Clinical trial NCT05157152: Elevated Liver Enzymes as a Predictor of Acute Kidney Injury in Hospitalized Patients With COVID-19
Official title: Elevated Liver Enzymes as a Predictor of Acute Kidney Injury in Hospitalized Patients With COVID-19
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19 Pandemic
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2021-12-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with respirator symptoms of COVID-19 admitted at Sohag university hospital

Brief summary: In critically ill patients, AKI is a common complication of COVID-19 infection, occurring in 23% to 43% of cases, and was correlated with poor clinical outcomes.

An increase in liver function tests ( LFTs) has been found in patients with COVID-19 ranging 14%-75% Some studies found higher levels of transaminases in patients with severe COVID-19 pneumonia and in patients dying for COVID-19.

Initial reports indicate a high incidence of abnormal liver tests and acute kidney injury (AKI) in the novel coronavirus infection (COVID-19).

We hypothesis that there is a relationship between COVID-19 patients who are critically ill, liver enzymes and level of serum creatinine

Detailed description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects multiple organ systems and imparts significant morbidity and mortality \[1\]. Approximately 5% to 14% of patients affected with SARS-CoV-2 will become critically ill \[2-4\]. While coronavirus disease 2019 (COVID-19) generally begins as a respiratory tract infection, it can damage any organ system. Thus, to improve outcomes, clinicians should search actively for multi-organ involvement to guide appropriate early management \[5\].

Among affected organs, the kidney is particularly susceptible to COVID-19. Indeed, SARS-CoV-2 has been shown to share the same functional receptor, angiotensin-converting enzyme 2 (ACE2), with a wide variety of organs (such as lung, heart, kidney) \[6\]. SARS-CoV-2 initiates its infection process by binding to functional receptors on the membrane of a host cell. Postmortem examination of COVID-19 patients revealed varying degrees of acute tubular necrosis, lymphocytic infiltration, and viral RNA, suggesting direct invasion of kidney tubules \[7\]. In addition to direct kidney damage by the virus, acute kidney injury (AKI) can occur through several proposed mechanisms including acute tubular necrosis induced by sepsis, hypoxia, hypoperfusion, rhabdomyolysis, nephrotoxic drugs, etc.

In critically ill patients, AKI is a common complication of COVID-19 infection, occurring in 23% to 43% of cases, and was correlated with poor clinical outcomes. AKI was defined as per Kidney Disease Improving Global Outcomes (KDIGO) criteria: a change in the serum creatinine of 0.3 mg/dL over 48 h period or 50% increase in baseline creatinine.

An increase in liver function tests ( LFTs) has been found in patients with COVID-19 ranging 14%-75% Some studies found higher levels of transaminases in patients with severe COVID-19 pneumonia and in patients dying for COVID-19.

The clinical relevance of LFTs abnormalities has been controversial, with some studies suggesting its association with the severity of COVID-19 pneumonia, whereas others not.Some limitations affected those studies involving the lack of information about concomitant or previous use of hepatotoxic drugs among the others.

Initial reports indicate a high incidence of abnormal liver tests and acute kidney injury (AKI) in the novel coronavirus infection (COVID-19). However, outcomes in hospitalized patients with COVID-19 and elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels at admission and their associations with AKI are not well understood.

Aim of the work

The aim of this study is to investigate the incidence of liver injury at admission and its contribution to the development of AKI, severity of COVID-19 and outcomes in Sohag University hospital

Patients and methods

Type of the Study:

A prospective, observational cohort study will be conducted between December 2021 and May 2022 among hospitalized COVID-19 patients in Sohag University Hospital.

Patients:

Inclusion criteria :

Patients who are positive for COVID-19 infection in Sohag University Hospital whose ages \< 18 years old. (confirmed by polymerase chain reaction (PCR) from nasopharyngeal or oropharyngeal samples) who developed AKI at time of admission or during admission.

Exclusion criteria :

Patients whose ages \>18 years old.

Methods A prospective, observational cohort study will be conducted between December 2021 and April 2022 among hospitalized COVID-19 patients in Sohag University Hospital.

The routine laboratory parameters will be measured before the beginning of this Study After conducting a complete physical examination.

demographic, clinical, radiological and laboratory data will be collected at admission. Information on medical history, including comorbidities, symptoms of infection and drugs taken in the previous 14 days before admission will be collected. Vital signs (respiratory rate \[RR\], body temperature \[BT\], arterial blood pressure, heart rate \[HR\], pulse oxygen saturation \[SatO2\] were collected. Laboratory tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum Albumin, Total protein, serum creatinine, Blood urea nitrogen, serum electrolytes and bilirubin were collected at admission and every 7 ± 2 days during the admission.

Patients diagnosed with COVID-19 will be divided into three groups as mild, moderate, and severe disease to evaluate the relationship between disease severity and AKI. Patients with clinical signs of pneumonia (fever, cough, dyspnoea, fast breathing) plus one of the following: respiratory rate \>30 breaths/min; severe respiratory distress;or SpO2 \< 90% on room air will be considered as severe cases.

Patients with pneumonia and have no above severity criteria will be considered as moderate cases. Symptomatic patients without evidence of viral pneumonia or hypoxia will be considered as mild cases.

Statistical analysis :

All data will be collected and analysed using Statistical Package for Social Science ( SPSS to investigate the incidence of liver injury at admission and its contribution to the development of AKI, severity of COVID-19 and outcomes in Sohag University hospital

Ethical Consideration :

The study will be assessed by scientific and ethical committee of Sohag faculty of medicine, an informed written consent will be obtained from all patients enrolled in the study.

Eligibility criteria: Inclusion Criteria:

* Patients who are positive for COVID-19 infection in Sohag University Hospital whose ages \< 18 years old. (confirmed by polymerase chain reaction (PCR) from nasopharyngeal or oropharyngeal samples) who developed AKI at time of admission or during admission.

Exclusion Criteria:

* Patients whose ages \>18 years old.
* Patients known to have any liver disease.

Primary outcomes:
measure: Relationship between liver enzymes and AKI in patients with COVID19
timeFrame: 4 months
Secondary outcomes:
measure: Severity of COVID19 infection
timeFrame: 4 months
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: SOHAGU
Study officials:
affiliation: Sohag university-faculty of medicine
name: Ahmed Ka Osman, Resident
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ngiam JN, Chew N, Tham SM, Lim ZY, Li TY, Cen S, Tambyah PA, Santosa A, Muthiah M, Sia CH, Cross GB. Elevated liver enzymes in hospitalized patients with COVID-19 in Singapore. Medicine (Baltimore). 2021 Jul 30;100(30):e26719. doi: 10.1097/MD.0000000000026719.