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Predictive value of the early postoperative hemoglobin-to-red blood cell distribution width ratio for acute kidney injury in elderly intertrochanteric fracture patients

BMC Musculoskeletal Disorders volume 25, Article number: 630 (2024) Cite this article

Abstract

Background

Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients.

Methods

We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).

Results

The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618–0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714–46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415–5.811, p = 0.040).

Conclusions

Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.

Peer Review reports

Introduction

As the global population ages, the prevalence of osteoporotic hip fracture is increasing every year [1]. Hip fracture has become a global public health challenge due to its high morbidity, high mortality and significant socioeconomic burden [2, 3]. The number of hip fractures was estimated to be 1.3 million worldwide in 1990, and it dramatically increased to 14.2 million in 2019, with the age-standardized rate increasing by 0.4% each year [4]. The one-year mortality after hip fracture was reported to be 14–58% in older adults [5]. The economic burden of hip fracture was reported to be 5.96 billion dollars in United States, and the intertrochanteric hip fracture accounted for 44% of total costs [6]. Acute kidney injury (AKI) is a clinical syndrome caused by a sudden decrease in the glomerular filtration rate, and the rapid accumulation of metabolites leads to severe disturbance of the internal environment. AKI is a common postoperative complication in patients who undergo surgical treatment for hip fracture [7]. Current findings indicate that AKI can result in the deterioration of other organs and systems, leading to multiple organ dysfunction syndrome (MODS), sepsis, and even death [8, 9]. Subclinical AKI is also associated with prolonged hospital stays, increased medical costs, and elevated mortality rates [10]. There is growing evidence that early recognition and intervention of AKI can improve the clinical prognosis [11, 12]. Therefore, an accurate, accessible, and economical biomarker is crucial for clinicians to make timely and appropriate decisions on AKI.

Complete blood count (CBC) is a routine blood test for patients upon admission to the hospital. In recent years, the hemoglobin-to-red blood cell distribution width ratio (HRR), as an important parameter of CBC, has attracted extensive attention due to its predictive value for the prognosis of cancer patients [13,14,15]. HRR is calculated by dividing the value of hemoglobin (Hb) by the value of red blood cell distribution width ratio (RDW). It has been proved to have great predictive value for the prognosis of malignant tumors and cardiovascular disease, and HRR and Hb were negatively correlated with the occurrence of AKI while the value of RDW was positively correlated with it in these studies [16, 17]. To our knowledge, no study has evaluated the correlation between the HRR and the risk of postoperative AKI in hip fracture patients. Therefore, we conducted this study to determine the relationship between postoperative HRR and AKI in intertrochanteric fracture patients who received surgical treatment using univariate and multivariate logistic regression analysis and applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to verify the reliability, aiming to find an effective predictor for postoperative AKI in femoral intertrochanteric fracture patients.

Methods

Patients

The level of evidence of this retrospective cohort study is level III. We reviewed the medical records of all patients who received surgical treatment for femoral intertrochanteric fracture at The Second Affiliated Hospital of Chongqing Medical University from July 1, 2019, to December 31, 2022. The inclusion criteria were as follows: (1) patients who were older than 65 years old; (2) patients with femoral intertrochanteric fracture; and (3) patients who received total hip arthroplasty, hemiarthroplasty, or internal fixation surgery. The exclusion criteria were as follows: (1) patients diagnosed with preoperative abnormal renal function and (2) incomplete medical data. Total arthroplasty, hemiarthroplasty, and internal fixation are three most common surgical methods to treat intertrochanteric fractures. They are different in the severity of surgical trauma, operation time, blood loss, and postoperative bedridden time, which may affect the outcome.

There were 363 elderly patients with femoral intertrochanteric fracture who received surgical treatment in our hospital, and 42 patients were excluded because of incomplete data, and another 14 patients were excluded because of confirmed preoperative kidney injury. A total of 307 patients who received surgical treatment for femoral intertrochanteric fracture were included in this retrospective study. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University (Approval Number: 2023-80).

