DOI: https://doi.org/10.21203/rs.3.rs-1749087/v1
Background
Acute kidney injury (AKI) is common among patients hospitalized with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in hospitalized patients in Damascus hospital.
Design
A case control study conducted in Damascus hospital.
Methods
The study reviewed 299 medical records of hospitalized covid 19 patients between 2021 to 2021 after, a self-administered forms used to fill demographical, comorbid conditions, vital signs, laboratory studies, the goal is to gauge the risk factors for having acute kidney injury in covid-19 and the effect on prognosis and mortality. The study was performed in accordance with the principles of the Declaration of Syrian private university Research Ethics Committee.
Result
Through this study prevalence rate of AKI were 145 (48.5%) in hospitalized patients, the median age was (67+-12.3) years in AKI patients. hypertension, diabetes, and chronic kidney disease, have increased the risk of having a new onset AKI, this study shows that AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, and poor prognosis.
Conclusion
AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, and poor prognosis. We demonstrate an independent association between some factors and the development of AKI and mortality, early detection of comorbidities and renal complications is essential to improve the outcomes of COVID-19 patients.
In late December, 2019, an unidentified microbial agent was reported in Wuhan, China patients manifesting as viral pneumonia. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus. (1) The illness mainly manifests as fever, cough, myalgia or fatigue sputum production, headache, and diarrhea. (2) The severity of COVID-19 illness can run the spectrum from asymptomatic infection, self-limited flu-like illness, and acute pneumonia to sepsis leading to life-threatening complications, including acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury (AKI), and septic shock. (3)
Acute kidney injury (AKI) has been reported as a severe complication of COVID-19 with a higher risk of mortality. (4)
but the incidence of AKI among those infected with COVID-19 is currently only based on reports from studies utilized USA, UK, China patients. (5) Therefore, in this work, the goal is to gauge the incidence in low-income country in our case the population is derived from Syria and asses demographic factors and comorbid conditions that carry an increased risk for AKI in these patients, also to evaluate the association between AKI and mortality rate.
Many studies have suggested an incidence of AKI in covid-19 as high as 37–40%. (6.7.8)
The recovery from severe COVID-19 often takes a long time in hospital, so previously published studies may result in potential biasing toward adverse outcomes. (9.10.11).
A case-control study was conducted on patients' records were hospitalized in Damascus hospitals with confirmed COVID-19 diagnosis.
The case control study sample included 299 hospitalized covid-19 patients from 2021 until 2022 in Damascus hospital.
145 covid-19 patients with a new onset AKI.
154 covid-19 patients without AKI, that had all the data about risk factors were screened in the study.
A self-administered form was designed to fill in data about (gender, age, comorbid conditions, smoking, vital signs, laboratory studies).
The forms were then filled out and entered into the Excel data program and a comparison was made in terms of risk factors assumed for AKI between case group and control group.
Comorbid conditions were token from patients and their health records. Patients with chronic kidney disease were receiving long-term dialysis treatment. Cardiac disease was defined as chronic heart conditions including but not restricted to (coronary artery disease, myocardial infarction, congestive heart failure, arrhythmias, bypass grafting, implantable defibrillator, percutaneous coronary intervention).
Acute kidney injury was identified as defined by the criteria from kidney disease: Improving Global Outcomes and the International Society of Nephrology (12).
We did not have access to preadmission baseline creatinine values for most patients. Therefore, we considered the lowest creatinine level recorded during admission as the baseline and then retrospectively compared this “baseline” with the highest creatinine level recorded.
We could not determine AKI status for patients with only 1 creatinine value recorded during the hospital stay and thus excluded these patients from analysis (n = 13), the final analysis included 299 patients.
The statistical study was conducted using the SPSS program version 26. The demographic characteristics were described, and the sample distribution according to the study variables was described, Also, the Chi-Square test of independence was used to test the independence of qualitative variables, and the use of correlation tests according to the Cramer's coefficient to study the relationship between qualitative variables, and the spearman's coefficient to study the relationship between quantitative variables. The averages of the comparative independent groups were compared using T-Test Independent Samples, one way ANOVA), with the test for homogeneity to compare group variance and dimensional comparisons using LSD and Games-Howell. Multivariate analysis was used to identify factors associated with acute kidney injury. Statistical significance was adopted when (p < 0.05).
