key: cord-0923294-b4ay5vyp authors: Xu, S.; Fu, L.; Fei, J.; Xiang, H.-X.; Xiang, Y.; Tan, Z.-X.; Li, M.-D.; Liu, F.-F.; Li, Y.; Han, M.-F.; Li, X.-Y.; Yu, D.-X.; Zhao, H.; Xu, D.-X. title: Acute kidney injury at early stage as a negative prognostic indicator of patients with COVID-19: a hospital-based retrospective analysis date: 2020-03-26 journal: nan DOI: 10.1101/2020.03.24.20042408 sha: c6d952ab85aab233d282487552404d981a55f05b doc_id: 923294 cord_uid: b4ay5vyp Coronavirus disease 2019 (COVID-19) is a newly emerged infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been pandemic all over the world. This study described acute kidney injury (AKI) at early stage of COVID-19 and its clinical significance. Three-hundred and fifty-five COVID-19 patients with were recruited and clinical data were collected from electronic medical records. Patient's prognosis was tracked and risk factors of AKI was analyzed. Of 355 COVID-19 patients, common, severe and critical ill cases accounted for 63.1%, 16.9% and 20.0%, respectively. On admission, 56 (15.8%) patients were with AKI. Although AKI was more common in critical ill patients with COVID-19, there was no significant association between oxygenation index and renal functional indices among COVID-19 patients with AKI. By multivariate logistic regression, male, older age and comorbidity with diabetes were three important independent risk factors predicting AKI among COVID-19 patients. Among 56 COVID-19 patients with AKI, 33.9% were died on mean 10.9 day after hospitalization. Fatality rate was obviously higher among COVID-+19 patients with AKI than those without AKI (RR=7.08, P<0.001). In conclusion, male elderly COVID-19 patients with diabetes are more susceptible to AKI. AKI at early stage may be a negative prognostic indicator for COVID-19. Since December 2019, a cluster of acute respiratory illness patients with unclear causes were found in several hospitals in Wuhan city, Hubei province, China (WHO. Novel coronavirus China. 2020; https://www.who.int/csr/don/12-january-2020-novelcoronavirus-china/en/ ). On February12, 2020, the International Committee on SARS-CoV-2 is mainly transmitted by droplets or direct contact and infected through respiratory tract 2 . In addition, SARS-CoV-2 can also be transmitted by feces 3 . Accumulating data demonstrate that SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) to enter human cells, mainly pulmonary epithelial cells, and probably cardiomyocytes and renal tubular epithelial cells [4] [5] [6] . The main symptoms and signs of COVID-19 patients are fever, companied by dry cough, dyspnea, diarrhea, fatigue and lymphopenia [7] [8] [9] [10] [11] . Although only a few cases died in mild COVID-19 patients, death risk was rapidly increased among critical ill patients with the fatality rate even more than 50% 12 . A large number of clinical data have revealed that infection with SARS-CoV-2 not only causes severe acute respiratory syndrome but also multiple organ injuries, including myocardial dysfunction, hepatic injury and even acute renal failure (AKI) 13 . Nevertheless, what factors influence the multiple organ injuries, especially AKI, during the pathogenesis of COVID-19 remains unclear. Moreover, the clinical significance of AKI needs to be further clarified. The objective of this study is to describe the clinical and laboratory features of AKI at early stage of 355 COVID-19 patients in two hospitals from different regions. We showed that male elderly COVID-19 patients with diabetes mellitus were more susceptible to AKI. We provide evidence that the development of AKI at early stage may be a potential negative prognostic indicator for survival of COVID-19 patients. In the present study, 200 patients, who were diagnosed as COVID-19 from January The medical record of each COVID-19 patient was evaluated. Following data were collected from the electronic medical records: demographic information, preexisting comorbidities, including chronic obstructive pulmonary disease, hepatic disease, cardiovascular disease, hypertension, diabetes and other disease. Patient's signs and symptoms, chest computed tomographic (CT) scan and laboratory test results were also collected. The dates of onset, admission and death were recorded. The onset time was defined as the date when patients' any symptom and sign were found. Patient's pharyngeal swab specimens were collected for extraction of SARS-CoV- All statistical analyses were performed using SPSS 22.0 software. Categorical variables were expressed with frequencies and percentages. Continuous variables were shown using median and mean values. Means for continuous variables were compared with independent-samples t tests when the data were normally distributed; if not, the Mann-Whitney test was used. Proportions for categorical variables were compared with the chi-square and Fisher's exact test. Univariable logistic regression between basic disease or different parameter and demise was performed. Moreover, the main risks related with demise were examined using multivariable logistic regression models adjusted for potential confounders. Statistical significance was determined at P＜0.05. