The Effects of Acute Kidney Injury on COVID-19 related Clinical Outcomes and Mortality in a Hispanic Population

doi:10.21203/rs.3.rs-4810763/v1

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The Effects of Acute Kidney Injury on COVID-19 related Clinical Outcomes and Mortality in a Hispanic Population

https://doi.org/10.21203/rs.3.rs-4810763/v1

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The effect of coronavirus disease (COVID)-19 has been severe in minority communities across the United States, especially in Hispanics. Acute kidney injury (AKI) is observed as a significant factor to worsening outcomes in patients with COVID-19. In this retrospective observational study, clinical outcomes related to renal impairment were assessed among Hispanic patients with COVID-19 by screening all patients hospitalized between March, 2020 and March, 2021 at a tertiary care hospital in El Paso, Texas, resulting in a total of 1,478 patients. The cohort consisted of 385 (26%) with renal impairment, including 195 (13.2%) AKI, 128 (8.7%) chronic kidney disease, and 60 (4.0%) end stage renal disease. Patients with any form of renal impairment with COVID-19 had an increased mortality risk. AKI yielded increased mortality and ICU transfer than other forms of renal impairment. Mitigation strategies and proactively monitoring of renal impairment patients with COVID-19 need to be implemented in Hispanics.

COVID-19 Infection

Hispanic

Acute Kidney Injury

Mortality

In the United States, chronic kidney disease (CKD) affects 14.9% of the population with the largest percentage in the Hispanic population (15.3%). Hispanic patients observed to have a 2- to 3-fold increase in progression to end-stage renal disease (ESRD). In addition, Hispanic patients had 1.5 times higher rates of ESRD than the general population. The most common cause of ESRD in the U.S. is diabetes followed by hypertension and glomerular disease, which also has an increased incidence in the Hispanic population [1–4]. Southern states were also observed to have a higher rate of ESRD than northern states [1]. Patients with impaired kidney function also have higher rates of infections, especially genitourinary and pulmonary infections [5]. A systematic review shows that coronavirus disease (COVID)-19 patients had the most common comorbidity of CKD or renal diseases (51%) compared to other comorbidities in the U.S. [6].

It has been well-established that Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality, likely due to differences in access to care and exposure risk [7]. Through the increased inflammatory process and cytokine storm in COVID-19, there will be less tissue perfusion and organ damage, worsening the prognosis of patients through acute kidney injury or worsening preexisting kidney disease [8]. Patients infected with COVID-19 who have concurrent CKD also had a worse prognosis with increased morbidity and mortality, possibly due to nephrotoxic medication regimens, low kidney perfusion, and hypercoagulable states [9, 10].

Acute kidney injury (AKI) has been observed as a common complication in patients with COVID-19 infection, in addition to proteinuria in 40% of those admitted [11]. The COVID-19 virus enters cells via the angiotensin-converting enzyme 2 (ACE2) membrane protein. This protein is abundant in proximal renal tubule epithelial cells and podocytes, making the kidney a common target during infection [12]. Other previous studies have shown that the virus also enters target cells through cell surface receptor CD147, which is widely expressed in the kidney [13, 14]. As the virus enters the kidney cells, it causes degeneration of vacuoles, swelling of cells, and delamination of cells, as well as through the virus causing tubular damage due to the membrane attack complex and infiltration by CD68 + macrophages [15–17]. In addition, the virus causes cytokine storm, which leads to ischemia, hypoxia, fibrosis, rhabdomyolysis, intrarenal inflammation, and increased vascular permeability which all lead to further kidney damage [18–20]. Thus, we sought to determine the clinical outcomes and management of COVID-19-infected patients with concurrent kidney impairment through a large single-center study among Hispanic patients.

We conducted a retrospective cross-sectional study at a tertiary care hospital providing care support to a predominantly Hispanic population living on the Mexico-U.S. border. A patient list of 4,000 was requested from the University Medical Center (UMC) of El Paso from March of 2020 to March of 2021. Any adults aged 18–85 years, self-reported Hispanic ethnicity, positive test for COVID-19 using reverse transcriptase-polymerase chain reaction and hospitalized at UMC for over 48 hours were considered eligible for the study. Patients discharged from the emergency department, cancer patients, patients on chemotherapy, immunosuppressive or immunotherapy, human immunodeficiency virus, organ transplant patients, and patients co-infected with Flu A or B were excluded from this study. This study was conducted after obtaining institutional review board approval from the Texas Tech University Health Sciences Center El Paso.