Table (1.1) the distribution of the sample according to gender showed the male participants were 182 (60.9%), females were 117 (39.1%). most of the participants were living in the city 195 (65.2%), 102 (34.1%) countryside, 2 (0.7%) in prison. 180 (60.2%) where smoker while non-smoker 119 (39.8%). The median age was 64.9, standard deviation was 13.9.
| Table (1.1) socio-demographic | ||
|---|---|---|
| variables | N (%) | |
| Gender | male | 182 (60.9%) |
| female | 117 (39.1%) | |
| living | city | 195 (65.2%) |
| rural | 102 (34.1%) | |
| prisoner | 2 (0.7%) | |
| smoking | smokers | 180 (60.2%) |
| Non-smokers | 119 (39.8%) | |
| Age | Median age | Standard deviation |
| 64.9 | 13.9 | |
Table (1.2) the distribution of comorbid conditions was 148 (49.5%) with HTN versus 151 (50.5%) without HTN. 137 (45.8%) were having DM versus 162 (54.2%) without DM. 21 (7%) were having CKD versus 278 (93%) without CKD. 51 (17.1%) were having heart diseases versus 248 (82.9%) without heart diseases. 17 (5.7%) with CVA versus 282 (94.3%) without CVA. 13 (4.3%) were having asthma and 286 (95.7%) without asthma. 8 (2.7%) with COPD and 291 (97.3%) without COPD. 6 (2%) with cancer and 293 (98%) without cancer.
| Table (1.2) comorbid conditions distribution | ||
|---|---|---|
| variables | YES N (%) | NO N (%) |
| HTN | 148.5 (49.5%) | 151 (50.5%) |
| DM | 137 (45.8%) | 162 (54.2%) |
| CKD | 21 (7%) | 278 (93%) |
| Heart Disease | 51 (17.1%) | 248 (82.9%) |
| Asthma | 13 (4.3%) | 286 (95.7%) |
| COPD | 8 (2.7%) | 291 (97.3%) |
| CVA | 17 (5.7%) | 282 (94.3%) |
| Cancer | 6 (2%) | 293 (98%) |
Table (1.3) AKI were founded in 145 (48.5%) versus 154 (51.5%). we did utilize the National Early Warning Score (NEWS2) for scoring the physiological measurements (respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness, temperature) that are routinely recorded in patients' records (13). Due to these criteria the 299 patients were distributed as 91 (30.4%) high risk patients, 106 (35.5%) medium risk, 102 (34.1%) low risk patients. 59 (19.7%) of patient received hemodialysis therapy. And 35 (11.7%) with diabetic ketoacidosis.
| Table (1.3) AKI features | ||
|---|---|---|
| variables | statues | N (%) |
| AKI | YES | 145 (48.5%) |
| NO | 154 (51.5%) | |
| NEWS (2) SCORE | High | 91 (30.4%) |
| Medium | 106 (35.5%) | |
| Low | 102 (34.1%) | |
| Dialysis | YES | 59 (19.7%) |
| NO | 240 (80.3%) | |
| Diabetic ketoacidosis | YES | 35 (11.7%) |
| NO | 264 (88.3%) | |
Table (1.4). 149 (49.8%) were having a high WBC's, 140 (46.8%) within the reference range, and 10 (3.3%) with low WBC's count. CRP were high in 214 (71.6%), 85 (28.4%) within the reference range. D-dimer were elevated in 69 (23.1%), and 230 (76.9%) within the reference range.
