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The increase in the life expectancy achieved following the introduction of more effective antiretroviral therapy (ART) in recent years now means that the HIV-infected population are for the first time being exposed to the age-related diseases that affect the general population. Nevertheless, the prevalence of these diseases (which include cardiovascular disease, dyslipidaemia, glucose intolerance and diabetes) is higher, and their onset earlier in the HIV population, probably due to the complex interplay between HIV infection, coinfection with hepatitis B and C, and ART. As a result, HIV physicians are now required to adopt a new approach to the management of HIV, which involves screening and regular monitoring of all HIV-infected individuals for the presence of comorbidities and prompt referral to other clinical specialties when required. If this challenge to patient management is to be overcome, it is clear that educating physicians in the diagnosis and treatment of age-associated comorbidities is essential, either through ongoing programmes such as the HIV and the Body initiative, an overarching independent medical education programme established in 2007 and overseen by an independent Steering Committee, organized and funded by Gilead, and/or through internal training. To assist in this process, this article provides an overview of common comorbidities affecting HIV-infected persons and provides practical guidance on their management.

Renal insufficiency is frequently seen in patients with cardiovascular disease. In contrast, coronary artery disease is the leading cause of death in patients with renal impairment. The recognition of renal insufficiency is essential in these patients and preventive measures must be put in place to prevent the progression or onset of cardiovascular disease. In this article, we explain the methods to assess kidney function, the epidemiology of coronary heart disease in patients with renal impairment, risk factors conventional and non-conventional found in these patients and the main recommendations for their therapeutic care.

Contrast media are excreted mainly by glomerular filtration. There is thus, a significant correlation between both body and renal clearances of contrast media and glomerular filtration rate, and their renal excretion will be delayed in patients with renal insufficiency. Contrast media can be efficiently removed from blood by hemodialysis (HD). Since most contrast media are middle-sized molecules, the main factors potentially influencing their removal by HD are blood flow, membrane surface area, molecular size, transmembrane pressure, and dialysis time. Peritoneal dialysis is also effective in removing contrast agents from the body but takes longer than HD. Dialysis immediately after radiographic contrast studies has been suggested for two groups of patients. Those on chronic HD and those at very high risk for contrast nephropathy. Three studies have examined the necessity of immediate dialysis after intravascular injection of contrast media in chronic HD patients; the authors found no evidence that it is effective at preventing contrast nephropathy. The reasons why HD treatment was not beneficial in those three studies are not known. Perhaps, the rapid onset of renal injury after administration of contrast media is one answer. It is also possible that HD per se was nephrotoxic and might have offset the beneficial effect of the removal of contrast media. Marenzi et al. randomized 114 consecutive patients with chronic renal failure undergoing coronary interventions to either hemofiltration in an intensive care unit or isotonic saline hydration. The authors concluded that periprocedural hemofiltration given in an intensive care unit setting appears to be effective in preventing the deterioration of renal function due to contrast agent induced nephropathy and is associated with improved in-hospital and long term outcomes. The concentration of contrast media can effectively be reduced by HD and peritoneal dialysis. HD does not offer any protection against contrast media induced nephrotoxicity. Hemofiltration may decrease the risk of contrast induced nephropathy and have some long-term benefits, but additional studies are needed to better define the appropriate population for this treatment.

Les multiples modifications pathophysiologiques secondaires a l’insuffisance renale entrainent des modifications du profil pharmacocinetique des medicaments en agissant sur l’absorption, la distribution et l’elimination des principes actifs. Des modifications de la pharmacodynamie des medicaments ont egalement ete mises en evidence. Nous ne traiterons ici que des modifications pharmacocinetiques liees a l’insuffisance renale. Le but de cet article est de montrer dans quelle mesure et par quel mecanisme la diminution de la fonction renale d’un patient influence l’absorption, la distribution, le metabolisme (hepatique ou renal) et l’elimination de la molecule–mere et/ou de ses metabolites. En effet, il est indispensable d’etudier la pharmacocinetique des medicaments dans la population particuliere des patients insuffisants renaux afin de determiner les modifications de la posologie et/ou du rythme d’administration necessaires pour assurer une bonne tolerance et une efficacite satisfaisante des traitements utilises chez ces patients. Si ces etudes semblent logiquement indispensables pour les medicaments a elimination renale majoritaire, elles le sont tout autant pour les produits majoritairement biotransformes par le foie, en s’attachant a l’etude du devenir des metabolites en fonction de leur activite pharmacologique d’une part et de leur toxicite potentielle d’autre part. De telles etudes sont necessaires pour tous les medicaments, certes, mais elles presentent un caractere incontournable lorsque l’index therapeutique est particulierement etroit comme c’est le cas pour les medicaments anticancereux. En effet, plus la marge entre seuil d’efficacite et seuil de toxicite est etroite et plus une non–adaptation ou une mauvaise adaptation de la posologie aura des consequences cliniques serieuses voire severes.