Outcomes

The primary outcomes included mortality and ICU transfer, while secondary outcomes included duration of hospitalization, and oxygen (O₂) supplementation at discharge.

Exposure

As per our objectives, all COVID-19 patients were divided into two groups (renal impairment and non-renal impairment). Patients with renal impairment were defined as patients who were diagnosed with AKI, CKD, or ESRD prior to being admitted to the hospital and patients who were or were diagnosed with AKI while hospitalized. The data was extracted based on the ICD-10 codes. Based on the distribution of outcomes in renal impairments, we further compared all outcomes between AKI and normal patients infected with COVID-19.

Covariates

We comprehensively collected all confounders and treatments that may influence the relationship between renal impairment and clinical outcomes. We collected demographic, clinical risk factors, comorbidities, and treatment profiles, which include age, body mass index (BMI), vitamin D level, troponin, gender, and smoking, neurological symptoms, gastrointestinal symptoms, respiratory symptoms, cardiac symptoms, diabetes mellitus, metabolic syndrome, myocardial infarction, stroke, pneumothorax, gastrointestinal bleeding, thrombocytopenia, deep vein thrombosis, eye symptoms, hypertension, hyperlipidemia. Treatment variables included remdesivir, dexamethasone, prednisone, hydroxychloroquine, azithromycin, aspirin, selective serotonin reuptake inhibitors, vitamin D therapy, convalescent plasma, monoclonal antibodies, and therapeutic anticoagulants.

Statistical Analysis

Quantitative data were described either using mean and standard deviation (SD) or median and interquartile range (IQR). Categorical data were summarized using frequencies and percentages. Association between baseline characteristics and renal impairment disbursement was assessed using an unpaired t-test, Wilcoxon rank sum test, Chi-square test, and Fisher’s exact test as appropriate with the distribution and type of variables. The association between renal impairment and binary clinical outcomes were evaluated using unadjusted and adjusted relative risk models (Dwivedi). The relative risk models estimate relative risk (RR) which is equivalent to prevalence ratio in a cross-sectional study. However, the log-transformed length of stay was analyzed with ordinary linear regression analysis. In the adjusted analyses, we performed propensity scores-adjusted relative risk models using an inverse probability treatment weighting (IPTW) method [21]. The propensity scores were determined by estimating propensity of renal impairment using a multivariable logistic regression model. All the baseline characteristics were included in the propensity-scores model. The propensity scores models allowed us to adjust for numerous covariates influencing the association between exposure and outcomes. These analyses were also replicated for evaluating the association between AKI and each clinical outcome. The associations were summarized with RR or regression coefficient (RC), 95% confidence intervals (CI), and p-values. Statistical significance was considered at p-values less than 5%. All statistical analyses and data management were carried out using Stata V17 and followed as per the statistical analysis guidelines [21].

A total of 1,478 patients met the inclusion criteria and were included in the study analysis. Of these patients, 385 (26.0%) patients had an impaired renal function. The study sample showed patients with a mean age of 57.5 years and BMI of 31.1 kg/m². The sample also resulted in 58.7% males, 12.1% smokers, 52.9% diabetes mellitus, 49.2% hypertension, and 13.3% hyperlipidemia. Table 1 shows the differences in baseline characteristics between patients with or without renal impairment. Patients with renal impairment were seen to be significantly older (64.3±11.4 vs. 55.7±13.5, p=<0.001). Renal impairment patients were also noted to have significantly lower levels of low-density lipoprotein (71.0 vs. 93.5) and high-density lipoprotein (36.0 vs. 41.0). Troponin levels were noted to be significantly higher in renal impaired patients (0.02 vs. 0.01, p=<0.001). Additionally, patients with renal impairment reported more patients with diabetes mellitus (67.0% vs. 49.3%) and hypertension (67.0% vs. 43.2%). Renal impairment was also noted to have significantly more patients with thrombocytopenia (22.9% vs. 8.2%), myocardial infarction (11.4% vs. 5.17). However, renal impaired patients had lower levels of respiratory symptoms (72.0% vs. 82.8%). As for treatments, patients with renal impairment had lower rates of remdesivir (49.7% vs. 61.2%), prednisone (16.4% vs. 23.8%), azithromycin (39.0% vs. 57.4%), and deep vein thrombosis prophylaxis regimens (39.2% vs. 53.7%). In contrast, renal impaired patients had higher rates of aspirin (36.6% vs. 29.3%), statins (48.8% vs. 39.9%), SSRI (11.4% vs. 7.6%), monoclonal antibodies (2.6% vs. 1.0%), and therapeutic anticoagulants/warfarin (43.6% vs. 29.5%) (Table 1).

Table 1: Comparison of baseline clinical and treatment profiles between patients with or without renal impairment

		Renal Impairment
Factor	Overall	No	Yes	p-value
N	1478	987	385
Demographics
Age (years), mean (SD)	57.49 (13.62)	55.72 (13.47)	64.26 (11.41)	<0.001
Gender – Male	864 (58.70%)	563 (57.22%)	246 (64.06%)	0.023
Risk Factors and comorbidities
BMI (kg/m²), mean (SD)	31.09 (6.38)	31.31 (6.40)	30.32 (6.22)	0.015
Vitamin D level, median (IQR)	27.60 (18.80, 40.00)	28.50 (19.40, 39.80)	27.20 (17.20, 37.90)	0.260
LDL level, median (IQR)	91.00 (65.00, 115.00)	93.50 (67.50, 120.00)	71.00 (57.00, 99.00)	<0.001
HLD level, median (IQR)	40.00 (32.00, 48.50)	41.00 (33.00, 50.00)	36.00 (29.00, 45.00)	<0.001
Troponin, median (IQR)	0.01 (0.01, 0.02)	0.01 (0.01, 0.02)	0.02 (0.01, 0.11)	<0.001
Smoking - Yes	179 (12.11%)	127 (12.87%)	38 (9.87%)	0.140
Diabetes Mellitus	601 (52.90%)	361 (49.25%)	199 (67.00%)	<0.001
Neurological symptoms	377 (25.51%)	241 (24.42%)	111 (28.83%)	0.099
GI symptoms	813 (55.01%)	526 (53.29%)	201 (52.21%)	0.720
Respiratory symptoms	1180 (79.84%)	817 (82.78%)	277 (71.95%)	<0.001
Cardiac symptoms	399 (27.00%)	271 (27.46%)	104 (27.01%)	0.890
Myocardial infarction	96 (6.50%)	51 (5.17%)	44 (11.43%)	<0.001
Stroke	44 (2.98%)	25 (2.53%)	16 (4.16%)	0.120
Pneumothorax	45 (3.04%)	25 (2.53%)	18 (4.68%)	0.056
GI bleeding	63 (4.26%)	38 (3.85%)	23 (5.97%)	0.110
Thrombocytopenia	180 (12.18%)	81 (8.21%)	88 (22.86%)	<0.001
Eye symptoms	43 (2.91%)	32 (3.24%)	11 (2.86%)	0.860
Hyperlipidemia	196 (13.26%)	121 (12.26%)	63 (16.36%)	0.052
Hypertension	727 (49.19%)	426 (43.16%)	258 (67.01%)	<0.001
Treatments
Remdesivir	862 (58.40%)	604 (61.26%)	191 (49.74%)	<0.001
Dexamethasone	1061 (71.79%)	715 (72.44%)	269 (69.87%)	0.350
Prednisone	317 (21.45%)	235 (23.81%)	63 (16.36%)	0.003
Hydroxychloroquine	31 (2.10%)	22 (2.23%)	7 (1.82%)	0.830
Azithromycin	766 (51.83%)	566 (57.35%)	150 (38.96%)	<0.001
Aspirin	444 (30.04%)	289 (29.28%)	141 (36.62%)	0.010
Statin	617 (41.75%)	394 (39.92%)	188 (48.83%)	0.003
SSRI	122 (8.25%)	75 (7.60%)	44 (11.43%)	0.032
Vitamin D therapy	705 (47.70%)	477 (48.33%)	165 (42.86%)	0.071
Convalescent plasma	98 (6.63%)	67 (6.79%)	28 (7.27%)	0.720
Monoclonal antibodies	20 (1.35%)	10 (1.01%)	10 (2.60%)	0.042
Therapeutic anticoagulants/Warfarin	459 (31.06%)	291 (29.48%)	168 (43.64%)	<0.001
Therapeutic anticoagulant	451 (30.51%)	286 (28.98%)	165 (42.86%)	<0.001

