Targeted Therapies for Renal Cell Carcinoma: Review of Adverse Event Management Strategies

With the advent of targeted agents for the treatment of renal cell carcinoma (RCC), overall survival has improved, and patients are being treated continuously for increasingly long periods of time. This has raised challenges in the management of adverse events (AEs) associated with the six targeted agents approved in RCC—sorafenib, sunitinib, pazopanib, bevacizumab (in combination with interferon alpha), temsirolimus, and everolimus. Suggestions for monitoring and managing AEs have been published, but there are few consensus recommendations. In addition, there is a risk that patients will be subjected to multiple unnecessary investigations. In this review, we aimed to identify the level of supporting evidence for suggested AE management strategies to provide practical guidance on essential monitoring and management that should be undertaken when using targeted agents. Five databases were systematically searched for relevant English language articles (including American Society of Clinical Oncology abstracts) published between January 2007 and March 2011; European Society of Medical Oncology congress abstracts were hand searched. Strategies for AE management were summarized and categorized according to the level of recommendation. A total of 107 articles were identified that describe a large number of different investigations for monitoring AEs and interventions for AE management. We identify and summarize clear recommendations for the management of dermatologic, gastrointestinal, thyroid, cardiovascular, and other AEs, based predominantly on expert opinion. However, because the evidence for the suggested management strategies is largely anecdotal, there is a need for further systematic investigation of management strategies for AEs related to targeted therapies for RC

Prevalence of chronic kidney disease among people living with HIV/AIDS in Burundi: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Since little is known about chronic kidney disease (CKD) among people living with HIV/AIDS (PLWHA) in Sub-Saharan Africa, the prevalence and nature of CKD were assessed in Burundi through a multicenter cross-sectional study.</p> <p>Methods</p> <p>Patients underwent assessments at baseline and 3 months later. Glomerular Filtration Rate (GFR) was estimated using abbreviated 4-variable Modification of Diet in Renal Diseases (MDRD) and Cockroft-Gault estimation methods. Patients were classified at month 3 into various CKD stages using the National Kidney Foundation (NKF) definition, which combines GFR and urinary abnormalities. Risk factors for presence of proteinuria (PRO) and aseptic leukocyturia (LEU) were further analyzed using multiple logistic regression.</p> <p>Results</p> <p>Median age of the patients in the study (N = 300) was 40 years, 70.3% were female and 71.7% were on highly active antiretroviral therapy. Using the MDRD method, CKD prevalence in patients was 45.7%, 30.2% of whom being classified as stage 1 according to the NKF classification, 13.5% as stage 2 and 2% as stage 3. No patient was classified as stage 4 or 5. Among CKD patients with urinary abnormality, PRO accounted for 6.1% and LEU for 18.4%. Significant associations were found between LEU and non-steroidal anti-inflammatory drug (NSAID) use, previous history of tuberculosis, low body mass index and female gender and between PRO and high viral load.</p> <p>Conclusion</p> <p>Our study, using a very sensitive definition for CKD evaluation, suggests a potentially high prevalence of CKD among PLWHA in Burundi. Patients should be regularly monitored and preventative measures implemented, such as monitoring NSAID use and adjustment of drug dosages according to body weight. Urine dipsticks could be used as a screening tool to detect patients at risk of renal impairment.</p

Syndrome d’antidiurèse inappropriée néphrogénique

Les troubles de l'équilibre de l'eau représentent une pathologie fréquente dans notre pratique clinique. L'étude du récepteur V2R est importante pour la compréhension de la physiologie de l'équilibre hydrique et a servi de prototype pour la biologie des récepteurs G couplés aux protéines. Le syndrome d'antidiurèse inappropriée néphrogénique (NSIAD) est un syndrome de sécrétion inappropriée d'hormone antidiurétique (SIADH)-like avec un dosage plasmatique de vasopressine bas. La preuve du rôle du récepteur V2R et de l'aquaporine (AQP) dans le mode d'action de l'hormone antidiurétique (ADH) est venue de l'identification de mutations dans les gènes de ces protéines dans le diabète insipide néphrogénique et dans le syndrome NSIAD. Des mutations activatrices du V2R ont été retrouvées dans le NSIAD, à l'opposé des nombreuses mutations inactivatrices du V2R liées à l'X décrites dans le diabète insipide néphrogénique

Anticancer Drug-Induced Acute Kidney Injury

Acute kidney injury (AKI) is a growing problem with untoward economic and medical consequences. Anticancer drug toxicity remains an important and increasing cause of AKI. Importantly, drug-induced AKI affects all nephron segments—vasculature, glomerulus, tubules, and interstitium. Recent studies have increased insight into the subcellular mechanisms of drug-induced AKI that include direct cellular toxicity and immune-mediated effects. Identification of patients with high-risk cancer before drug exposure may allow prevention or at least a reduction in the development and severity of nephrotoxicity. Recognition of drug-induced AKI and rapid discontinuation (or dose reduction) of the offending agents, when appropriate, are critical to maximizing kidney function recovery. Preventive measures require understanding patient and drug-related risk factors coupled with correcting risk factors, assessing baseline kidney function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations

Serum procalcitonin in systemic autoimmune diseases--where are we now

OBJECTIVES: To review the current evidence regarding the value of measuring procalcitonin (PCT) levels in patients with systemic autoimmune diseases, with a focus on the evidence for diagnostic and analytical performance of this biomarker. A brief description of the pathophysiological basis of this biomarker is also included. METHODS: Using PubMed from the National Library of Medicine, relevant English literature on PCT in patients with different systemic autoimmune diseases, from 1990 to 2009, was reviewed. The search used keywords referring to procalcitonin and systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated systemic vasculitis, Goodpasture syndrome, rheumatoid arthritis, and giant cell arteritis. RESULTS: When used in the appropriate clinical setting, the measurement of serum PCT levels is valuable as a marker of severe systemic bacterial and fungal infections and sepsis. Information regarding plasma PCT levels in patients with active underlying systemic autoimmune diseases is limited, primarily from observational studies and case series, with considerable variability of patient characteristics and clinical settings. In the detection of systemic infection concomitant with autoimmune diseases, PCT had a diagnostic sensitivity of 53 to 100% and a specificity of 84 to 97% (depending on the selection criteria) and was superior to other inflammatory markers tested. Most of the studies used a semiquantitative test for PCT measurement (functional assay sensitivity \u3c0.5 ng/mL), which can explain the low sensitivity of the test. PCT levels were not significantly affected by renal function abnormalities or immunosuppressive agents. Although high PCT levels commonly occurred with infection, elevated levels of PCT could be found in patients with vasculitis without evidence of infection, often correlated with high disease activity scores. CONCLUSIONS: Significantly elevated PCT levels offer good specificity and sensitivity for systemic infection in patients with systemic autoimmune diseases, regardless of the use of corticosteroids or immunosuppressive agents. PCT measurement may add to diagnostic accuracy in patients with systemic autoimmune diseases who present with a febrile illness, especially when highly sensitive PCT assays and specific PCT cutoff ranges are used in a predefined clinical setting (reflecting the likelihood of infection versus an autoimmune disease flare). However, there are limitations when using this biomarker in patients with systemic autoimmune diseases. PCT levels should not replace the necessary extensive diagnostic workup, which should include a thorough history and physical examination, combined with appropriate immunological, microbiological, radiological, and histological data

Ovarian tumor and glomerulopathies: case report and review of the literature

International audienceWe describe a patient who developed nephrotic syndrome in the setting of ovarian tumor. A kidney biopsy showed minimal change nephropathy (MCN). CT scan and MR imaging followed by surgery lead to diagnostic of ovarian dermoid cyst. Surgery combined with corticosteroids resulted in a complete remission of nephrotic syndrome with disappearance of proteinuria after 3 weeks. Ten other cases of ovarian tumor associated with glomerulopathy are reviewed. This is the second case of an ovarian teratoma associated with MCN. Accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis in such patients

Anticancer Drug-Induced Capillary Leak Syndrome

International audienceThe term capillary leak syndrome (CLS) describes the manifestations associated with an increased capillary permeability to proteins leading to an escape of plasma from the blood circulatory system to surrounding tissues, muscle, organs, or body cavities. This results clinically in the typical triad of hypotension, edema, and elevated hematocrit. The more severe cases of CLS may present with cardiovascular collapse, shock, and death. The most classic form of this pathology is represented by the idiopathic systemic CLS (SCLS) also called Clarkson's disease, but capillary leaks are also described as adverse drug reactions foremost among which are anticancer drugs. This review will focus on oncologic drugs such as gemcitabine, therapeutic growth factors or cytokines, and monoclonal antibodies (mAbs) that appear now as the strongest candidates for anticancer drug-induced CLS

Nephrotoxicity of Anti-Angiogenic Therapies

International audienceThe use of inhibitors of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling for the treatment of cancer has increased over the last decade. This signaling pathway plays a fundamental role in angiogenesis and also in kidney physiology. The emergence of anti-angiogenic therapies has led to adverse nephrotoxic effects, despite improving the outcomes of patients. In this review, we will present the different anti-angiogenic therapies targeting the VEGFR pathway in association with the incidence of renal manifestations during their use. In addition, we will discuss, in detail, the pathophysiological mechanisms of frequent renal diseases such as hypertension, proteinuria, renal dysfunction, and electrolyte disorders. Finally, we will outline the cellular damage described following these therapies

Two observations raising questions about risk factors of cutaneous necrosis induced by Terlipressin (Glypressin (R))

Introduction: Triglycyl lysine vasopressin (terlipressin, Glypressin (R)) is a potent vasoconstrictive drug which became popular because of its prolonged duration of action, ease of administration and lower incidence of side effects. Ischemic complications are rare but may be life threatening. Observations: Case 1, a 68-year-old man with alcoholic cirrhosis and hepatocellular carcinoma, was admitted due to acute functional renal failure. He was first treated for septic shock with intravenous catecholamines. He then developed hepatorenal syndrome and received terlipressin as intravenous bolus (4 mg/day). Three days later, he presented a diffuse purpuric and necrotic eruption with tongue ischemia. He died from Staphylococcus aureus infection. Case 2, a 74-year-old man with metastatic carcinoma, presented severe renal insufficiency. He developed sepsis and pseudohepatorenal syndrome, which was treated with terlipressin (0.5 mg/h) using an infusion pump. Four days later, he developed an isolated large erythematous and purpuric macular plaque of the scalp near skin metastases. The patient died a few weeks later from tumor progression. In both cases, skin biopsies showed ischemic necrosis caused by thrombosis of superficial dermal capillaries. Conclusion: These cases point to the risk of either widespread or localized necrosis. Although the precise incidence of these events as well as risk factors remain to be determined, hypovolemia, concomitant administration of vasoactive drugs and the mode of administration of terlipressin may influence the occurrence of these complications. Copyright (C) 2009 S. Karger AG, Base