Evaluation of incidence and risk factors of acute kidney injury development in hospitalized COVID 19 patients; A case-control study

doi:10.21203/rs.3.rs-1749087/v1

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Evaluation of incidence and risk factors of acute kidney injury development in hospitalized COVID 19 patients; A case-control study

https://doi.org/10.21203/rs.3.rs-1749087/v1

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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.

Urology & Nephrology

Acute kidney injury

covid-19

Syrian private university

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.

Participants

The case control study sample included 299 hospitalized covid-19 patients from 2021 until 2022 in Damascus hospital.

Case-group sample

145 covid-19 patients with a new onset AKI.

Control-group sample

154 covid-19 patients without AKI, that had all the data about risk factors were screened in the study.

Data acquisition

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.

Definition of Patient Characteristics

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.

Statistical analysis

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).

Socio-demographic characteristics

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%)
Gender	female	117 (39.1%)
living	city	195 (65.2%)
	rural	102 (34.1%)
	prisoner	2 (0.7%)
smoking	smokers	180 (60.2%)
smoking	Non-smokers	119 (39.8%)
Age	Median age	Standard deviation
Age	64.9	13.9

Comorbid conditions

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%)

Acute kidney injury features

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%)
AKI	NO	154 (51.5%)
NEWS (2) SCORE	High	91 (30.4%)
	Medium	106 (35.5%)
	Low	102 (34.1%)
Dialysis	YES	59 (19.7%)
Dialysis	NO	240 (80.3%)
Diabetic ketoacidosis	YES	35 (11.7%)
Diabetic ketoacidosis	NO	264 (88.3%)

WBC's, CRP, D-DIMER

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%)
CRP	Reference	85 (28.4%)
D-Dimer	Elevated	69 (23.1%)
D-Dimer	Reference	230 (76.9%)

Associations between AKI and socio-demographic factors

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
gender	female	52 (35.9%)	65 (42.2%)		0.261
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
smoking	no	61 (42.1%)	58 (37.7%)	0.605	0.437
Age		Cases N (%)	Control N (%)	T- test	P value
Age		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).

Associations between AKI and comorbid conditions

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
HTN	NO	56 (38.6%)	95 (61.7%)	15.897	0.000
DM	YES	81 (55.9%)	56 (36.4%)	11.437	0.001
DM	NO	64 (44.1%)	98(63.6%)	11.437	0.001
CKD	YES	20 (13.8%)	1 (0.6%)	19.758	0.000
CKD	NO	125 (86.2%)	153 (99.4%)	19.758	0.000
Heart disease	YES	33 (22.8%)	18 (11.7%)	6.469	0.011
Heart disease	NO	112 (77.2%)	136 (88.3%)	6.469	0.011
Asthma	YES	5(3.4%)	8 (5.2%)	0.548	0.459
Asthma	NO	140 96.6%))	146 (94.8%)	0.548	0.459
COPD	YES	3 (2.1%)	5 (3.2%)	0.398	0.528
COPD	NO	142 (97.9%)	149 (96.8%)	0.398	0.528
CVA	YES	9 (60.2%)	8 (5.2%)	0.143	0.706
CVA	NO	136 (93.8%)	146 (94.8%)	0.143	0.706
Cancer	YES	3 (2.1%)	3 (1.9%)	0.006	0.941
Cancer	NO	142 (97.9%)	151 (98.1%)	0.006	0.941

Association between AKI and NEWS2 score

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%)

Association between AKI and inflammatory markers

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
CRP	reference	36 (24.8%)	49 (31.8%)	1.794	0.180
D-dimer	elevated	36 (26.9%)	30 (19.5%)	2.314	0.128
D-dimer	reference	106 (73.1%)	124 (80.5%)	2.314	0.128

The association between AKI and poor prognosis and mortality

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
Dialysis	No	86 (59.3%)	154 (100%)	78.066	0.000
Diabetic ketoacidosis	Yes	31 (21.4%)	4 (2.6%)	26.222	0.000
Diabetic ketoacidosis	No	114 (78.6%)	150 (97.4%)	26.222	0.000
Mortality	Yes	84 (57.9%)	38 (24.7%)	34.195	0.000
Mortality	No	61 (42.1%)	116 (75.3%)	34.195	0.000

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).

