Proteinuria in COVID-19: prevalence, characterization and prognostic role

Abstract

Background: Proteinuria has been commonly reported in patients with COVID-19, suggesting a renal involvement in this infection. However, only dipstick tests have been used thus far. Here, the quantification and characterization of proteinuria and hematuria are investigated. Their potential association with mortality was assessed. Methods: This retrospective, observational and monocentric study includes 153 patients hospitalized with COVID-19 between March 28th and April 30th 2020, in whom total proteinuria and urine α1-microglobulin (a marker of tubular injury) have been measured. Association with mortality was evaluated with a follow-up until May 7th 2020. Results: According to the Kidney Disease Improving Global Outcomes staging, 14% (n=21) had stage 1 proteinuria (<150 mg/g of urine creatinine), 42% (n=64) had stage 2 (between 150 and 500 mg/g) and 44% (n=68) had stage 3 (over 500 mg/g). Urine α1-microglobulin concentration was higher than 10 or 15 mg/g in 94% and 89% of patients, respectively. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urine α1-microglobulin (as continuous and/or categorical variables) were associated with mortality in unadjusted and adjusted models. This association was even stronger in subgroups of patients with normal renal function or without urinary catheter. Conclusions: Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin with increased urine α1-microglobulin. Tubular proteinuria seems associated with mortality in COVID-19.

Association of AKI-D with Urinary Findings and Baseline eGFR in Hospitalized COVID-19 Patients

“…While mechanistic evaluation with kidney biopsies was not reported in our study, we feel that our data implicate a tubulointerstitial pattern of damage caused by the SARS-CoV2 virus, resulting in non-albumin proteinuria, trace glucosuria, and hematuria 20,27,28 . 25.5% of AKI-D patients had nephrotic-range proteinuria in our study, supporting what others have shown to be a range of kidney injury pathologies in COVID-19 including both tubular injury and glomerular processes [29][30][31][32][33][34][35][36][37][38] .…”

“…Notably, the incidence of proteinuria and hematuria may actually exceed that of AKI, raising the possibility that urinary abnormalities could serve as an earlier or more sensitive marker of disease 16 . Others have demonstrated an association of proteinuria and hematuria with mortality in the setting of COVID-19 4,[17][18][19][20][21][22][23][24][25] . However, to our knowledge, there has been only one other publication evaluating the association of proteinuria with the need for dialysis in 84 patients with formal urine protein/creatinine ratios 26 .…”

COVID-19–associated Nephropathy Includes Tubular Necrosis and Capillary Congestion, with Evidence of SARS-CoV-2 in the Nephron

“…COVID-19 is a novel nosological entity, with a broad clinical spectrum. The early description of the entity logically focused on lung involvement, although an increasing number of reports have progressively highlighted the impact of the SARS-CoV-2 on other organs including the kidneys 3,[6][7][8] . Furthermore, correlations between extra-respiratory viral tropism, disease severity, and increased risk of premature death within the first 3 weeks of disease have been highlighted 7 .…”

“…The earliest report showed that proteinuria and hematuria were detected at hospital admission in 43.9% and 26.7% of patients with COVID-19, while ~15% of them presented with elevated levels of serum creatinine and/or blood urea nitrogen 5 . Proteinuria characterization suggests a tubular origin 8 . Acute kidney injury (AKI) has been identified as an independent risk factor for in-hospital mortality [3][4][5]9 .…”

Survivors of COVID-19 mostly recover from tubular proteinuria and acute kidney injury after hospital discharge

“…Proteinuria might result from a proximal tubular dysfunction. COVID-19-induced AKI and proteinuria have been associated with poor short-term outcomes in hospitalized patients [2,3]. However, the middle-and long-term consequences of SARS-CoV-2 infection on kidney function remain unknown.…”