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Biomedical subjects

V Launay-Vacher

Publications and source records attributed to V Launay-Vacher.

At least 19 recordsLinked to original sources

COX-2 inhibitors and acute interstitial nephritis: case report and review of the literature.

We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days - 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 +/- 0.11 mg/dl, 5.66 +/- 3.50 mg/dl and 1.15 +/- 0.24 before treatment, at time of diagnosis and 1 - 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.

Anti-Inflammatory Agents, Non-Steroidal↗

Is low-dose methotrexate nephrotoxic? Case report and review of the literature.

Methotrexate (MTX) has become the most commonly prescribed disease-modifying anti-rheumatic drug. However, toxicity is an important drawback of MTX therapy and permanent discontinuation of MTX for adverse effects occurs in 1 patient out of 10. Although high-dose MTX is known to be nephrotoxic, data on low-dose MTX renal effects are scanty. We report an insidious and progressive deterioration of renal function during long-term low-dose MTX in a 59-year-old woman. Kidney biopsy revealed advanced kidney fibrosis with extensive interstitial and glomerular fibrosis, and vascular sclerosis. We suggest that patients on low-dose MTX therapy even alone, should be periodically monitored for creatinine levels.

Antirheumatic Agents↗

[Kidney and glitazones].

PPARgamma nuclear receptors are mainly expressed in adipose tissue. However, they are also expressed in renal glomerular tissue and in vascular walls, thus participating through various and complex mechanisms, to glomerular and vascular sclerosis and to nephropathy development and progression. Studies carried out with glitazones, pharmacological agonists of nuclear receptor PPARgamma, in experimental models, either in vitro, or in vivo in animal models, have demonstrated their favourable effects on arterial blood pressure and on prevention and/or progression of diabetic nephropathy. The few clinical studies conducted in type 2 diabetic patients to assess these effects, are also in favor of a beneficial effect of glitazones on blood pressure and nephropathy in these patients. Thus, it appears extremely important and fully justified to conduct specific studies in patients with type 2 diabetes, with the aim to establish and to better characterize these effects in various clinical conditions (antihypertensive effect in treated hypertensive patients according to the class of antihypertensive agents used, prevention of diabetic nephropathy and/or effect on its progression, renal protection, etc.). Some adverse events, although with a low incidence, may be associated with glitazone use (weight gain, peripheral oedema, fluid retention, etc.), and may limit their use in some patients. It is clearly important to better understand the pathophysiological mechanisms of these effects and their possible long term consequences. Finally, it is important to emphasize the easiness to use glitazones in patients with renal insufficiency, without the need to adjust the drug regimen.

Animals↗

PPAR-gamma-agonists' renal effects.

PPAR-gamma ligands, including thiazolidinediones, have recently become clinically available for treating insulin-resistant diabetes mellitus. Accumulating evidence suggests that these drugs not only significantly improve insulin sensitivity but also may have antiproteinuric effects in genetically obese diabetic rodents and patients with type II diabetes and diabetic nephropathy. Moreover, troglitazone reduced expression of ECM proteins and transforming growth factor-beta in glomeruli from streptozotocin-induced diabetic rats. Many other properties including antiproteinuric, hemodynamic, and antihypertensive effects in insulin-dependent diabetes mellitus suggest that PPAR-gamma ligands might have a direct, beneficial renal effect, independent of their capacity to improve glucose tolerance. Besides their antidiabetic effects, thiazolidinediones have been shown to lower blood pressure in diabetic patients with hypertension and patients with diabetic nephropathy through multiple mechanisms. Several studies showed the efficacy of PPAR-gamma agonists to ameliorate the progression of glomerulosclerosis. The effect is independent of insulin effects and could only be partially due to lipid effects. These renal protective effects of PPAR-gamma agonists suggest that they may provide a novel intervention strategy to prevent vascular and glomerular sclerosis.

