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      Subclinical Acute Kidney Injury in COVID-19 Patients: A Retrospective Cohort Study


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          Dear Editor, We read with great interest the recent article “COVID-19 Infection in a Patient with End-Stage Kidney Disease” by Fu et al. [1]. Previous studies have reported that ∼10% of infected patients may develop acute kidney injury (AKI), which is a strong prognostic factor increasing risk of death [2, 3, 4]. We agree with the authors that SARS-CoV2 affects the kidney function and special care of renal function should be taken into account in COVID-19 patients. However, the current definition of AKI does not provide a measurement of loss of kidney function because serum creatinine level is not a sensitive marker of early tubular injury (elevation of serum creatinine requires damage/dysfunction of >50% of the nephron mass), whereas biomarkers of tubular injury provide information on early kidney injury and response to noxious stimuli [5]. All COVID-19 infection patients without a prior history of chronic kidney disease included in our study (n = 32) were consecutively admitted to our hospital in February, who were confirmed, classified as 3 subtypes (common, severe, and critical), and discharged from our hospital based on the guidelines for the diagnosis and treatment of novel coronavirus disease (version 6) [6]. Most of these patients had mean levels of estimated glomerular filtration rate (eGFR) within the normal range, whereas 31.3% (n = 10) had proteinuria, 9.4% (n = 3) had macroalbuminuria, and 12.5% (n = 4) had microalbuminuria (Table 1). The proportion of patients with increased urinary levels of β2-microglobulin (β2MG), α1-microglobulin (α1MG), retinol binding protein (RBP), and N-acetyl-β-d-glucosaminidase (NAG) levels were 20, 20, 10, and 10%, respectively. On the first day of hospital admission, there were no significant differences in mean levels of serum creatinine, blood urea nitrogen, and eGFR among the common, severe, and critical subtypes. However, the proportion of albuminuria as well as the levels of urinary β2MG-creatinine ratio, α1MG-creatinine ratio, RBP-creatinine ratio, and NAG-creatinine ratio significantly increased according to the severity of disease. During the hospital stay, the proportion of proteinuria (dipstick >1+) in critically ill COVID-19 patients was significantly higher than that observed in common COVID-19 patients on the first check and gradually improved during the patients' hospital admission (Fig. 1). No significant differences were observed in the mean levels of eGFR both on the first day of admission and during the hospital stay amongst the 3 patient subtypes. Furthermore, Kaplan-Meier survival curves showed that patients with elevated urinary β2MG and α1MG levels had significantly lower rates of hospital discharge compared to those with normal urinary β2MG and α1MG levels. In conclusion, we suggest that COVID-19 infection may induce early development of abnormal albuminuria and impair kidney tubular function. Because SARS-CoV-2 has been isolated from urinary samples of an infected patient and the receptor of this virus is the angiotensin converting enzyme II which is expressed on podocytes and proximal straight tubule cells [4, 7]. Notably, podocytes and proximal straight tubule cells are particularly vulnerable to viral attacks, and our findings suggested that the excretion of these urinary biomarkers may be related to the severity of the infection. Therefore, more careful medical surveillance of urinary biomarkers of early AKI is required in COVID-19-infected patients because early detection and treatment can slow or prevent progression of kidney disease. Disclosure Statement The authors have no conflicts of interest to declare. Funding Sources This work was supported by grants from the National Natural Science Foundation of China (81500665), High Level Creative Talents from Department of Public Health in Zhejiang Province and Project of New Century 551 Talent Nurturing in Wenzhou. G.T. is supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. C.D.B. is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK. Author Contributions Dan-Qin Sun and Ming-Hua Zheng conceived and designed the study; Ting-Yao Wang and Yong-Ping Chen collected the data; Dan-Qin Sun and Ting-Yao Wang analyzed and interpreted the data; Dan-Qin Sun and Kenneth I. Zheng drafted the manuscript; Giovanni Targher and Christopher D. Byrne reviewed and edited the manuscript. All authors contributed to the manuscript for important intellectual content and approved the submission.