All data were expressed with N(%) otherwise explained. SD: standard deviation; IRQ: interquartile range; BMI: body mass index; LDL: low-density lipoprotein; HDL: high-density lipoprotein; GI: gastrointestinal; SSRI: selective serotonin reuptake inhibitor

Comparison of clinical outcomes by renal impairment status

There was also a significant difference in mortality (33% vs. 12%, p=<0.001), ICU transfer (65% vs. 54%, p=<0.001), and O₂ supplementation at time of discharge (38% vs. 48%, p=0.007). The median hospital length of stay (HLOS) was found to be statistically different between renally impaired and non-renally impaired patients (11 days (5, 17) vs 11 days (6.4, 19), p=0.017) (Table 2).

Table 2: Unadjusted associations of renal impairment with each outcome.

	Renal Impairment
Outcomes	No	Yes	p-value
N	987	385
Mortality			<0.001
Discharged from Hospital	869 (88.22%)	256 (66.67%)
Died	116 (11.78%)	128 (33.33%)
ICU transfer			<0.001
No	452 (45.80%)	133 (34.55%)
Yes	535 (54.20%)	252 (65.45%)
O₂ supplementation at discharge			0.007
No	461 (52.45%)	162 (62.07%)
Yes	418 (47.55%)	99 (37.93%)
PE			1.000
No	635 (97.54%)	264 (97.42%)
Yes	16 (2.46%)	7 (2.58%)
HLOS, median (IQR); mean ± SD	11.00 (5.00, 17.00); 13.7±16.3	11.00 (6.40, 19.00); 14.3±12.7	0.017

IQR: interquartile range; SD: standard deviation; ICU: intensive care unit; O₂: oxygen; PE: pulmonary emboli; HLOS: hospital length of stay

Unadjusted and adjusted associations of renal impairment with clinical outcomes

In the unadjusted analyses, all the outcomes were found to be associated with renal impairment except pulmonary emboli (Table 2). COVID-19 patients with renal impairment had an increased risk of mortality (RR = 2.38; 95% CI: 2.2-3.64; p=<0.001) and ICU transfer (RR = 1.21; 95% CI: 1.04-1.4; p=0.014) while a decreased risk of O₂ at the time of discharge (RR = 0.79; 95% CI: 0.64-0.99; p=0.043). In the propensity scores-adjusted analyses, renal impairment was only significantly associated with increased risk of mortality (RR = 1.93; 95% CI: 1.38-2.71; p=<0.001). The results remained unchanged in the ordinary multivariable logistic regression analyses (Table 3).

Table 3: Unadjusted and adjusted associations of renal impairment with each clinical outcome variables

	Unadjusted association		PS-Adjusted association		Adjusted association
Outcomes	RR (95% CI)	p-value	RR (95% CI)	p-value	RR (95% CI)	p-value
Mortality	2.83 (2.2-3.64)	<.0001	1.93 (1.38-2.71)	<0.001	1.86 (1.31-2.63)	<0.001
ICU transfer	1.21 (1.04-1.4)	0.014	1.04 (0.95-1.14)	0.375	1.02 (0.84-1.24)	0.874
O₂ at discharge	0.79 (0.64-0.99)	0.043	1.09 (0.79-1.5)	0.609	1.01 (0.72-1.41)	0.968
	RC (95% CI)	p-value	RC (95% CI)	p-value
HLOS*	0.13 (0.02-0.23)	0.016	0.15 (-0.07-0.37)	0.191	0.02 (-0.07-0.1)	0.701