Data collection

We first collected demographic data of patients, including age, sex, body mass index (BMI), and time between fracture and surgery. Comorbidities primarily included hypertension, diabetes, congestive heart failure, and chronic kidney disease (CKD). We collected perioperative clinical and laboratory data, including dynamically monitored serum creatine (Scr) values at baseline and after surgery, and Hb and RDW before surgery and in the early postoperative period. If patients received the CBC test more than once within 24 h after surgery, the lowest value was chosen in this study. Because patients received multiple tests usually received blood transfusion, which may increase the value of Hb and HRR, and the lowest value was most credible. Other laboratory parameters, such as preoperative urea nitrogen, estimated glomerular filtration rate (eGFR), and the lowest serum albumin level within 24 h after surgery, were also collected.

For these intraoperative parameters, we focused on the methods of surgery and anesthesia, duration of surgery, ASA physical status classification, and intraoperative hypotension (systolic blood pressure < 80 mmHg and mean arterial blood pressure < 55–60 mmHg) [18]. We also documented perioperative blood transfusion and the usage of nephrotoxic drugs, including antibiotics such as first-generation cephalosporins, vancomycin, and aminoglycosides, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs).

Definition of AKI

AKI was diagnosed using KDIGO 2012 guidelines [19]. Patients were diagnosed with AKI if they met one of the following criteria: increase in Scr by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 h; increase in Scr to ≥ 1.5 times baseline within the previous 7 days; or urine volume < 0.5 ml/kg/h for 6 h. Only changes in Scr levels were selected as the diagnostic criteria in this study because of the lack of postoperative urine volume in the medical records, and Scr levels could be obtained retrospectively.

Statistical analysis

Normally distributed measurement data are expressed as the mean ± standard deviation, and Student’s t test was used for comparisons between two groups. Skewed distribution measurement data are shown as the median (quartile 1, quartile 3), and the rank sum test was used for comparison. Enumeration data were exhibited in cases and percentages (%), and comparisons between two groups were performed using the chi-square test or Fisher’s exact probability test. The multiple imputation method was used to handle data with less than 20% missing values. We used univariate and multivariate logistic regression analyses to determine the independent risk factors for AKI. Univariate logistic regression analysis included the most relevant factors for AKI. Multivariate logistic regression analysis included all covariates with a p value < 0.05 in univariate logistic regression analysis. We used the receiver operating characteristic curve (ROC) and the Youden index to determine the cutoff value of the early postoperative HRR. Subsequently, PSM and IPTW were used to further clarify the correlation between early postoperative HRR and postoperative AKI in elderly patients with femoral intertrochanteric fracture. Multivariate logistic regression and adjusted odds ratio (OR) values were used to evaluate the predictive ability of early postoperative HRR for AKI in this research. Data analysis was performed using SPSS 25.0 (IBM Corp., Armonk, NY) and R 4.2.1. A P value < 0.05 was considered statistically significant.

Results

From June 2018 to December 2022, 363 patients received surgical treatment for intertrochanteric fracture in our hospital. Fifty-six patients were excluded due to incomplete medical records or preoperative kidney injury. Accordingly, 307 elderly patients were eventually included in the analysis (Fig. 1).

Fig. 1
figure 1

Flow diagram of the research. There were 363 elderly patients who received surgical treatment for femoral intertrochanteric fracture, and 307 patients were included in this study. Patients were classified according to the occurrence of AKI, and multivariate logistic regression was performed for analysis. Based on the cutoff value of early postoperative HRR (5.44), patients were divided into two groups, and PSM and IPTW were used for further analysis

Full size image

Based on the KDIGO guidelines, 33 elderly patients were diagnosed with early postoperative AKI after surgery (10.75%). Multivariate logistic regression analysis indicated that early postoperative HRR (OR = 0.586, 95% CI: 0.370–0.928, p = 0.023), congestive heart failure (OR = 2.708, 95% CI: 1.113–6.593, p = 0.028), and intraoperative hypotension (OR = 5.313, 95% CI: 1.977–14.273, p = 0.001) were closely related to the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture (Table 1). We calculated the predictive probability of early postoperative HRR for AKI, and the results of ROC curve analysis showed that the area under the curve (AUC) was 0.714. The cutoff value of the early postoperative HRR was 5.44, and the sensitivity and specificity were 72.7% and 70.8%, respectively (Fig. 2).