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

          Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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            The Novel Coronavirus 2019 Epidemic and Kidneys

            I. Introduction II. Diagnosis III. Kidney involvement in COVID-19 infection IV. Pathogenesis of kidney injury V. Treatment A. General management B. Antiviral therapy C. Extracorporeal treatments D. Glucocorticoids E. Convalescent plasma F. Monoclonal antibody VI. COVID-19 in patients with kidney disease VII. Management of patients on dialysis VIII. Operational strategies for family member and caregivers IX. References Introduction Novel coronavirus disease (COVID-19) is a newly discovered contagious disease caused by SARS-CoV-2 virus, primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, but can affect multiple organs such as kidney, heart, digestive tract, blood and nervous system 1 . The rapidly spreading outbreak which first emerged in Wuhan, Hubei Province in China in December 2019 has raised concerns about a global pandemic. To date (2 March 2020), 88,948 cases of COVID-19 have been reported worldwide in 65 countries (and a cruise ship) and 79,842 in mainland China, with 3,043 deaths worldwide (mainland China 2,915 deaths). 2 SARS-CoV-2 has been identified as a bat-origin coronavirus (CoV). The full-length genome sequence of the COVID-19 virus showed a close relationship with the bat SARS-like coronavirus strain BatCov RaTG13 belonging to the Betacoronavirus genus. 3 Previous coronavirus infections, severe acute respiratory syndrome (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-Co-V), have infected more than 10,000 people in the past 2 decades, with mortality rates of 10% and 37% respectively 4 , 5 . COVID-19 is more contagious than these illnesses, spreads by human-to-human transmission via droplets, fecal or direct contact, and has an incubation period estimated at 1 to 14 days (usually 3 to 7 days). Infection has been reported in all ages, including children. The majority of infections are mild, presenting with a flu-like illness. The common clinical presentations of COVID-19 are fever (98%), cough (76%), and myalgia and fatigue (18% each) 6 , with accompanying leucopenia (25%) and lymphopenia (63%). Symptoms of upper respiratory infection with rhinorrhea and productive cough are uncommon, except in children. About 16-20% cases have been classified as ‘severe’ or ‘critical’. Of the 41 patients described by Huang et al 6 , all had pneumonia with abnormalities on computerized tomographic examination of the chest (bilateral lobular and subsegmental areas of consolidation), and 32% required ICU care. Higher plasma cytokine levels (IL2, IL7, IL10, GSCF, IP10, MCP1, MIPIA, TNFα) were present in patients requiring ICU admission. Limited reports suggest that severe complications are uncommon in children. 7 Diagnosis The diagnosis is mainly based on epidemiological factors (history of contact), clinical manifestations, and laboratory examination (hemogram, chest CT and virological examination, etc) 8 . Of note, there are recent cases without any travel history or apparent contact with infected individuals. Several COVID-19 nucleic acid detection assays have been developed, both in-house and commercial. They use fluorescence PCR, and probe anchoring polymerization technique. Gene sequencing has also been utilized. The World Health Organization has appointed several referral laboratories in different countries. 9 A serological test has been developed and allowed detection of a cluster of cases in Singapore 10 . More sensitive and convenient detection methods continue to be developed. Kidney involvement in COVID-19 infection In previous reports of SARS and MERS-CoV infections, acute kidney injury (AKI) developed in 5-15% cases and carried a high (60-90%) mortality. Early reports suggested a lower incidence (3-9%) of AKI in those with COVID-19 infection 1 , 11, 12, 13. Recent reports, however, have shown higher frequency of renal abnormalities. A study of 59 patients with COVID-19 found that 34% of patients developed massive albuminuria on the first day of admission, and 63% developed