Resume Le fluconazole est un medicament antifongique tres largement utilise chez des patients qui souvent presentent une insuffisance renale (reanimation, infectiologie, hematologie...). Une bonne connaissance de son maniement chez ce type de patient est donc essentielle. L’elimination du fluconazole s’effectue majoritairement sous forme inchangee dans les urines. Il est donc necessaire d’adapter la posologie chez le patient insuffisant renal. De plus, il faut prendre en compte l’elimination du medicament dans le liquide de dialyse chez les patients traites par epuration extrarenale. Dans cette revue, nous proposons une synthese des donnees existantes sur le mode d’administration du fluconazole en fonction de l’indication, de la voie d’administration et du degre d’insuffisance renale du patient.

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.

Resume La toxicite renale des produits de contraste est un probleme d’actualite. La N’acetylcysteine est un agent oxydant efficace experimentalement dans des modeles d’ischemie renale et qui a ete propose dans la prevention des accidents renaux secondaires a l’injection de produit de contraste iode. L’auteur de cette revue rapporte et commente ces etudes afin de definir les indications de la prescription de la N’acetylcysteine dans ce contexte.

Myeloproliferative neoplasms (MPNs, formerly called chronic myeloproliferative disorders) are clonal hematopoietic stem cell disorders characterized by the expansion of one or more of the myeloid lineages, including polymorphonuclear, erythroid, megakaryocytic, and mastocytic. The major complications of MPN are transformation into acute myeloid leukemia (occurring particularly in chronic myelogenous leukemia) and thrombotic and hemorrhagic events (most commonly observed in polycythemia vera and essential thrombocythemia). Renal involvement by MPN is infrequent. MPN-related glomerulopathy enlarges the spectrum of glomerular diseases associated with haematological neoplasms. MPN-related glomerulopathy is an under recognized late renal complication of MPN with poor prognosis. It is characterized clinically by heavy proteinuria and renal insufficiency. The histologic features of MPN-related glomerulopathy include variable degree of mesangial sclerosis and hypercellularity, segmental sclerosis, features of chronic thrombotic microangiopathy, and intracapillary hematopoietic cell infiltration. PDGF and TGFβ likely have a crucial role in the pathogenesis of MPN-related glomerulopathy. Furthermore, aggregation of circulating hematopoietic cells within glomerular capillaries could potentially result in endothelial injury and morphologic changes resembling chronic thrombotic microangiopathy. Greater awareness of this entity is needed to define diagnosis and possible therapies.

