The human immunodeficiency virus (HIV) significantly impacts the kidneys, which are primarily responsible for filtering waste, maintaining fluid balance, and regulating blood pressure. While modern antiretroviral therapy (ART) has reduced HIV-specific kidney disease, complications remain a major health concern for individuals living with HIV. The relationship is complex, involving both the direct effects of the virus and the long-term consequences of infection and treatment. Understanding these mechanisms is crucial because kidney disease often progresses silently, requiring proactive monitoring and management.
HIV’s Direct Assault on Kidney Cells
The most recognized direct form of kidney damage is HIV-Associated Nephropathy (HIVAN), a condition characterized by a severe and distinct pathology. HIVAN is classified as a type of collapsing focal segmental glomerulosclerosis (FSGS), where the kidney’s filtering units, the glomeruli, become scarred and collapse. This is not simply an immune response; the virus itself infects and damages the specialized cells within the kidney.
The HIV virus, or its gene products like Nef and Vpr, invades the renal epithelial cells, particularly the podocytes, which are responsible for the blood filtration barrier. Infected podocytes change their structure and behavior, losing their ability to function correctly, which leads to massive protein leakage into the urine. The damage also results in the characteristic microcystic dilation of the tubules, further contributing to kidney failure.
HIVAN shows a strong genetic predisposition, occurring predominantly in individuals of African descent. This heightened risk is largely attributed to specific genetic variants in the APOL1 gene. Individuals carrying two copies of these risk variants face a significantly increased likelihood of developing HIVAN and other kidney diseases.
Secondary Contributors to Kidney Dysfunction
While HIVAN represents the direct viral attack, many other factors contribute to kidney dysfunction in people living with HIV. The long-term use of certain antiretroviral therapy (ART) medications can cause drug-induced nephrotoxicity. For example, the drug tenofovir disoproxil fumarate (TDF) can specifically cause damage to the proximal tubules, leading to conditions like Fanconi syndrome or acute tubular necrosis.
Other ART drugs, particularly some protease inhibitors like indinavir, can cause damage through crystal formation within the kidney tubules. These drug-related issues are distinct from HIVAN because they affect the tubules rather than the glomeruli, and they can often be reversed by switching the medication. Careful monitoring is necessary, as the risk of toxicity increases with the use of multiple nephrotoxic agents.
The prolonged inflammation and immune dysfunction associated with chronic HIV infection accelerate traditional causes of chronic kidney disease (CKD). Conditions like hypertension and diabetes, major drivers of CKD in the general population, are often more prevalent and progress faster in HIV-positive individuals. Furthermore, co-infections such as Hepatitis C virus (HCV) can directly contribute to kidney damage through immune complex formation.
Signs, Symptoms, and Screening
Kidney disease is often described as a silent killer because it typically causes no noticeable symptoms in its early stages. Significant damage usually occurs before a person feels unwell, making routine screening important for all individuals with HIV. When symptoms do appear, they are usually non-specific and include swelling in the legs or face, persistent fatigue, and a reduced appetite. Changes in urination patterns, such as needing to urinate more frequently, especially at night, can also be a sign.
Screening relies on two simple, non-invasive tests performed regularly. A blood test measures creatinine levels, a muscle waste product, allowing doctors to calculate the estimated Glomerular Filtration Rate (eGFR). The eGFR estimates how well the kidneys are filtering blood. A urine test checks for the presence of protein or albumin (proteinuria or albuminuria), which is one of the earliest and most sensitive indicators of kidney damage.
Treating Kidney Disease in the Context of HIV
Managing kidney disease involves a delicate balance between protecting the kidneys and maintaining effective viral suppression. For patients diagnosed with HIVAN, the primary treatment is the immediate initiation or optimization of ART. Effective ART can dramatically slow or even reverse the progression of HIVAN by reducing the viral load and the direct viral damage to kidney cells.
If kidney dysfunction is suspected to be drug-related, the ART regimen is typically adjusted. This often means switching from a potentially nephrotoxic drug like TDF to a safer alternative, such as tenofovir alafenamide (TAF) or abacavir (ABC). The goal is to select an antiretroviral combination that is both potent against the virus and poses the least risk to the kidneys.
Symptomatic management is a critical component, especially using blood pressure medications to reduce kidney strain. Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) are often preferred because they help lower blood pressure and reduce protein leakage into the urine, offering a protective effect to the glomeruli. For advanced kidney failure, or end-stage renal disease (ESRD), patients may require dialysis or a kidney transplant. Both are viable options for individuals with HIV who are achieving viral suppression.