From the Guidelines
HIV-associated focal segmental glomerulosclerosis (FSGS) should be managed with antiretroviral therapy (ART) as the primary treatment, with the goal of controlling HIV and improving or resolving kidney disease, as recommended by the most recent guideline 1.
Symptoms and Diagnosis
HIV-associated FSGS is a kidney disorder that can develop in HIV-infected individuals, with symptoms including:
- Proteinuria (protein in urine)
- Edema (swelling) particularly in the legs and feet
- Hypertension
- Progressive decline in kidney function
- Foamy urine
- Fatigue
- Symptoms of uremia such as nausea, vomiting, and confusion in advanced cases Diagnosis begins with urinalysis showing significant proteinuria, followed by blood tests revealing elevated creatinine, hypoalbuminemia, and hyperlipidemia. HIV testing is essential, with CD4 count and viral load assessment to determine disease stage. Kidney biopsy is the definitive diagnostic test, showing focal and segmental sclerotic lesions in glomeruli with tubulointerstitial inflammation.
Workup and Management
The workup should include:
- Complete blood count
- Comprehensive metabolic panel
- Lipid profile
- Serologic tests to exclude other causes of glomerular disease Management focuses on controlling HIV with ART, which can lead to improvement or resolution of kidney disease.
- Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are used to reduce proteinuria and slow progression.
- Corticosteroids may be considered in selected cases with significant proteinuria despite ART, as suggested by 1 and 1.
- Supportive care includes sodium restriction, diuretics for edema, and statins for hyperlipidemia. The pathogenesis involves direct HIV infection of kidney cells, immune complex deposition, and inflammatory responses, with HIV viral proteins causing podocyte injury leading to the characteristic lesions of FSGS.
Key Considerations
- Renal biopsy is recommended unless there is strong suspicion of a nonglomerular etiology of renal dysfunction, such as nephrotoxic combination antiretroviral therapy (cART) medications, acute tubular necrosis (ATN), or other comorbid conditions, as stated in 1.
- The use of immunosuppressive medications is unlikely to be beneficial in FSGS-UC or in those with secondary FSGS, and a limited case-by-case trial of glucocorticoid therapy may be warranted in HIV-associated nephropathy (HIVAN), as recommended by 1.
From the Research
HIV Associated Focal Segmental Glomerulosclerosis
- Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide, with various etiologies including primary, adaptive, genetic, virus-associated, and medication-associated FSGS 2.
- HIV-associated nephropathy (HIVAN) is a prominent kidney disease in HIV-infected individuals, with a high risk of progression to end-stage renal disease (ESRD) and increased mortality 3.
- The classification of FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and genetic testing, with kidney biopsy being helpful in distinguishing FSGS from other glomerular diseases 2.
Symptoms and Diagnosis
- Symptoms of FSGS may include proteinuria, hematuria, and decreased glomerular filtration rate (GFR) 2.
- Diagnosis of FSGS is based on kidney biopsy, with features on light microscopy, immunofluorescence, and electron microscopy providing clues for diagnosis 2.
- HIVAN is diagnosed based on clinical presentation, laboratory testing, and kidney biopsy, with a high risk of developing HIVAN increasing with decreasing CD4 count, higher viral load, and genetic factors 3.
Workup and Treatment
- Workup for FSGS includes clinical history, laboratory testing, kidney biopsy, and genetic testing, with treatment guided by the underlying etiology 2.
- Treatment for HIVAN includes combined anti-retroviral therapy (cART), with adjunctive therapies such as RAAS blockade and prednisone considered in certain cases 3.
- Sirolimus therapy has been associated with nephrotoxicity in some patients with FSGS, particularly those with prolonged disease duration and prior cyclosporine therapy 4.
- Response to therapy in FSGS patients cannot be predicted based on histology alone, and nephrotic patients with primary FSGS should receive a trial of therapy irrespective of the histologic lesion when not contraindicated 5.
HIV-Associated FSGS
- HIV-associated FSGS has emerged as a common cause of glomerular disease in HIV-infected individuals, particularly in those with metabolic and cardiovascular risk factors 6.
- Patients with HIV-associated FSGS tend to have less severe renal failure and lower CD4 counts compared to those with HIVAN 6.
- The epidemiology of HIVAN and FSGS in HIV-infected individuals is influenced by factors such as CD4 count, viral load, and genetic factors 3, 6.