Prevalence of kidney injury in patients taking tenofovir based antiretroviral therapy at a primary health care clinic, in East Rand,Gauteng Province.

Background: Tenofovir disoproxil fumarate (TDF) is currently one of the key medicines in the management of HIV-1 infection across the globe. Conversely, various studies indicate that TDF is associated with an increased risk of kidney injury. Furthermore, data from different studies indicate that clinically significant TDF-related kidney toxicity is uncommon, with an estimated incidence of reduction in creatinine clearance to below 50 ml/min ranging from 3% to 8%.Objective: This study investigated the prevalence of TDF-induced kidney injury, risk factors associated with the exacerbation of kidney injury, and reversibility of TDF-induced kidney injury in a South African cohort.Methods: A retrospective cross-sectional descriptive study was conducted, where quantitative data were collected through patient file reviews. Files of 600 patients initiated on TDF-based antiretroviral therapy (ART) were reviewed. The degree of kidney function was monitored using the eGFR at baseline, 3, 6, 12, and 36 months of TDF therapy. eGFR after TDF discontinuation was monitored to determine its reversibility. HIV parameters (CD4 count and viral load) were monitored to determine patients' immune response to treatment throughout the study. Comorbidities and other factors that affect kidney function were extracted from the patients' files.Results: Final sample comprised 413 files, 272 (65.9%) were females. Significant variability in the eGFR overtime was observed; 20 (5.9%) experienced mild-moderate kidney injury, four (1.2%) developed moderate-severe kidney injury and three (1%) had severe kidney injury. Significant association with decline in eGFR included high viral load, low CD4 count and long duration of treatment. Six (1.5%) patients were discontinued from TDF treatment and five patients of those fully recovered.Conclusions: TDF-induced kidney injury was uncommon in this setting and where it occurred was associated with full reversibility after discontinuation. Therefore, lack of resources in health-care settings in terms of frequent monitoring of renal function should not prevent prescribing TDF-based therapy.

Decreased expression of megalin and cubilin and altered mitochondrial activity in tenofovir nephrotoxicity.

Tenofovir disoproxil fumarate (TDF) is a commonly used antiretroviral drug for HIV, rarely causing Fanconi syndrome and acute kidney injury. We retrospectively analyzed the clinico pathological presentation of 20 cases of tenofovir-induced tubulopathy, and investigated the renal expression of the megalin and cubilin proteins, as well as the mitochondrial respiratory chain activity. Estimated glomerular filtration rate (eGFR) before TDF exposure was 92 ml/min/1.73m2, decreasing to 27.5 ml/min/1.73m2 at the time of biopsy, with 30% of patients requiring renal replacement therapy. Proximal tubular expression of megalin and cubilin was altered in 19 and 18 cases, respectively, whereas it was preserved in patients exposed to TDF without proximal tubular dysfunction and in HIV-negative patients with acute tubular necrosis. Loss of megalin/cubilin was correlated with low eGFR and high urine retinol binding protein at the time of biopsy, low eGFR at last follow-up, and was more severe in patients with multifactorial toxicity. Patients with additional nephrotoxic conditions promoting tenofovir accumulation showed a lower eGFR at presentation and at last follow-up, and more severe lesions of acute tubular necrosis, than those with isolated tenofovir toxicity. Altered mitochondrial COX activity in proximal tubules was observed and may be an early cellular alteration in tenofovir nephrotoxicity. In conclusion, altered megalin/cubilin expression represents a distinctive feature in tenofovir-induced tubulopathy, and its severity is correlated with urine retinol binding protein loss and is associated with a poor renal prognosis. Concomitant exposure to other nephrotoxic conditions severely impacts the renal presentation and outcome.

[Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients]. / Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por el virus de la inmunodeficiencia humana.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

Hepatitis B virus and human immunodeficiency virus drugs in pregnancy: findings from the Antiretroviral Pregnancy Registry.

BACKGROUND & AIMS: Fetal safety of antiviral therapies is important given the long-term treatment of women with chronic hepatitis B (CHB) infection who may become pregnant. We analyzed neonatal safety data from the Antiretroviral Pregnancy Registry (APR), the largest safety database in pregnancy for antivirals used for HIV and CHB. METHODS: Data were extracted from APR cases prospectively enrolled between 1989 and 2011. Primary outcomes were major birth defects rates with exposure to all antivirals, individual classes, and drugs compared to population-based controls. Relevant to CHB, only lamivudine (LAM) and tenofovir disoproxil fumarate (TDF) had sufficient individual data for review (≥200 cases). RESULTS: Of 13,711 cases analyzed, the overall birth defect prevalence (2.8%, 95% CI 2.6-3.1%) was comparable to Centers for Disease Control population-based data (2.72%, 2.68-2.76%, p=0.87) and two prospective antiretroviral exposed newborn cohorts (2.8%, 2.5-3.2%, p=0.90 and 1.5%, 1.1-2.0%, p<0.001). The birth defects prevalence between first and second/third trimesters exposure was similar (3.0% vs. 2.7%). No increased risk of major birth defects with LAM or TDF exposure compared to population-based controls was observed. No specific pattern of major birth defects was observed for individual antivirals or overall. CONCLUSIONS: No increased risk of major birth defects including in non-live births was observed for pregnant women exposed to antivirals relevant to CHB treatment overall or to LAM or TDF compared to population-based controls. Continued safety and efficacy reporting on antivirals in pregnancy are essential to inform patients on their risks and benefits during pregnancy.

Final report on the safety assessment of Sodium Metaphosphate, Sodium Trimetaphosphate, and Sodium Hexametaphosphate.

These inorganic polyphosphate salts all function as chelating agents in cosmetic formulations. In addition, Sodium Metaphosphate functions as an oral care agent, Sodium Trimetaphosphate as a buffering agent, and Sodium Hexametaphosphate as a corrosion inhibitor. Only Sodium Hexametaphosphate is currently reported to be used. Although the typical concentrations historically have been less than 1%, higher concentrations have been used in products such as bath oils, which are diluted during normal use. Sodium Metaphosphate is the general term for any polyphosphate salt with four or more phosphate units. The four-phosphate unit version is cyclic, others are straight chains. The hexametaphosphate is the specific six-chain length form. The trimetaphosphate structure is cyclic. Rats fed 10% Sodium Trimetaphosphate for a month exhibited transient tubular necrosis; rats given 10% Sodium Metaphosphate had retarded growth and those fed 10% Sodium Hexametaphosphate had pale and swollen kidneys. In chronic studies using animals, growth inhibition, increased kidney weights (with calcium deposition and desquamation), bone decalcification, parathyroid hypertrophy and hyperplasia, inorganic phosphaturia, hepatic focal necrosis, and muscle fiber size alterations. Sodium Hexametaphosphate was a severe skin irritant in rabbits, whereas a 0.2% solution was only mildly irritating. A similar pattern was seen with ocular toxicity. These ingredients were not genotoxic in bacterial systems nor were they carcinogenic in rats. No reproductive or developmental toxicity was seen in studies using rats exposed to Sodium Hexametaphosphate or Sodium Trimetaphosphate. In clinical testing, irritation is seen as a function of concentration; concentrations as high as 1% produced no irritation in contact allergy patients. Because of the corrosive nature of Sodium Hexametaphosphate, it was concluded that these ingredients could be used safely if each formulation was prepared to avoid skin irritation; for example, low concentration in a leave-on product or dilution of a higher concentration as part of product usage.