Evaluation of mortality of COVID-19 patients with acute kidney injury (AKI) in comparison to the non-AKI patients

: Some studies reported that the incidence of acute kidney injury (AKI) in COVID-19 patients was higher than the incidence of AKI in non-COVID-19 patients. The study was conducted on 194 COVID-19 patients admitted to Golestan and Razi hospitals in Ahvaz, Iran. According to our results, COVID-19 does not cause serious and permanent kidney injury. Since the rate of mortality of COVID-19 patient is higher in the AKI group, it is recommended that patients with COVD-19 should be assessed for AKI. Please cite this paper as: Shahbazian H, Tafazoli M, Sabet Nia L, Ghorbani A, Ahmadi Halili S, Jahangiri Mehr F. Evaluation of mortality of COVID-19 patients with acute kidney injury (AKI) in comparison to the non-AKI patients. J Nephropathol. 2022;11(x):e18376. DOI: 10.34172/jnp.2022.18376.

aldosterone system (RAAS) disorder, and increased proinflammatory cytokines in terms of the viral infection and microvascular thrombosis have been proposed (8).
SARS-CoV-2 starts the infection process by attaching to receptors on the host cell membrane that are functional. The post-mortem examination of COVID-19 patients showed varying degrees of acute tubular necrosis, lymphocyte infiltration, and viral RNA, suggesting a direct invasion to the renal tubules (3). AKI is known to cause fluid overload, metabolic disorders, fluid-electrolyte imbalance, impaired neutrophil function and immune system dysfunction, all of which might additionally make contributions to worsening outcomes in COVID-19 individuals (9).
In brief, AKI affects the prognosis of patients with COVID-19, expanded mortality and morbidity and, the need for renal replacement therapy (RRT), and imposes a greater burden on the hospitals and patients (10).
The link between renal dysfunction and COVID-19 prognosis is in general poorly understood. As well as, it is unclear how much the AKI condition predisposes COVID-19 individuals to severe illness and negative outcomes (11). In this regard, a rapid and primary diagnosis of AKI, leads physicians to help manage patients with COVID-19.

Objectives
This study aimed to determine the consequences of AKI in COVID-19 patients admitted to Golestan and Razi hospitals in Ahvaz, Iran.

Study design
This is a retrospective cohort study of AKI prevalence in admitted COVID-19 patients at Razi and Golestan hospitals from 20 December 2021 to 20 March 2022. COVID-19 infection was defined based on positive reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 nucleic acid. The medical documents of 194 individuals with laboratory-confirmed COVID-19, more than 18 years old, were analyzed. Children, those with established end-stage renal disease, and people who had a kidney transplant were all excluded. Two groups of patients were formed. The control group was COVID-19 patients who have normal kidney function and the case group was characterized by the COVID-19 patients who showed AKI during their hospitalization.
Acute kidney injury was determined based on KDIGO guidelines; including 1) increase in serum creatinine by ≥0.3 mg/dL within 48 hours, 2) increase in creatinine by >1.5 times the base in the last 7 days, and 3) urine output <0.5 mL/kg/h for> 6 hours. AKI stage was determined using the peak serum creatinine level from baseline after diagnosis of AKI, therefore the increase in serum creatinine by 1.5-1.9 mg/dL, 2-2.9 mg/dL, and 3 times the baseline values were determined as stages 1, 2, and 3 of AKI, respectively (12).
The severity of lung involvement was defined as mild ground glass opacity (GGO) (less than 25%), moderate (25%-50%), and severe (more than 50%) (13). The daily values of urea and creatinine were recorded. For each patient, we collected baseline patient features such as primary laboratory tests, consisting lung computed tomography (CT) scan information, demographic data, medications usage, clinical characteristics, treatment (respiratory supports), RRT and clinical outcomes in the designed questionnaire. Laboratory data included serum electrolytes, complete blood count, admission time serum creatinine, discharge time serum creatinine, blood gas analysis, and serum albumin and also urine analysis tests. Finally, primary outcomes such as death were recorded, as well as secondary outcomes such as duration of admission, intensive care unit (ICU) admission, degree of pulmonary involvement, use of mechanical ventilation in the ICU and its duration, requirement for RRT, and renal function status at discharge.

Statistical analysis
Statistical analysis was performed by SPSS software version 22 (IBM, Chicago, USA). The quantitative and qualitative variables were indicated as mean ± SD and number (percentage), respectively. Kolmogorov-Smirnov and Shapiro-Wilk tests were conducted to test for the distribution. Differences were compared by using the t test or Mann-Whitney U test as appropriate. For the test of significances, chi-square/Fisher's exact test was calculated to compare the frequencies among groups. P value less than 0.05 was considered statistically significant.

