Fig. 4.

Glomerular filtration barrier (GFB) and sustained kidney damage. c, d Under normal physiological conditions, the GFB filter 30% of blood flow to form protopuria, and 65–70% of water is reabsorbed at proximal tubules, which markedly increase the viscosity of efferent arterioles and tubule capillaries. Congested RBCs push other blood cells to the edge of the bloodstream. b After SARS-CoV-2 infection, cytokine storm activates massive blood cells/ECs, leading to uncontrolled phosphatidylserine (PS) exposure. At the renal tubules, these excess PS (mainly PS⁺ PLT and MPs) are crowded at the edge of the bloodstream (or closed to the damaged ECs), which discriminatorily increase peritubule thrombosis and tubule injury. a Simultaneously, damage of glomerular ECs results in loss of glycocalyx, decreased fenestrae, barrier opening (leakage of plasma or erythrocytes), cells swelling and microthrombi. SARS-CoV-2, cannot cross the endothelial fenestrations, infects podocytes either after infecting ECs or by crossing the damaged endothelial barrier. Damaged podocytes lose foot processes and reduce the release of VEGF A, further aggravating the injury of ECs. Persistent inflammation and immune dysregulation in convalescent patients maintain and exacerbate these injuries, leading to persistently reduced eGFR. c, e Severe glomerular endothelial injury can result in the accumulation of plasma in Bowman’s capsule, increasing the blood viscosity of glomerular capillaries and efferent arterioles. Leakage of plasma or erythrocyte in initial urine eventually forms proteinuria or hematuria. Additionally, diffuse microthrombi can result in stagnation of blood flow in part of glomeruli and subsequent retention of initial urine. The leaking plasma protein (erythrocytes) in initial urine ultimately forms protein (erythrocyte) casts after concentration and acidification in renal tubules (e). HCT hematocrit; PS phosphatidylserine; MPs microparticles; PLT platelets