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Clinical implications of persistently increased blood urea nitrogen/serum creatinine ratio (PI-BUN/Cr) in severe COVID-19 patients

Pneumonia volume 16, Article number: 20 (2024) Cite this article

This article has been updated

Abstract

Background

Patients with COVID-19 may experience a persistent increase in the blood urea nitrogen over creatinine ratio (PI-BUN/Cr). Its elevation could reflect multiple underlying pathophysiological processes beyond prerenal injury but also warrants nuanced interpretation due to its complex interplay with various factors, underscoring the importance of investigating its effects on mortality and acute kidney injury in this population.

Methods

We analized a retrospective and longitudinal cohort of patients admitted to a single center in Mexico City for patients with severe COVID-19. Between March 5, 2020 and August 25, 2021, we included patients with confirmed positive diagnosis for SARS-CoV-2, age > 18 years, disease severity was defined by clinical data of respiratory distress syndrome and a ratio of partial oxygen pressure to inspired oxygen fraction < 300 mmHg on admission. We excluded patients with End Stage Kidney Disease. Data was obtained from electronic medical records. PI-BUN/Cr was defined as an increase in the BUN/Cr ratio > 30 in more than 60% of measurements in the hospital. The outcomes included: risk factors to mortality and AKI in-hospital.

Results

The cohort included 3,007 patients with a median age of 54.6 ± 14.5 years. 35% of patients died; 44.6% developed PI-BUN/Cr ratio and 71.4% AKI. Mortality was associated with older age > 60 years [Hazard ratio (HR)] = 1.45, 95% CI: 1.28–1.65; p < 0.001); male (HR 1.25, 95% CI 1.09–1.44; p = 0.002) and AKI (HR 3.29, 95% CI 2.42–4.46; p < 0.001); PI-BUN/CR & Non-AKI (HR = 2.82, 95% CI: 1.61–4.93; p < 0.001); Non PI-BUN/CR & AKI (HR = 5.47, 95% CI: 3.54–8.44; p < 0.001); and PI-BUN/CR & AKI (HR = 4.26, 95% CI: 2.75–6.62, p < 0.001). Only hiperuricemia was a risk factor for AKI (HR = 1.71, 95% CI: 1.30–2.25, p < 0.001).

Conclusions

While PI-BUN/Cr alone may not directly associate with mortality, its capacity to sub-phenotype patients according to their AKI status holds significant promise in offering valuable insights into patient prognosis and outcomes. Understanding the nuanced relationship between PI-BUN/Cr and AKI enhances our comprehension of renal function dynamics. It equips healthcare providers with a refined tool for risk stratification and personalized patient management strategies.

Introduction

In severe Coronavirus disease 2019 (COVID-19), multisystem inflammation and cytokine storm increase the catabolic state [1]. There has been limited research on the role of catabolic biomarkers in these patients [4, 5].

Serum urea and creatinine levels (SCr) are the end products of nitrogen metabolism in humans, which are overproduced in catabolic states; both are filtered by the glomerulus, but only urea is reabsorbed by 40–50% in the tubules [2]. Blood urea nitrogen (BUN) is a laboratory test that measures the amount of nitrogen from urea and is used in clinical practice as an index of kidney function [2, 3]. Their levels in the blood are influenced by a complex balance between production, metabolism, and excretion [2]. The blood urea nitrogen over creatine ratio (BUN/Cr), is indeed a diagnostic tool used to assess kidney function. In general, an elevated BUN/Cr ratio may indicate prerenal AKI. However, in seriously ill patients, its persistent elevation may have another connotatation [5].

Several cross sectional studies have associated the increase in BUN/Cr with high mortality in patients with acute decompensated heart failure [10], on hemodialysis [11], sepsis [12], trauma-related acute respiratory distress syndrome (ARDS) [14], and more recently, it has been identified as an independent predictor of severity and survival in COVID-19 patients [13]. In addition to a catabolic state, there are various factors that can affect the BUN/Cr in COVID-19 patients, such as increased neurohormonal activity, exogenous glucocorticoid-dependent catabolism, and upper gastrointestinal bleeding [6, 8, 9, 50].

Because the BUN/Cr ratio is a phenotype that reflects the severity of the disease, we conducted a research that can give us valuable information about the clinical implications of the persistently increased Blood Urea Nitrogen/Serum Creatinine Ratio (PI-BUN/Cr) in patients with COVID-19, which could lead to better risk stratification, better management, and a better understanding of the pathophysiology of the disease.

