Understanding the relationship between HCV infection and progression of kidney disease

Abstract

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Keywords: acute kidney injury; cryoglobulinaemia; diabetic nephropathy; glomerulonephritis; hepatitis C virus; lupus nephritis; renal cell carcinoma.

Figure 1

HCV infection not only affects the liver but also has many extrahepatic manifestations. In the liver, the effects of HCV include acute and chronic hepatitis C, cirrhosis, severe hepatitis, and hepatic failure. In the brain, memory loss, cognitive dysfunction, changes in brain metabolism, and fatigue may occur. In the heart, cardiovascular disease, myocarditis, pericarditis, and palpitations may be caused by HCV. HCV may also cause some lung diseases, such as pneumonia, bronchitis, and emphysema. In the kidney, HCV causes acute kidney injury, glomerular nephropathy, diabetic nephropathy, lupus nephritis, chronic kidney disease, and renal cell carcinoma.

Figure 2

HCV replication within cells and the effects of direct-acting antivirals. HCV binds to cell surface receptors and undergoes endocytosis. Membrane fusion results in the release of the nucleocapsid containing viral RNA into the cytoplasm. RNA is replicated in the membrane network and is then translated, forming a large polymeric protein. NS3/NS4 proteases include NS3/4A proteases, NS5B polymerases that function in HCV RNA replication, and multifunctional NS5A, which is involved in HCV replication and cleaves polymers into structural components and nonstructural proteins. Direct-acting antivirals (DAAs) can inhibit HCV replication and processing. NS3/4A, Nonstructural protein 3/4A; NS5A, Nonstructural protein 5A; NS5B, Nonstructural protein 5B.

Figure 3

Pathogenesis of HCV infection in various kidney diseases. AKI, Acute kidney injury; Akt, Protein kinase B; BAFF, B-cell activating factor; CKD, Chronic kidney disease; DN, Diabetic nephropathy; GN, Glomerulonephritis; IgG, Immunoglobulin G; IgM, Immunoglobulin M; NK cell, Natural killer cell; NS5A, Nonstructural protein 5A; PPAR-α, peroxisome proliferator-activated receptor α; PPAR-γ, Peroxisome proliferator-activated receptor γ; PP2A, Protein phosphatase 2; RCC, Renal cell carcinoma; RF, rheumatoid factor; SPIK24, Serine protease inhibitor Kazal protein 24; SOCS3, Suppressor of cytokine signaling 3; TEC, Tubular epithelial cell; TNF-α, Tumor necrosis factor-α; IRS-1/2, Insulin receptor substrate 1/2.