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      Acute kidney injury is associated with severe infection and fatality in patients with COVID-19: a systematic review and meta-analysis of 40 studies and 25,278 patients

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          Abstract

          Currently, coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. This study aimed to investigate whether the presence of acute kidney injury (AKI) might increase the risk of severe infection and fatality in COVID-19 patients. We searched the PubMed, Web of Science, ScienceDirect, MedRxiv and COVID-19 academic research communication platforms for studies reporting severe infection rates and case-fatality rates in COVID-19 patients with and without AKI up to June 20, 2020. The main outcomes were the comparisons of the severe infection rates and fatality rates in COVID-19 patients with and without AKI and the estimation of the odds ratio ( OR) and its 95% confidence interval (CI) for severe infection and mortality. Statistical analyses were performed with R statistical software. A total of 40 studies involving 25,278 patients with COVID-19 were included in our meta-analysis. The incidence of AKI was 10% (95% CI 8%–13%) in COVID-19 patients. The patients had higher severe infection and fatality rates (55.6% vs. 17.7% and 63.1% vs. 12.9%, respectively, all P <  0.01) with COVID-19. AKI was a predictor of fatality ( OR = 14.63, 95% CI: 9.94 – 21.51, P < 0.00001) and severe infection ( OR = 8.11, 95% CI: 5.01-13.13, P <  0.00001) in patients with COVID-19. Higher levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were associated with a significant increase in fatality [Scr: mean difference (MD): 20.19 μmol/L, 95% CI: 14.96–25.42, P < 0.001; BUN: MD: 4.07 mmol/L, 95% CI: 3.33–4.81, P < 0.001] and severe infection (Scr: MD: 7.78 μmol/L, 95% CI: 4.43–11.14, P < 0.00001, BUN: MD: 2.12 mmol/L, 95% CI: 1.74–2.50, P < 0.00001) in COVID-19 patients.

          In conclusion, AKI is associated with severe infection and higher fatality rates in patients with COVID-19. Clinicians should pay more attention to the monitoring and treatment of COVID-19 patients with AKI.

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          Most cited references65

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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                Author and article information

                Contributors
                Journal
                Pharmacol Res
                Pharmacol. Res
                Pharmacological Research
                Published by Elsevier Ltd.
                1043-6618
                1096-1186
                31 July 2020
                31 July 2020
                : 105107
                Affiliations
                [a ]Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
                [b ]Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
                Author notes
                [* ]Corresponding authors at: Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, No.137, South Liyushan Road, Xinshi Zone, Urumqi, Xinjiang, China. luojunyi3130@ 123456126.com yangyn5126@ 123456163.com
                [1]

                The first two authors contributed equally to this work.

                Article
                S1043-6618(20)31415-8 105107
                10.1016/j.phrs.2020.105107
                7393179
                32739424
                e3548fb9-179d-47b0-8902-e0b7619def89
                © 2020 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 18 May 2020
                : 10 July 2020
                : 22 July 2020
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                covid-19,acute kidney injury,disease severity,fatality,meta-analysis

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