Materials and methods

Study design and patients

During the surge of COVID-19, the Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER) served as the largest hospital system providing care to patients with severe COVID-19 infection in Mexico. The INER Research Ethics Committee approved the study and waived the requirement for informed consent due to the retrospective design of the study (Approval No. E05-20). We included consecutive patients admitted with ARDS caused by SARS-CoV-2, as evidenced by a ratio of partial arterial oxygen pressure to inspired oxygen fraction (PaO2/FiO2) < 300 mmHg on admission [35], confirmed by a positive result on real-time transcription-polymerase chain reaction (rRT-PCR) test.

Patients with End Stage Kidney Disease (ESKD) and pregnant women, were excluded from the study as these factors could confound the interpretation of changes in serum creatinine (SCr) and blood urea nitrogen (BUN).

Data sources

Data on all patients admitted to the INER between March 5, 2020, and August 25, 2021, were obtained from electronic medical records. Our study included a total of 3,007 individuals. The database contains comprehensive information on demographics and clinical findings, with daily recording of blood laboratory results from admission to hospital discharge. Comorbidities such as obesity (Body mass index > 30), diabetes mellitus (DM), chronic kidney disease (CKD), congestive heart failure (CHF), and HIV/AIDS were extracted from interviews with patients or their relatives. Blood samples were evaluated using standard procedures in the central laboratory of INER.

Definitions

Baseline SCr was defined as the mean creatinine value between 7 and 365 days before hospitalization, which was available for 215 patients (7.18%). For those without a baseline SCr (n = 2792; 92.8%), the minimum creatinine value during hospitalization was used as the baseline creatinine, following the method described by Siew et al. [24].

AKI severity was staged according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria in each evaluation. Urine output criteria to define AKI were not used due to unreliable data collection [25].

The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation by SCr [26]. Patients with CKD-EPI < 60 ml/min/1.73, were classified as having CKD [27]. PI-BUN/Cr was defined as an increase in the BUN/Cr ratio > 30 in more than 60% of hospital measurements.

Kaplan Meier curves were plotted with BUN/Cr values of 30 and 31, and no differences were found regarding the mortality prognosis. Therefore, was decided to round the BUN/Cr value to 30.

Hyperuricemia was defined as a uric acid level at hospital admission higher than 6.5 mg/dL in women or 7.0 mg/dL in men.

Outcomes

The primary objective was to analyze risks factor for mortality and development of AKI in hospitalized patients with COVID-19, and whether PI-BUN/Cr had implications for these outcomes.

Statistical analysis

Descriptive statistics were summarized as mean (SD) or median (interquartile range [IQR]) for continuous variables and number (%) for categorical variables. The proportion of sociodemographic and clinical data, laboratory values in survivors vs. non-survivors were tested using Student’s T-test and Mann-Whitney testing for parametric and nonparametric continuous data respectively. The Pearson χ2 test and proportions test were applied to categorical variables. For multiple comparisons, the Bonferroni correction was performed.

Multivariate Cox proportional hazards regression models were fitted to evaluate association between variables of severity of the disease with mortality and AKI. Variables were entered into the models when the alpha level of risk factor was < 0.20 in the univariate analysis. All statistical test were two sided, and a p value < 0.05 was considered statistically significant.

We also performed the Kaplan-Meier survival analysis for the time to death, comparing the groups with Non PI-BUN/Cr & Non-AKI, PI BUN/Cr & Non-AKI, PI-BUN/Cr & AKI,

Non PI-BUN/Cr & AKI. Stata Statistics software (Version 14) was used for all statistical analysis.

Results

Characteristics of study population

Between March 5, 2020, and August 28, 2021, a total of 3,146 individuals were admitted to the INER. Among them, 13 individuals had a negative result for the SARS-CoV-2 rRT-PCR test, 6 patients had ESKD, we were unable to obtain complete information for 120 patients.

We included 3,007 patients in the study, 1,982 (66%) were men. Hypertension was present in 1,016 (33.8%) patients, diabetes mellitus (DM) in 885 (29.4%), obesity in 1,079 (35.9%), and chronic kidney disease (CKD) in 598 (19.9%); the average length of stay in the hospital was 20.8 (±16.5) days. A total of 1,040 (35%) died; 2,146 (71.4%) developed AKI, and 1,341 (44.6%) developed PI-BUN/Cr. Table 1 displays patient demographics, preexisting conditions, and laboratory values stratified by hospital survival.

