BACKGROUND.: The Renal Insufficiency and Cancer Medications (IRMA) study is a French national observational study. The results from this study of nearly 5000 patients demonstrated the high prevalence of renal impairment in a population of patients with solid tumors.METHODS.: Every cancer patient who presented at oncology departments that participated in the study over at least 1 of 2 predefined periods during 2004 were included. Renal function was calculated using Cockcroft‐Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulae to estimate the prevalence of renal insufficiency (RI) according to the Kidney Disease Outcomes Quality Initiative‐Kidney Disease Improving Global Outcomes definition and stratification. Anticancer drugs were studied with regard to their potential renal toxicity and dosage adjustment.RESULTS.: Of the 4684 patients from the 15 centers, 7.2% had serum creatinine levels >110 μmol/L. However, when they were assessed using Cockcroft‐Gault and aMDRD formulae, 57.4% and 52.9% of patients had abnormal renal function or RI, respectively. Of the 7181 anticancer drug prescriptions, 53.4% required dose adjustments for RI. Of the patients treated, 79.9% received at least 1 such drug. And 80.1% received potentially nephrotoxic drugs.CONCLUSIONS.: RI was common in patients with cancer, and drug dosage adjustments often were necessary. Renal function should be evaluated in all cancer patients using either the Cockcroft‐Gault formula or the aMDRD formula, including patients with normal serum creatinine levels. In patients who are at high risk for drug toxicity, the dosage should be adapted to renal function, and the use of nephrotoxic therapies should be avoided whenever possible. Cancer 2007. © 2007 American Cancer Society.

Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of ‘intergenic splicing’. We also explored the implications of these non-pathological fusions in cancer and in evolution.

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Background: The increased incidence of malignancies in patients with chronic renal failure has been discussed since the mid-70s. On the other hand, the high frequency of chronic renal insufficiency among cancer patients has been recently assessed in the Insuffisance Rénale et Médicaments Anticancéreux Study which demonstrated a prevalence as high as 50%–60% of the patients for all stages of kidney disease. Furthermore, the incidence of end-stage renal disease is growing worldwide and so is the number of patients on chronic dialysis, hemodialysis (HD) for the large majority of them. As a result, the question of cytotoxic drug handling in those patients in terms of dosage adjustment and time of administration regarding the dialysis sessions needs to be addressed to optimize cytotoxic drug therapy in those patients. Methods: We reviewed the international literature on the pharmacokinetics, efficacy, tolerance and dosage adjustment of cytotoxic drugs used to treat solid tumor patients and when available, specific literature on HD cancer patients. Results: From these data, dosing recommendations are given for the most prescribed cytotoxic drugs in clinical practice. Conclusions: Dosage adjustments are often necessary in HD cancer patients. These adaptations have to be carefully carried out to optimize drug exposure, ensure efficacy and reduce the risk of side-effects.

Contrast medium (CM)-induced nephropathy (CIN), defined as acute renal failure after administration of CM when alternative causes of renal damage have been excluded, is the third leading cause of acute renal injury necessitating hospitalization. However, the pathophysiology of CIN is complex and not fully understood. Gadolinium chelates, originally introduced as intravenous CM for magnetic resonance imaging and regarded as nonnephrotoxic, have been recommended to replace iodinated contrast agents in patients at risk for acute renal failure. Since then, some gadolinium-based CM have been reported to be associated with CIN, especially in patients with advanced renal disease. However, the biochemical and physicochemical properties of the gadolinium-chelates that are responsible for such nephrotoxicity have not been clearly defined, and the issue of gadolinium-induced nephrotoxicity remains controversial. This review surveys the literature with the purpose of clarifying the renal effects of gadolinium-based CM in patients with renal insufficiency.

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) <60 ml/min required a dosage adjustment. Among the patients with GFR <60 ml/min, 83–90% received at least one drug that required a dosage adjustment and 67–70% received at least one drug that was potentially nephrotoxic, according to aMDRD or CG formulae, respectively. Five (50%) and 8 (47%) patients did not have appropriate MTX dosage adjustment according to their stage of KD with aMDRD or CG formulae, respectively. Conclusion. Systematic estimation of RF with CG or aMDRD formulae and urine dipstick are necessary in RA patients. In patients with KD at high risk for drug toxicity, dosage should be adapted to RF.