| Table (1.4). laboratory studies | ||
|---|---|---|
| Test | Result | N (%) |
| WBC's | elevated | 149 (49.8%) |
| Reference | 140 (46.8%) | |
| low | 10 (3.3%) | |
| CRP | Elevated | 214 (71.6%) |
| Reference | 85 (28.4%) | |
| D-Dimer | Elevated | 69 (23.1%) |
| Reference | 230 (76.9%) | |
| Table (2.1). Associations between AKI and socio-demographic factors | |||||
|---|---|---|---|---|---|
| Cases N (%) | Controls N (%) | Chi-square | P value | ||
| gender | male | 93 (64.1%) | 89 (57.8%) | 1.263 | 0.261 |
| female | 52 (35.9%) | 65 (42.2%) | |||
| accommodation | city | 100 (69%) | 95 (61.7%) | 3.272 | 0.195 |
| rural | 45 (31%) | 57 (37%) | |||
| prisoner | 0 (0%) | 2 (1.3%) | |||
| smoking | yes | 84 (57.9%) | 96 (96.3%) | 0.605 | 0.437 |
| no | 61 (42.1%) | 58 (37.7%) | |||
| Age | Cases N (%) | Control N (%) | T- test | P value | |
| 67 (12.3) | 62.2 (14.7) | 3.583 | 0.000 | ||
Table (2.1). When studying the relationship between acute kidney injury patients and the median age of patients, the results showed a statistically significant relationship between acute kidney injury and the median age of patients. The mean age of those with acute kidney injury was 67 years compared to 62.2 years for the control group (p < 0.001). The results did not show any differences between sex, residence, and smoking with acute kidney injury (p > 0.05).
Table (2.2). When studying the relationship between acute kidney injury and comorbid conditions, the results showed a statistically significant relationship between each of the following comorbidity:
Most patients with acute kidney injury had a history of significantly hypertension in 61.4% versus 38.3% of the controls (p < 0.001). The majority of acute kidney injury patients had a history of diabetes mellitus, 55.9% more than 36.4% of the controls (p < 0.001). Acute renal injury patients had a history of chronic renal disease 13.8% significantly more compared to 0.6% controls (p < 0.001). Most patients with acute kidney injury had a history of heart disease in 22.8% versus 11.7% of the controls (p = 0.011).
| Table (2.2). Associations between AKI and comorbid conditions | |||||
|---|---|---|---|---|---|
| Cases N (%) | Controls N (%) | Chi-square | P value | ||
| HTN | YES | 89 (61.4%) | 59 (38.3%) | 15.897 | 0.000 |
| NO | 56 (38.6%) | 95 (61.7%) | |||
| DM | YES | 81 (55.9%) | 56 (36.4%) | 11.437 | 0.001 |
| NO | 64 (44.1%) | 98(63.6%) | |||
| CKD | YES | 20 (13.8%) | 1 (0.6%) | 19.758 | 0.000 |
| NO | 125 (86.2%) | 153 (99.4%) | |||
| Heart disease | YES | 33 (22.8%) | 18 (11.7%) | 6.469 | 0.011 |
| NO | 112 (77.2%) | 136 (88.3%) | |||
| Asthma | YES | 5(3.4%) | 8 (5.2%) | 0.548 | 0.459 |
| NO | 140 96.6%)) | 146 (94.8%) | |||
| COPD | YES | 3 (2.1%) | 5 (3.2%) | 0.398 | 0.528 |
| NO | 142 (97.9%) | 149 (96.8%) | |||
| CVA | YES | 9 (60.2%) | 8 (5.2%) | 0.143 | 0.706 |
| NO | 136 (93.8%) | 146 (94.8%) | |||
| Cancer | YES | 3 (2.1%) | 3 (1.9%) | 0.006 | 0.941 |
| NO | 142 (97.9%) | 151 (98.1%) | |||
Table (2.3). When studying the relationship between acute kidney injury and NEWS 2 classification, the results revealed a statistically significant relationship between them. Whereas acute renal injury patients had a high prognosis of 35.9% versus 25.3% of the controls, and most of the acute renal injury patients had a mean prognosis of 37.9% versus 33.1% of the controls. While the controls had a significant low prognosis 41.6% compared to 26.2% of acute kidney injury patients (p = 0.015).