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . https://doi.org/10.1101/2020.03.24.20042408 doi: medRxiv preprint The clinical characteristics of 355 COVID-19 patients were analyzed. The most common symptom of COVID-19 patients was fever (75.0%), followed by cough (48.5%), diarrhea (36.6%) and fatigue (32.1%). Of 355 patients, common cases, defined as oxygenation index higher than 300, accounted for 63.1% (224/355). Severe cases, whose oxygenation index was from 200 to 300, accounted for 16.9% (60/355). Critical ill cases, oxygenation index lower than 200, accounted for another 20.0% (71/355). Moreover, 50.1% COVID-19 patients had at least one of comorbidity with either diabetes (41.4%) or hypertension (35.2%). The blood routine indices were analyzed. As shown in Table 1 , mean WBC count was 5.67×10 9 /L. In addition, mean neutrophil and lymphocyte counts was 4.21×10 9 /L and 1.02×10 9 /L, respectively ( In addition, 33% COVID-19 patients have hemoglobin below normal range (Table 1) . Hepatic functional indices were then analyzed. As shown in Table 1 , the levels of serum total bilirubin, direct bilirubin, total protein and albumin were 14.16 μmol/L, 5.17 μmol/L, 67.30 g/L and 38.53 g/L, respectively. Moreover, serum ALT and AST were 35.03 and 40.76 U/L, respectively. As shown in Table 1 , 25.6% COVID-19 patients have ALT above normal range. In addition, 28.7% COVID-19 patients have AST above normal range. Next, myocardial functional indices are shown in Table 1 . Mean creatine kinase, LDH and D-dimer were 257.69 U/L, 296.42 U/L and 2762.41 μg/L, respectively. As shown in Table 1 , 45.6% COVID-19 patients have LDH above normal range. In addition, 71.8% COVID-19 patients have D-dimer above normal range. Renal functional indices, as determined by serum creatinine, urea nitrogen and uric acid, were measured among 355 COVID-19 patients. As shown in Table 1 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . Table 2 , the levels of serum creatinine, urea nitrogen and uric acid were higher in critical ill patients than those of mild patients. In addition, the levels of serum urea nitrogen were higher in severe patients than those of mild patients ( Table 2 ). The correlationship between oxygenation index and renal functional indices was then analyzed. There was no significant association between oxygenation index and all renal functional indices among COVID-19 patients with AKI ( Fig.1A-C) . As shown in Fig. 1 , a negative correlation was observed between oxygenation index and blood urea nitrogen among COVID-19 patients without AKI. There was no significant association between oxygenation index and creatinine as well as uric acid among COVID-19 patients without AKI (Fig.1D-E) . AKI was defined as any of renal functional indices beyond normal range 14 The effects of different genders on renal functional indices were analyzed. As shown in Table 3 , the levels of serum creatinine, urea nitrogen and uric acid were higher in males than those of females. The effects of ages on renal functional indices were then analyzed. As shown in Table 3 , the levels of serum urea nitrogen were higher in patients over 70 years old than those from 50 to 69 years old and under 50 years old (Table 3) . Moreover, the levels of serum urea nitrogen were higher in patients from 50 to 69 years old than those under 50 years old (Table 3 ). In addition, the levels of serum creatinine and uric acid were higher in patients over 70 years old than those under 70 years old (Table 3 ). The effects of comorbidity with either hypertension or diabetes on renal functional indices are shown in Table 4 . The levels of serum creatinine, urea nitrogen and uric acid were higher in COVID-19 patients with diabetes than those without diabetes. No significant difference on serum creatinine, urea nitrogen and uric acid was observed between COVID-19 patients with hypertension and without hypertension ( (Table 5) . An early study found that SARS patients with AKI were at an increased death risk 17 . In the present study, we analyzed the association of AKI with death risk of COVID-19 patients. Among 56 subjects with AKI on admission, about a third of patients died on mean 10.9 day after hospitalization. The fatality rate was obviously higher among COVID-19 patients with AKI than those without AKI. These results provide evidence that AKI at the early stage elevated death risk of COVID-19 patients. The mechanism by which SARS-CoV-2 injection induces AKI is likely to be multifactorial. Several reports showed that most COVID-19 patients were companied with multiple organ damage 9, 14 . However, the present study found that there was no significant association between oxygenation index and all measured renal functional indices among COVID-19 patients with AKI, suggesting that SARS-CoV-2-induced AKI is independent of respiratory failure. Two early reports showed that ACE2, as a receptor for SARS-CoV-2, was highly expressed in renal tubular epithelium 18, 19 . Another early study found that SARS viral particles were detected in the epithelium of the renal distal tubules 20 . Therefore, the present study does not exclude that SARS-CoV-2 induces AKI through directly infecting renal epithelium. Further experiments are required to explore whether renal tubular epithelium is another target of SARS-CoV-2 injection. In summary, the present study described the clinical and laboratory characteristics of AKI among 355 COVID-19 patients in two hospitals from different regions. Our results showed that AKI was more common in critical ill patients with COVID-19. Moreover, male elderly COVID-19 patients with diabetes mellitus were more susceptible to AKI. We found that AKI at the early stage elevated death risk of COVID-19 patients. We provide evidence that the development of AKI at the early stage may be a potential negative prognostic indicator for survival of COVID-19 patients. Therefore, the improvement of renal function is beneficial for elevating the survival rate of COVID-19 patients especially critical ill patients. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2 Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a singlecentered, retrospective, observational study Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study Clinical features of patients infected with 2019 novel coronavirus in Wuhan Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention Acute renal impairment in coronavirus-associated severe acute respiratory syndrome A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9 Renal ACE2 expression in human kidney disease Multiple organ infection and the pathogenesis of SARS City for recruiting participators.