HIV-Associated CKDs in Children and Adolescents

Abstract

Introduction: Limited information is available describing the current prevalence of proteinuria and HIV-associated CKDs (HIV-CKDs) in children and adolescents living with HIV and receiving antiretroviral therapy in the United States.

Methods: To address this issue, we performed a retrospective study of children and adolescents living with HIV who received medical care at Children's National Hospital in Washington, DC, between January 2012 and July 2019. Demographic data, clinical parameters (mode of HIV transmission, viral loads, CD4 cell counts, serum creatinine, glomerular filtration rate [GFR], plasma lipid levels, proteinuria, blood pressure, renal biopsies), and medical treatments, all done as a standard of clinical care, were collected and analyzed.

Results: The majority of the 192 patients enrolled were of African descent (88%) and acquired HIV through vertical transmission (97%). The prevalence of all HIV-CKDs was 6%. Of these patients, 39% had intermittent or persistent proteinuria, and 7% percent had proteinuria with a mild decline in GFR (60-80 ml/min per 1.73 m²), and 6% had a mild decline in GFR without proteinuria. Documented hypertension was present in 6% of the patients, mainly in association with HIV-CKD. Patients with persistent proteinuria (3%) and biopsy-proven HIV-CKD had a slow but constant progression of their renal diseases.

Conclusions: The prevalence of persistent proteinuria and HIV-CKD was lower than that reported in previous studies conducted in the United States. However, intermittent proteinuria, mild reductions in GFR, and progression of established HIV-CKD were common findings in this group of patients with predominantly vertically acquired HIV who were receiving antiretroviral therapy.

Keywords: HIV-associated nephropathy; adolescents; children; kidney diseases; proteinuria.

Graphical abstract

Figure 1

HIV RNA viral load and CD4 cell counts in children and adolescents living with HIV. The study controls were patients with trace or no proteinuria. Patients with intermittent proteinuria (≥1+ by dipstick) are described in the Methods section. HIV–chronic kidney disease (CKD) indicates patients with persistent proteinuria, those with biopsy-proven HIV-CKD, or both, and estimated glomerular filtration rates less than 90 ml/min per 1.73 m². The red area shows the HIV RNA viral load values expressed as the area under the curve (AUC) for the corresponding years of follow-up. The black area shows representative CD4 cell counts obtained within 3 months of the end study period. ∗P < 0.05 was considered statistically significant by 1-way analysis of variance (Kruskal-Wallis test).

Figure 2

Estimated glomerular filtration rate (eGFR) decline overtime and viral load in children living with HIV-1. The study controls were patients with trace or no proteinuria; Patients with intermittent proteinuria (≥1+ by dipstick) are described in the Methods section. HIV–chronic kidney disease (CKD) indicates patients with persistent proteinuria, those with biopsy-proven HIV-CKD, or both and eGFR values less than 90 ml/min per 1.73 m². The graph shows the median eGFR decline in values between January 2012 and July 2019. The dashed lines indicate the percent number of patients in each group with mean viral load (VL) values less than 10,000 viral copies/ml.

Figure 3

Longitudinal follow-up of children and adolescents with biopsy-proven HIV–chronic kidney disease (HIV-CKD); patients with persistent proteinuria, biopsy-proven HIV-CKD, or both; and estimated glomerular filtration rate less than 90 ml/min per 1.73 m². The panels show the relationship between the serum creatinine (SCr) and HIV RNA viral load in patients with HIV-associated nephropathy (HIVAN) (a–c), and those with HIV-associated immune complex kidney diseases (HIVICD) (d–f). Each panel shows 1 representative SCr value and HIV RNA values per year of follow-up. The dashed lines indicate the cutoff normal SCr values adjusted to the age of each patient.