Table 1 General characteristics of COVID-19 patients
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Patients who died were generally older and more likely to have hypertension, obesity and baseline eGFR < 60 ml/min/1.73 m2. On admission, biomarkers of inflammation, such as leukocytes, D-dimer, procalcitonine and C-reactive protein, were higher in the non-survivor group, as well as blood urea nitrogen (BUN), BUN/Cr ratio, and serum creatinine (SCr). Moreover, the non-surviving group had higher rates of invasive mechanical ventilation, use of vasoactive drugs, and incident acute kidney injury (AKI). Patients who died received with lower frecuency treatment with systemic intravenous steroids.

Median values of BUN/Cr, BUN and SCr from hospital admission to day 30 in non surviving vs. surviving patients

In all patients, Fig. 1A displays the median values of BUN/Cr per day in survivors vs. non survivors patients from admission to day 30. Figure 2 panel A, B and C, showed that in all patients, the slope was steeper in the mean values of BUN/Cr in non survivors vs. survivors patients [slope in non survivors patients = 0.386 (95% CI: 0.358, 0.414) vs. slope in survivivors patients = 0.187 (95% CI: 0.169, 0.205)], p < 0.001; the slope was steeper in the mean values of BUN in non survivors vs. survivors patients [slope in non survivors patients = 0.514 (95% CI: 0.470, 0.558) vs. slope in survivors patients = -0.348 (95% CI: -0.371, -0.325)], p < 0.001; and the slope was steeper in the mean values of SCr in non survivors vs. survivors patients [slope in non-survivors patients = 0.012 (95% CI: 0.010–0.014) vs. slope in survivors patients = -0.016 (95% CI: -0.017, -0.015), p < 0.001].

Fig. 1
figure 1

A, B and C. Illustrates the changes of BUN/Cr ratio from hospital admission to day 30, in all patients, Non AKI and AKI patients. Box plots in green represent the survivors patients and red box plots represent non survivors patients per day. Within each box, horizontal black lines denote median values; boxes extend from the 25th and 75th percentile of each group´s distribution values, vertical extending lines denote adjacent values (i.e., the most extreme values within the 1.5 interquartile range of the 25th and 75th percentile of each group); dots denote observations outside the range of adjacent values. Horizontal red line denote the cutoff of BUN/Cr ratio = 30. * Median differences between survivors and non survivors patients were evaluated using Mann-Whitney test, Bonferroni correction was performed and a significant difference was considered with a p-value < 0.002

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Fig. 2
figure 2

Visual representation of the blood urea nitrogen/serum Creatinine (mgdL/mgdL) slopes in all patients (A) and non AKI patients (B); blood urea nitrogen (mg/dL) slopes in all patients (C) and non AKI patients (D); and serum creatinine mg/dL slopes in all patients (E) and non AKI patients (F)

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In non-AKI patients, Fig. 1B shows the median values of BUN/Cr per day in non surviving vs. surviving patients from admission to day 30. Panel D, E and F, showed that in non-AKI patients, the slope was steeper in the mean values of BUN/Cr in non survivors vs. survivors patients [slope in non survivors patients = 1.311 (95% CI: 0.920, 1.702) vs. slope in survivors patients = 0.155 (95% CI: 0.107, 0.203)], p = 0.011; and a steeper slope in the mean values of BUN in non survivors vs. survivors patients [slope in nons survivors = 0.569 (95% CI: 0.394, 0.743) vs. slope in surviving patients = -0.008 (95% CI: -0.018, 0.035)], p < 0.001. There were no significant differences in the slopes of the mean values of SCr in non survivors vs. survivors patients [slope in non survivors patients = -0.005 (95% CI: -0.007, -0.003) vs. slope in survivors patients = -0.003 (95% CI: -0.004, -0.003), p = 0.590].

Characteristics of patients stratified by PI-BUN/Cr and AKI

A total of 620 patients (20.1%) neither had PI-BUN/Cr nor developed AKI during hospitalization (the Non PI-BUN/Cr & Non-AKI group); 233 patients (7.8%) developed PI-BUN/Cr but did not experience AKI (the PI-BUN/Cr & Non-AKI group); among AKI patients, 1,154 (38.7%) had PI-BUN/Cr (the PI-BUN/Cr & AKI group), and 979 (32.8%) did not have PI-BUN/Cr (the Non PI-BUN/Cr & AKI group) (see Table 1).

