A 50 years old lady, a diabetic, hypertensive and ischemic heart disease patient, who underwent CABG in 2023 was admitted with complaints of bilateral lower limb swelling, low grade fever, nausea and vomiting since 10 days. She was a case of PLHA since 13 years on regular ART with Tenofovir, lamivudine and dolutegravir regimen. She was found to have elevated creatinine levels in March 2024 (around 1.7mg/dl), but was not evaluated further. She now presented with serum creatinine of around 6mg/dl with non oliguric status. She was initiated on hemodialysis in view of the renal parameters and planned for a renal biopsy.

HIV associated kidney disease encompasses several types of kidney damage related to HIV infection. The most common and severe form is HIV-associated nephropathy (HIVAN), but other kidney-related issues also arise in HIV-positive individuals. They can have acute kidney injury as well as chronic kidney disease associated with retroviral infection.

The causes of AKI in patients with HIV can be similar to those with no HIV along with specific effects like:

• Pre-renal states
• Acute tubular necrosis
• Crystalluria with obstruction
• Interstitial nephritis

Medication nephrotoxicity:

Drugs used in ART as well the medications used to treat the opportunistic infections pose a threat to kidney health. The most common includes the effect of protease inhibitors (eg: indinavir, atazanavir)- which cause crystalluria and AKI. Tenofovir (a nucleoside reverse transcriptase inhibitor) causes AKI as well as proximal tubular dysfunction. Other drugs like acyclovir, trimethoprim used to treat opportunistic infections affect the kidneys.

Thrombotic microangiopathy related to HIV is a very important cause of AKI.

CKD and HIV:

The prevalence of CKD in HIV patients is expected to increase with increase in patients with HIV. Risk factors include low CD4 count, HCV co-infection, high viral load, associated comorbidities like diabetes mellitus or hypertension.

CKD in HIV manifests as:

• HIVAN- HIV associated nephropathy
• HIVICK- HIV immune complex kidney disease
• HIV + HCV associated glomerulonephritis

HIVAN:

It is a collapsing form of focal and segmental glomerulosclerosis with associated tubular microcysts and interstitial inflammation, more common in African Americans (associated with the presence of APOL1 genes). It presents with significant proteinuria (nephrotic range) and rapidly progressive kidney disease with normal/enlarged kidneys. HIVAN is less common in patients with ART and those with good CD4 count.

HIVICK:

• Lupus -like proliferative glomerulonephritis
• Mesangial proliferative glomerulonephritis
• Membranoproliferative GN
• Membranous nephropathy

have been reported in patients with HIV.

Management:

Guidelines recommend screening and early detection of CKD in patients with HIV with urine analysis, quantification of proteinuria, etc. The ART should be adjusted to the creatinine clearance and safer medications prescribed to improve the outcomes of patients with kidney disease and HIV. With ESRD, they can be initiated on HD or PD with specific safety precautions.

References:

• Friedman, A. L., & Adler, S. (2017). Pathogenesis of HIV-associated nephropathy. Current HIV/AIDS Reports, 14(4), 159-166.
• Kopp, J. B. (2013). HIV-associated nephropathy: Epidemiology, pathogenesis, and treatment. American Journal of Kidney Diseases, 61(3), 488-496.
• Mills, A., & Boffito, M. (2008). Impact of antiretroviral therapy on kidney function: A review. Antiviral Therapy, 13(7), 665-675.
• Pozniak, A. L., & Miller, J. M. (2017). Tenofovir and kidney disease: A review of the evidence and its impact. AIDS Reviews, 19(1), 30-38.

Dr Rashmi Shivram
DrNB Nephrology
Resident 2^nd Year
Kauvery Hospital, Chennai