title: Renal and Bone Toxicity with the Use of Tenofovir: Understanding at the End.
abstract: The use of tenofovir disoproxil fumarate has been associated with side effects on renal function and bone mineral density, but whether this toxicity is of clinical relevance in the middle or long term is highly debated. Current knowledge supports that the use of and time on tenofovir disoproxil fumarate, modulated by other factors such as age, baseline renal function, or classical risk factors, could led to progressive wasting in the urine of low molecular weight proteins, phosphate, uric acid, or glucose. This "partial" Fanconi syndrome seems to be slowly progressive, with increases in the proportion of patients and in the severity of different tubular abnormalities with the long term use of tenofovir disoproxil fumarate. Although progression to chronic kidney disease is relatively rare in patients on tenofovir disoproxil fumarate, in part attributed to the capacity of kidneys to compensate for loss of functioning nephrons, the severity of tubular dysfunction is associated with greater kidney function decline. In large cohorts, the use of tenofovir disoproxil fumarate is one of the main risk factors associated to chronic kidney disease. In addition, hyperphosphaturia secondary to tubular dysfunction could alter the interplay between bone, kidney, and regulatory hormones, leading to progressive bone loss in a similar manner, but in a lesser extent, to hypophosphatemic osteomalacia observed in the Fanconi syndrome. This component of osteomalacia secondary to altered phosphate metabolism explains the partial improvement observed with vitamin D supplementation, the association with altered bone-specific alkaline phosphatase, and the rapid benefit in terms of bone mineral density after tenofovir disoproxil fumarate discontinuation.
authors.affiliation: Department of Infectious Diseases, Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Casado
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density; D001847:Bone Diseases / Q000139:chemically induced*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir