reported.A total of 571 patients were included. A total of 50.3% received GBCA. Among them, 93.4% received a macrocyclic GBCA, usually gadoteric acid (88.9%). All in all, 22 patients (3.9%) reported a DE. Dermatological diagnoses did not reveal any evidence of NSF.The incidence of NSF after a single dose of a macrocyclic GBCA is null in our sample of 268 patients undergoing dialysis (hemodialysis and peritoneal dialysis). This incidence is just lower than 0.5%. When contrast-enhanced MRI can be essential, or even decisive, to the diagnosis, these results are important and reassuring if physicians need to perform contrast-enhanced MRI in patients undergoing dialysis.

Resume L'amprenavir est un inhibiteur de la protease du VIH-1, son metabolisme est essentiellement hepatique (> 80 %) et son elimination renale est faible. Il n'est donc theoriquement pas necessaire d'adapter la posologie de l'amprenavir chez le patient insuffisant renal. Cependant, il n'existe aucune etude de la pharmacocinetique de l'amprenavir chez le patient insuffisant renal pour verifier cette theorie. Nous rapportons les cas de deux patients contamines par le VIH et presentant une insuffisance renale, severe pour l'un, et terminale pour l'autre. La pharmacocinetique de l'amprenavir chez nos patients ne differait pas de celle des patients ayant une fonction renale normale. Enfin, l'amprenavir n'est pas dialysable, son FHD etant inferieur a 25 %. Par consequent, chez le patient insuffisant renal, le medicament peut etre administre aux doses normales, sans avoir recours a une adaptation de la posologie. De plus, chez le patient hemodialyse, l'administration de l'amprenavir peut etre realisee indifferemment avant ou apres la seance, les jours d'hemodialyse.

International audience; Background & AimsFew data are available on the prevalence of renal abnormalities in chronic hepatitis B virus (HBV)-infected patients. The multicentric cross-sectional HARPE study evaluated the prevalence of kidney disease indicators, in chronic HBV surface antigen carriers patients (HBsAg+) with active or inactive infection.Patients and methodsTwo hundred and sixty-eight HBsAg+ adult patients, naïve of any oral antihepatitis B virus treatment were prospectively included over 2 years. Data for renal assessment were collected once from patient files. Univariate tests and multiple linear regressions were performed with the SAS software, version 8.02 (SAS, Inc., Cary, NC, USA).ResultsAmong the 260 patients analysed, 58% were men, the mean age was 42 ± 14 years, 59.6% were inactive carriers whereas 47 patients, mostly active, were about to start an antiviral therapy. Prevalence of proteinuria, haematuria, glycosuria, uninfectious leukocyturia was 38.1%, 20.6%, 3.9% and 9% respectively. According to the international definition, a total of 64.6% of patients were found to have kidney disease. Diabetes, hypertension and dyslipidaemia were observed, respectively, in 4.6%, 9.2% and 38.8% patients. There were no significant differences in these results within the three subgroups.ConclusionRenal abnormalities are highly prevalent in our population and pre-exist before the initiation of any antihepatitis B virus treatment. This emphasizes the need for: (i) a baseline renal evaluation in all HBs antigen-positive patients; (ii) a regular renal monitoring before and during antihepatitis B virus treatment to diagnose and manage renal impairment and adjust antihepatitis B virus treatment doses to renal function when necessary.

Malaria is an endemic and potentially lethal disease transmitted by the protozoan parasite Plasmodium. It is currently endemic in more than 100 countries, which are visited by 125 million international travellers every year. For dialysis and renal insufficiency patients it becomes increasingly easier to travel to these countries thanks to the recent advances in renal replacement therapy. However, the pharmacokinetics of some prophylactic agents in malaria are altered, which may modify the effectiveness and safety of such treatments and the way they should be prescribed. Clinicians should be aware of these alterations which require subsequent dosage adjustments. This review provides recommendations on the use of antimalarial drugs, alone or in combination, in patients with renal impairment. These recommendations depend on the prevalence of Plasmodium falciparum chloroquine resistance, as defined by the WHO. Furthermore, fixed-dose combinations cannot be used in patients with creatinine clearance below 60 mL/min since the tablets available do not allow appropriate dosage adjustment for each drug. Chloroquine and proguanil require dosage adjustments, while atovaquone, doxycycline and mefloquine do not.

Introduction Parmi les personnes âgees, 30,1 % ont une insuffisance renale (IR) [1] et les ordonnances n’incluent aucune information sur les comorbidites et notamment sur IR. L’objectif de l’etude IPOP etait d’evaluer le contenu des ordonnances des patients âges afin de decrire le risque iatrogene et notamment leur exposition au risque de surdosage en cas d’IR. Patients et methodes Les patients âges (≥ 65 ans), polymediques (≥ 3 medicaments) et se presentant a l’une des 81 officines participantes ont ete inclus. Les ordonnances ont ete analysees sur SiteGPR afin de savoir si elles contenaient des medicaments necessitant une adaptation posologique en cas d’IR. Par ailleurs, chaque pharmacien devait repondre a un questionnaire par patient. Resultats Neuf cent cinq ordonnances (1 ordonnance/patient) ont ete incluses (âge median : 77 ans). Neuf cent cinq ordonnances (1 ordonnance/patient) ont ete incluses (âge median : 77 ans), pour 6839 prescriptions, 96,5 % comprenaient au moins un medicament necessitant une adaptation posologique en cas d’IR ( Tableau 1 ). Huit cent soixante-dix-sept reponses au questionnaire ont ete obtenues. Parmi elles, 6,0 % des pharmaciens declarent savoir que leurs patients presentaient une IR. Discussion La majorite des personnes âgees recoivent au moins un medicament necessitant une adaptation posologique en cas d’IR. Le sous-diagnostic de l’IR les expose donc a un risque de surdosage. En effet, un DFG Conclusion Afin de prevenir ce risque iatrogene, il est necessaire de depister l’IR et de transmettre cette information aux pharmaciens afin de verifier s’il est necessaire ou non d’adapter la posologie des medicaments grâce au SiteGPR ( www.SiteGPR.com ). Une modification de l’ordonnance permettrait de transmettre cette information en y precisant la fonction renale.

Background One million people worldwide benefit from chronic dialysis, with an increased rate in Western countries of 5% yearly. Owing to increased incidence of cancer in dialyzed patients, the management of these patients is challenging for oncologists/nephrologists. Patients and methods The CANcer and DialYsis (CANDY) retrospective multicenter study included patients under chronic dialysis who subsequently had a cancer (T0). Patients were followed up for 2 years after T0. Prescriptions of anticancer drugs were studied with regard to their renal dosage adjustment/dialysability. Results A total of 178 patients from 12 institutions were included. The mean time between initiation of dialysis and T0 was 30.8 months. Fifty patients had received anticancer drug treatment. Among them, 72% and 82% received at least one drug needing dosage and one drug to be administered after dialysis sessions, respectively. Chemotherapy was omitted or prematurely stopped in many cases where systemic treatment was indicated or was often not adequately prescribed. Conclusions Survival in dialysis patients with incident cancer was poor. It is crucial to consider anticancer drug treatment in these patients as for non-dialysis patients and to use current available specific drug management recommendations in order to (i) adjust the dose and (ii) avoid premature elimination of the drug during dialysis sessions.