The human immunodeficiency virus (HIV) is now managed as a chronic condition, allowing people to live long and healthy lives. The kidneys, a pair of organs, filter waste products and excess fluid from the blood, and are susceptible to damage from the virus itself and some of its treatments. This damage can lead to chronic kidney disease (CKD) and, if left unchecked, progress to end-stage kidney failure. Although the risk of severe kidney disease has decreased significantly with modern treatment, a clear connection remains between HIV infection and kidney health.
The Primary Condition: HIV-Associated Nephropathy (HIVAN)
The most direct and aggressive form of kidney damage caused by the virus is HIV-Associated Nephropathy (HIVAN). This condition is a specific type of collapsing focal segmental glomerulosclerosis, which is a pattern of injury to the kidney’s filtering units. The primary mechanism involves the direct infection of specialized kidney cells called podocytes. Viral replication within these podocytes causes them to proliferate and lose their differentiated function, leading to the collapse of the glomerular filtering structure and a rapid loss of kidney function. Before the widespread use of effective Antiretroviral Therapy (ART), HIVAN was a leading cause of kidney failure in people with HIV.
Clinically, HIVAN presents with a rapid decline in the estimated Glomerular Filtration Rate (eGFR), the measure of how well the kidneys are filtering. It is accompanied by nephrotic-range proteinuria, meaning a massive amount of protein leaks into the urine. This condition has a strong genetic component, being significantly more prevalent in people of African ancestry due to specific polymorphisms in the APOL1 gene. Prompt initiation of ART is the single most effective treatment for HIVAN, often slowing or reversing the damage.
Secondary Damage: Medication Effects on Kidney Function
Beyond the direct viral effect, some medications used to treat HIV can indirectly impact kidney function through nephrotoxicity. The most well-known example involves certain Nucleoside Reverse Transcriptase Inhibitors (NRTIs), particularly tenofovir disoproxil fumarate (TDF). This drug can cause damage to the proximal tubules of the kidney. The mechanism involves the drug accumulating in the tubular cells, leading to mitochondrial toxicity and impairing the tubule’s ability to reabsorb essential substances. This condition, called proximal tubular dysfunction, can manifest as Fanconi syndrome, characterized by the loss of phosphate, glucose, and bicarbonate in the urine.
Other antiretroviral drugs, such as certain protease inhibitors and the boosting agent cobicistat, can also affect kidney function through a different mechanism. These drugs inhibit the active transport of creatinine, a waste product, out of the blood and into the urine. This effect causes an apparent, but false, increase in serum creatinine levels and a corresponding drop in the calculated eGFR, without causing actual kidney damage. For drugs cleared by the kidney, like many NRTIs, a reduction in the drug dose is necessary for patients with true kidney impairment to prevent drug accumulation and toxicity.
Monitoring and Managing Kidney Health
Regular monitoring of kidney health is a standard part of HIV care due to the various risks. The primary screening tools are a blood test for serum creatinine to calculate the eGFR, and a urine test to measure protein or albumin levels. The preferred urine test is the Protein-to-Creatinine Ratio (PCR) or Albumin-to-Creatinine Ratio (ACR), which provides a more accurate measure of protein loss. For stable patients, monitoring the eGFR is recommended at least twice a year, with proteinuria screening conducted annually. More frequent testing is advised when starting a new ART regimen or for individuals with other risk factors. The presence of glucose in the urine without high blood sugar is a specific indicator of TDF-induced tubular damage and requires immediate attention.
Management of kidney disease in this population also requires controlling non-HIV related co-morbidities. Hypertension and diabetes are the most common causes of CKD globally and significantly accelerate kidney damage in people with HIV. Medications like Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) are often used to control blood pressure and reduce protein leakage from the kidneys. For advanced kidney failure, treatments include dialysis or kidney transplantation for carefully selected individuals with stable, well-controlled HIV.
The Role of Modern Treatment in Prevention
The outlook for kidney health in people with HIV has vastly improved because of advances in ART. The most impactful preventative measure is the early and consistent initiation of effective ART, which suppresses the virus to undetectable levels. Viral suppression effectively removes the primary cause of HIVAN, the direct viral infection of kidney cells. Newer formulations of NRTIs have also been instrumental in reducing drug-related toxicity. For example, tenofovir alafenamide (TAF) achieves high levels of the active drug inside immune cells with approximately 90% lower concentrations in the blood plasma compared to TDF, dramatically limiting the drug’s exposure to the kidney tubules and minimizing nephrotoxicity.