proteinuria during their stay in hospital 14 . BUN was elevated in 27% overall and two thirds of patients who died. CT scan of the kidneys showed reduced density, suggestive of inflammation and edema. Cheng et al 13 recently reported that amongst 710 consecutive hospitalized patients with COVID-19, 44% had proteinuria and hematuria and 26.7% had hematuria on admission. The prevalence of elevated Scr and BUN were 15.5% and 14.1% respectively. AKI was an independent risk factor for patients’ in-hospital mortality 13 , 14 . Pathogenesis of kidney injury The exact mechanism of kidney involvement is unclear: postulated mechanisms include sepsis leading to cytokine storm syndrome or direct cellular injury due to the virus. Angiotensin converting enzyme and dipeptidyl peptidase 4, both expressed on renal tubular cells, were identified as binding partners for SARS-CoV and MERS-CoV respectively 15 , 16 . Viral RNA has been identified in kidney tissue and urine in both infections 17 , 18 . Recently, Zhong’s lab in Guangzhou has successfully isolated SARS-CoV-2 from the urine sample of an infected patient, suggesting the kidney as the target of this novel coronavirus 19 . Treatment The current treatment of COVID-19 with AKI includes general and supportive management, and kidney replacement therapy. There is no effective anti-viral therapy available at present. General management All the patients with confirmed COVID-19 should be quarantined. A N-95 fit-tested respirator and protective clothes and equipment are essential. Early admission to ICUs in designated hospitals is recommended for severely ill patients. Supportive care, namely bed rest, nutritional and fluid support, maintenance of blood pressure and oxygenation are important measures, as for all critically ill patients. Other measures include prevention and treatment of complications by providing organ support, maintaining hemodynamic stability and prevention of secondary infection. Antiviral therapy There is no specific effective antiviral drug for COVID-19 at present. The guidelines of the Chinese National Health Commission recommend aerosolized inhalation of interferonα, and Lopinavir/Ritonavir. The specific therapeutic value and safety of Lopinavir/Ritonavir in COVID-19 patients is under investigation (ChiCTR2000029308)20. Successful treatment with remdesivir has been reported in a COVID-19 patient; a clinical trial on the efficacy of remdesivir in COVID-19 patients is currently underway in China (NCT0425266; NCT04257656) and is expected to be completed in April 2020. Chloroquine phosphate has been shown to have some efficacy against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. 21 Extracorporeal treatments CRRT has been successfully applied in the treatment of SARS, MERS and sepsis 22 , 23 . High-volume hemofiltration (HVHF) in a dose of 6L/hr removed inflammatory cytokines (IL-6) and improved the SOFA (Sequential Organ Failure Assessment) scores at day 7 in patients with sepsis 24 . Therefore, CRRT may play a role in patients with COVID-19 and sepsis syndrome. The potential role of extracorporeal therapy techniques needs to be evaluated, however. Glucocorticoids In a retrospective study of patients with SARS-CoV and sepsis, steroids, in a mean daily dose of 105.3 +/- 86.1 mg in 147 of 249 noncritical patients (59.0%) reduced mortality and shortened duration of hospitalization, while 121 of 152 critical patients (79.6%) received corticosteroids at a mean daily dose of 133.5 +/- 102.3 mg, and 25 died 25 . A subsequent retrospective observational study of 309 MERS patients showed that those who received high dose steroids were more likely to require mechanical ventilation, vasopressors and RRT 26 . In a metanalaysis of corticosteroid use in SARS patients, 4 studies provided conclusive evidence of harm (psychosis, diabetes, avascular necrosis and delayed viral clearance) 27 . Therefore, the use of steroids is controversial and not recommended by WHO due to potential inhibition of viral clearance and prolongation of the duration of viremia 28 . Convalescent plasma Preliminary clinical studies in China have shown that early application of convalescent plasma in patients with COVID-19 could accelerate clinical recovery 6 . Currently two trials: an open-label, non-randomized clinical trial (NCT04264858) and a multicenter, randomized and parallel controlled trial (ChiCTR2000029757) on the efficacy of convalescent plasma in patients with COVID-19 are underway in China. Monoclonal antibody Monoclonal antibody directed against the RBD domain of the S protein of MERS-CoV has been found to have neutralizing activities in plaque assays in vitro. 