Estudio de factores farmacogenéticos y farmacocinéticos asociados con alteraciones renales en pacientes VIH positivos a tratamiento con tenofovir

Abstract

Kidney disease has been a recognized complication of HIV infection since the onset of the HIV epidemic, but its epidemiology, underlying causes and management has evolved with the increased availability of highly active antiretroviral therapy (HAART). Besides the involvement of HIV itself as a cause of organ damage, the introduction of HAART and other medications frequently used in this population have been followed by an increasing rate of drug-related renal complications. Kidney toxicity produced by drugs may lead to acute kidney injury, chronic kidney disease, and features of proximal tubular injury. Tenofovir disoproxil fumarate (TDF) is currently widely used as an effective first-line therapy, for both HIV and Hepatitis B virus (HBV) infection, due to its excellent properties, combining good potency, tolerability and convenience. Despite demonstration of a relatively good renal safety profile in early prospective trials and postmarketing studies, numerous cohort observational studies and case reports have highlighted cases of renal dysfunction, including the development of Fanconi´s syndrome, in patients treated with TDF. An early sign of tubular dysfunction is hypophosphatemia although other signs and symptoms of kidney tubulopathy include glucosuria with normal serum glucose levels, mild proteinuria, acidosis and hypokalemia. The chronic consequences of significant loss of phosphate, proteins and glucose are currently unknown, but an increased risk of premature osteoporosis and osteomalacia is a worrisome complication. The most frequent risk factors for developing TDF-induced nephrotoxicity include baseline renal dysfunction, low CD4 counts, older age and low body weight. Classic risk factors associated with renal damage in HIV patients such as pre-existing systemic conditions, HIV itself, ARV therapy or use of nephrotoxic agents may also enhance the potential risk of nephrotoxicity associated with TDF. More recently, TFV plasma levels have been associated with the risk of tubular damage and TDF-associated renal proximal tubulopathy has been linked to genetic variants in transporter proteins involved in TFV excretion...