key: cord-0993005-lcgdzvgg
authors: Cai, Xiaoyue; Wu, Guiming; Zhang, Jie; Yang, Lichuan
title: Letter to the Editor: Risk factors for acute kidney injury in adult patients with COVID-19
date: 2021-10-01
journal: Nefrologia
DOI: 10.1016/j.nefro.2021.09.007
sha: dbd3e9e808d4a5e61cbd2a80f6737690a2b7a59d
doc_id: 993005
cord_uid: lcgdzvgg

nan

To the Editor, Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Studies found that the incidence of acute kidney injury (AKI) in COVID-19 patients was more than double the incidence of AKI in non-COVID-19 patients [1] . Some findings confirmed that AKI is a strong independent risk factor for mortality in patients with COVID-19 and is associated with a 3-fold increase in the odds of in-hospital mortality [2] .

However, little information is available about AKI in COVID-19 patients. We aimed to analyse the risk factors for AKI in adult patients with COVID-19.A systematic literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, VIP and WanFang Data from 1 December 2019 to 30 January 2021. Search strategy as shown in Table 1 , We extracted data from eligible studies to compare the effects of age, sex, chronic diseases and potential risk factors for AKI on the prognosis of adult patients with COVID-19. A total of 38 eligible studies involving 42,779 patients were ultimately enrolled in our study. The characteristics of the included studies are described in Table 2 . The Newcastle-Ottawa Scale (NOS) was used as a bias assessment tool for cohort studies and case-control studies, and a score > 7 indicated good quality.The meta-analysis was performed using RevMan 5.4.

The meta-analysis showed that male sex ( "2019-nCoV" or "SARS-CoV-2" or "COVID-19" or "coronavirus disease 2019" #2 "acute kidney injury" or "acute kidney failure" or "acute renal failure" or "acute renal injury" or "AKI" #3 "risk factor" or "influence factor" Search #1 and #2 and #3 Data are presented as the means ± SD, n (%) or median (interquartile range). COPD, chronic obstructive pulmonary disease; CVD, cardiovascular diseases; CKD, chronic kidney disease; NA, data not available.

Our study found that male sex, age, smoking, obesity, hypertension, diabetes, pneumopathy, cardiovascular disease, cancer, CKD, mechanical ventilation and use of vasopressors were independent risk factors for AKI in adult patients with COVID-19. To our knowledge, this study had the largest number of included studies and the largest sample size. Currently, the mechanism underlying kidney injury in patients with COVID-19 is believed to involve SARS-CoV-2 directly attacking intrinsic renal cells. Invasion by SARS-CoV-2 causes the T lymphocyte count to decrease, especially CD4+T cells and CD8+T cells, and the levels of IL-6, IL-10, IL-2, and interferon to increase [3] . These inflammatory cytokine levels are increased due to the recruitment and infiltration of inflammatory cells and participate in tissue damage and repair, resulting in cell, tissue and organ oedema and other injuries. SARS-CoV-2 can penetrate the proximal tubule by connecting ACE2 to CD147 and can also penetrate podocytes by linking ACE2 [4] . SARS-CoV-2 results in an imbalance in renin-angiotensin system (RAS) activation and promotes the progression of glomerular dysfunction, fibrosis, vasoconstriction, and inflammation [5] .

Many comorbidities in the elderly population, such as hypertension, diabetes and CKD, are treated with ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), which upregulate ACE2, thereby increasing the risks of SARS-CoV-2 infection and severe disease. The proliferative ability of stem cells, which play an important role in renal cell repair, gradually decreases with age [6] . Our study showed that age was an independent risk factor for AKI; the older the patient was, the higher the risk of AKI. Recently, CKD emerged as the most common risk factor for severe COVID-19, and alarmingly, after age, it is also the strongest risk factor for severe COVID-19 [7] . The removal of CKD as a risk factor would decrease the percentage of the global population at increased risk of severe COVID-19 from 22% to 17% [8] .

Some studies have shown that the protein expression level of ACE2 in smokers is significantly higher than that in non-smokers. This may be evidence that a history of smoking is a risk factor for AKI in patients with COVID-19. We also found that hypertension, diabetes and cardiovascular disease were independent risk factors for AKI, and these comorbidities were associated with micro-and macrovascular complications, all of which affected the renal blood flow. Any minor haemodynamic or nephrotoxic insult can lead to substantial AKI in these patients. Related studies have reported that AKI is a common complication in patients with malignant tumours, and the incidence of AKI in such patients is as high as 30%, which may be attributed to the renal toxicity of anti-cancer regimens [9] . Our study also confirms that mechanical ventilation is a risk factor for AKI in adult patients with COVID-19. Mechanical ventilation can increase the pressure in the thoracic cavity, resulting in reduced venous return, decreased cardiac output and decreased renal perfusion. In addition, mechanical ventilation can also induce proinflammatory reactions, change the neuro-humoural system, affect glomerular filtration, and cause or promote the occurrence and development of AKI [10] .

Although we identified 11 risk factors for AKI, we believe that there are more potential risk factors for AKI that need to be investigated in future studies. Early identification and early intervention can reduce the occurrence of AKI and further improve the prognosis of patients with COVID-19.

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Acute kidney injury associated with COVID-19: A retrospective cohort study

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

Reninangiotensin-aldosterone system inhibitors in patients with COVID-19

Meta-analysis of risk factors for acute renal injury in patients with septic shock

Factors associated withCOVID-19-related death using OpenSAFELY

Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Acute kidney injury in patients with cancer

Sepsis associated acute kidney injury