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BMJ Open
BMJ Open
bmjopen
bmjopen
BMJ Open
2044-6055
BMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR

39038861
10.1136/bmjopen-2024-085912
bmjopen-2024-085912
Original Research
Neurology
1713
1506
Association between blood urea nitrogen to creatinine ratio and 3-month outcome in patients with acute ischaemic stroke: a retrospective cohort study from a large healthcare system
Wang Liumin 1wliumin113@163.com

Zhu Xinmei 1zhuxm24@tkhealthcare.com

Li Hui 2lihui195@tkhealthcare.com

Jia Boluo 3563059166@qq.com

Xie Wen 1xiewen08@tkhealthcare.com

Zhang Yanli 1zhangyl198@tkhealthcare.com

Wang Lina 1wangln66@tkhealthcare.com

Liu Ling 4*0liuling8210@126.com

http://orcid.org/0000-0001-7242-5786
Li Mingquan 10lmqneurology@163.com

1 Department of Neurology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
2 Taikang Community Su Garden, Nanjing, China
3 Nanjing Qixia District Xigang Community Health Service Center, Nanjing, China
4 Department of Neurology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
DrMingquanLi; lmqneurology@163.com
DrLingLiu; liuling8210@126.com
None declared.

LL and ML contributed equally.

2024
22 7 2024
14 7 e08591229 2 2024
09 7 2024
Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Abstract

Objectives

The blood urea nitrogen to creatinine (BUN/Cr) ratio is associated with early neurological deterioration in acute ischaemic stroke (AIS). However, the predictive value of the BUN/Cr ratio for the AIS prognosis remains unclear. Therefore, we evaluated the correlation between the BUN/Cr ratio and the 3-month outcome in patients with AIS, further testing their dose–response relationship.

Design

This retrospective cohort study enrolled patients with AIS who were admitted between 1 January 2013 and 31 May 2022. Poor clinical outcome was defined as 3-month Modified Rankin Scale (mRS) >2. Cox proportional HR was used to evaluate the correlation between the BUN/Cr ratio and 3-month outcome. Restricted cubic spline and robust locally weighted regression analyses were conducted to determine the dose–response relationship between the BUN/Cr ratio and the 3-month outcome.

Results

A total of 4952 eligible patients were included in the study. The patients were divided into three groups according to the tertiles of BUN/Cr ratio (T1, <0.071; T2, 0.071–0.093; and T3, >0.093). After logistic regression adjustment for demographic and clinical characteristics, the BUN/Cr ratio was found to be independently associated with the 3-month outcome in patients with AIS. The restricted cubic spline and locally regression smoothing scatterplot graph showed a strong dose–response relationship between the BUN/Cr ratio and the 3-month outcome in patients with AIS.

Conclusion

A dose–response relationship was observed between the BUN/Cr ratio and the 3-month outcome in patients with AIS, suggesting that the BUN/Cr ratio could serve as a reliable predictor for the AIS prognosis.

stroke
clinical decision-making
neurology
the Scientific Research Foundation of Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University No. TKKYZD20232602 Clinical Medical Research Projects of Nanjing Health Commission YKK20228
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pmcSTRENGTHS AND LIMITATIONS OF THIS STUDY

We used more flexible functions (limited cubic splines and locally regression smoothing scatterplot) to detect the dose–response relationship between blood urea nitrogen to creatinine ratio and 3-month outcome in patients with acute ischaemic stroke.

The main limitation was the retrospective observational design, and selection bias could not be avoided.

The short follow-up periods may affect the final outcome and compromise the prevalence.

Introduction

The incidence of acute ischaemic stroke (AIS) has been increasing mainly due to the ageing population. Statistical data have shown that AIS is gradually becoming one of the leading causes of death and long-term disability in patients worldwide.1 Thus, timely identification of patients with AIS with poor prognosis and corresponding adjustments to treatment strategies are crucial. Several studies have reported the predictive potential of certain haematological markers for disease prognosis.24 However, the scarcity of effective and reliable haematological markers for assessing AIS prognosis in clinical practice remains an important issue.

