4.4 Acute kidney injury in COVID-19
Acute kidney injury is one of the severe complications in COVID-19 patients(Huang et al. , 2020) because ACE2 is abundantly expressed in kidney and the activity of ACE2 is even higher in the renal cortex than renal medulla(Wysocki et al. , 2010). The prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high(Cheng et al. , 2020). ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts by analyzing ACE2 expression on the online datasets(Fan et al. , 2020). The expression of ACE2 has been confirmed to be related with acute kidney injury and several models of chronic kidney disease induced by hypertension(Fang et al. , 2013; Soler et al. , 2013). ACE2 has emerged as a protective molecule against kidney diseases(Oudit et al. , 2009). ACE2 knockout can lead to blood pressure rise, glomerular injury and renal fibrosis in diabetic mice(Liu et al. , 2017). Meanwhile, deletion of ACE2 leads to late-onset nephrotic glomerulosclerosis spontaneously(Ouditet al. , 2006). On the contrary, the increase of Ang Ⅱ in the damaged renal tubules may be a possible mediator for further renal damage in human renal diseases. Ferrario found that ACE2 in renal cortex activity was significantly augmented in rats medicated with ACEI/ARB but not changed in the group which given the combination(Ferrario et al. , 2005). Furthermore, the high plasma levels of Ang (1-7) also have effects in the kidney. Ang (1-7) administration attenuated kidney injury without affecting blood glucose levels in Akita mice(Shi et al. , 2015). In addition, Ang (1-7) could ameliorated the renal injury of nephrectomized rats, and the combination of Ang (1-7) treatment alongside losartan exerted a superior effect to that of Ang (1-7) alone on regression of glomerulosclerosis(Xu et al. , 2013). The physiological effects reported for alamandine, the novel RAAS mediator, were similar to Ang (1-7), including vasodilation, anti-fibrosis, anti-inflammation and so on. The higher alamandine in plasma was associated with the renal size and functions(Paquette et al. , 2018). At the same time, alamandine level in plasma of patients was fluctuating and was related with chronic renal failure(Hrenak et al. , 2016). In conclusion, clinicians should pay attention to the risk of testicular lesions in patients of COVID-19.