29 A monoclonal antibody against COVID-19 has not yet been developed. Trastuzumab, a monoclonal antibody against the IL-6 receptor, has achieved encouraging preliminary clinical results. The safety and efficacy of Trastuzumab in COVID-19 infection is undergoing evaluation by a multicenter randomized controlled trial (ChiCTR2000029765). COVID-19 in patients with kidney disease Pregnant women, newborn and the elderly, and patients with comorbidities like diabetes mellitus, hypertension, cardiovascular disease are susceptible to COVID-19 infection and likely to have more severe illness often requiring ICU care. The impact of COVID-19 on CKD has not been reported 30 . COVID-19 infection presents a special threat to patients on dialysis. There are 7184 hemodialysis (HD) patients in 61 treatment centers in Wuhan city. At a single HD center in Renmin Hospital, Wuhan University, 37 HD out of 230 HD patients, and 4 of 33 staff members developed COVID-19 infection between 14 January and 17 February 2020 30 . A total of 7 patients on HD died, of whom 6 had COVID-19 infection. HD patients with COVID-19 had less lymphopenia, lower serum levels of inflammatory cytokines and milder clinical disease than other patients with COVID-19 infection. Management of patients on dialysis COVID-19 infection presents particular challenges for patients on dialysis, in particular, in center hemodialysis. Uremic patients are particularly vulnerable to infection and may exhibit greater variations in clinical symptoms and infectivity. In center HD significantly increases the risk of transmission of infection, including to medical staff and facility workers, patients themselves and family members, and all others. The Chinese Society of Nephrology 31 and the Taiwan Society of Nephrology 32 have recently developed guidelines for dialysis units during the COVID-19 outbreak. A summary of these guidelines is provided below: 1. A working team consisting of dialysis physicians, nursing staff and technologists should receive training in updated clinical knowledge of epidemic COVID-19, notification of infection at risk, epidemic prevention tools, and guidelines from the government, academic society, and hospital authority. The list of staff should be recorded and be retained by dialysis hospitals. 2. Information on travel, occupation, contacts, and clusters history (TOCC) of each medical staff, dialysis patient, their family members, residents of the same institution, and colleagues at work should be collected and updated regularly. 3. Latest care recommendations and epidemic information should be updated and delivered to all medical care personnel as needed. Training can be done peer to peer or online. 4. Group activities, including group rounds, group studies, and case discussions should be minimized. 5. It is recommended that staff members have meals at different time to avoid dining together. Goggles, masks, and hats should be removed before meals, and hands washed with flowing water. Talking during meals should be minimized to reduce the spread of droplets. 6. Staff should self-monitor their symptoms and should inform the team leader in case they or their family members develop symptom(s) suggestive of COVID-19 infection. 7. Entrance control, identification and shunting of people at risk of infection, body temperature measurement, hand washing, wearing proper (surgical or N95) masks throughout the process, machine disinfection, environmental cleanliness, good air conditioning and ventilation conditions, should be instituted. 8. Patients and accompanying persons should be given hands-free hand sanitizer while entering the dialysis room. Patients should wear medical masks and avoid meals during dialysis. They can bring convenience food such as candy to prevent hypoglycemia. 