The risk of dehydration in patients with AIS is substantially increased by the combination of impaired consciousness, dysphagia and aphasia.5 6 Previous studies have shown that dehydration in patients with AIS can worsen cerebral ischaemia and affect the disease prognosis.7 Therefore, early detection of dehydration in patients with AIS and timely intervention are imperative. At present, the commonly used marker for evaluating dehydration is the blood urea nitrogen to creatinine (BUN/Cr) ratio.8 Bhatia et al9 found that a BUN/Cr ratio >15 at admission is an independent risk factor for early neurological deterioration (END). Another study also reported that an elevated BUN/Cr ratio is associated with poor 3-month outcome in patients with AIS with high-density lipoprotein (HDL).10 However, no studies have explored the dose–response relationship between the BUN/Cr ratio and the 3-month Modified Rankin Scale (mRS) outcome in patients with AIS.

The present study aimed to evaluate the correlation between the BUN/Cr ratio and the 3-month mRS outcome using the proportional HR of Cox models and further examine the dose–response relationship between them.

Materials and methods

Study design

The data used in this study were obtained from two tertiary-care hospitals (Department of Neurology of Taikang Xianlin Drum Tower Hospital and Jinling Hospital, both affiliated with the Medical School of Nanjing University).2 4 11 The research group prospectively collected data from patients with AIS admitted from 1 January 2013 to 31 May 2022. From 1 January 2013 to 31 May 2022, patients with AIS were continuously enrolled in the Nanjing Stroke Registry Program. All procedures that involved human participants were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments of comparable ethical standards.12

AIS was diagnosed according to the latest diagnostic guidelines.13 The inclusion criteria were patients who underwent whole blood examination and brain imaging (CT, MRI or both) within 24 hours after the onset of AIS. The exclusion criteria were (1) patients with concomitant cancer and (2) patients who discontinued treatment or died from non-medical reasons (eg, hospital transfer, suicide or financial reasons).

Covariates

The acquisition and processing of baseline blood sample parameters and clinical information were similar to those in our previous studies.2 11 All data were extracted from the electronic medical record system, including patient demographics and disease characteristics (Trial of ORG in Acute Stroke Treatment (TOAST) classification and baseline stroke severity). The vascular risk factors for stroke were also determined, such as hypertension, diabetes mellitus, hypercholesterolaemia, coronary heart disease, atrial fibrillation, a history of stroke, and current smoking and drinking habits. The classification of smoking or drinking patients has been reported in our previous studies.2 11 The National Institutes of Health Stroke Scale (NIHSS) scores were collected at admission, and scores exceeding 14 were defined as severe stroke. The primary end point for this study was 3 months of mRS after discharge. A specialised neurologist used mRS to evaluate the prognosis of patients via telephone follow-up. A 3-month mRS of >2 indicated a poor clinical prognosis.

BUN/Cr ratio and serum biomarker are testing

After admission, venous blood samples of patients in the fasting state were collected for routine blood examination, including haemoglobin and C reactive protein, and serum biochemistry analysis, including blood urea nitrogen, creatinine, estimated glomerular filtration rate (eGFR), albumin and homocysteine. An eGFR rate of <60 mL/min/1.73 m2 was considered to indicate chronic kidney disease (CKD).14

Statistical analysis

We compared the baseline characteristics of patients according to the tertiles of the BUN/Cr ratio. BUN/Cr tertiles were <0.071 (tertile 1), 0.071–0.093 (tertile 2) and >0.093 (tertile 3). The reference group for the analyses was the lowest tertile (T1 group). Data that conformed to the normal distribution and equality of variance were analysed via one-way analysis of variance using the Bonferroni multiple comparison test; otherwise, the Kruskal–Wallis test was employed. The χ2 test was used to compare the categorical variables among the three groups. Because the BUN/Cr ratio was a continuous variable, we tested the correlation between the BUN/Cr ratio and other continuous variables using Pearson’s correlation. The proportional HR of Cox models was used to evaluate the association between the BUN/Cr ratio and the 3-month mRS outcome. Furthermore, we constructed dose–response curves using constrained cubic splines (two sections) and robust local weighted regression and smoothed scatter plots. The optimal cut-off points for continuous variables in multivariate models were determined on the basis of previous research and clinical guidelines.15 In terms of sensitivity, we further adjusted for variables that may have confounding factors. In the case of missing data in the covariates, multiple imputation was employed. To verify the predictive value of the BUN/Cr ratio for stroke prognosis, we plotted a receiver operating characteristic (ROC) curve. All statistical tests were two-sided at the significance level of p=0.05. All analyses were conducted using Stata V.17.0 for Mac (StataCorp).