Table 1 Univariate and multivariate regression analysis of AKI-related risk factors
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Fig. 2
figure 2

ROC curve analysis of postoperative early HRR for predicting postoperative AKI. AUC = 0.714; 95% CI: 0.618–0.809; sensitivity = 72.7%; specificity = 70.8%; maximal Youden index = 0.435; cutoff value = 5.44

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Patients were divided into two groups based on the cutoff value of early postoperative HRR determined by ROC curve analysis. Among 307 patients, there were 104 patients (33.9%) with an early postoperative HRR lower than or equal to 5.44 and 203 patients (66.1%) with an HRR higher than 5.44. Forty-six pairs of matches were generated after applying 1:1 PSM, and patients were divided into a low HRR group (n = 46) and a high HRR group (n = 46). All parameters were balanced after matching without significant differences between the two groups (Table 2).

Table 2 Demographic and clinical characteristics of patients classified according to the cutoff point of the HRR
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Patients in the low HRR group had a higher risk of AKI than those in the high HRR group both before (23.1% [24/104] vs. 4.4% [9/203]) and after matching (23.9% [11/46] vs. 4.3% [2/46]) (Fig. 3). Logistic regression analysis showed that in the matched cohort, early postoperative HRR was closely correlated with the risk of postoperative AKI (OR = 6.914, 95% CI 1.714–46.603, p = 0.016) (Table 3).

Table 3 Demographic data, clinical characteristics, and laboratory parameters of patients after IPTW
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Fig. 3
figure 3

The incidence of postoperative AKI in the low HRR and high HRR groups before and after PSM. The incidence of postoperative AKI was higher in the low HRR group both before and after PSM

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Subsequently, the original cohort was weighted using the IPTW method, and the demographic and clinical characteristics are shown in Table 4. The imbalanced variables in the weighted group, including age, hypertension, ASA physical status classification, and early postoperative HRR level, were included in the multivariate logistic regression analysis. The results indicated that the early postoperative HRR level was closely associated with the risk of postoperative AKI in patients (OR = 2.784, 95% CI 1.415–5.811, p = 0.040) (Table 3).

Table 4 Logistic regression analysis results of the original queue, matching queue, and weighted queue
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Discussion

Previous studies have indicated that postoperative AKI can extend the length of hospital stay, increasing medical costs and the incidence and mortality of renal function-related surgical complications, which is an independent risk factor for poor prognosis [20, 21]. Statistical data have shown that in industrialized countries, AKI causes an estimated economic loss of one billion dollars, 300,000 deaths, and another 300,000 cases of chronic kidney diseases annually [22, 23]. In China, a recent national multicenter study involving 44 hospitals reported that the rate of all-cause in-hospital AKI was 12.4% [24]. In a retrospective study of 450 elderly patients with hip fracture, Hong et al. concluded that the incidence of AKI during hospitalization was 21.1%, and AKI was associated with extended hospital stay and higher mortality based on the Acute Kidney Injury Network (AKIN) criteria [20]. In addition, Rantalaiho et al. reviewed the medical records of 486 patients with hip fracture. A total of 8.4% of these patients were diagnosed with AKI based on the KDIGO guidelines, and the 3-month postoperative mortality of AKI patients was three times that of patients without AKI [25]. Because of the tremendous burden and poor prognosis of AKI, it is essential to classify high-risk patients and identify biomarkers to guide early intervention.

In the past few years, new biomarkers for AKI, such as kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), have become the focus of translational research, aiming to improve the detection and prognosis of AKI [26, 27]. In the field of AKI and hip fracture, there are several studies reporting other biomarkers for the prediction. Ana et al. conducted a prospective observational cohort study to unveil the relationship between inflammatory markers and AKI in hip fracture patients, and the result showed that circulating levels of fibroblast growth factor 23 (FGF-23), and interleukin-15 (IL-15) were significantly correlated with the incidence of postoperative AKI [28]. Cagatay et al. conducted a prospective cohort study discovering the risk factors of postoperative AKI of hip fracture patients. The result indicated that decreased preoperative eGFR is the independent predictor for AKI in hip fracture patients who received arthroplasty surgery [29]. Joon et al. retrospectively reviewed the clinical data of hip fracture patients who underwent surgery, and the result indicated that AKI was correlated with blood loss and low postoperative albumin level [30]. However, it seems unlikely that a single biomarker can diagnose AKI due to the complicated pathophysiological mechanism, and current applications of these biomarkers are still limited to clinical research [31].

