Sabine Amet

Incidence of nephrogenic systemic fibrosis in patients undergoing dialysis after contrast-enhanced magnetic resonance imaging with gadolinium-based contrast agents: the Prospective Fibrose Nephrogénique Systémique study.

BackgroundNephrogenic 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. Materials and MethodsAdult 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. ResultsA 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. ConclusionsThe 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.

Acute renal failure associated with the new BRAF inhibitor vemurafenib: A case series of 8 patients

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.

Prevalence of renal abnormalities in chronic HBV infection: The HARPE study

Few 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.

Malaria Prophylaxis in Patients with Renal Impairment

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.

Toxicité rénale des produits de contraste chez le patient oncologique

Cancer patients frequently undergo imaging examinations to diagnosis but also to evaluate their responses to treatment. These patients are also at high risk of kidney impairment before considering the possible nephrotoxicity of their chemotherapy. In this context, it is overriding to know contrast agents induced risks and what are the good practices to avoid them. Renal function evaluation takes a major part in there. The X-ray radiology using iodinated contrast agent (ICA) exposes patients to acute renal failure. This induced nephropathy is prevented by adequate hydration prior to injection when the glomerular filtration rate (GFR) of the patient is less than 60 ml/min/1.73 m(2). For hardly nephrotoxic, gadolinium-based contrast agents (GBCA) injected in magnetic resonance imaging, were considered for a long as a safe alternative to ICA. Yet they may induce nephrogenic systemic fibrosis (NSF). The recommendations of European and U.S. drugs safety agencies have recently converged defining groups at risk of NSF based on the level of patients GFR and the type of GBCA used. How to assess the risk-benefit balance of the cancer patient for whom you should choose an informative, effective and safe imaging examination?

Néphrotoxicité des médicaments

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.

Néphrotoxicité des antirétroviraux autres que le ténofovir

The remarkable improvement of the outcome of HIV infection came with the price of substantial toxicity of some antiretrovirals. The first molecules used to treat HIV included an important nephrotoxicity. Zalcitabine, stavudine and didanosine can induce severe lactic acidosis. Lactate production is enhanced and the renal capacity to regulate pH is overwhelmed. However, this side effect is not due to a direct dysfunction of the kidneys. Zalcitabine was withdrawn from the market because of this risk. Indinavir, a protease inhibitor, is soluble only in very acidic solutions. Consequently, the small fraction that is excreted in the urine precipitates and can be responsible for uro-nephrolithiasis, leukocyturia, cristalluria, obstructive acute kidney failure, and acute or chronic interstitial nephritis. This is the reason why indinavir is almost not prescribed nowadays, even if it is still marketed. In addition to the direct nephrotoxicity of some antiretrovirals, anti-HIV treatment also includes a toxicity which pathophysiology is not completely elucidated. This nephrotoxicity is the consequence of organ accelerated ageing and of an increased vascular risk. Kidney vascularization (from renal arteries to capillaries) is essential to kidney function and all cardiovascular risks are also renal risks. It is now clearly established that combined antiretroviral treatment increases the vascular risk. A better comprehension of the links between HIV infection, its treatment and very long-term kidney risk is needed to improve the complex management of patients who have now cumulated several decades of HIV infection and treatment with various toxicities.

405 HARPE STUDY: PREVALENCE OF RENAL ABNORMALITIES IN CHRONIC HBV INFECTION

Background and Aims: A close relationship exists between HBV infection and renal dysfunction. This study was undertaken to evaluate the degree of renal dysfunction in HBV positive patients in a university hospital in Mumbai and factors predicting it. Methods: We retrospectively analyzed 663 HBV positive patients presenting to our clinic from January 2010-June 2012 for renal dysfunction (estimated Glomerular Filtration rate (eGFR) by MDRD formula). Excluding 13 patients on maintenance hemodialysis and 66 with missing data, 584 patients (467 males; median age 43, range 9–80 years) were included. Results: Of 584 patients, 24 had acute hepatitis, 209 non-cirrhotic Chronic Hepatitis B (CHB), 214 were inactive carriers, 108 had CHB with cirrhosis, 22 were in immunotolerant phase, 6 had acuteon-chronic liver failure, 1 patient post liver transplant. Majority of patients were HBeAg negative (74.82%). 141 patients (24.1%) had comorbidities (diabetes mellitus and/or systemic hypertension). Serum creatinine was elevated (>1.5mg/ml) in 20 patients (2.7%) while eGFR (MDRD) was below normal ( 90ml/min/1.72m, 293 patients. Based on HBV disease status, renal function was different: In acute group (acute hepatitis, immunotolerant), 26.53% patients had mild renal dysfunction (eGFR 60–90ml/min/1.72m) versus chronic disease group (inactive carrier status, CHB, cirrhosis, others) with 44.49% (p =0.008). In multivariate analysis, age, gender, hypertension and chronic disease stage had significant association with reduced eGFR. 1 year follow-up eGFR values were available for 321 patients, of which 79 (25%) showed worsening of renal function by >20% while 58 patients (15%) showed >20% improvement. Within the cirrhotic population, Diabetes was significantly more prevalent than in other populations (33% of patients). 62/108 (57%) of cirrhotic patients had reduced renal function. Conclusion: HBV infection is associated with significant degree of reduced renal function, reaching up to 50% in the chronic population of our clinic. Comorbidities (25%) or antiviral treatment might further increase renal risk, therefore regular monitoring of renal function is recommended. MDRD formula was shown to be more sensitive than serum creatinine for renal function evaluation.

Pulmonary Hypertension: Use of Oral Drugs in Patients with Renal Insufficiency

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.

Toxicité rénale des produits de contraste chez le patient oncologiqueRenal toxicity of contrast agents in oncologic patients

Cancer patients frequently undergo imaging examinations to diagnosis but also to evaluate their responses to treatment. These patients are also at high risk of kidney impairment before considering the possible nephrotoxicity of their chemotherapy. In this context, it is overriding to know contrast agents induced risks and what are the good practices to avoid them. Renal function evaluation takes a major part in there. The X-ray radiology using iodinated contrast agent (ICA) exposes patients to acute renal failure. This induced nephropathy is prevented by adequate hydration prior to injection when the glomerular filtration rate (GFR) of the patient is less than 60 ml/min/1.73 m(2). For hardly nephrotoxic, gadolinium-based contrast agents (GBCA) injected in magnetic resonance imaging, were considered for a long as a safe alternative to ICA. Yet they may induce nephrogenic systemic fibrosis (NSF). The recommendations of European and U.S. drugs safety agencies have recently converged defining groups at risk of NSF based on the level of patients GFR and the type of GBCA used. How to assess the risk-benefit balance of the cancer patient for whom you should choose an informative, effective and safe imaging examination?