Patient and public involvement

No patients were involved.

Results

Baseline characteristics

Between January 2013 and May 2022, 4974 patients with AIS underwent qualification evaluations. Among them, 22 were excluded and 4952 were included in the study. According to the BUN/Cr ratio tertiles, eligible patients were divided into three groups: T1, <0.071; T2, 0.071–0.093; and T3, >0.093. The prevalence of dysphagia was 3%. There was no difference in the prevalence of dysphagia between the three groups. The baseline data indicated that the patients with higher BUN/Cr levers were mostly female and had higher body mass index (BMI) values. Furthermore, the incidence of diabetes and coronary heart disease, the risks of severe stroke (NIHSS>14) and 3-month mortality were higher in patients with higher BUN/Cr levels. Conversely, patients with higher BUN/Cr levels had substantially lower rates of smoking and alcohol consumption as well as lower levels of homocysteine, haemoglobin and serum albumin (table 1).

Table 1 Baseline characteristics of acute ischaemic stroke patients according to BUN/Cr tertile

	All	BUN/Cr tertile	P value	
T1	T2	T3	
<0.071	0.071–0.093	>0.093	
n	4952	1652	1652	1648	
Age, y, X±SD	61.49±2.14	59.98±17.97	61.49±12.26	63.02±10.92		
Male, n (%)	3525 (71.16)	1421 (86.02)	1221 (73.91)	882 (53.52)	<0.001	
BMI, kg/m2, X±SD	26.90±6.54	26.56±6.35	26.78±6.33	27.07±6.92	<0.001	
Vascular risk factors						
 Hypertension, n (%)	3184 (64.48)	1045 (63.49)	1065 (64.58)	1074 (65.37)	0.527	
 Diabetes mellitus, n (%)	1304 (26.39)	360 (21.83)	421 (25.53)	523 (31.83)	<0.001	
 Hypercholesterolaemia, n (%)	2568 (51.86)	883 (53.45)	825 (49.94)	860 (52.18)	0.123	
 Coronary heart disease, n (%)	301 (6.11)	82 (4.98)	104 (6.33)	115 (7.02)	0.045	
 Atrial fibrillation, n (%)	351 (7.12)	114 (6.93)	115 (6.99)	122 (7.45)	0.818	
 Previous stroke, n (%)	676 (13.72)	213 (12.98)	231 (14.03)	232 (14.15)	0.560	
 Current smoker, n (%)	1949 (39.49)	784 (47.57)	672 (40.83)	493 (30.02)	<0.001	
 Current drinking, n (%)	1185 (24.03)	468 (28.45)	404 (24.53)	313 (19.09)	<0.001	
 Family history of stroke, n (%)	151 (3.07)	52 (3.17)	46 (2.81)	53 (3.24)	0.744	
Stroke features						
NIHSS admission score, median (IQR)		9 (5–12)	9 (6–13)	8 (5–12)	<0.001	
 ≤14	4386 (88.57)	1522 (92.13)	1491 (90.25)	1373 (83.31)	0.012	
 >14	566 (11.43)	130 (7.87)	161 (9.75)	275 (16.69)	<0.001	
Prestroke treatment, n (%)						
 Antiplatelet agents, n (%)	4803 (98.28)	1604 (98.34)	1598 (98.34)	1601 (98.16)	0.900	
 Statin, n (%)	4842 (99.24)	1622 (99.51)	1612 (99.32)	1608 (98.89)	0.116	
Acute treatment, n (%)						
 Venous thrombolysis, n (%)	199 (4.08)	62 (3.81)	68 (4.20)	69 (4.24)	0.793	
TOAST subtype					<0.001	
 LAA, n (%)	3697 (74.66)	1194 (72.28)	1242 (75.18)	1261 (76.52)		
 SAO, n (%)	413 (8.34)	158 (9.56)	138 (8.35)	117 (7.10)		
 CE, n (%)	485 (9.79)	154 (9.32)	154 (9.32)	177 (10.74)		
 SOD, n (%)	155 (3.13)	53 (3.12)	51 (3.09)	51 (3.09)		
 SUD, n (%)	202 (4.08)	93 (5.63)	67 (4.06)	42 (2.55)		
Serum biomarkers						
 Homocysteine (mmol/L)	14.84±9.96	17.49±12.09	14.57±9.64	12.68±7.18	<0.001	
 C reactive protein (mg/L)	2.5 (0.8, 8.3)	2.7 (0.9, 8.6)	2.3 (0.7, 7.4)	2.5 (0.8, 8.7)	0.178	
 Haemoglobin (g/L)	137.62±18.07	139.12±18.44	138.62±17.19	115.12±18.29	0.008	
 Albumin (g/L)	39.42±4.86	39.48±4.93	39.70±4.48	39.07±5.15	<0.001	
 Blood urea nitrogen (mmol/L)	5.79±2.48	4.81±2.26	5.55±1.69	7.00±2.83	<0.001	
 Creatinine (μmol/L)	70.76±37.34	85.31±54.71	68.56±21.20	58.39±20.33	<0.001	
 BUN/Cr	0.08±0.03	0.06±0.01	0.08±0.01	0.12±0.03	<0.001	
 eGFR, mL/min/1.73 m2	109.54±33.92	95.42±28.98	108.61±28.15	124.61±37.34	<0.001	
 CKD, n (%)	280 (5.65)	169 (10.23)	72 (4.36)	39 (2.37)	<0.001	
 mRS>2	1730 (34.94)	463 (28.03)	531 (32.14)	736 (44.66)	<0.001	
 mRS, median (IQR)	1 (1–4)	1 (1–4)	1 (1–3)	2 (1–4)	<0.001	
 Early mortality, n (%)	62 (1.25)	17 (1.03)	19 (1.15)	26 (1.58)	0.330	
 Three-month mortality, n (%)	248 (5.06)	50 (3.06)	69 (4.21)	129 (7.09)	<0.001	
BMI, body mass index; BUN/Crblood urea nitrogen to creatinineCE, cardioembolism; CKDchronic kidney diseaseeGFR, estimated glomerular filtration rate; LAA, large artery atherosclerosis; mRSModified Rankin ScaleNIHSS, National Institutes of Health Stroke Scale; SAO, small artery occlusion; SOD, other determined aetiology; SUD, other undetermined aetiologyTOASTTrial of ORG in Acute Stroke Treatment

