Proteinuria in COVID-19

Abstract

Upper respiratory and pulmonary diseases are the primary manifestations of coronavirus disease 2019 (COVID-19). However, kidney involvement has also been recognized and extensively described. A large percentage of affected patients present with acute kidney injury (AKI). However, specific phenotypic aspects of AKI or other renal manifestations of COVID-19 remain sparsely characterized. Many reports indicate that proteinuria can be detected in AKI associated with COVID-19 (CoV-AKI) despite CoV-AKI being largely described as a form of acute tubular injury. On the other hand, individuals of African ancestry with the high-risk APOL1 genotype are uniquely at risk of developing collapsing glomerulopathy when they are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the entity now known as COVID-19-associated nephropathy (COVAN). Patients with COVAN typically present with nephrotic-range proteinuria. The exact incidence of proteinuria in COVID-19 is unclear due to heterogeneity in the frequency with which proteinuria has been assessed in cases of COVID-19, as well as methodological differences in the way proteinuria is measured and/or reported. In this review we discuss the current evidence of proteinuria as a manifestation of COVID-19 and elaborate on potential pathophysiological mechanisms associated with it.

Keywords: AKI; SARS-CoV-2; albuminuria; nephrotic; protein-to-creatinine.

FIGURE 1:

Pathogenesis of proteinuria in COVID-19. Individuals infected with SARS-CoV-2 develop an acute respiratory illness that is followed by multiple pathological mechanisms that may lead to the development of AKI. Low-grade proteinuria can be observed in COVID-19 presenting with a subclinical form of AKI, i.e. without elevation of the serum creatinine concentration. The most common type of AKI in COVID-19 is ATI. In cases of ATI, low-grade proteinuria can also be detected, presumably resulting from damage to the proximal convoluted tubule, when detached and sloughed tubular cells cannot reabsorb the filtered protein that is normally reclaimed through the apical endocytic apparatus. Susceptible individuals of African ancestry who are carriers of the APOL1 high-risk genotype can acquire collapsing glomerulopathy when they are infected with COVID-19 (i.e. COVAN) and present with nephrotic-range proteinuria and AKI. Systemic inflammatory response has been linked to an increase in glomerular permeability. Other acute glomerular insults can occur in patients with COVID-19 (e.g. thrombotic microangiopathy). Preexisting CKD can lead to detection of proteinuria in a patient with COVID-19 and the magnitude of the proteinuria in those cases could be of any degree, stable or worse than its baseline value.