Animals↗

Renal effects of PPARalpha-agonists.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the large nuclear receptor superfamily. Its main role is to activate genes involved in fatty acid oxidation in the liver, heart, kidney and skeletal muscle. While they are mainly used as hypolipidemic agents, PPARalpha agonists may also be postulated to exhibit renoprotective effects. This review summarizes current knowledge regarding the effects of PPARalpha agonists on the kidney.

Humans↗

Assessing residents' prescribing behavior in renal impairment.

OBJECTIVE: Although fitting orders to renal function avoids overdosage and therefore iatrogenic risk, dosage adjustment is rarely made. The objective of this study was to assess residents' prescribing behavior in renal impairment, through a standardized simulated clinical setting. METHOD: This criterion-referenced study was carried out in a French teaching hospital. The hospital had 118 residents; 71 of them were asked to complete a questionnaire including four vignettes, simulating drug prescription in four 'patients' with various degrees of renal impairment (16 orders). The patients had an order of gentamicin sulfate, diclofenac sodium, and amlodipine bensylate. For each drug, the resident could maintain the order, discontinue the order, or change the dosage. A fourth drug, enalapril maleate, was to be started, with three possible dosages and the possibility of not prescribing it. The reference chosen for assessment was the Vidal dictionary, which corresponds to the Physician's Desk Reference and is the French reference for prescription. RESULTS: All the residents approached for the survey accepted the offer to complete the questionnaire. Among the 16 simulated orders, the median number of appropriate orders per resident was nine. Considering the renal function of their patients, 62% of residents wrote an inappropriate order for gentamicin, 42% wrote an inappropriate order for didofenac, and 52% wrote an inappropriate order for enalapril. Although no adjustment to renal function was required, 28% of the residents decreased the dosage of amlodipine and ordered an underdose. CONCLUSION: Considering the iatrogenic risk related to the lack of dosage adjustment, attention should be drawn to increasing residents' awareness of dosage adjustment in renal impairment and to providing them with better information on patients' renal function.

Aged↗

Medication misuse in hospitalized patients with renal impairment.

OBJECTIVES: The potential consequences of medication misuse in renal impairment have not been assessed in a population of in-patients. The purpose of this study was to determine the frequency and potential consequences of a lack of dosage adjustment in hospitalized patients with renal impairment. DESIGN: Order sheets for in-patients having a creatinine above 0.7 mg/dl were analysed. We considered the appropriateness of prescriptions for medications having potential nephrotoxicity and/or eliminated through renal excretion or metabolism (TEM medications) and having manufacturer's guidelines for dosage adjustment in renal impairment. MAIN MEASURES: On the basis of these guidelines, each line of prescription was rated as 'appropriate order', 'inappropriate dosage', or 'contra-indicated order'. Experts also rated prescriptions as potentially fatal or severe, serious, significant, or without potential for increased adverse effects. RESULTS: Two hundred and two order sheets were completed for 164 patients. They totalled 1469 lines of prescription, 85% of which were TEM medications, with guidelines for dosage adjustment for 71% of them (n = 886). Of these 886 prescriptions, 34% were inappropriate, 14% being contra-indicated and 20% with inappropriate dosage given the patient's renal function. Among the 202 order sheets, 75% included at least one inappropriate prescription. Sixty-three per cent included at least one prescription with potentially adverse consequences, 3% of these having potentially fatal or severe consequences. CONCLUSION: This study confirms that physicians do not take into account sufficiently patient renal function when prescribing. In light of these results, improving the quality of drug prescription in patients with renal impairment could be of importance for improving the quality of care.

Aged↗

Antiviral drug-induced kidney and electrolytes disorders.

HIV patients are at a high risk for nephrotoxicity (HIV-induced nephrotoxicity, HIVAN). As a result, renal insufficiency, tubular dysfunction and renal-related biological disorders are frequently observed in those patients. However, in some cases those defects or anomalies in renal function may be related to antiviral therapies rather than the disease itself. This article reviews the incidence, presentation, prevention and management of antiviral drug-induced renal dysfunction.

