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The changing landscape of HIV-associated kidney disease

Nature Reviews Nephrology volume 20, pages 330–346 (2024)Cite this article

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Abstract

The HIV epidemic has devastated millions of people globally, with approximately 40 million deaths since its start. The availability of antiretroviral therapy (ART) has transformed the prognosis of millions of individuals infected with HIV such that a diagnosis of HIV infection no longer automatically confers death. However, morbidity and mortality remain substantial among people living with HIV. HIV can directly infect the kidney to cause HIV-associated nephropathy (HIVAN) — a disease characterized by podocyte and tubular damage and associated with an increased risk of kidney failure. The reports of HIVAN occurring primarily in those of African ancestry led to the discovery of its association with APOL1 risk alleles. The advent of ART has led to a substantial decrease in the prevalence of HIVAN; however, reports have emerged of an increase in the prevalence of other kidney pathology, such as focal segmental glomerulosclerosis and pathological conditions associated with co-morbidities of ageing, such as hypertension and diabetes mellitus. Early initiation of ART also results in a longer cumulative exposure to medications, increasing the likelihood of nephrotoxicity. A substantial body of literature supports the use of kidney transplantation in people living with HIV, demonstrating significant survival benefits compared with that of people undergoing chronic dialysis, and similar long-term allograft and patient survival compared with that of HIV-negative kidney transplant recipients.

Key points

  • The widespread use of antiretroviral therapy has led to a change in the histological pattern of kidney disease in people living with HIV (PLWH) away from HIV-associated nephropathy and towards comorbid diseases of ageing and antiretroviral therapy-related nephrotoxicity.

  • Biopsy remains crucial for the appropriate management of an array of kidney diseases in PLWH; the current classification of kidney histology is based on the major tissue compartments affected, and is aimed at reducing heterogeneity in the biopsy definitions of HIV-related kidney disease and encouraging awareness of potential secondary causes of disease.

  • The new race-neutral creatinine-based equation for estimating the glomerular filtration rate identified more Black individuals with a lower estimated glomerular filtration rate than previously recognized, and exposed a subgroup of Black individuals living with HIV who are at an increased risk of chronic kidney disease progression.

  • The presence of APOL1 risk alleles influences the pattern of kidney disease in PLWH, its response to therapy and its outcomes; clinical trials are investigating therapeutic options to reduce APOL1 protein and/or its activity, which may ameliorate its potential harm.

  • Kidney transplantation in PLWH from both HIV-negative and HIV-positive donors is highly successful, and the donation of organs from PLWH may be an option for increasing the number of organs available for transplantation; however, this approach requires further evaluation before being adopted as standard clinical practice.

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Fig. 1: Global HIV prevalence amongst adults and children in 2022.
Fig. 2: Pathological classification of HIV-associated kidney disease.
Fig. 3: Proposed major mechanisms by which HIV infection promotes kidney injury.

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    Nina E. Diana & Saraladevi Naicker

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Diana, N.E., Naicker, S. The changing landscape of HIV-associated kidney disease. Nat Rev Nephrol 20, 330–346 (2024). https://doi.org/10.1038/s41581-023-00801-1

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