Role of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C in Prediction of Acute Kidney Injury in Patients With Covid-19 Infection

Since December 2019, a novel coronavirus called SARSCoV-2 (severe acute respiratory syndrome coronavirus 2) has caused an international outbreak of respiratory illness described as COVID-19. Among 85 patients with COVID-19 an incidence of acute kidney injury was reported to be 23%. The kidney histology from autopsies of six patients showed severe acute tubular necrosis with macrophage and lymphocyte infiltration. Another important paper revealed prominent acute proximal tubular injury, accumulation of peritubular erythrocyte and glomerular fibrin microthrombi after autopsy. However, this kidney injury was not detected by routine measures (creatinine and/or BUN) in some patients denoting subclinical kidney injury. The pathophysiology of AKI associated with COVID-19 could be due to specific mechanisms such as direct cell injury from viral entrance through highly expressed renal ACE2 receptors. Also pro-inflammatory cytokines, an imbalanced renin-angotensin-aldosterone system and thrombotic events are accused in renal damage. Non-specific mechanisms include hypovolemia, haemodynamic changes, right heart failure, high levels of PEEP in mechanically ventilated patients, nephrotoxic drugs and nosocomial infections. A significant association between kidney failure and death was documented in five studies. Hypoxemia and impairment of gas exchange has been identified as elements associated with AKI in patients with acute respiratory distress syndrome (ARDS).

Studies focusing on AKI with COVID-19 are needed urgently in order to identify the mechanism of renal affection and to predict the risk of AKI. Pharmaceutical industries with academia have made a lot of progress in the field of sensitive and specific preclinical biomarkers of kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is composed of 178 amino acids. this glycoprotein is reabsorbed in the proximal tubules after its filtration through the glomeruli.

In a mouse model of renal ischemia, NGAL gene was rapidly expressed and upregulated within 3 hours of injury. The NGAL mRNA level increased more than 1000-fold 24-48 hours after injury. Thus, NGAL can be a useful tool to diagnose infection mediated AKI. Nonglycosylated Cystatin C is a protein produced by nucleated cells at constant rate. It is easily filtered through the glomeruli due to its positive charge at physiological pH and its low molecular weight. Then, it is reabsorbed and completely catabolized in the proximal tubules. Use of serum cystatin C as a marker of glomerular filtration rate (GFR) is well documented, and some authors have suggested that it may be more accurate than serum creatinine for this purpose. Complete evaluation of the clinical and laboratory picture of COVID-19 associated AKI is crucial to design preventive strategies and to suggest targeted interventions