Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives

Abstract

Since the outbreak of COVID-19 disease, a bidirectional interaction between kidney disease and the progression of COVID-19 has been demonstrated. Kidney disease is an independent risk factor for mortality of patients with COVID-19 as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with COVID-19. However, the detection of kidney damage in patients with COVID-19 may not occur until an advanced stage based on the current clinical blood and urinary examinations. Some studies have pointed out the development of subclinical acute kidney injury (subAKI) syndrome with COVID-19. This syndrome is characterized by significant tubule interstitial injury without changes in the estimated glomerular filtration rate. Despite the complexity of the mechanism(s) underlying the development of subAKI, the involvement of changes in the protein endocytosis machinery in proximal tubule (PT) epithelial cells (PTECs) has been proposed. This paper focuses on the data relating to subAKI and COVID-19 and the role of PTECs and their protein endocytosis machinery in its pathogenesis.

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

“…In contrast, biomarkers of kidney damage, particularly NGAL, more clearly signified renal aggression, whatever the cause, likely to lead to AKI, and consequently its performance in predicting such cases was better. Thus, our results and those of others [ 12 , 37 , 40 , 41 ] suggest to use urinary biomarkers to better define renal involvement in COVID-19, reflecting the heterogeneity in the clinical presentation and severity and including subclinical AKI which concerned almost 20% of our cohort.…”

“…Our observations corroborate the existence of a continuum in the spectrum of COVID-19 associated AKI [ 4 , 24 , 39 ]. Indeed, some patients may present only subclinical AKI syndrome characterized by significant tubule injury (particularly, changes in the protein endocytosis machinery in proximal tubule epithelial cells) without changes in the glomerular filtration rate [ 12 , 37 , 40 , 41 ] while others may exhibit AKI related to various mechanisms [ 4 , 24 , 39 ]. This approach may explain why we found that proximal tubular dysfunction was a sensitive marker for detecting persistent AKI, but its specificity was relatively low and, conversely, it appeared less sensitive for identifying transient AKI.…”

Case Report: Multisystem inflammatory syndrome in children with associated proximal tubular injury

“…Subclinical AKI, defined as the presence of kidney dysfunction not meeting the criteria for AKI, has been described in SARS-CoV-2 infection. Even if clinical data are still poorly known, especially in MIS-C, it seems to be correlated to a more severe course of the disease ( 18 ). Our patient experienced a subclinical AKI by presenting, at admission, serum creatinine values that were double those when discharged.…”

Urine Parameters in Patients with COVID-19 Infection

“…Especially in those patients requiring ICU support, AKI is associated with poor prognosis and increased risk of mortality. As a result of the studies mentioned above, we have observed that many laboratory parameters are useful as potential biomarkers to predict renal damage associated with COVID-19 [ 15 , 17 , 21 , 22 , 23 , 24 , 27 , 30 , 48 , 49 , 50 ].…”