* Log transformed HLOS; RR: relative risk; RC: regression coefficient; CI: confidence interval; ICU: intensive care unit; O₂: oxygen; HLOS: Day of illness to patient discharge/death; PS-propensity scores-adjusted association was carried out using inverse probability of treatment weighting analyses. Adjusted regression analyses were carried out using multivariable logistic regression models

Comparison of clinical outcomes by renal impairment types

We compared clinical outcomes according to the different types of renal impairment, including AKI, CKD, and ESRD. There was a significant difference in mortality rates, O₂ at time of discharge, ICU transfer, and HLOS between types of renal impairment. Specifically, most deaths occurred in patients with AKI (Normal=12.4%, AKI=44% CKD=23.4%, ESRD=16.7%, p=<0.001), most ICU transfers occurred in AKI patients (Normal=53.7%, AKI=75.4%, CKD=53.1, ESRD=58.3% p=<0.001), most O₂ at discharge was observed in patients with normal renal function (Normal=47.8%, AKI=37.2%, CKD=38.8%, ESRD=38.0%, p=0.043), and longest HLOS estimated to be in AKI patients [Normal median=10 (IQR: 5,17), AKI median=13 (IQR:7, 20), CKD median=11 (IQR: 6, 19), ESRD median=9 (IQR: 4.95, 14.5)]. There was no significant difference in pulmonary emboli between groups (Table 4).

Table 4: Comparisons of all outcomes between renal impairment types

	Renal Impairment Type
Factor	Normal	AKI	CKD	ESRD	p-value
N	1095	195	128	60
Mortality					<0.001
Discharged from Hospital	956 (87.63%)	108 (55.67%)	98 (76.56%)	50 (83.33%)
Died	135 (12.37%)	86 (44.33%)	30 (23.44%)	10 (16.67%)
O₂ supplementation at discharge					0.043
No	505 (52.17%)	71 (62.83%)	60 (61.22%)	31 (62.00%)
Yes	463 (47.83%)	42 (37.17%)	38 (38.78%)	19 (38.00%)
ICU transfer					<0.001
No	507 (46.30%)	48 (24.62%)	60 (46.88%)	25 (41.67%)
Yes	588 (53.70%)	147 (75.38%)	68 (53.13%)	35 (58.33%)
PE					0.77
No	736 (97.61%)	153 (96.84%)	72 (97.30%)	37 (100.00%)
Yes	18 (2.39%)	5 (3.16%)	2 (2.70%)	0 (0.00%)
Day of illness patient discharge/death, median (IQR)	10 (5, 17)	13 (7, 20)	11 (6, 19)	9 (4.95, 14.5)	<0.001
Day of illness to patient discharge/death, mean (SD) *	2.30 (0.89)	2.56 (0.78)	2.38 (0.85)	2.13 (0.81)	<0.001

* Log transformed variable; SD: standard deviation; IQR: interquartile range; ICU: intensive care unit; O2: oxygen; PE: pulmonary emboli

Unadjusted and adjusted associations of acute kidney injury with clinical outcomes

In the unadjusted analyses, AKI patients infected with COVID-19 were associated with an increased risk of mortality (RR=3.58; 95% CI: 2.73-4.69; p=<0.001) and ICU transfer (RR=1.40; 95% CI: 1.17-1.68; p=<0.001) and extended HLOS (RC=0.26, 95% CI: 0.12-0.39; p=<0.001). However, AKI was not associated with O₂ supplements. In the propensity scores-adjusted analyses, AKI patients with COVID-19 remained significantly associated with increased risk of mortality (RR=1.83; 95% CI: 1.06-3.17; p=0.031) and ICU transfer (RR=1.22; 95% CI: 1.15-1.30; p=<0.001). The association between AKI and mortality was unchanged in the ordinary multivariable logistic regression analysis (Table 5).