To evaluate the contribution of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E), and left atrial diameter were measured at rest, during, and after graded upright standardised bicycle exercise in 8 healthy male subjects after single-dose administration of placebo, tertatolol (5 mg), prazosin (1 mg), or combination of tertatolol (5 mg) and prazosin (1 mg). Systolic and diastolic left atrial diameters were measured before, during, and just after exercise by bidimensional echocardiography. Exercise raised plasma ANP concentrations. This rise was greater on tertatolol alone and tertatolol and prazosin than on placebo or prazosin alone: mean area under the plasma ANP concentration curve increased by 35% on tertatolol alone, 45% on tertatolol and prazosin when compared with placebo (p0.01), and by 82 and 94%, respectively, when compared with prazosin alone (p0.01). The rise in plasma ANP was greater during the postexercise period: 80% for tertatolol alone, 67% for tertatolol and prazosin when compared with placebo (p0.01) and 133 and 115%, respectively, when compared with prazosin alone (p0.01). The rise in plasma ANP was accompanied by an increase in both systolic and diastolic atrial diameters which was significantly greater on tertatolol alone and on the tertatolol and prazosin combination than on placebo or prazosin alone (p0.001). Beta-blockade alone did not affect plasma catecholamine concentrations but exercise-induced increase in plasma NE was significantly potentiated by prazosin and the prazosin and tertatolol combination, and that of plasma E by the prazosin and tertatolol combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction Pour apprehender le questionnement ethique pose par la prise en charge des « nouveaux » patients tres fragiles avec disparite de reponses variant du traitement « conservateur » aux classiques 3 × 4 h/semaine, nous avons diffuse une enquete aupres de nephrologues (N) et d’infirmieres de nephrologie (IN). Patients et methodes Un questionnaire de 10 questions a ete distribue en mars 2014 lors de la reunion du Club des jeunes nephrologues et lors de celle de l’Association des infirmieres de dialyse de transplantation renale et de nephrologie. Resultats Quarante-deux N sur 76 (55 %) et 70 IN sur 110 ont repondu (64 %). Les reponses etaient comparables respectivement entre N et IN : perception des nouveaux enjeux ethiques (95 % versus 93 %), mise en cause de la pertinence de la dialyse (D) (88 % versus 87 %) avec doute eprouve deja (98 % versus 92 %), utilite d’une formation en ethique (95 % versus 92 %), pertinence variable de la D (90 % versus 84 %) et interet d’une modulation de la reponse therapeutique dans le temps (83 % pour les 2). Seule la connaissance d’une option de traitement non dialytique etait differente (72 % des N versus 16 %IN). Bien que peu formes (19 % N versus 0 %), 55 % des N interroges le proposent comme option therapeutique. Les difficultes apparaissent liees a l’aspect routinier de la technique (62 versus 53 %), a la degradation clinique des patients malgre la D (41 versus 40 %) et au phenotype de la population de plus en plus fragile (31 % versus 41 %). Discussion et conclusion Le taux de reponse > 50 % temoigne de l’importance de ces questions ethiques. La pertinence percue par les N et les IN du recours a la D pour ces nouveaux patients fragiles semble evoluer avec des reponses tres comparables. Ces acteurs semblent prets a moduler leurs therapeutiques dans le temps pour mieux honorer la promesse hippocratique du « primum non nocere ».

Dermatological effects are among the most frequent side-effects in patients receiving erlotinib (Tarceva). However, there no official recommendations on the preventive or curative management of those erlotinib-related skin effects (ERSE). The "Prise En Charge des Effets Dermatologiques sous Erlotinib" (PRECEDE) study was designed to study how ERSE are being managed in France.The PRECEDE study is an observational retrospective study which included every nonsmall cell lung cancer patients treated with erlotinib in seven cancer centers in France from January 2005 to December 2007. Data related to preventive or curative treatment of ERSE were collected from the medical files of the patients.Two hundred and thirty-four patients were included; 48.7% of them had been delivered information on the potential occurrence of ERSE and 15.8% of those 234 patients had had prescription of drugs to be taken in case of ERSE, while 65.0% presented with ERSE which resolved in the majority of cases (86.2% of the patients), either spontaneously or under treatment. In the 85 patients in whom treatment was successful, 178 drug prescriptions comprising 35 different drugs were recorded.ERSE are frequent but regress in most cases, spontaneously or under treatment. However, there is still a wide variety of drugs used. This demonstrates that there is a need for recommendations on the management of ERSE in order to prevent and treat this erlotinib-related effect.

Renal insufficiency is frequently seen in patients with cardiovascular disease. In contrast, coronary artery disease is the leading cause of death in patients with renal impairment. The recognition of renal insufficiency is essential in these patients and preventive measures must be put in place to prevent the progression or onset of cardiovascular disease. In this article, we explain the methods to assess kidney function, the epidemiology of coronary heart disease in patients with renal impairment, risk factors conventional and non-conventional found in these patients and the main recommendations for their therapeutic care.

The authors had for aim to define the threshold of nephrotoxicity before switching to other antifungal treatment in hematological patients treated by conventional amphotericin B (AmB) as an empiric antifungal treatment.A prospective randomised multicenter study was made on 32 neutropenic hematological patients receiving conventional AmB for empirical antifungal treatment. The patients were randomised after a greater than or equal to 30% increase of serum creatinine (sCr). Patients in the early-switch group received liposomal AmB just after randomisation and patients in the late-switch group received liposomal AmB only when serum creatinine increase was greater or equal to 100% or sCr reached 170mumol/L.Thirty-one patients were analysed: 16 patients in the early-switch group and 15 patients in the late-switch group (seven switched to liposomal AmB and eight continued conventional AmB treatment). The mean age of patients was 48 years and 68% were men. The most frequent underlying haematological malignancy was acute leukemia (94%). In the late-switch group, the degradation of renal function continued after randomisation contrary to the early-switch group: median variations of calculated sCr clearance in early- and late-switch groups were -16.8 and -1.5%, respectively (P=0.03). Moreover, an early switch was cost-effective with a sCr lower duration of hospitalisation in comparison with a late switch.This randomised trial suggests that an early switch to Liposomal AmB improves and preserves renal function in comparison with a late switch.