9. Patients with suspected or confirmed COVID-19 infection should be admitted to negative pressure isolation ward of specified hospitals. If the capacity of the isolation facility is overloaded, the "Fixed Dialysis Care Model" as below is recommended for dialysis patients under the 14-day period of quarantine for possible contact with COVID-19. 10. Place of dialysis treatment: patients should continue hemodialysis at the original hemodialysis center and not change to another center. 11. Dialysis shift and personnel: Do not change dialysis shifts and caregiver staff to avoid cross contamination and infection. Minimize the relevant contacts. 12. Patients who need vascular access surgery should be screened for novel coronavirus before the surgery. Operations on patients with confirmed or suspected novel coronavirus infection should be carried out in a designated room with necessary protection for medical staff. 13. Transportation: Public transport should not be used. Patients should arrange personal transportation and take fixed transportation routes. Transport personnel and escorts should wear surgical grade or N95 masks throughout. 14. All patients who have fever should be screened for novel coronavirus infection, and should be given dialysis in the last shift of the day until infection is excluded. 15. Pass route for entering hospital and dialysis unit: The pick-up and drop-off should not be shared with other dialysis patients. Entering and exiting with other patients at the same time should be avoided. The route, mode and time of transport of dialysis personnel should be fixed. 16. Precautions in dialysis unit: Patients should not be in close proximity; treatment and waiting areas should have good air conditioning and ventilation to remove droplet particles from the air. 17. Designated care personnel: All personnel involved in direct patient care should undertake full protection, including long-sleeved waterproof isolation clothing, hair caps, goggles, gloves and medical masks (surgical mask grade or above). Hand hygiene should be strictly implemented. 18. Dialysis machine: Equipment that may come into contact with patients or potentially contaminated material should be disinfected according to standard protocols. 19. If a new confirmed or highly suspected case of novel coronavirus infection in dialysis centers is identified, disinfection should be carried out immediately. Areas in close contact with these patients should not be used for other patients until cleared. 20. The medical waste from confirmed or suspected patients with novel coronavirus infection should be considered as infectious medical wastes and disposed accordingly. Operational strategies for family member and caregivers 1. All the family members living with dialysis patients must follow all the precautions and regulations given to patients to prevent person-to-person and within family transmission of the COVID-19, which include body temperature measurement, good personal hygiene, handwashing, and prompt reporting of potentially sick people. 2. Dialysis patients, who have a family member or caregiver subject to "basic quarantine", can have dialysis as usual in accordance during the 14-day period. 3. Once the family members or caregiver of dialysis patients have been converted to a confirmed case, the patient's identity should be upgraded and treated in accordance with the above-mentioned conditions. In summary, COVID-19, a disease caused by a novel coronavirus, is a major global human threat with a potential to turn into a pandemic. Kidney involvement seems to be frequent in this infection and AKI is an independent predictor of mortality. The impact of this infection in those with CKD has not been studied, and the management of patients on dialysis who have been suspected to have been in contact with COVID-19 should be carried out according to strict protocols to minimize risk to other patients and healthcare personnel taking care of these patients. Uncited reference 20..
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              Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis

              Dear Editor, Tens of thousands of humans were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a short period of time, and the infection spread quickly across China and throughout the world. Acute kidney injury (AKI) is one of the important complications of the 2019 novel coronavirus disease (COVID-19), occurring in 0.5–7% of cases and in 2.9–23% of ICU patients [1–3]. However, whether the AKI of COVID-19 is caused by a coronavirus-induced cytopathic effect or cytokine storm-induced systemic inflammatory response remains unclear. Similar to SARS-CoV infection, the spike (S) protein of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2), a host cell receptor, and the S protein is activated and cleaved by cellular transmembrane serine proteases (TMPRSSs), allowing the virus to release fusion peptides for membrane fusion [4]. Therefore, the coexpression of ACE2 and TMPRSSs is a key determinant for the entry of SARS-CoV-2 into host cells, and improves host conditions for coronavirus. To deduce the underlying mechanism of AKI during the COVID-19 outbreak, we performed single-cell RNA sequencing (scRNA-seq) analysis to identify candidate kidney host cells in the present study. First, we drafted the human kidney cell atlas with 42,589 cells from 15 normal kidney samples in three data sets for scRNA-seq analysis (Fig. S1A, Methods in the eSupplement). Subsequently, we clearly identified 19 clusters with significant differences in transcriptional activity and signature gene expression (Fig. S1A–C). Colocalization analysis of ACE2 and TMPRSS genes showed relatively high coexpression in podocytes and proximal straight tubule cells, which were identified as candidate host cells (Fig. 1a, b). The TMPRSS2 gene, as one of the most important mediators of SARS-CoV-2 enter into host cells [4], was found to be coexpressed with ACE2 in podocytes (Fig. S2A). Fig. 1 Identification of kidney host cells by scRNA-seq analysis. a Feature plots show the expression of ACE2 (red) and TMPRSS genes (blue) in kidney epithelial cells. The merged image shows the coexpression of ACE2 and TMPRSS genes, especially in proximal tubules and podocytes. b Box plots show the expression of ACE2 and the mean expression of the TMPRSS family genes in the 19 clusters of kidney cells. The expression is presented as the log2 (TP10K + 1) value Second, although there was no significant difference in the expression of TMPRSS genes, the expression of the receptor ACE2 in podocytes and proximal straight tubule cells in Occidental donors was more pronounced than that in Asian donors (Fig. S2B), suggesting that Occidental populations might be at higher risk for developing AKI in COVID-19. In addition, comparative analysis showed that the coexpression of the receptor ACE2 and TMPRSS genes in kidney cells was no less than that in the lung, oesophagus, small intestine and colon (Fig. S2C), suggesting that the kidney might also be an important target organ for SARS-CoV-2. Finally, our study clearly identified podocytes and proximal straight tubule cells as kidney host cells. Podocytes and proximal straight tubule cells play critical roles in urine filtration, reabsorption and excretion. Notably, podocytes are particularly vulnerable to viral and bacterial attacks, and podocyte injury easily induces heavy proteinuria [5]. As recent research data showed, 43.9% of SARS-CoV-2-infected patients, especially those with AKI, had proteinuria [6]. Moreover, a recent study reported the detection of SARS-CoV-2 infection in urine samples of patients with severe COVID-19 [3]. Furthermore, the entry of SARS-CoV-2 into the systemic circulation is also a key process that leads to AKI. According to published data, the length of time between the detection of SARS-CoV-2 in blood samples and AKI occurrence was approximately 7 days [1]. Based on our findings, we conclude that the cytopathic effects of SARS-CoV-2 on podocytes and proximal straight tubule cells may cause AKI in patients with COVID-19, especially in patients with SARS-CoV-2 infection in blood samples. Therefore, we need to pay more attention to the early monitoring of renal function and cautiously handle the urine of COVID-19 patients with AKI to prevent accidental infection. However, our findings were based on an analysis of normal kidney cells: the proposed mechanism of the pathophysiology of AKI during COVID-19 still needs to be validated in autopsy tissues from COVID-19 patients and functional experiments in animals and cells. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 17 kb) Supplementary material 2 (JPEG 3466 kb) Supplementary material 3 (JPEG 2693 kb) Supplementary material 4 (DOCX 21 kb)

                Author and article information

                Nephron Clin Pract
                Nephron Clin Pract
                Nephron. Clinical Practice
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                26 May 2020
                : 1-4
                [1 ] aDepartment of Nephrology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China
                [2 ] bDepartment of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
                [3 ] cNAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
                [4 ] dSection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
                [5 ] eSouthampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, United Kingdom
                [6 ] fInstitute of Hepatology, Wenzhou Medical University, Wenzhou, China
                [7 ] gKey Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
                Author notes
                *Dr. Ming-Hua Zheng, NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou 325000 (China), zhengmh@ 123456wmu.edu.cn

                Dan-Qin Sun and Ting-Yao Wang are co-first authors.

                Copyright © 2020 by S. Karger AG, Basel

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                : 15 April 2020
                : 7 May 2020
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                Figures: 1, Tables: 1, References: 7, Pages: 4
                Clinical Practice: Letter to the Editor


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