Case Published: December 2019
Diagnosis: HIV-associated nephropathy (HIVAN)
Case Summary: Well done! Let’s review this case.
Here we have a patient with poorly controlled HIV and a high viral load and low CD4 count presenting with hypertension, nephrotic range proteinuria, impaired kidney function, and edema.
Labs are notable for a urine protein:creatinine ratio greater than 3-3.5g of protein and hypoalbuminemia, consistent with nephrotic range proteinuria & nephrotic syndrome. Let’s start to build our differential diagnosis…
Membranous nephropathy
Minimal change disease
IgA nephropathy (nephrotic or nephritic)
Systemic lupus erythematosus (SLE)
Hepatitis B or C (more commonly HBV)
Nonsteroidal anti-inflammatory drugs
HIV
Amyloidosis
Multiple myeloma
Preeclampsia

Now that we have established a broad differential, let’s try to determine which etiology is most likely in our patient. In this case, HIV may be playing a significant role in his kidney dysfunction. There are several ways the kidneys can be affected in HIV.
HIV immune complex disease of the kidney (HIVICK)
Thrombotic microangiopathy (TMA)
Nephrolithiasis (protease inhibitors)
Papillary necrosis (protease inhibitors)
HBV-related kidney disease
This patient’s laboratory work-up is not suggestive of a thrombotic microangiopathy (TMA), nor is it consistent with significant tubular damage or Fanconi syndrome, a potential complication of tenofovir therapy. We therefore proceed with kidney biopsy.
The histology of patients with HIV-associated nephropathy (HIVAN) reveals collapsing variant of focal segmental glomerulosclerosis (FSGS), which we see here in this patient! Below are two light microscopy images (Jones Methamine Silver stain and Periodic-Acid Schiff stain) showing collapsing glomerulopathy. Tubuloreticular inclusions (TRI) are also commonly seen in viral or autoimmune disease.


Classically, HIVAN presents with kidney dysfunction, proteinuria (often but not necessarily nephrotic range), enlarged kidneys on ultrasonography, most frequently in a patient with uncontrolled HIV.
HIV immune complex disease of the kidney (HIVICK), as it is named, is immune-complex mediated and more commonly presents as a nephritic syndrome. We might expect to see IgA nephritis, or even SLE-like proliferative glomerulonephritis. Based on this patient’s presentation and most importantly biopsy findings, the diagnosis is most likely HIVAN.
Reducing HIV viremia and achieving undetectable viral loads is the most important management strategy. Angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are useful for proteinuria, and adequate blood pressure control should be achieved. Corticosteroids have very limited data, and no randomized control trials have been done.
For further reading on this subject:
- Ganesh K, Nair RR, Seethaleskhmy NV, Kurian G, Mathew A, Sreedhraran S, Paul Z. A study of clinical presensattion and correlative hisopathological patterns in renal parenchymal disease. Indian J Nephrol. 28(1): 28-34, 2018
- Kalayjian RC. The treatment of HIV-associated nephropathy. Adv Chronic Kidney Dis.17(1):59–71, 2010
- Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 28(6):513–522,2008 doi:10.1016/j.semnephrol.2008.08.005
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Case 41 Introduction
Case 41 Physical Exam
Case 41 Diagnostic Testing
Case 41 Pathology
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