Amprenavir is an HIV-1 protease inhibitor which is hepatically metabolized (80%) with a low renal elimination. It has thus been suggested that no dosage adjustment is necessary in patients with renal dysfunction. However, no data are available on the pharmacokinetics of amprenavir in patients with renal insufficiency. We report on the pharmacokinetics of amprenavir in two HIV patients with severe and end-stage renal insufficiency. Amprenavir pharmacokinetics did not differ in our patients as compared with normal renal function subjects. Furthermore, amprenavir was not dialysable (FHD25%). As a result, the drug may be administered at its normal dose in patients with renal failure, even when severe. In dialysis patients, amprenavir may be administered before or after the session.

In this study, the contributions of each of the authors have been collected and reviewed by the entire group of participants. The recommendations that follow are supported by clinical and experimental data. Wherever possible, prospective randomized trial data formed the basis for the recommendation. In some cases, a single trial with a relatively small number of subjects constituted the only such data. Less rigorous but more encompassing data from observational studies and systematic analyses were used to provide context and robustness to the recommendations. RECOMMENDATION NO. 1 All patients receiving contrast should be evaluated for their risk of contrast-induced nephropathy A number of risk stratification methods have been developed in interventional cardiology and radiology. These strategies use the present and past history of the patient together with knowledge of renal function to identify ‘high risk for contrast-induced nephropathy (CIN)’ individuals. Renal function is usually assessed with a serum creatinine, which is used in either the Cockcroft–Gault or modification of diet on renal disease formula to estimate glomerular filtration rate. The risk of CIN increases as the estimated glomerular filtration rate falls, particularly below 60 ml/min. When the serum creatinine is not known (as is often the case in outpatient radiologic examinations), the present and past history of the patient (hypertension, renal disease, dyslipidemia, hyperuricemia, diabetes, heart failure, myeloma, treatment with nephrotoxic drugs) can be used to identify those patients who require further assessment of renal function by measurement of serum creatinine. This is particularly important in patients receiving suprarenal intraarterial contrast where the risk of CIN appears to be increased. A baseline level of serum creatinine is necessary to estimate renal function and to be compared to serum creatinine levels following contrast exposure. The baseline level should be obtained prior to maneuvers which themselves might affect serum creatinine, such as intravenous (i.v.) volume expansion. Future research Adequate, prospective, cohort studies should be conducted to: K Compare the incidence of CIN following intraarterial and i.v. administration of contrast. K Assess the attributable risk of end-stage renal disease following contrast vis a vis other patient-related and procedure-related factors.

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.

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.

Renal toxicity of contrast agents remains an up-to-date challenge. N'Acetyl cystein is an antioxyde agent which efficacy has been proved in various models of experimental renal ischemia and therefore proposed in the prevention of renal failure due to intravenous iodine contrast media. The Author of this review reports and comments these studies in order to better define indications of N'Acetyl cystein in this clinical context.

Les patients atteints de neoplasie presentent souvent une atteinte renale associee. Les manifestations renales peuvent etre multiples et se manifester par une insuffisance renale et/ou par des troubles hydro–electrolytiques, isoles ou associes. Ces manifestations peuvent etre la consequence de la maladie cancereuse ou etre secondaires aux chimiotherapies utilisees dans le traitement de ces patients. Devant l’apparition d’une insuffisance renale, le raisonnement doit etre similaire a celui mene habituellement devant cette atteinte et nous detaillerons pour chaque etape les pathologies renales particulieres aux patients atteints de neoplasie. Les troubles hydro–electrolytiques frequemment observes chez ces patients seront detailles secondairement.

L’insuffisance renale est une maladie frequente et constitue un indicateur de morbidite et de mortalite. Il est donc essentiel de la depister le plus rapidement possible. La creatininemie a longtemps ete l’indicateur utilise pour evaluer la fonction renale. Cependant, une elevation, meme moderee, de la creatininemie correspond, en regle, a une alteration importante de la fonction renale. En pratique clinique quotidienne, pour apprecier la fonction renale, il faut utiliser le taux sanguin de creatinine et sa clairance estimee par la formule de Cockcroft a partir de la creatininemie, du sexe, de l’âge, du poids du patient.

