Prognostic Value of Lactate/albumin Ratio for Mortality in Patients With Complicated Urinary Tract Infection

doi:10.21203/rs.3.rs-1945581/v1

Background

Lactate to albumin ratio (LAR) is an emerging sepsis biomarker that has been tested for mortality in patients with sepsis of different focus. Our goal is to evaluate the prognostic value of LAR in patients admitted to hospital due to complicated urinary tract infection.

Methods

Prospective observational study of patients older than 65 years diagnosed with UTI. Area under the ROC curve, sensibility, and specificity to predict 30-day mortality were calculated for LAR, qSOFA and SOFA and compared.

Results

341 UTI cases were analyzed. 30-day mortality (20.2% vs. 6.7%, p < 0.001) and longer hospital stay (5 [4–8] vs. 4 [3–7], p 0.018) were associated with LAR ≥ 0.708. LAR has no statistically significant differences compared to qSOFA and SOFA for predicting 30-day mortality (AUROC 0.737 vs. 0.832 and 0.777 respectively, p 0.119 and p 0.496). The sensitivity of LAR was similar to the sensitivity of qSOFA and SOFA (60.8% vs. 84.4% and 82.2, respectively, p 0.746 and 0.837). However, its specificity was lower than the specificity of qSOFA (60.8% vs. 75%, p 0.003), but similar to the specificity of SOFA (60.8% vs. 57.8%, p 0.787).

Conclusion

LAR has no significant differences with other well-stablished scores in sepsis, such as qSOFA and SOFA, to predict 30-day mortality in patients with complicated UTI.

sepsis

prognostic scores

outcomes

lactate

albumin

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection (1), being one of the main causes of mortality (1, 2). Delay in recognition and treatment of sepsis has been associated with increased mortality (2). Organ dysfunction and tissue hypoperfusion is pathophysiologically related to sepsis (1, 3), and lactate, a biomarker increased by cellular ischemia and hypoxia, is a long-known prognostic factor in infection (4, 5). Hypoalbuminemia is also a well-known independent risk factor for mortality in patients with sepsis (6), which add to other biomarkers the consideration of nutritional status and comorbidities of the patient (7, 8). Both parameters are among the rutinary test for patients with suspected infection at the Emergency Department (ED), with no need for extra analysis.

Early recognition of high-risk patients with infection remains a challenge and has clinical implications (2). One emerging sepsis biomarker is lactate to albumin ratio (LAR) (9, 10). It has been tested as predictor of mortality in septic patients in the ED (7, 9) and ICU (10–13), as well as patients with heart failure (14), cardiac arrest (15) and acute respiratory failure (16).

However, as a predictor factor in infection, it has been tested only in patients with sepsis of different focus (9, 11, 12), although it seems to have different prognostic value according to site infection (7). Urinary tract infection is one of the main infectious causes of hospital admission and mortality (17). Our goal is to evaluate the prognostic value of LAR in patients admitted to hospital due to complicated urinary tract infection.

Cohort prospective observational study of patients older than 65 years, consecutively admitted to a university hospital, diagnosed with community acquired UTI, from 2017 to 2021. Lactate and albumin were obtained in the ED within the first 24 hours of admission. Cases with a negative urine culture or a clinical syndrome compatible with any other condition after reviewing the case were excluded, as well as nosocomial UTI, as well as patients without lactate or albumin. Epidemiological and clinical variables were collected from the electronic medical records by the authors following a protocol. All the cases were reviewed by two independent researchers before being included in the study.

SOFA and qSOFA scores were used according to their original definitions (3, 18). UTI was defined as complicated according to the UTI severity grade and the specific risk phenotypes, following the European Association of Urology Section of Infections in Urology classification system (19). Community-acquired healthcare-associated UTI (HCA-UTI) was defined as a community onset UTI with any of the following criteria: (i) to have been admitted to an acute care hospital ≥ 48 h within 90 days prior to current hospital admission; (ii) to have received antimicrobial therapy within 90 days prior to admission; and (iii) residing in a nursing home (20, 21).

Quantitative variables were compared using Student's t-test or analysis of variance (ANOVA) when the distribution was normal, or Mann-Whitney U-test when it was not normal. Qualitative variables were compared with chi square test and Fisher’s exact test, considering an α significance level of 0.05 for all tests. All tests were two sided. If any data was missing other than lactate or albumin, a normal value was attributed for the calculation. Epidat v 3.2 was used to calculate sensibility, specificity, positive and negative predictive value of the scores to predict 30-day mortality, the area under the ROC curve (AUROC) and to compare the AUROC using the DeLong test. McNemar test was used to compare sensibility, specificity, positive and negative predictive values. The optimal cut-off value of LAR for 30-day mortality was calculated using the Youden’s index, prioritizing sensibility over specificity. The statistical package SPSS version 22 from IBM for Windows was used for other statistical analysis.

