RÉSUMÉ
INTRODUCTION: Human immunodeficiency virus (HIV) infection is associated with the development of a wide spectrum of kidney diseases. HIV-associated nephropathy (HIVAN) is the most common cause of chronic kidney disease (CKD) in HIV-infected individuals and predominantly affects patients of African ancestry. HIVAN is a leading cause of end-stage renal disease (ESRD) among African-Americans. AREAS COVERED: An overview of the spectrum of kidney disease in patients with HIV is given. Current pharmacologic interventions to treat kidney disease in HIV are discussed. This review will enhance knowledge regarding the most common causes of kidney disease in HIV-infected patients. An understanding of the principles related to pharmacotherapy in HIV-infected patients with kidney disease will also be gained. EXPERT OPINION: Kidney disease is an important cause of morbidity and mortality in HIV-infected patients. The most common cause of chronic kidney disease in this population is HIV-associated nephropathy, which is caused by viral infection of the renal epithelium. Several medications that are commonly used in HIV-infected patients can have adverse effects on the kidneys and the doses of many antiretroviral medications need to be adjusted in patients with impaired renal function.
Sujet(s)
Infections à VIH/complications , Maladies du rein/traitement médicamenteux , Adulte , Agents antiVIH/effets indésirables , Prédisposition génétique à une maladie , Infections à VIH/traitement médicamenteux , Humains , Maladies du rein/complications , Maladies du rein/génétique , Adulte d'âge moyenSujet(s)
Biopsie/effets indésirables , Infections à VIH/complications , Maladies du rein/anatomopathologie , Études cas-témoins , Contre-indications , Prise de décision , Hématome/étiologie , Hématurie/étiologie , Hémorragie/étiologie , Hépatite C chronique/complications , Humains , Facteurs de risque , Échographie interventionnelleRÉSUMÉ
OBJECTIVE: HIV-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease in persons with HIV/AIDS and is characterized by focal glomerulosclerosis and dysregulated renal tubular epithelial cell (RTEC) proliferation and apoptosis. HIV-1 viral protein r (Vpr) has been implicated in HIV-induced RTEC apoptosis but the mechanisms of Vpr-induced RTEC apoptosis are unknown. The aim of this study was therefore to determine the mechanisms of Vpr-induced apoptosis in RTEC. METHODS: Apoptosis and caspase activation were analyzed in human RTEC (HK2) after transduction with Vpr-expressing and control lentiviral vectors. Bax and BID were inhibited with lentiviral shRNA, and ERK activation was blocked with the MEK1,2 inhibitor, U0126. RESULTS: Vpr induced apoptosis as indicated by caspase 3/7 activation, PARP-1 cleavage and mitochondrial injury. Vpr activated both caspases-8 and 9. Inhibition of Bax reduced Vpr-induced apoptosis, as reported in other cell types. Additionally, Vpr-induced cleavage of BID to tBID and suppression of BID expression prevented Vpr-induced apoptosis. Since sustained ERK activation can activate caspase-8 in some cell types, we studied the role of ERK in Vpr-induced caspase-8 activation. Vpr induced sustained ERK activation in HK2 cells and incubation with U0126 reduced Vpr-induced caspase-8 activation, BID cleavage and apoptosis. We detected phosphorylated ERK in RTEC in HIVAN biopsy specimens by immunohistochemistry. CONCLUSIONS: These studies delineate a novel pathway of Vpr-induced apoptosis in RTEC, which is mediated by sustained ERK activation, resulting in caspase 8-mediated cleavage of BID to tBID, thereby facilitating Bax-mediated mitochondrial injury and apoptosis.
Sujet(s)
Néphropathie associée au SIDA/métabolisme , Apoptose/physiologie , Caspase 8/métabolisme , Extracellular Signal-Regulated MAP Kinases/métabolisme , Produits du gène vpr/métabolisme , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Défaillance rénale chronique/métabolisme , Néphropathie associée au SIDA/génétique , Néphropathie associée au SIDA/virologie , Apoptose/génétique , Caspase 8/génétique , Prolifération cellulaire , Régulation de l'expression des gènes viraux , Produits du gène vpr/génétique , Humains , Défaillance rénale chronique/génétique , Défaillance rénale chronique/virologie , Tubules rénaux/virologie , ARN viral , Réplication viraleRÉSUMÉ
Renal failure in cirrhosis poses unique diagnostic and therapeutic challenges. Laboratory values and predictive equations grossly overestimate renal function in patients with cirrhosis. Development of renal failure connotes a worse prognosis; mortality is especially high with hepatorenal syndrome. Classification of the causes of renal failure in patients with cirrhosis is provided with more extensive discussion of selected causes. Finally, a suggested diagnostic approach to renal failure in cirrhosis is given.