La frequence de l’insuffisance renale chez les patients atteints de cancer n‘est pas precisement definie. Trois-cent seize patients ont ete inclus sur une periode d’un mois, independamment de leur pathologie (outre leur cancer), de leur traitement, ou de tout autre critere. L’estimation de la fonction renale par le calcul de la clairance de la creatinine avec la formule de Cockcroft et Gault a montre que 28 % des patients avaient un debit de filtration glomerulaire estime de moins de 80 mL/min. Pour 23 % d’entre-eux la clairance de la creatinine etait comprise entre 80 et 50 mL/min et elle etait inferieure a 50 mL/min pour 5 % d’entre eux. L’insuffisance renale est donc frequente chez les patients atteints de cancer puisque presque un tiers de ces patients presente une insuffisance renale. Par ailleurs, la disponibilite de l’information relative a l’adaptation de la posologie des medicaments anticancereux chez les patients insuffisants renaux a ete evaluee pour les 10 medicaments les plus prescrits aux patients de l’etude. Seuls les RCP de 1 et de 2 medicaments dans le Vidal® et le Physicians Desk Reference® respectivement donnent une information complete a ce sujet d’ou l’interet de se reporter a d’autres sources bibliographiques pour obtenir cette information.

The aim of this study was to evaluate the effects of Ioxaglate on renal haemodynamics and tubular function in renal transplant patients at increased risk of nephrotoxicity. 21 patients undergoing either intravenous pyelography or arteriography with Ioxaglate were studied. Renal clearance studies were carried out 1 day before and 1 day after administration of Ioxaglate (173 +/- 37 ml) injected into each patient. None experienced any adverse reaction. Mean serum creatinine, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary NAG excretion were unaltered by ioxaglate. No patient suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed. In the subset of 10 patients with a GFR lower than 60 ml/min before injection of Ioxaglate were also observed no significant change in mean GFR, ERPF and urinary NAG excretion. Only two patients had a transient decrease of GFR of between 10 and 20%. The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant thus extending previous data obtained in patients with chronic renal failure.

’augmentation des connaissances sur l’abord vasculaire avait n effet sur l’augmentation des symptomes anxieux du groupe xperimental (p

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.

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).

ANTIINFLAMMATORY DRUGS: Non-steroidal antiinflammatory drugs (NSAID) constitute one of the most widely prescribed drug classes. Selective inhibitors of cyclooxygenase type 2 (Cox-2) can have antiinflammatory and antialgesic activities without affecting prostaglandin synthesis at sites where classical NSAID have known toxicity. This fact has led to the development of celebrex and rofecoxib, the leading selective inhibitors of Cox-2. We review here the renal effects of steroidal antiinflammatory drugs. RENAL EFFECTS OF NSAID: The renal effects of NSAID are, in decreasing order: electrolyte imbalance (hyperkaliemia, edema, hypertension), acute renal failure, nephrotic syndrome associated with interstitial nephropathy, papillary necrosis. Electrolyte disorders and acute renal failure are observed more frequently in patients with risk factors. INTRARENAL LOCALIZATION OF CYCLOOXYGENASE: Cox-1 is present in endothelial and smooth muscle cells of pre- and postglomerular vessels as well as in the cortex, the medullary tubes and in interstitial cells. Cox-2 expression has been identified in the interstitium, medullary tubes and intercalate cells, and in the deep medulla. The regulatory role of Cox-2 on renin production has been demonstrated in the macula densa. RENAL EFFECTS OF COX-2 INHIBITORS: Several studies have demonstrated that Cox-2 inhibitors inhibit prostaglandin synthesis much like conventional NSAID. The long-term effects of selective inhibitors of Cox-2 on blood pressure, edema, kaliemia and renal function have also been described. All these studies point to the strictly identical renal effects of these new drugs and conventional NSAID.

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.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.

We report on a patient with a past history of Pott's abscess who suffered both from a retroperitoneal fibrosis and a membranous glomerulonephritis. Five cases of retroperitoneal fibrosis and immune complex glomerulonephritis are already reported in the literature. These associations might result from a particular systemic immune response to an unknown antigen. Consequently, we consider the role of tuberculosis in our case.