| Table (2.3). Association between AKI and NEWS2 score | |||||
|---|---|---|---|---|---|
| Cases N (%) | Control N (%) | Chi- square | p- value | ||
| score | high | 52 (35.9%) | 39 (25.3%) | 8.372 | 0.015 |
| medium | 55 (37.9%) | 51 (33.1%) | |||
| low | 64 (26.2%) | 64 (41.6%) | |||
Table (2.4). the relationship between acute kidney injury patients with laboratory inflammatory cues, the results showed a statistically significant relationship between them, as most of the acute kidney injury patients had an increase in leukocytes 60% compared to 40.4% of the controls (p = 0.003).
| Table (2.4). Association between AKI and inflammatory markers | |||||
|---|---|---|---|---|---|
| Cases N (%) | Control N (%) | Chi- square | P value | ||
| WBC | elevated | 87 (60%) | 62 (40.3%) | 11.963 | 0.003 |
| reference | 55 (37.9%) | 85 (55.2%) | |||
| low | 3 (2.1%) | 7 (4.5%) | |||
| CRP | elevated | 109 (75.2%) | 105 (68.2%) | 1.794 | 0.180 |
| reference | 36 (24.8%) | 49 (31.8%) | |||
| D-dimer | elevated | 36 (26.9%) | 30 (19.5%) | 2.314 | 0.128 |
| reference | 106 (73.1%) | 124 (80.5%) | |||
Table (3.1). When studying the relationship between acute kidney injury patients and the need for dialysis, the results showed a statistically significant relationship between them, where acute kidney injury patients required 40.7% more dialysis than control patients 0% (p < 0.001).
When examining the relationship between acute kidney injury and ketoacidosis, the results showed a statistically significant relationship between them, where the patients with kidney injury had positive ketoacidosis 21.4% more than the control patients 2.6% (p < 0.001).
| Table (3.1). The association between AKI and poor prognosis and mortality | |||||
|---|---|---|---|---|---|
| Cases N (%) | Control N (%) | Chi- square | P-value | ||
| Dialysis | Yes | 59 (40.7%) | 0 (0.0%) | 78.066 | 0.000 |
| No | 86 (59.3%) | 154 (100%) | |||
| Diabetic ketoacidosis | Yes | 31 (21.4%) | 4 (2.6%) | 26.222 | 0.000 |
| No | 114 (78.6%) | 150 (97.4%) | |||
| Mortality | Yes | 84 (57.9%) | 38 (24.7%) | 34.195 | 0.000 |
| No | 61 (42.1%) | 116 (75.3%) | |||
When studying the relationship between patients with acute kidney injury and death, the results revealed a statistically significant relationship between them, where death occurred in patients with acute kidney injury 57.9% more prominently compared to 24.7% of the control patients (p < 0.001).
Table (3.2). When studying the relationship between the occurrence of death in patients with Covid 19 with the warning, the results revealed a statistically significant relationship between them, where the patients who had death had a high warning 50.8% compared to those who did not have death 16.4% (p < 0.001).
| Table (3.2). Association between NEWS2 score and mortality | |||||
|---|---|---|---|---|---|
| Death | Chi-square | P-value | |||
| Yes | No | ||||
| prognosis | High | 60 (50.8%) | 29 (16.4%) | 40.476 | 0.000 |
| Medium | 30 (24.6%) | 76 (42.9%) | |||
| Low | 30 (24.6%) | 72 (40.7%) | |||
Table (3.3). When studying the relationship between death and inflammatory indicators in patients with Covid 19, the results showed a statistically significant relationship between death and the following inflammatory indicators:
Of COVID-19 patients who died had a significant leukocytosis in 71.3% compared to 35% who did not (p < 0.001).
Of COVID-19 patients who died had a significant increase in CRP 79.5% compared to 66.1% of the patients who did not die (p = 0.012).
Most of the patients who did not die had a D-dimer value within normal limits of 86.4% versus 63.1% of those who died (p < 0.001).