Table 5: Unadjusted and adjusted associations of acute kidney injury with each clinical outcome variable

	Unadjusted association		PS-Adjusted association		Adjusted association
Outcomes	RR (95% CI)	p-value	RR (95% CI)	p-value	RR (95% CI)	p-value
Mortality	3.58 (2.73-4.69)	<0.001	1.83 (1.06-3.17)	0.031	1.98 (1.38-2.84)	<0.001
ICU transfer	1.40 (1.17-1.68)	<0.001	1.22 (1.15-1.30)	<0.001	1.12 (0.89-1.39)	0.331
O₂ at discharge	0.78 (0.57-1.07)	0.118	0.92 (0.45-1.89)	0.826	1.04 (0.69-1.56)	0.868
	RC (95% CI)	p-value	RC (95% CI)	p-value
HLOS*	0.26 (0.12-0.39)	<0.001	0.15 (-0.07-0.37)	0.191	0.08 (-0.02-0.18)	0.108

In this large cohort of Hispanic patients with COVID-19 infection, renal impairment was found to be associated with increased risk of mortality without associated risk of ICU transfer, O₂ at the time of discharge, pulmonary emboli, or HLOS. When analyzing AKI to patients with normal renal function, AKI patients were associated with increased risk of mortality and ICU transfer without any association with O₂ at the time of discharge, PE, or HLOS.

Previous studies have also shown similar outcomes of COVID-19 among renally impaired patients. In a large metropolitan study, the incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1–3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. When compared to patients without AKI, greater risks were observed for in-hospital death for patients with AKI 1–3 and AKI 3D [22]. Similarly, in our study with Hispanic patients, any form of renal impairment had an increased risk of death (RR: 2.83; p = < .001), with the largest significant difference occurring in patients with AKI (44%), compared to no renal impairment (12%), CKD (23%), or ESRD (17%). This increase in mortality in renally impaired patients may be due to hyperuricemic effects of the disease, causing decreased immunity and increased coagulability and inflammation [23–25].

The literature has also shown that the mortality of patients with AKI caused by COVID-19 ranged from 1.0–14.4% in non-ICU patients and increased to 21.8% in the ICU. It was seen that these patients in the ICU had increased exposure to renal hypoperfusion, sepsis, critical illness, and more co-morbidities, which may have contributed to AKI and mortality [26]. Some studies suggest that while cytokine storm may contribute to the AKI in COVID-19 infections, it may predominantly have to do with the COVID-19 N protein. This protein interacts with Smad3 in kidney cells and disrupts transforming growth factor β signaling, leading to cell cycle arrest and renal tubular cell necrosis [27]. Age has also been observed to be a risk factor for AKI. A meta-analysis by Lin et al. showed that age over 60 in COVID-19 patients was an independent risk factor for AKI [28]. In our study, patients with renal impairment were observed to be older than those without renal impairment. It was also observed that the odds of death from AKI were higher among men with AKI. Similarly, renal impairment in our study were significantly more men than women. Patients who developed AKI were 13 times more likely to have mortality than patients who did not [9]. Žulpaitė et al. conducted a retrospective study at a regional hospital and showed patients with AKI alone were 7.79 times more likely to die than those without CKD or AKI [29]. In our cohort, patients with AKI were found 1.2 times more likely to be in the ICU and 2.3 times more likely to die. If patients develop AKI from COVID-19 infection, the literature suggests that patients should undergo renal replacement therapy, fluid maintenance, maintenance of oxygen saturation, and avoidance of nephrotoxins [30].

While AKI in itself is concerning, not much emphasis has been placed on CKD [31]. Diabetes and hypertension are the leading causes of CKD in many developed countries, especially among Hispanic patients in the United States [2, 3, 32].In addition, it has been shown patients with CKD and ESRD are increasingly immunosuppressed and at an increased risk of COVID-induced pneumonia [33]. A literature review by Zhou S. et al. noted that mortality significantly increased with CKD and ESRD in patients infected with COVID-19, with CKD being greater [34]. Our study also showed a significant increase in mortality in both CKD and ESRD, with CKD was noted to be greater than ESRD as well. As for management, it was suggested that patients avoid diuretics in CKD and ESRD patients due to neutropenia and worsening of symptoms [35].