Association between BUN/Cr and 3-month mRS

A total of 4952 patients underwent mRS testing via telephone follow-up 3 months after discharge. Univariate analysis revealed that the BUN/Cr ratio was positively correlated with the 3-month mRS outcome. Patients with higher BUN/Cr levels had a higher risk of developing an adverse 3-month mRS outcome (T2 vs T1 HR=1.15, 95% CI: 1.01 to 1.30, p=0.031; T3 vs T1, HR=1.59, 95% CI: 1.42 to 1.79, p<0001). After logistic regression adjustment for sex, BMI, coronary heart disease, diabetes mellitus, NIHSS score, TOAST type, eGFR and haemoglobin, homocysteine and albumin levels, a high BUN/Cr ratio (T3) was still found to be independently associated with 3-month mRS outcome (T2 vs T1 HR=1.06, 95% CI: 0.89 to 1.26, p=0.53; T3 vs T1, HR=1.39, 95% CI: 1.17 to 1.65, p<0001) (table 2). The collinearity test showed that the highest variance inflation factor was 1.64, with the mean value being 1.25, indicating that the collinearity between variables was not significant.

Table 2 Sensitivity analyses: Cox proportional hazard regression between BUN/Cr ratio and 3-month Modified Rankin Scale (mRS) outcomes

