Similarities and Differences between COVID-19-Associated Nephropathy and HIV-Associated Nephropathy

Abstract

Kidney disease is a major complication of viral infection, which can cause both acute and chronic kidney diseases via different mechanisms such as immune-mediated injury, kidney cell injury from a direct viral infection, systemic effects, and antiviral drug-induced nephrotoxicity. HIV-associated nephropathy (HIVAN), characterized by collapsing focal segmental glomerulosclerosis (cFSGS), has been described 2 decades ago as a major complication of acquired-immunodeficiency syndrome. The pathogenesis of HIVAN has been well studied, including viral entry, host response, and genetic factors. The incidence of this disease has been dramatically dropped with current antiretroviral therapy. In the recent severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, acute kidney injury was also found to be a major complication in patients with (coronavirus disease) COVID-19. These patients also developed glomerular disease such as cFSGS in African Americans with apolipoprotein L1 risk alleles, similar to HIVAN. Whether SARS-CoV-2 can infect kidney cells locally remains controversial, but both local infection and systemic effects are likely involved in the pathogenesis of this disease. In this review, we present a comparison of the clinical presentations, pathological findings, disease mechanisms, and potential treatments between HIVAN and COVID-19. Leveraging the knowledge in HIVAN and experimental approaches used to study HIVAN will facilitate the exploration in the pathogenesis of COVID-19-associated kidney disease and improve our management of COVID-19 patients.

Keywords: Acute kidney injury; COVID-19 nephropathy; Collapsing FSGS; HIV-associated nephropathy; Viral nephropathy.

Fig. 1

Summary of HIV-associated kidney disease. HIV-associated kidney disease is caused by direct infection of kidney cells or deposition of IC or drug-toxicity. HIVAN is caused by viral infection of the kidney cells likely through cell-cell transmission between infected lymphocytes and tubular epithelial cells or podocytes. HIVCK, immune-mediated GN in HIV-infected patients, is caused by IC deposition in the glomeruli. Antiviral drugs such as tenofovir can induce nephrotoxicity in HIV patients. The pathological features of HIVAN include cFSGS and tubular dilatation with microcysts. Clinically, these patients present with AKI, nephrotic syndrome, and enlarged kidneys. The pathological and clinical findings of HIVCK are similar to those of other GN. Drug-induced nephrotoxicity presents as ATN, AIN, or Fanconi syndrome. HIV-1: human immunodeficiency virus-1; RTEC: renal tubular epithelial cells; APOL1: apolipoprotein L1; HIVCK: HIV immune complex kidney disease; GN: glomerulonephritis; cFSGS: collapsing focal segmental glomerulosclerosis; ATN: acute tubular necrosis; AIN: acute interstitial nephritis; IC, immune complex.

Fig. 2

Summary of COVID-19-associated kidney disease. SARS-CoV-2 may directly infect RTECs, podocytes, and endothelial cells through ACE2 receptor. The local infection and the systemic effects caused by SARS CoV-2 jointly cause acute tubular injury, cFSGS, and thrombotic microangiopathy. Clinically, these patients present with AKI, with or without proteinuria and hematuria. SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; ACE2, angiotensin-converting enzyme 2; RTEC, renal tubular epithelial cells; APOL1, apolipoprotein L1; cFSGS, collapsing focal segmental glomerulosclerosis; AKI, acute kidney injury; ATI, acute tubular injury.