Diabetes and hypertension are considered independent risk factors for developing severe COVID-19, it is important to look at them in the context of developing heart complications such as a myocardial infarction (MI). Our results showed 6.5% of patients without renal impairment were found to have MI versus 11.43% with renal impairment. Additionally, 67% of our patients were found to have hypertension and diabetes mellitus, respectively. In relation to cardiovascular disease and COVID-19, hypertension and diabetes are noted as being the most prevalent comorbidities among individuals with COVID-19 who require hospitalization [36]. An important link between renin-angiotensin-aldosterone system dysregulation and cardiac injury as well as cardiac injury has been suggested (defined as elevated troponin I and inflammation biomarkers (IL-6 and C-reactive protein (CRP), hyperferritinemia, and leukocytosis)).

Thrombosis has been widely investigated and reported upon in COVID-19 in relation to systemic organ damage. It seems not a single organ is left untouched by this destructive mechanism. Evidence of fibrin deposits in glomerular loops supports the role of COVID-19 in dysregulating coagulation homeostasis leading to microcirculatory problems and AKI [37]. Pulmonary embolism was the most common manifestation, which may contribute to venous congestion and the development of AKI. Anti-coagulation was recommended in the setting of renal replacement therapies, but evidence was inconclusive regarding anticoagulant prophylaxis in AKI [38]. More recently, a retrospective study by Tang et al. showed that prophylactic anticoagulant therapy was associated with decreased mortality in COVID-19 patients [37]. This was further refined when a subsequent study not only suggested that thrombosis prophylaxis be given to all COVID-19 patients admitted to the ICU, but rather the specific use of high doses [39]. However, in considering these recommendations, to our knowledge, no data exists investigating the impact of anticoagulant therapy on renal outcomes. Overall, it is a reassuring finding that we found statistical significance in starting therapeutic anticoagulation for patients with renal impairment and our results showing no significant association with pulmonary emboli.

There are limitations within this study that should be addressed upon further research. First, these results were determined from a relatively small sample size of > 1,000 people. If research with larger sample sizes were to find similar results, conclusions made within this study would have a much greater impact. Additionally, as a retrospective study designed to discover different variables associated with COVID-19, randomization did not occur. Randomization within future studies investigating renal impairment in COVID-19 is needed.

Among the very valuable strengths of this study, the foremost is that it was among the first to examine the treatment of COVID-19 solely in a minority population, specifically Latinos. With health disparities surfacing during the pandemic, this research can provide important insight and lead to better health outcomes. Furthermore, this is a new study with no previous research exploring the concept among this population. Finally, this research brings evidence in support of the hypothesis that comorbidities, such as hypertension and diabetes, are associated with AKI and poor outcomes. It is hoped that greater understanding will spark more educational conversations and inspire change within patients to control their modifiable risk factors.

We observed significant evidence showing that patients with COVID-19 and renal impairment had poorer outcomes as measured by mortality, length of stay, and ICU admission. Patients with renal impairment were more likely to have comorbidities of hypertension and diabetes and subsequent myocardial infarctions, consistent with other well-known studies. Patients were more likely to have elevated troponin and thrombocytopenia and be treated with therapeutic anti-coagulants. We therefore suggest a focus on modifiable factors like hypertension, diabetes, and obesity which are within the grasp of the patient and will reduce their probability of developing renal impairment and overall mortality. Early and aggressive treatment of acute respiratory distress syndrome, sepsis, and AKI is critically needed to prevent prolongation of recovery since rates of AKI are strikingly similar to other forms of sepsis.

Ethics Approval and Consent to Participate:

This study involves human participants and was approved by the Texas Tech University Health Sciences Center El Paso Institutional Review Board. This study was conducted as a retrospective cohort study and was exempted.

Consent for Publication:

All authors have agreed to publish this manuscript.

Competing Interests:

The authors have no financial or proprietary interests in any material discussed in this article.

Funding:

None

Author Contribution

KH, FD designed this study. SK, JE, TL, KT, and KH participated in collecting data. FD, AD, SK, KH, and JE participated in data analysis. SK, KH, JE, FD, AD participated in interpreting the data. AD prepared figures 1-5. SK, KH, and JE participated in self drafting the manuscript. FD, AD participated in critical revising of the manuscript. All authors read and approved the final manuscript.

Acknowledgements:

None

Data Availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at the University Medical Center (UMC) of El Paso.

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The Effects of Acute Kidney Injury on COVID-19 related Clinical Outcomes and Mortality in a Hispanic Population

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