In AKI patients, the basal eGFR was higher in the group with PI-BUN/Cr, 79.21 ml/min/1.73 m² (SD ± 26.86) vs. 74.63 ml/min/1.73m2 (SD ± 31.36) in non-PI-BUN/Cr, p < 0.001; in addition, the final eGFR was higher in the group with PI-BUN/Cr, 82.35 ml/min/1.73 m2 (SD ± 41) vs. 71 ml/min/1.73 m2 (SD ± 44), p < 0.001. AKI severity (AKI stages 2–3) was lower in patients with PI-BUN/Cr, 368 (27.4%) vs. 507 patients (30.4%) in the non-PI-BUN/Cr group, p < 0.001. There were no differences in mortality in the group of patients with Non-PI-BUN/Cr 444 (42.9%) vs. PI-BUN/Cr 540 (52.2%), p = 0.506.

In the group with non-AKI, mortality was higher in the group with PI-BUN/Cr, 27 (11.59%) vs. 23 (3.71%) in the non PI-BUN/Cr, p < 0.001.

Survival curves for all groups decreased over time, the decrease was steeper in the groups PI-BUN/Cr & Non-AKI, Non PI-BUN/Cr & AKI, and PI-BUN/Cr & AKI groups compared to the Non PI-BUN/Cr & Non-AKI group (p < 0.001), Fig. 3.

Fig. 3
figure 3

Kaplan-Meir survival curves. Time to death for the Non PI-BUN/Cr & Non-AKI group (green line), the PI-BUN/Cr & Non-AKI group (orange line), the Non PI-BUN/Cr & AKI (blue line) and the PI-BUN/Cr & AKI (brown line). Time 0 corresponded to hospital admission. All patients were censored at 30 days. Patients who were discharged alive before 30 days were treated as still as risk and not censored at discharge

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Characteristis of patients requiring kidney replacement therapy (KRT)

One hundred fifty-nine patients required KRT, of which 115 (72.3%) died. The requirement for KRT was greater in the group of patients with non-PI-BUN/Cr, 89 (56%), compared to the group with PI-BUN/Cr, 70 (44%), p = 0.008.

The univariate and multivariate analysis after adjustment to age > 60 and male gender indicates that PI-BUN/Cr was a risk factor for requiring KRT (HR = 1.53, 95% CI = 1.05–2.23, p = 0.026) and (aHR = 1.52, 95% CI = 1.04–2.22, p = 0.030) respectively.

Risk factors for mortality

Univariate and multivariate Cox regression analysis revealed that several factors were associated with higher mortality, including age above 60 years, male gender, and AKI; PI-BUN/Cr was not associated with mortality. Conversely, the use of intravenous steroids decreases the risk significantly (Table 2, model A). Subsequently, we built a model that stratified patients based on whether or not they had PI-BUN/Cr and AKI status, and we observed a greater risk of mortality in the groups with EPI-BUN/CR & No-AKI, No PI-BUN/Cr & AKI, and PI-BUN/Cr & AKI. (Table 2, model B).

Table 2 Univariate and multivariate risk factors for mortality
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Risk factors for AKI

The univariate analysis indicated that patients with baseline hyperuricemia had a higher risk of AKI (HR = 1.68, 95% CI = 1.42–1.98, p < 0.001); and higher serum levels of procalcitonine > 1.0 ng/ml (HR = 1.79, 95% CI = 1.25–2.55, p = 0.001). After adjusting for possible confounding variables, the multivariate analysis indicated that only hyperuricemia was a risk factor for AKI (HR = 1.71, 95% CI = 1.30–2.25, p < 0.001) Table 3.

Table 3 Univariate and multivariate risk factors for AKI in COVID-19 patients
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Discussion

During the COVID-19 pandemic, patients with severe illness experienced overwhelming inflammatory and catabolic states leading to increased risk of complications and organ dysfunction [36]. The BUN/Cr ratio, a simple and routinely available biomarker of kidney function can have limitations in terms of its accuracy and ability to fully characterize kidney involvement or disease severity when taken as a single sample o in isolation [2, 3, 5]. However, its continuous monitoring has been shown to be an appropriate than frames a phenotype by being in a severe catabolic state [17]. We aimed to investigate the impact on mortality and development of AKI in patients with PI-BUN/Cr.