	Crude model	Model 1	Model 2	
HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	
BUN/Cr ratio							
All							
 Tertile 1	1 (reference)		1 (reference)		1 (reference)		
 Tertile 2	1.15 (1.01 to 1.30)	0.031	1.14 (1.00 to 1.29)	0.045	1.06 (0.89 to 1.26)	0.53	
 Tertile 3	1.59 (1.42 to 1.79)	<0.001	1.53 (1.36 to 1.73)	<0.001	1.39 (1.17 to 1.65)	<0.001	
Non-CKD							
 Tertile 1	1 (reference)		1 (reference)		1 (reference)		
 Tertile 2	1.14 (1.00 to 1.30)	0.044	1.13 (0.99 to 1.29)	0.062	1.06 (0.88 to 1.27)	0.544	
 Tertile 3	1.60 (1.42 to 1.81)	<0.001	1.55 (1.36 to 1.76)	<0.001	1.39 (1.17 to 1.66)	<0.001	
CKD							
 Tertile 1	1 (reference)		1 (reference)		1 (reference)		
 Tertile 2	1.47 (0.96 to 2.24)	0.075	1.44 (0.94 to 2.21)	0.094	0.99 (0.48 to 2.04)	0.985	
 Tertile 3	2.17 (1.38 to 3.41)	0.001	1.93 (1.20 to 3.11)	0.007	1.32 (0.62 to 2.81)	0.473	
Cox proportional hazard regression models were used to estimate HRs with 95% CI. Crude model: no covariates were adjusted; Model 1: covariates were adjusted for demographic characteristics (BMI and sex); Model 2: covariates were adjusted for demographic (BMI and sex) and clinical characteristics (coronary heart disease, diabetes mellitus, NIHSS score, TOAST type, eGFR, haemoglobin levels, homocysteine levels and albumin levels).

BMIbody mass indexBUN/Crblood urea nitrogen to creatinineCKD, chronic kidney diseaseeGFRestimated glomerular filtration rateNIHSSNational Institutes of Health Stroke ScaleTOASTTrial of ORG in Acute Stroke Treatment

Dose–response relationship between BUN/Cr and 3-month mRS and sensitivity analyses

We further analysed the data using a restricted cubic spline and locally regression smoothing scatterplot (LOESS) graph and found a strong dose–response relationship between the BUN/Cr ratio and the 3-month mRS outcome. The correlation strength did not decrease after adjusting the covariates (including demographics and clinical characteristics) (figure 1). The curve fitting showed that the inflection point of the BUN/Cr ratio was 0.05. Because of the correlation between BUN/Cr ratio and eGFR, sensitivity analysis was conducted based on the patient’s eGFR at admission. In patients without CKD, the 3-month mRS outcome increased with the increase in BUN/Cr ratio (T2 vs T1 HR=1.06, 95% CI: 0.88 to 1.27, p=0.544; T3 vs T1, HR=1.39, 95% CI: 1.17 to 1.66, p<0.001). However, in patients with CKD, no significant correlation was observed between the BUN/Cr ratio and the 3-month mRS outcome (T2 vs T1 HR=0.99, 95% CI: 0.48 to 2.04, p=0.985; T3 vs T1, HR=1.32, 95% CI: 0.62 to 2.81, p=0.473) (table 2).

Figure 1 Restricted cubic spline (RCS) and robust locally regression smoothing scatterplot (LOESS) were employed to evaluate the potential nonlinear relationship between the blood urea nitrogen to creatinine ratio and the 3-month Modified Rankin Scale (mRS) outcome. Green curves and bands represent RCS regression, and the yellow curve represents LOESS regression. The two curves were nearly coincident without displacement. RMSE, root mean square error.

ROC analysis

We used the ROC curve to illustrate the predictive value of the BUN/Cr ratio for the 3-month outcome of AIS. The area under the BUN/Cr ratio curve was 0.5959 (figure 2).

Figure 2 Receiver operating characteristic (ROC) curves demonstrate the ability of the blood urea nitrogen to creatinine ratio to predict 3-month Modified Rankin Scale (mRS) outcome. The area under the ROC curve was 0.5959.

Discussion

In this retrospective cohort study, we confirmed the predictive value of the BUN/Cr ratio for the prognosis of patients with AIS without CKD and found that the correlation was not weakened after multivariate adjustment. Furthermore, a strong dose–response relationship was observed between the BUN/Cr ratio and the 3-month mRS outcome in patients with AIS.

Early prediction of AIS prognosis is crucial for the timely adjustment of treatment plans; therefore, reliable biomarkers with a predictive value for AIS prognosis need to be identified. Previous studies have reported that a high BUN/Cr ratio can increase the risk of hospitalisation and all-cause mortality in patients with chronic heart failure.3 In patients with chronic heart failure, the all-cause mortality rate of the high BUN/Cr ratio category is 77% higher than that of the low BUN/Cr ratio category. Bhatia et al9 found that BUN/Cr>15 at admission is associated with an independent risk factor for END.9 Some studies have also explored the association between BUN/Cr ratio and 3-month mRS outcome in patients with AIS. However, previous studies have demonstrated that a positive correlation between BUN/Cr ratio and 3-month outcome is observed only in patients with high HDL levels (OR 1.03, 95% CI: 1.00 to 1.07, p=0.04). This correlation is not significant in patients with low or medium HDL.10