A total of 341 cases were analyzed, with a median age of 81 [75-87.5] years, most of them with significant comorbidities (Charlson index ≥3 97.1%) and approximately half of them females (51%). The main comorbidities were diabetes mellitus (39.9%), chronic kidney disease (37.2%) and dementia (32%). Almost half of the patients were septic (47.5%) and 10.6% had septic shock on admission. In-hospital mortality was 9.4% and 30-day mortality was 13.2% (see Table 1).

Table 1. Epidemiological and clinical characteristics and outcomes of complicated community-acquired urinary tract infection in patients according to lactate-albumin ratio

	Total cases n 341	LAR ≥0.708 n 148	LAR <0.708 n 193	p
Female sex, n (%)	174 (51)	79 (53.4)	95 (49.2)	0.512
Age (years), median [IQR]	81 [75-87.5]	83 [77-88]	80 [75-86]	0.020
HCA-UTI, n (%)	208 (61)	88 (59.5)	120 (62.2)	0.655
Nursing home residence, n (%)	26 (7.6)	14 (9.5)	12 (6.2)	0.306
Previous hospitalization, n (%)	118 (34.6)	52 (35.1)	66 (34.2)	0.909
Previous antimicrobial therapy, n (%)	175 (51.3)	66 (44.6)	109 (56.5)	0.038
Comorbidities
Dementia, n (%)	109 (32)	56 (37.8)	53 (27.5)	0.047
Diabetes mellitus, n (%)	136 (39.9)	66 (44.6)	70 (36.3)	0.147
COPD, n (%)	47 (13.8)	17 (11.5)	30 (15.5)	0.342
CKD, n (%)	127 (37.2)	52 (35.1)	75 (38.9)	0.500
Cancer, n (%)	78 (22.9)	31 (20.9)	43 (22.3)	0.796
Indwelling urinary catheter, n (%)	74 (21.7)	33 (22.3)	41 (21.2)	0.895
Charlson index ≥3, n (%)	331 (97.1)	143 (96.6)	188 (97.4)	0.752
Barthel <40, n (%)	131 (38.4)	67 (45.3)	64 (33.2)	0.025
Clinical characteristics
APACHE II, median [IQR]	12 [9-17]	14 [10-19]	11 [8-15]	<0.001
Fever, n (%)	260 (76.2)	111 (75)	149 (77.2)	0.700
RR ≥22, n (%)	74 (21.7)	40 (27)	34 (17.6)	0.046
Altered mental status, n (%)	155 (45.5)	77 (52)	78 (40.4)	0.037
SBP <100, n (%)	64 (18.8)	38 (25.7)	26 (13.5)	0.005
qSOFA ≥2, n (%)	95 (27.9)	60 (40.5)	35 (18.1)	<0.001
Sepsis (SOFA≥2), n (%)	162 (47.5)	88 (59.5)	74 (38.3)	<0.001
Septic shock, n (%)	36 (10.6)	35 (23.6)	1 (0.5)	<0.001
Albumin, median [IQR] (gr/dL)	3.3 [2.9-3.6]	3.1 [2.7-3.4]	3.4 [3-3.6]	<0.001
Lactate	1.8 [1.3-2.6]	3 [2.5-4.1]	1.5 [1.1-1.8]	<0.001
WBC, median [IQR] (cel/mm³)	12800 [9200 -18350]	14500 [10950-20050]	11600 [8500-16100]	<0.001
Polymicrobial UTI, n (%)	33 (9.7)	17 (11.5)	16 (8.3)	0.358
Bacteremia, positive/total blood cultures (%)	78/193 (40.4)	44/92 (47.8)	34/101 (33.7)	0.009
IEAT, n (%)	87 (25.5)	34 (23)	53 (27.5)	0.381
Outcomes
In-hospital mortality, n (%)	32 (9.4)	24 (14.7)	8 (4.5)	<0.001
30-day mortality, n (%)	45 (13.2)	32 (20.2)	13 (6.7)	<0.001
Length of hospital stay (days), median [IQR]	5 [4-8]	5 [4-8]	4 [3-7]	0.018

LAR, lactate-albumin ratio; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; HCA-UTI, healthcare associated-UTI; RR, respiratory rate; SBP, systolic blood pressure; IEAT, inadequate empiric antimicrobial therapy; WBC, white blood cell

148 patients (43.4%) had a LAR ≥0.708, which was related by the univariate analysis to age, dependency (Barthel <40), severity on admission (APACHE II), qSOFA and SOFA ≥2, septic shock, hypoalbuminemia, elevated lactate, longer hospital stay and in-hospital and 30-day mortality (see Table 1). We choose 0.708 as the cut-off value for LAR because other values with a similar Youden’s index had poorer specificities with similar sensitivities.

Although qSOFA had a greater specificity and positive predictive value than LAR ≥0.708 (75% vs. 60.8%, p 0.003 and 40% vs. 21.6%, p 0.002, respectively), the AUROC showed no differences in its accuracy to predict 30-day mortality (AUROC 0.823 vs. 0.737, p 0.119, respectively), as we can see in Table 2 and Figure 1. LAR ≥0.708 showed no statistically significant differences with SOFA in sensibility, specificity or AUROC.