In our cohort of patients with severe COVID-19, the risk factor for mortality were older age, male gender and AKI. Likewise, after characterizing the patients into groups based on their BUN/Cr ratio and presence or absence of AKI, we observed a higher risk of death in the groups of patients with PI-BUN/Cr & Not AKI, Not PI-BUN/Cr & AKI, and PI-BUN/Cr & AKI. Only hyperuricemia was a risk factor for AKI.

In this research, we integrated an extensive retrospective longitudinal data from Mexican patients hospitalized with severe COVID-19, making it the largest study of its kind. Initially, we observed significantly higher levels of BUN/Cr ratio in patients who died daily. These changes were particularly rapid and pronounced in patients without AKI (Fig. 1A, B & C). To better understand this disproportionate elevation of BUN/Cr in non survivors patients, we analyzed the BUN and creatinine slopes separately; and we found, that the increase was mainly due to elevated BUN slopes (Fig. 2, panel B & E) rather than a decline in serum creatinine slopes (Fig. 2, panel C & F). These findings align with previous studies in patients with severe disease, which suggest that the BUN/Cr ratio is mainly increased by excessive BUN generation (catabolic state) combined with increased renal tubular reabsorption (neurohormonal activity) [7, 10, 11, 14]. This opposite trend between creatinine and urea contributes to elevated BUN/Cr levels [2]. Several cross-sectional and longitudinal studies in seriously ill patients, have given the BUN/Cr ratio a role that reflects a catabolic phenotype that are linked to adverse outcomes [7, 11, 14]. Recently, one study in patients with COVID-19 showed that a BUN/Cr > 33, was an independent predictor of disease severity and survival [13]. In our research, we found similar cut-off points for the BUN/Cr ratio in severe COVID-19 patients. These values ​​are higher than those traditionally described for prerenal azotemia, a term that has been dogmatically associated with better outcomes than other forms of AKI [31, 37, 38]. The disproportionately high values of the BUN/Cr ratio in COVID-19 patients takes the opposite direction in terms of prognosis [10, 11, 30], and its increase should be interpreted taking into account the clinical context and the pathophysiological states that influence its elevation [6, 8, 9].

An elevated BUN/creatinine ratio may indicate renal failure, which may exacerbate overall clinical severity and contribute to multiple organ dysfunction. Furthermore, it could reflect underlying physiological alterations, such as dehydration, reduced renal perfusion, or systemic inflammation, all of which are associated with worse outcomes in patients with COVID-19. To further quantify this persistent state of severity, we created the variable PI-BUN/Cr that could reflect a subphenotype involved in adverse outcomes.

In our research, PI-BUN/Cr was not directly associated with mortality or the development of AKI during hospitalization. However, after stratifying patients based on both AKI status and PI-BUN/Cr, we notice different characteristics. In non-AKI patients but with PI-BUN/Cr, the risk of mortality was markedly increased and suggest that this sub-phenotype may capture aspects of systemic illness serverity beyond just renal dysfunction.

On the other hand, the PI-BUN/Cr in patients with AKI allowed us to identify a series of characteristics that have several clinical implications. Firstly, these patients tend to present with better baseline eGFR, indicating relatively healthier kidney function prior to the onset of AKI. Secondly, the group with the PI-BUN/Cr phenotype are less likely to progress to stages 2–3 of AKI and required KRT. Lastly, the group with PI-BUN/Cr was discharged with better eGFR indicates potential recovery of renal function during hospitalization. This last point should be taken with considerable restrained because one possible interpretation is that better eGFR at discharge is a reflection of having had less severity of AKI or rather, the PI-BUN/Cr sub-phenotype caused greater muscle consumption that was reflected in lower serum creatinine levels at discharge [53].

Despite, both groups having an elevated risk of death, it appears that patients with non PI-BUN/Cr sub-phenotype face a higher mortality risk compared to those with the sub-phenotype. In this regard, the severity of AKI [47, 48] and the baseline eGFR [49] in the group non PI-BUN/Cr & AKI were critical factors that could impact in the prognosis and survival of this patients. This differentiation based on PI-BUN/Cr is similar in some results to that described by Rachoin et al [30].

The utilization of diverse biomarkers has indeed offered a more nuanced understanding of AKI. By leveraging these biomarkers, researchers and clinicians can distinguish between various subtypes of AKI, each with its own underlying causes, physiological processes, and prognostic implications [33, 40]. In this context, the use of PI-BUN/Cr to sub-phenotyping AKI, could allowed us to understand various pathophysiological mechanisms involved in its elevation and that led to mortality [45].