Association between NEWS2 score and mortality

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	Chi-square	P-value
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%)

Association between (inflammatory markers, complications) and mortality rate

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	Chi-square	P-value
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
CRP	Reference	25 (20.5%)	60 (33.9%)	6.380	0.012
D-dimer	High	45 (36.9%)	24 (13.6%)	22.136	0.000
D-dimer	Reference	77 (63.1%)	153 (86.4%)	22.136	0.000
Dialysis	Yes	41 (33.6%)	18 (10.2%)	25.047	0.000
Dialysis	No	81 (66.4%)	159 (89.8%)	25.047	0.000

Multivariate analysis

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.

ACE-2

angiotensin converting enzyme 2

AKI

acute kidney injury

HTN

hypertension

diabetes mellitus

CKD

chronic kidney disease

COVID-19

coronavirus disease 2019

NEWS2

national early warning score 2

KDIGO

kidney disease improving global outcomes

WBC

white blood count

AKI

acute kidney injury

AOD

adjusted odd ratio

CRP

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.

Lu, Roujian, et al. "Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding." The lancet 395.10224 (2020): 565–574.
Huang, Chaolin, et al. "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China." The lancet 395.10223 (2020): 497–506.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel corona virus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
Ali, Hatem, et al. "Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis." Renal failure 42.1 (2020): 393–397.
Chen, Yih-Ting, et al. "Incidence of acute kidney injury in COVID-19 infection: a systematic review and meta-analysis." Critical Care 24.1 (2020): 1–4.
Hirsch, Jamie S., et al. "Acute kidney injury in patients hospitalized with COVID-19." Kidney international 98.1 (2020):209–218.
Gameiro, Joana, et al. "Acute kidney injury in hospitalized patients with COVID-19." (2020).
Acute kidney injury in admitted COVID-19 patients – Epic Health Research Network. Published July 1, 2020. Accessed July 11, 2020.
Robbins-Juarez, S. Y., et al. "A systematic review and meta-analysis of outcomes for patients with COVID-19 and acute kidney injury." Kidney Int Rep 5.8 (2020): 1149–1160.
Gündoğan, Kürşat, et al. "Acute kidney injury in SARS-CoV-2 infected critically ill patients." Turk J Nephrol 29.3 (2020): 185–189.
Ng, Jun Jie, et al. "Acute kidney injury in hospitalized patients with coronavirus disease 2019 (COVID-19): a meta-analysis." Journal of Infection 81.4 (2020): 647–679.
Kellum, J. A., et al. "kidney disease: improving global outcomes (KDIGO) acute kidney injury work group." Kidney Int Suppl 2.1 (2012): 1–38.
Gary B., et al. "The National Early Warning Score 2 (NEWS2)." Clinical Medicine, Journal of the Royal College of Physicians of London 19.3(2019).
Nimkar, Abhishek, et al. "Incidence and risk factors for acute kidney injury and its effect on mortality in patients hospitalized from Covid-19." Mayo Clinic Proceedings: Innovations, Quality & Outcomes 4.6 (2020): 687–695.
Pan XW, Xu D, Zhang H, Zhou W, Wang LH, Cui XG: Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: A study based on single-cell transcriptome analysis [published online ahead of print Mar 31, 2020]. Intensive Care Med doi:10.1007/s00134-020-06026-1.
Leblanc, Martine, et al. "Risk factors for acute renal failure: inherent and modifiable risks." Current opinion in critical care 11.6 (2005): 533–536.

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You are reading this latest preprint version

Evaluation of incidence and risk factors of acute kidney injury development in hospitalized COVID 19 patients; A case-control study

Status:

Version 1

Abstract

Background

Methods

Participants

Case-group sample

Control-group sample

Data acquisition

Definition of Patient Characteristics

Statistical analysis

Results

Socio-demographic characteristics

Comorbid conditions

Acute kidney injury features

WBC's, CRP, D-DIMER

Associations between AKI and socio-demographic factors

Associations between AKI and comorbid conditions

Association between AKI and NEWS2 score

Association between AKI and inflammatory markers

The association between AKI and poor prognosis and mortality

Association between NEWS2 score and mortality

Association between (inflammatory markers, complications) and mortality rate

Multivariate analysis

Discussion

Conclusions

Abbreviations

Declarations

References

Status:

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