OVERVIEW

What is HIV-associated nephropathy?

HIV-associated nephropathy (HIVAN) is a classic kidney disease related to human immunodeficiency virus (HIV) infection. It was first reported in 1984 as a complication of acquired immunodeficiency syndrome (AIDS).

HIV-associated nephropathy is more common in advanced stages of HIV infection and predominantly affects Black individuals. Clinical manifestations include severe proteinuria and rapid decline in kidney function. Hematuria, hypertension, and edema may also occur.

The prognosis is poor, with many patients progressing to end-stage renal disease (ESRD) and requiring dialysis.

Is HIV-associated nephropathy common?

HIV-associated nephropathy is more frequently observed in HIV-positive Black individuals. Data from the US Renal Data System (USRDS) indicate that HIVAN is a leading cause of ESRD among young African American adults.

However, in recent years, with the introduction of highly active antiretroviral therapy (HAART), the risk of progression to ESRD has decreased.

SYMPTOMS

What are the common clinical manifestations of HIV-associated nephropathy?

• Foamy urine: If there is a large amount of fine foam in the urine that does not dissipate easily, proteinuria should be suspected. Further tests such as urinalysis and 24-hour urine protein quantification are needed for confirmation. HIV-associated nephropathy often presents with significant proteinuria, though some patients may only exhibit mild proteinuria.

• Rapid decline in kidney function: Blood tests for serum creatinine and estimated glomerular filtration rate (eGFR) can determine whether kidney function is impaired. HIV-associated nephropathy may lead to decreased kidney function, manifested as elevated serum creatinine and reduced eGFR.

Other possible manifestations of HIV-associated nephropathy include:

• Hematuria: This can be categorized as gross hematuria (visible red or brown urine) or microscopic hematuria. In both cases, urinalysis will show an increased number of red blood cells.

• Edema

• Hypertension

CAUSES

What are the causes of HIV-associated nephropathy?

HIV-associated nephropathy is related to HIV infection. It often occurs in the late stages of HIV infection but may also develop in non-advanced HIV patients or those with acute HIV infection. It is more common in Black individuals.

The pathogenesis of HIV-associated nephropathy may include:

• HIV infection of renal epithelial cells, with HIV genes being expressed in infected kidney cells.

• The strong association between HIV-associated nephropathy and Black individuals suggests that host genetic factors, including genetic susceptibility, also play a significant role.

DIAGNOSIS

What tests are needed for HIV-associated nephropathy?

First, relevant tests are required to confirm HIV infection. After HIV infection is diagnosed, the following tests can be performed to determine whether there is kidney damage.

• Urinalysis: Mainly used to detect proteinuria, hematuria, etc. Precautions for urinalysis include: Avoid strenuous exercise 72 hours before urine collection, and women should avoid collecting urine during menstruation. Morning urine is most suitable for urinalysis, while random urine samples are appropriate for outpatient or emergency patients. Ensure the external genitalia are cleaned before collecting midstream urine.

• Urinary microalbumin or urinary microalbumin-to-creatinine ratio: Primarily used to identify the types of proteins in proteinuria. Specimen collection precautions are the same as for urinalysis.

• 24-hour urine protein quantification: Mainly used to measure the total amount of protein excreted in urine over 24 hours. Collect all urine within 24 hours in a clean container, mix well, and measure the total volume with a measuring cup.

• Serum creatinine and glomerular filtration rate (GFR): Tested via venous blood draw.

The above tests can determine the presence of proteinuria, hematuria, or abnormal kidney function. For patients suspected of having HIVAN based on clinical manifestations, a kidney biopsy is necessary for definitive diagnosis. There are various methods for kidney biopsy, with percutaneous kidney biopsy under ultrasound guidance being the most widely used. Kidney biopsy can clarify the pathological type of kidney disease and is a crucial diagnostic procedure.

What precautions should be taken for a kidney biopsy in HIV-associated nephropathy?

• During the biopsy, the patient is typically placed in a prone position with a pillow about 10 cm high under the abdomen.

• Patients scheduled for a kidney biopsy should practice this position and train to hold their breath in this posture.

• After the biopsy, the patient must lie flat and should practice urinating and defecating while lying in bed.

• Post-biopsy, follow-up urinalysis and kidney ultrasound are required.

What are the characteristic findings of kidney biopsy in HIV-associated nephropathy?

• The hallmark of HIV-associated nephropathy is collapsing focal segmental glomerulosclerosis (FSGS).

• Other typical features include dilated tubules and prominent interstitial inflammation. Electron microscopy may also reveal tubuloreticular inclusions.

• Glomerular lesions in HIV-associated nephropathy also feature dedifferentiation and proliferation of glomerular epithelial cells, leading to pseudocrescent formation, even though these cells are usually considered terminally differentiated.

What diseases should be differentiated from HIV-associated nephropathy?

For HIV-positive patients with proteinuria and decreased GFR, the following conditions should be considered for differential diagnosis:

• Non-collapsing FSGS, amyloidosis, diabetic nephropathy, or other non-infectious glomerulopathies.

• Immune complex-mediated glomerulonephritis, including HIV immune complex kidney disease (HIVICK), IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, and "lupus-like" proliferative glomerulonephritis.

• Glomerulonephritis caused by hepatitis C virus coinfection.

TREATMENT

Which department should I visit for HIV-associated nephropathy?

Since it usually presents with symptoms of kidney disease initially, patients should typically visit the nephrology department within the kidney disease specialty.

How should HIV-associated nephropathy be treated?

• HIV-associated nephropathy can be treated with highly active antiretroviral therapy (HAART), renin-angiotensin system inhibitors, and glucocorticoids.

• For patients who have not yet received HAART, initiating this therapy is recommended.

• For patients with proteinuria and/or hypertension, we suggest treatment with renin-angiotensin system inhibitors.

• Routine use of glucocorticoids is not recommended. However, some experts may consider glucocorticoids for patients with progressive disease despite optimal treatment with HAART and angiotensin inhibition.

DIET & LIFESTYLE

What should HIV-associated nephropathy patients pay attention to in daily life?

Lifestyle and dietary precautions should be determined based on the patient's condition (e.g., presence of hypertension, proteinuria, or renal dysfunction).

• If the patient has hypertension, a low-salt diet is recommended (daily salt intake of 2–3 g).

• If nephrotic syndrome is present, follow the precautions for nephrotic syndrome.

• If renal insufficiency is present, adhere to the precautions for renal insufficiency.

• Regular outpatient follow-ups are necessary, including blood tests, liver and kidney function tests, urinalysis, and 24-hour urine protein quantification to monitor disease progression and adjust medications.

PREVENTION

Can HIV-associated nephropathy be prevented? How to prevent HIV-associated nephropathy?

• For people who are not yet infected with HIV, it is important to avoid HIV infection as much as possible.

• For patients already infected with HIV, standardized treatment for HIV infection should be sought at a qualified hospital.

• Avoiding fatigue, infections, and the use of nephrotoxic drugs can reduce the risk of kidney damage.