In line with previous researchers, AKI was strongly associated with mortality. The incidence of AKI in our cohort was 71.4%, an incidence that has been also reported in other studies. Large observational studies and meta-analyses report an AKI incidence of 28–34% in all inpatients and 46–77% in intensive care unit (ICU) [51]. The reasons for a high number of patients with COVID-19-associated AKI seen in our center can stem from various factors including the fact that our center was transformed into a COVID-19 reference center and most severe cases of COVID-19 were refered and admitted most of them requiring IMV, most of patients had systemic inflammation, pre-existing kidney conditions in Mexican population, and the presence of comorbidities such as hypertension or diabetes, all of which can contribute to renal complications [52].

Furthermore, we observed that hyperuricemia was a risk factor for the development of AKI. In COVID-19 patients, higher mortality, greater oxygen requirements and longer hospital stays have been observed in patients with hyperuricemia. To our knowledge, hyperuricemia had not been associated with AKI in patients with covid-19. Uric acid can potentially cause kidney damage by impairing renal autoregulation [42, 44, favoring the activation of an inflammatory cascade and causing direct cytotoxic damage of the renal cells or through the intratubular deposit of crystals [34, 43].

Given the complex and multifactorial nature of AKI in COVID-19, we incorporated procalcitonin serum level at a cut point linked to severe sepsis, conditions characterized by systemic inflammation and organ dysfunction, including AKI [39, 40]. However, the limited availability of procalcitonine measurement in our study population may have hindered the ability to detect significant associations.

Limitations, strengths and weakness

Our study had a number of limitations. First, the inherent limitation of a retrospective observational study, that was limited to a single center involving only Mexican population. Second, these findings may not apply to non COVID-19 populations. Third, although we did careful data analysis, our database was designed from electronic medical records, and we had limited information on renal function status before hospital admission, which could influence the definition of AKI and CKD. Fourth, data from our medical records may not capture relevant information about the fluid status including urine output which are relevant for the analysis of some outcomes, including the AKI definition. Finally, measures to estimate baseline SCr can either underestimate or overestimate AKI incidence, which affect outcomes associated with presumed AKI. We used prehospitalization SCr values whenever available or first SCr measured at admission minimize bias as AKI incidence and outcomes can be significantly affected with the use of the other various surrogate methods.

This study has the main advantage of being one of the first in patients with COVID-19 with a daily longitudinal follow-up that allowed us to be strict in the variables designed.

Conclusions

PI-BUN/Cr, as a readily accessible and cost-effective marker derived from routine laboratory assessments, emerges as a pivotal phenotype indicative of a profound catabolic state linked to adverse outcomes in severe COVID-19 patients. This study underscores the critical significance of ongoing surveillance of the BUN/Cr ratio, shedding light on its prognostic implications and the necessity for a nuanced comprehension of the underlying pathophysiological mechanisms governing its sustained elevation.

The implications of these findings extend beyond mere clinical observation, emphasizing the imperative for proactive intervention strategies to mitigate the detrimental impact of heightened catabolic states in COVID-19. Continuous monitoring of PI-BUN/Cr levels holds promise as a predictive tool, empowering healthcare practitioners to anticipate and address potential complications, thereby optimizing patient care trajectories and enhancing overall prognosis.

Data availability

All data generated and analyzed during this study will be available via email by requesting it directly from the corresponding author.

Change history

  • 14 November 2024

    Following publication of the original article, the authors identified an error in the author name of Luz María Torres-Espíndola. The given name and family name were erroneously transposed.

Abbreviations

PI-BUN/CR:

Persistent increase in the blood urea nitrogen over creatinine ratio

AKI:

Acute Kidney Injury

COVID-19:

Coronavirus disease 2019

SCr:

Serum creatinine

BUN:

Blood urea nitrogen

BUN/Cr:

Blood urea nitrogen over creatinine

ARDS:

Acute Respiratory Distress Syndrome

INER:

Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas

PAFIO2:

Partial arterial oxygen pressure to inspiratory oxygen fraction

ESKD:

End stage kidney disease

KRT:

Kidney replacement therapy

CKD:

Chronic kidney disease

DM:

Diabetes mellitus

CHF:

Chronic heart failure

KDIGO:

Kidney disease global outcomes

eGFR:

Estimated glomerular filtration rate

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Acknowledgements

Not applicable.

