Can Human Immunodeficiency Virus (HIV) cause Chronic Kidney Disease (CKD)?

HIV and Chronic Kidney Disease

Yes, HIV infection can directly cause chronic kidney disease (CKD) through various mechanisms, including direct viral infection of renal cells and immune-mediated kidney damage. 1

Pathophysiology of HIV-Related Kidney Disease

HIV affects the kidneys through several mechanisms:

1. Direct HIV-associated nephropathy (HIVAN):

   • Characterized by collapsing focal segmental glomerulosclerosis
   • Results from direct infection of renal epithelial cells by HIV
   • Involves intrarenal viral gene expression and dysregulation of host genes 1
   • More common in individuals of African ancestry with genetic predisposition

2. HIV immune complex-mediated kidney disease:

   • Second most common HIV-related kidney pathology
   • Results from immune dysregulation and deposition of immune complexes 1, 2

3. Non-collapsing focal segmental glomerulosclerosis:

   • Distinct from classic HIVAN but still associated with HIV infection 1

4. Other HIV-related kidney pathologies:

   • Minimal change disease
   • Diffuse mesangial hypercellularity
   • Tubular damage 1

Epidemiology and Risk Factors

Kidney function is abnormal in up to 30% of HIV-infected patients, and HIV-related kidney disease has become a relatively common cause of end-stage renal disease (ESRD) requiring dialysis 1.

High-risk groups for HIV-related kidney disease include:

• African American individuals
• Patients with CD4+ counts <200 cells/mL
• Patients with HIV RNA levels >14,000 copies/mL
• Those with comorbidities:
  • Hepatitis C coinfection
  • Diabetes mellitus
  • Hypertension 1

Clinical Impact

CKD in HIV-positive individuals is associated with:

• Progression to AIDS
• Increased mortality
• Need for dialysis in advanced cases 1, 2

Before the widespread use of antiretroviral therapy (ART), patients with newly diagnosed AIDS and ESRD survived only 1-3 months after initiating hemodialysis. With modern treatment, survival rates have improved significantly, approaching those of the general ESRD population 1.

Prevention and Management

1. Early detection through screening:

   • All HIV patients should be screened for kidney disease at diagnosis
   • High-risk individuals should undergo annual screening with:
     • Urinalysis for proteinuria
     • Estimated glomerular filtration rate (eGFR) 1

2. Antiretroviral therapy:

   • ART has reduced the incidence of HIVAN
   • Early initiation of ART can preserve kidney function 1, 2
   • Caution with potentially nephrotoxic agents:
     • Tenofovir disoproxil fumarate (TDF) requires monitoring 3
     • Consider tenofovir alafenamide (TAF) in patients with or at risk for CKD 4, 5

3. Management of comorbidities:

   • Control hypertension and diabetes
   • Treat hepatitis C coinfection 1

4. Medication adjustments:

   • Dose adjustment for antiretrovirals eliminated by the kidney in patients with reduced eGFR
   • Avoid nephrotoxic combinations (e.g., TDF with NSAIDs) 3

Staging and Monitoring

CKD in HIV patients is staged according to standard criteria:

Stage	Description	GFR (mL/min per 1.73m²)
I	Kidney damage with normal or increased GFR	≥90
II	Kidney damage with mildly decreased GFR	60-89
III	Moderately decreased GFR	30-59
IV	Severely decreased GFR	15-29
V	Kidney failure	<15 (or dialysis)

Regular monitoring should include:

• eGFR calculation
• Urinalysis for proteinuria
• In those with CKD: serum phosphorus, especially if on TDF 1, 3

Conclusion

HIV can cause CKD through multiple mechanisms, with HIVAN being the classic manifestation. Early detection through screening, prompt initiation of ART, careful selection of antiretroviral agents, and management of comorbidities are essential to reduce the risk of kidney disease progression in HIV-infected individuals.