Urinary biomarkers of kidney diseases in HIV‐infected children

Abstract

A significant number of children infected with the HIV-1 virus all over the world are at risk of developing renal diseases that could have a significant impact on their treatment and quality of life. It is necessary to identify children undergoing the early stages of these renal diseases, as well as the potential renal toxicity that could be caused by antiretroviral drugs, in order to prevent the development of cardiovascular complications and chronic renal failure. This article describes the most common renal diseases seen in HIV-infected children, as well as the value and limitations of the clinical markers that are currently being used to monitor their renal function and histological damage in a non-invasive manner. In addition, we discuss the progress made during the last 10 years in the discovery and validation of new renal biomarkers for HIV-infected children and young adults. Although significant progress has been made during the early phases of the biomarkers discovery, more work remains to be done to validate the new biomarkers in a large number of patients. The future looks promising, however, the new knowledge needs to be integrated and validated in the context of the clinical environment where these children are living.

The role of β-2-microglobulin and cystatin C as urinary biomarkers of focal segmental glomerulosclerosis in the setting of paediatric HIV infection

“…In contrast to our study, elevated levels of cystatin C in the urine of HIV-infected children with proteinuria have been reported by Garcia et al, suggesting a compromised capacity of the proximal tubular epithelial cells to reabsorb and metabolise cystatin C in these patients. [26,27] This apparent contradiction with our study results may also be explained by a discordance between the immunological and clinical stages of HIV disease as all patients were on ART. [28] Nevertheless, in one study, serum cystatin C, which reflects kidney proximal tubular dysfunction, directly correlated with HIV viral load.…”

Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms

“…Compared to HIV-uninfected controls, the prevalence of albuminuria has been reported to be 2-5-fold higher in HIV-infected children [20]. Main risk factors are family history of renal disease, genetic predisposition (such as Apoliprotein (APOL)-1 renal risk variants), immune suppression, history of proteinuria, diabetes, hepatitis C virus co-infection, and treatment with certain antiretroviral drugs [20,21]. ART has dramatically reduced the incidence of HIVAN, but a clear benefit in non-HIVAN kidney disease has not been demonstrated [22].…”

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

“…Urine albumin/total protein ratio (uAPR) < 0.4 identifies tubular pathology in proteinuric patients and this was not measured in our study [33]. Although increased fractional excretion of phosphate, hypophosphatemia and normoglyacemic glycosuria are established markers of proximal tubular dysfunction and are easy to screen for, they are less sensitive than tubular protein excretions (NGAL, B2M and RBP) and have been suggested to be the most appropriate alternatives when these are not available [6,34,35]. In addition better markers for proximal tubular function (Retinol-binding protein, β-2 microglobulin and N-acetyl-β-d-glucosaminidase) could not be used due non-availability of tests and cost constraints.…”