Funding

This work was carried out by medical specialists from different Institutes dependent on the Secretary of Health of the government of Mexico, we did not receive additional funds for the current research than our assigned salary.

Author information

Author notes

  1. Gustavo Casas Aparicio, Rosario Fernández Plata, and Anjarath Higuera Iglesias have the same contribution as the first authors.

  2. David Martínez Briseño, Luz María Torres Espíndola, Arnoldo Aquino Gálvez and Hugo Ahumada Topete contributed equally to this work.

Authors and Affiliations

  1. Titular de la Coordination de Nefrología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México, 14080, México

    Gustavo Casas Aparicio & Arnoldo Aquino-Gálvez

  2. Unidad de Epidemiología Hospitalaria e Infectología, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de México, 14080, CP, México

    Rosario Fernández Plata, Anjarath Higuera Iglesias, David Martínez Briseño, Manuel Castillejos Lopez, Graciela Hernández Silva & Victor Hugo Ahumada Topete

  3. Division de Nefrología, Cochabamba Bolivia and IIBISMED, Facultad de Medicina, Universidad Mayor de San Simón, Hospital Obrero No. 2 – CNS, Cochabamba, Bolivia

    Rolando Claure-Del Granado

  4. Laboratorio de Biología Molecular de Enfermedades Emergentes y EPOC, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México, 14080, México

    Joel Vázquez Pérez

  5. Departmento de Investigación en Biomedicina Molecular e Investigación Translacional, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México, 14080, México

    Noé Alvarado Vásquez

  6. Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica, Periferico Sur 4809, Ciudad de México, 14610, Mexico

    Rafael Velázquez Cruz

  7. Laboratorio de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México, 14080, México

    Victor Ruiz

  8. SecciÓn de Estudios de Posgrado e InvestigaciÓn, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz MirÓn s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, Ciudad de México, 11340, México

    Victor Ruiz

  9. Laboratorio de Inmunobiología y Genética, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Ciudad de México, 14080, México

    Ángel Camarena

  10. Laboratorio de Patología, Instituto Nacional de Neurología y Neurocirugía “Manuel Velazco Suarez”, Insurgentes Sur 3877, Ciudad de México, 14269, México

    Citlaltepetl Salinas Lara & Martha Tena Suck

  11. Departamento de Neuropatologia, Instituto Nacional de Neurología y Neurocirugia, Manuel Velasco Suarez, Insurgentes Sur 3877, Ciudad de México, 14269, México

    Citlaltepetl Salinas Lara

  12. Facultad de Estudios Superiores Iztacala (Programa MEDICI), Universidad Nacional Autónoma de México, Av. de los Barrios 1, Tlalnepantla de Baz, Ciudad de México, 54090, México

    Iñaki Montes de Oca Ambriz, Oswaldo Ortiz Toledo, Vianey Arvizu Serrano & Yared Almazan Chaparro

  13. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, 04510, México

    Edgar Flores-Soto

  14. Laboratorio de Farmacología, Instituto Nacional de Pediatría, Insurgentes Sur 3700, Ciudad de México, 04530, México

    Luz María Torres-Espíndola

Authors
  1. Gustavo Casas Aparicio
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  2. Rosario Fernández Plata
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Contributions

Authors contributions: Conceptualization GCA, MCL, and VHA; Methodology, RFP, DMB, RVC, MTS, IMO, GHS, and CSL; Supervision, AHI, AAG, and LMT; Visualization, EFS, YSA, VMA, OOT, JVP, VR, and AC; Writing-Original draft preparation and Writing-Review and editing: LMT, VR, GCA and MCL; Writing-original draft preparation: RCG.

Corresponding authors

Correspondence to David Martínez Briseño or Manuel Castillejos Lopez.

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The Institutional Review Board approved the study (Approval No E05-20).

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Not applicable. Given the retrospective nature of the study, we obtained a waiver of informed consent from the ethics committee.

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The authors declare no competing interests.

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Casas Aparicio, G., Fernández Plata, R., Higuera Iglesias, A. et al. Clinical implications of persistently increased blood urea nitrogen/serum creatinine ratio (PI-BUN/Cr) in severe COVID-19 patients. Pneumonia 16, 20 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41479-024-00140-0

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Keywords

Pneumonia

ISSN: 2200-6133

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