Table 2. Performance of LAR, qSOFA and SOFA for 30-day mortality in patients with complicated community-acquired urinary tract infection

	AUROC (IC 95%)	Sensitivity (IC 95%)	Specificity (IC 95%)	PPV (IC 95%)	NPV (IC 95%)
LAR ≥0.662	0.737 (0.656-0.818)	73.3 (59.3-87.4)	56.1 (50.3-61.9)	20.2 (13.8-26.7)	93.3 (89.3-97.2)
LAR ≥0.685		71.1 (56.8-85.5)	58.1 (52.3-63.9)	20.5 (13.9-27.2)	92.9 (89-96.9)
LAR ≥0.708		71.1 (56.8-85.5)	60.8 (55.1-66.5)	21.6 (14.7-28.6)	93.3 (89.5-97.1)
qSOFA ≥2	0.823 (0.750-0.896)	84.4 (72.7-96.1)	75 (69.2-80.8)	40 (29.6-50.4)	96.1 (92.9-99.2)
SOFA ≥2	0.777 (0.696-0.858)	82.2 (69.9-94.5)	57.8 (51.9-63.5)	22.8 (16.1-29.6)	95.5 (92.2-98.3)
LAR ≥0.708 vs. qSOFA	0.119	0.746	0.003	0.002	0.433
LAR ≥0.708 vs. SOFA	0.496	0.837	0.787	0.472	0.662

LAR, lactate-albumin ratio; PPV, Positive predictive value; NPV, Negative predictive value

LAR has been related to mortality in patients with suspected infection in studies in the ICU (10-13) (Wang 2015 lichternauer, chen, cakir) and in the ED (7, 9), but our study is the first to evaluate the use of LAR in non-UCI hospitalized patients.

Our patients were older (median 81 years old) compared to other studies (median 64.9 to 71.19 years old (7, 12), since we selected patients older than 65 years. Our patients also had more comorbidities than in another study performed in the ICU (9), but similar to Bou et al. (7), with patients in the ED. As expected, our patients had less severe infection (APACHE II 12) than patients in the ICU (APACHE II 18-25 (9, 10, 12).

In-hospital mortality was higher in these studies with ICU patients (42.7% to 62.4% (10, 13), compared to our study (9.4%), as well as 28-day mortality in one study in the ED (22.5%) (9), compared to our 30-day mortality (13.2%).

In our study, the prognostic accuracy of LAR for 30-day mortality was good, with an AUROC of 0.737 (95% CI 0.656-0.818), similar to those described in other studies (AUROC 0.61 to 0.869) (7, 10, 13). Bou et al. (7), in a study with 1381 patients in the ED, evaluate sensibility and specificity, with poorer results than our study (59% and 62 % vs. 71.1% and 60.8%, respectively for Bou et al. and our results). On the other hand, Wang et al. (11), in their study with 54 septic patients in ICU, obtained better sensibility than ours (100%), with lower specificity (51%). However, Bou et al. (7) suggested that the performance of the score varies according to the infection source, with better results for UTI (69% and 54% sensibility and specificity, similar to our results).

The cut-off value of LAR is not well stablished yet, varying from 0.15 to 1.735 (11, 12). In their study, Bou et al. (7) obtained a cut-off value of 1.47 for septic patients, however, the cut-off value for patients with UTI was 0.85, similar to ours and to those of Cakir et al. (cut-off value 0.71) (10).

The main strength of our study is the homogeneity of the infections source. As we have seen in Bou et al. (7), the performance of the score may be affected by the source of the infection, therefore, studies with patients with sepsis from different sources may underestimate or overestimate the predictive capacity of the score. The main limitation of our work is that it was carried out in a single center. However, we think our study shows that LAR may help the clinicians to stratify mortality risk of patients with complicated UTI with an ease to calculate score obtained from routine analytical parameters.

Lactate-albumin ratio is an easy to obtain score with acceptable sensitivity and specificity to predict 30-day mortality in hospitalized patients with UTI, with no significant differences with other well-stablished scores in sepsis, such as qSOFA and SOFA.

Ethics approval and consent to participate

The study was approved by the Clinical Research Ethics Committee of the Doctor Peset University Hospital.

Treatment of data, information sheet and informed consent are in accordance under the provisions of the Declaration of Helsinki (version of Fortaleza 2013)

Informed consent was signed by every patient or his legal representative when the patient was unable to consent.

Consent for publication

Informed consent was signed by every patient or his legal representative when the patient was unable to consent.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors have no relevant conflicts of interest.

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No competing interests reported.

Prognostic Value of Lactate/albumin Ratio for Mortality in Patients With Complicated Urinary Tract Infection

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Abstract

Background

Methods

Results

Conclusion

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Introduction

Material And Methods

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Discussion

Conclusion

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References

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