When studying the relationship between death in patients with Covid 19 and the need for dialysis, the results showed a statistically significant relationship between them. Those who died had a greater need for dialysis 33.6% compared to 10.2% who did not die (p < 0.001).
| Table (3.3). Association between (inflammatory markers, complications) and mortality rate | |||||
|---|---|---|---|---|---|
| Death | Chi-square | P-value | |||
| Yes | No | ||||
| WBC | High | 87 (71.3%) | 62 (35%) | 38.080 | 0.000 |
| Reference | 33 (27%) | 107 (60.5%) | |||
| Low | 2 (1.6%) | 8 (4.5%) | |||
| CRP | High | 97 (79.5%) | 117 (66.1%) | 6.380 | 0.012 |
| Reference | 25 (20.5%) | 60 (33.9%) | |||
| D-dimer | High | 45 (36.9%) | 24 (13.6%) | 22.136 | 0.000 |
| Reference | 77 (63.1%) | 153 (86.4%) | |||
| Dialysis | Yes | 41 (33.6%) | 18 (10.2%) | 25.047 | 0.000 |
| No | 81 (66.4%) | 159 (89.8%) | |||
Table (4). Multivariate analysis revealed factors associated with acute kidney injury in COVID-19 patients and were statistically significant (p < 0.05) as follows:
Whereas, patients with a history of diabetes mellitus, patients with medium score NEWS2, and those who had died had a higher risk of acute kidney injury.
| Table (4). Multivariate regression | ||
|---|---|---|
| AKI (Aor) CI (95%) | P value | |
| Age | 1 (0.9-1) | 0.140 |
| HTN | 1.6 (0.9–2.9) | 0.071 |
| DM | 2 (1.1–3.5) | 0.015 |
| Heart disease | 1.5 (0.7–3.1) | 0.207 |
| Medium score (NEWS2) | 2.2 (1.1–4.1) | 0.012 |
| Mortality | 4.3 (2.4–7.7) | 0.000 |
Our study revealed that AKI prevalence in covid-19 hospitalized patients were 48.5%. This is much higher than other studies (6.8.7). Pan et al (15) demonstrated higher ACE-2 expression in kidney of donors from western countries compared with Asian, which is suggesting of ACE-2 protein expression variation
We saw higher odds of developing AKI associated with covid-19 infection (increased age, HTN, DM, CKD, And heart disease, medium stage of NEWS2 criteria, and elevated WBC's count).
We also saw a higher odd of mortality with (AKI development, higher score on NEWS2 scale, elevated WBC's, CRP, D-dimer, need for dialysis, and diabetic ketoacidosis).
A study by Nimkar et al (14) identified almost identical risk factors for developing AKI, and mortality. In their study, the authors described increasing odds of developing AKI with HTN, DM, CKD, increased age, similar to our analysis, supporting the validity of our findings.
We observed that higher odds of AKI in CKD and higher prevalence of CKD in patients with AKI is not surprising because CKD is a well-known risk factor for AKI. (16)
One of study limitations that previous creatinine values were unavailable and thus a decision to use the lowest creatinine level in the hospital stay as a 'baseline creatinine' was made which didn't make any significance deference according to Nikmar et al study. (14)
kidneys are a target by COVID-19 infection and potential risk factors for the development of AKI in patients with COVID-19 infection. We found significantly higher odds of AKI with increasing age, patients with HTN, DM, heart disease, and those with CKD. We demonstrate an independent association between AKI and mortality with increasingly higher odds of mortality.
angiotensin converting enzyme 2
acute kidney injury
hypertension
diabetes mellitus
chronic kidney disease
coronavirus disease 2019
national early warning score 2
kidney disease improving global outcomes
white blood count
acute kidney injury
adjusted odd ratio
C-Reactive Protein.
Author contribution statement
Zakaria Al-Dammad: Conceived and designed the experiments.
Zakaria Al-Dammad and Anas Halawat: performed the experiments.
Mhd Obai alchallah: analyzed and interpreted the data.
Farida Al-Dammad: contributed reagents, materials, wrote the paper.
Nihad S. Assaf: Supervised data collection and revision of the draft.
Funding statement
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data availability statement
Data included in article/supplementary material/ referenced in article.
Potential Conflict of Interests
The authors declare no competing interests.
Additional information
No additional information is available for this paper.
Acknowledgements
We would like to thank Syrian private university research committee, also special thanks for Damascus hospital located in Damascus, Syria.