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.

A Systematic Review Exploring the Range of Renal Complications of Human Immunodeficiency Virus

“…In addition, the podocytes may proliferate to form a pseudo-crescentic structure [ 27 ]. HIVAN occurs mainly in African Americans with apolipoprotein L1 (APOL1) risk alleles and is a leading cause of ESRD in African Americans [ 3 ]. Disease expression and renal complications, and subsequent kidney injury risk require two APOL1 risk alleles.…”

“…A year later (1982), the same disease entity was diagnosed in Europe, and it was named AIDS by the Center for Disease Control (CDC) [ 2 ]. Since the first diagnosed case, about 79.3 million (55.9-110 million) have been infected with the virus [ 3 ], while over 25 million people have died already [ 4 ]. In addition, about two million new cases are diagnosed annually [ 4 ].…”

Renal, cardiac, neurological, cutaneous and coagulopathic long-term manifestations of COVID-19 after recovery; A review

“…Theoretically, Transient Receptor Potential Canonical Channel 6 (TRPC6), as an ion channel in podocytes, can directly be activated by ANGII, which leads to proteinuria [13,25]. The most common COVID-19-related renal complications are including acute tubular injury (ATI), collapsing glomerulopathy, thrombotic microangiopathy, complement activation, and IL-6-induced renal vascular permeability [13,17]. Therefore, the kidney injury leads to: (i) hypoxia-induced acute tubular necrosis with high level of creatinine, (ii) collapsing focal segmental glomerulosclerosis (cFSGS) together with hematuria, which are common in patients with APOL1 alleles, (iii) direct viral tropism of renal tissue with high levels of micro-or macro-albuminuria, and (iv) hemodynamic changes mediated by endothelitis along with electrolyte imbalance [26].…”

Mechanisms and treatment of COVID-19-associated acute kidney injury

“…Next, Lan and colleagues explored the protective effects of quercetin, a flavonoid purified from traditional Chinese medicine, in renal injury induced by the SARS-CoV-2 N protein. 7 As aging and diabetes are two comorbidities of COVID-19-associated nephropathy, 9 the authors tested the therapeutic effects of quercetin in aged mice with diabetes and showed that quercetin could attenuate the renal injury caused by the SARS-CoV-2 N protein. Mechanistically, quercetin can block the binding of the N protein and Smad3, hence lifting the cell-cycle arrest and reducing renal tubular cell necrosis.…”