The results of the present study indicated a correlation between BUN/Cr ratio and 3-month mRS outcomes after discharge, and the correlation did not decrease after multivariate adjustment (HR=1.39, 95% CI: 1.17 to 1.65, p<0.001). We further analysed and found a strong dose–response relationship between the BUN/Cr ratio and the 3-month mRS outcome. Previous studies on the predictive value of the BUN/Cr ratio did not include patients with end-stage renal failure. However, renal dysfunction is common in elderly patients, and CKD is not only closely related to cardiovascular disease but is also a risk factor for acute stroke.16 Therefore, we included patients with CKD and conducted a sensitivity analysis based on their eGFR at admission. The sensitivity analysis revealed that the relationship only existed in patients without CKD. CKD can trigger various pathological mechanisms such as inflammation, oxidative stress, neurohormonal imbalance and the formation of uremic toxins.17 We hypothesised that azotaemia and electrolyte disorders caused by CKD would interfere with the predictive effect of the BUN/Cr ratio on the AIS prognosis.

The underlying pathophysiological mechanism of the association between BUN/Cr ratio and AIS is hydration. Adequate hydration is crucial for ensuring oxygen delivery and normal organ function.18 Dehydration on admission is associated with increased risk for morbidity and mortality.19 20 Furthermore, it has been linked to poor cognitive performance in adults, including memory, attention, mathematical calculations and perceptual-motor speed.21 The risk of dehydration in patients with AIS is substantially increased by the decline in consciousness, dysphagia, communication disorders and other factors. Dehydration plays a crucial role in the pathological process of AIS, such as increasing blood viscosity, reducing cerebral blood flow and impairing neuroplasticity.22 In the early stages of stroke recovery, autoregulatory systems are damaged, making the brain susceptible to changes in blood viscosity and pressure, which may further damage the areas already compromised by reduced oxygen and nutrients. A CTP-based study showed that BUN/Cr>15 may be significantly associated with a lower core-penumbra mismatch, which indicates a greater proportion of core volume within the total ischaemic volume.23 Thus, early identification of dehydration and timely intervention are crucial for improving AIS prognosis. The BUN/Cr ratio is a commonly used marker for assessing dehydration and has been used in several studies to evaluate the hydration status.7 24 Because BUN and Cr are part of the routine haematology examination of patients at admission, the BUN/Cr ratio is readily available and simple to calculate. Therefore, it is appropriate to use the BUN/Cr ratio as a marker for evaluating the prognosis of patients with AIS.

The main strength of this study was that we used more flexible functions (limited cubic splines and LOESS) to detect the dose–response relationship between BUN/Cr ratio and 3-month outcome in patients with AIS. For potentially complex models, this is critical and credible. However, this study also had some limitations: (1) the main limitation was patients' selection bias due to the retrospective observational nature; (2) the relatively few centres and the short follow-up duration may influence the generalisability of our results; (3) as this was an observational study, although we have attempted to take measures to reduce bias, other confounding factors may still exist; (4) this study did not evaluate any other dehydration indicators, such as urine osmolarity, natriuresis, urine-to-plasma urea and creatinine ratios, which deserved further investigation.

Conclusion

Our results indicated a dose–response relationship between the BUN/Cr ratio and the 3-month mRS outcome after discharge, and the BUN/Cr ratio is a potentially reliable biomarker for predicting the prognosis of patients with AIS. Further research is warranted to confirm the predictive role of the BUN/Cr ratio in clinical practice.

Data availability statement

Data are available upon reasonable request.

Review Process File
22 7 2024

Funding: This work was supported by Clinical Medical Research Projects of Nanjing Health Commission (grant no YKK20228) and the Scientific Research Foundation of Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University (No TKKYZD20232602).

Prepublication history for this paper is available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2024-085912).

Patient consent for publication: Not applicable.

Ethics approval: The study protocol was approved by the Clinical Research Ethics Committee of Jinling and Xianlin hospitals (approval no 2019-014). The Clinical Research Ethics Committee of Jinling and Xianlin hospitals granted an individual informed consent exemption due to the retrospective nature of the study and non-involvement of any intervention. All data remained de-identified for this analysis.

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
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