Anti-HIV Agents↗

Anti-viral drugs in continuous ambulatory peritoneal dialysis (CAPD).

The prevalence of HIV-positive subjects in dialysis (hemodialysis and peritoneal dialysis) population varies from 0.13 to 0.36% in italian and french studies, respectively. Most drugs used in HIV therapy are primarily excreted by the kidney. In patients with renal insufficiency, careful dosage adjustment is mandatory to optimize drug exposure and reduce the risk for adverse events. We review the impact of peritoneal dialysis on the pharmacokinetics of antiviral drugs, and discuss on the dosage recommendations needed to achieve efficacy and avoid toxicity in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD).

Adamantane↗

[How and when to search for a renal artery atheromatous stenosis in diabetic patients?].

The prevalence of RAAS in non-insulin-dependent diabetic patients ranges from 17 to 44%. The prevalence increases exponentially in the presence of several risk factors such as severe arterial hypertension, severe renal insufficiency, macroangiopathy, smoking, and insulin requirement. In diabetic patients, RAAS should be investigated in patients with severe arterial hypertension, repeated pulmonary oedemas, and renal insufficiency without any clear etiology associated with a mild proteinuria and/or with a renal insufficiency secondary to the administration of angiotensin converting enzyme inhibitors or angiotensin II receptors antagonists. Asymmetrical size of the kidneys should also prompt the physician with a suspicion of RAAS. There are several specific criteria, that may confirm the suspicion of a RAAS. Renal arteriography is still the goal standard for diagnosing renal artery stenosis.

Adult↗

[Pharmacokinetic changes in renal failure].

DRUG PHARMACOKINETICS: One of the first steps in the clinical development of drugs consists in studies of their pharmacokinetics. Dosage and administration interval necessary to ensure secure and efficient plasma levels are derived from the values of pharmacokinetic parameters. Renal disease usually implies multiple pathophysiological modifications that generate alteration in drugs pharmacokinetic profile. Those modifications mainly occur on elimination phase but also to a significant extent on absorption and distribution. PATHOPHYSIOLOGICAL CHANGES: In this article we describe potential alteration in drugs absorption, distribution (volume of distribution, binding to plasma proteins), hepatic or renal metabolism, and parent compound and/or metabolites elimination in patients with renal insufficiency. Furthermore, in patients with end-stage renal disease treated by dialysis, drugs are likely to be removed by extracorporal epuration and dosage and/or interval modifications should thus be applied to treatments in those patients. CLINICAL ASSESSMENT: Pharmacokinetics of drugs should be evaluated in patients with renal failure to determine whereas dosage and/or administration interval should thus be modified to enhance tolerance and pharmacological efficacy. Such studies are obviously necessary for drugs that are mainly excreted unchanged in urine. They should also be performed for drugs that are mainly degraded in the liver with emphasis on metabolites pharmacokinetics.

Glomerular Filtration Rate↗

An appraisal of antiretroviral drugs in hemodialysis.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS)-related kidney disorders concern 30% of those patients and can lead to end-stage renal disease (ESRD; 6 to 10%). Therefore, the administration of antiretroviral drugs in human immunodeficiency virus (HIV) patients with nephropathy is not uncommon. METHODS: The influence of ESRD on the different phases of the pharmacokinetic profile of drugs in general is examined in light of bioavailability, distribution, protein binding, metabolism, and elimination. Then, the pharmacokinetics of antiretroviral drugs in hemodialysis are detailed. RESULTS: From these data, dosing recommendations are given for nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs, and protease inhibitors (PIs). CONCLUSION: Dosage adjustments are often necessary for patients with renal insufficiency. These adaptations have to be carefully performed to optimize drug exposure and reduce the risk of side effects.

Acquired Immunodeficiency Syndrome↗