Proximal renal tubular function in HIV-infected children on tenofovir disoproxil fumarate for treatment of HIV infection at two tertiary hospitals in Harare, Zimbabwe

• Published in: PloS one Vol. 15; no. 7; p. e0235759
• Main Authors: Mashingaidze-Mano, Runyararo, Bwakura-Dangarembizi, Mutsawashe F, Maponga, Charles C, Morse, Gene D, Monera-Penduka, Tsitsi G, Mtisi, Takudzwa J, Mudzviti, Tinashe, Mujuru, Hilda A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-07-2020; Public Library of Science (PLoS)
• Subjects: Abnormalities; Adolescent; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biology and Life Sciences; Biomarkers; Child; Children; Complications and side effects; Confidence intervals; Creatinine; Cross-Sectional Studies; Demographic aspects; Developed countries; Developing countries; Diagnosis; Drug therapy; Epidermal growth factor receptors; Excretion; Fanconi Syndrome - chemically induced; Fanconi Syndrome - etiology; Female; Glomerular Filtration Rate; Glucose; Health sciences; HIV; HIV infections; HIV Infections - complications; HIV Infections - drug therapy; Hospitals; Human immunodeficiency virus; Humans; Hypophosphatemia; Infections; Kidney diseases; Laboratories; LDCs; Male; Mathematical analysis; Medicine and Health Sciences; Metabolism; Methods; Patients; Pediatric diseases; Pharmacy; Phosphates; Physical Sciences; Protease inhibitors; Proteinase inhibitors; Proteins; Proteinuria; Proteinuria - etiology; Reduction; Regression analysis; Renal function; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - therapeutic use; Risk factors; Studies; Tenofovir; Tenofovir - adverse effects; Tenofovir - therapeutic use; Tertiary Care Centers; Urine; Zimbabwe; Zimbabwe; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0235759

Renal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction.
A descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDF-containing antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%.
One hundred and ninety-eight children below 18 years of age were recruited over a period of six months. The prevalence of tubular dysfunction was 0.5%. Normoglycaemic glycosuria occurred in 1 (0.5%), fractional excretion of phosphate >18% in 4 (2%), and hypophosphatemia in 22 [11.1%] patients. Severe stunting was associated with increased risk of hypophosphatemia (OR 9.31 CI (1.18, 80.68) p = 0.03). Reduction in estimated glomerular filtration rate (eGFR) < 90ml/min/1.73m2 and proteinuria was evident in 35.9% and 32.8% of children, respectively. Concurrent TDF and HIV-1 protease inhibitor-based regimen was the only independent factor associated with reduction in GFR (OR 4.43 CI (1.32; 4.89) p = 0.016).
Tubular dysfunction was uncommon in Zimbabwean children on a TDF-based ART regimen. Hypophosphatemia, proteinuria and reduction in eGFR were common. Reassessing renal function using more sensitive biomarkers is needed to examine the long-term tolerance of TDF.