Results
A total of 194 patients were included in this study, with 115 having normal creatinine levels and being referred to the non-AKI group, since 79 having abnormal serum creatinine levels (rising tendency) and being referred to the AKI group. There was no significant association between gender and the groups (P =0.053). Moreover, the clinical symptoms were not different among the groups; however, vital signs, blood pressure, and temperature were different. Furthermore, the history of the pre-existing disease has shown 49 (25.2%) with diabetes mellitus, 50 (27.75%) with hypertension, 17 (8.76%) with ischemic heart disease, and 10 (5.15%) with heart failure, and also nine patients (4.63%) with malignancies. Further, 18 (22.78%) and 13 (16.45%) in the AKI group had used non-steroidal anti-inflammatory drugs and ACE inhibitors and angiotensin II receptor blockers (ARBs), www.nephropathol.com Journal of Nephropathology, Vol 11, No x, xx 2022 COVID19-with AKI 3 respectively. Patients with AKI were more likely to have ICU admission (P < 0.001) and thereby had a higher death rate than the normal group (P < 0.001; Table 1).
According to AKI stages, 39 patients (49.37%) were classified as stage 1, 29 patients (36.71%) as stage 2 and 11 patients (13.92%) as stage 3. For 17.72% of AKI patients, RRT was conducted. Our study showed serum creatinine levels at baseline and before discharge differed considerably across stages. There was no statistically significant correlation between AKI severity and outcome (P=0.49; Table 2). The prevalence of leukopenia and anemia in COVID-19 patients with AKI was significantly higher, although the lymphopenia between two groups was not significant (Table 3). Besides, in AKI group, the value of erythrocyte sedimentation rate (ESR), and serum concentrations of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), blood sugar, ferritin and potassium was significantly higher, which represents the relation between disease severity and kidney involvement.
As well, the rate of metabolic acidosis was considerably higher in this group (Table 4).

Discussion
The aim of this study was to detect how AKI affected The incidence of hyperglycemia, hyperkalemia, hyperphosphatemia, elevated lactate dehydrogenase, CPK, ESR, and ferritin were higher in AKI patients.
In addition, the AKI group had a greater incidence of metabolic acidosis. However, there were no significant differences in the serum levels of sodium, calcium. C-reactive protein, albumin, D-dimer, and liver enzymes between the two groups. The mortality in the AKI group was 41.7%, and in the non-AKI group was about 14.7%. The current study findings demonstrated a significant correlation between outcome and the study group (P <0.001; Table 1).
The study by Robbins-Juarez et al showed that AKI was related to the increased risk of mortality among COVID-19 patients, which was similar to our findings (16). The death rate in AKI cases was 63.9% in the study by Dai et al, which was substantially higher than in patients without AKI (17). Patients with AKI also had a higher death rate in the study by Xiao et al (14). The results of these studies are the same as our study. Regarding urinary findings, in AKI group, the incidence of hematuria was significantly higher than the non-AKI group, whereas the incidence of proteinuria and leukocyturia were not different between the two groups. Our study showed most of the patients were in stage І of AKI (43.36%). Furthermore, 29 out of 79 patients (36.70%) and 11 patients (13.92%) were stages 2 and 3, respectively. In a study by Fominskiy  In these studies, similar to our findings, most of AKI patients were in stage І, indicating that renal involvement in COVID-19 patients is more reversible and mild. Of note, the occurrence of stage І of AKI is high in critically ill patients; since most patients of this category seems having favorable outcomes. However, progression to stage III of AKI is associated with an extremely high mortality rate. In this regard, evaluation of renal function and prevention of AKI play a significant role in the clinical

Conclusion
In conclusion, AKI is linked to a noticeably higher mortality rate among hospitalized COVID-19 patients as compared to non-AKI patients. The kidneys are the target organ of SARS-CoV-2 and the outbreak of AKI in admitted COVID-19 patients is high. Accordingly, the deterioration of kidney function exacerbates damage to other organs. Additionally, COVID-19 cases have a higher mortality rate when it is associated with AKI. In our study, AKI is a common finding in COVID-19 patients. Our study showed most patients were in stage І, which returned to normal kidney function after COVID-19 treatment. According to our study, COVID-19 leads to less severe and permanent kidney damage. We recommend that kidney function should be evaluated in COVID-19 patients and renal function monitoring should be continued after discharge to control for progression to CKD. We recommend that larger, multicenter studies to be conducted in the future to learn more about the impact of AKI on prognosis and disease outcomes.

Limitations of the study
There were various limitations in this study. Since nonhospitalized patients were not included in the present investigation, we were unable to extrapolate our findings to outpatient AKI settings. Second, we received no followup information after discharge. Third, the causality interpretation of the association between effects and exposures was not attainable owing to the observational character of the research.

Ethical issues
The study protocol conforms to the ethical guidelines of Declaration of Helsinki (1975). The study was approved by the Ethics Committee of Ahvaz Jundishapur university of medical sciences, Ahvaz, Iran (Ethics number: IR.AJUMS.REC.1400.023). Written informed consent was obtained from all patients. The present research was extracted from the nephrology fellowship dissertation of Mina Tafazoli at this university (registration no: 4386). Besides, ethical issues (including plagiarism, data fabrication and double publication) have been completely observed by the authors.