As a new hematological indicator, the HRR has been widely studied for its correlation with the prognosis of malignant tumors [16]. It was also reported that the HRR had great predictive value for the prognosis of cardiovascular disease [17]. Other studies have reported that a reduction in the HRR is related to increased mortality and frailty in elderly patients in the decompensation stage of cirrhosis after hepatitis B [32, 33]. In our study, we found a significant correlation between early postoperative HRR and AKI. Multivariate logistic regression results showed that decreased HRR was an independent predictor of postoperative AKI in elderly patients with femoral intertrochanteric fracture. After using PSM and IPTW to reduce the impact of possible confounding factors, a low level (⩽ 5.44) of early postoperative HRR was still related to an increased risk of AKI. Compared with other biomarkers, HRR is a parameter of CBC test, which is more accessible and economical. Abnormal early postoperative HRR value can give the doctor the message that the patient may potentially suffer from AKI, and the doctor should routinely monitor the renal function and correct AKI at the early stage.

Currently, the underlying reasons why decreased HRR is associated with AKI remain unclear and deserve further investigation. HRR is calculated by Hb and RDW. The association between low Hb and AKI has been proven. Shaver et al. found that a decrease in Hb was associated with an increased incidence of AKI in patients with sepsis [34]. Luca et al. conducted a follow-up study on 1214 patients who received CABG surgery, and the results indicated that patients with preoperative anemia had twice the risk of AKI compared with patients without anemia [35]. Similarly, Alparslan et al. found that postoperative anemia was correlated with AKI in patients who received noncardiac surgery [36]. RDW is an important parameter of whole blood cell count, indicating the variability of red blood cell count, which is often used for the diagnosis and classification of anemia. Recently, several studies have reported that RDW should be recognized as an inflammation-related indicator with predictive value for AKI in many clinical settings. Cai et al. conducted a retrospective cohort study of 193 acute respiratory distress syndrome (ARDS) patients, and the results indicated that RDW was an important predictor of AKI [37]. Ramires et al. reported that RDW could predict sepsis-related AKI [38]. A recent meta-analysis including 26 studies and 48,092 patients showed that preoperative increased RDW was related to AKI after cardiac surgery [39]. Nanjarapalle et al. reported that RDW has better predictive value for the prognosis of AKI in severe patients compared with commonly used disease severity scoring systems [40].

This study indicates that the HRR is closely associated with postoperative AKI in elderly patients with femoral intertrochanteric fracture who received surgical treatment. The possible underlying mechanisms are as follows. First, the hematopoietic function of elderly patients gradually decreases with aging, and the response to erythropoietin weakens. Patients are prone to suffer from anemia due to the blood loss caused by fracture and surgery [41]. It has been reported that up to 86% of patients with hip fracture have varying degrees of postoperative anemia [42]. Decreased Hb levels lead to a shortened lifespan of red blood cells, and a large number of immature red blood cells are released into the blood, resulting in increased RDW [43, 44]. Second, elderly patients with hip fracture are often in a state of oxidative stress before surgery. Oxidative stress-induced cytokines can also reduce the survival time of red blood cells and increase RDW. In addition, the pathogenesis of AKI is complex and is related to many factors, including the inflammatory response, tissue ischemia and hypoxia, and surgical stress [8]. As the combined parameter of Hb and RDW, the HRR has better predictive value than a single parameter. Perhaps in future studies, we could utilize our findings to further investigate whether regulating HRR in peripheral blood can reduce the occurrence of postoperative AKI.

Based on the results of this study, there are several measures the medical team can take to prevent postoperative AKI in elderly intertrochanteric fracture patients who received surgical treatment. Before the surgery, the medical team should evaluate the risk of postoperative AKI, identify underlying kidney disease, avoid the application of nephrotoxic medication, and correct the reversible factors including hypotension, hypovolemia, and heart failure. During the operation, the orthopedic surgeon should optimize the operation plan and shorten the operation time to reduce surgical trauma. Monitoring the blood pressure and avoiding intraoperative hypotension can help maintain the kidney perfusion and protect renal function. After surgery, the medical team should continuously monitor the renal function, especially for these high-risk patients. According to our research, in addition to low early postoperative HRR value, intertrochanteric fracture patients with abnormal preoperative renal function parameters, preoperative HRR, or early postoperative serum albumin, and patients who received blood transfusion have higher risk of AKI. Identifying and correcting AKI at early stage can prevent its progression and reduce the mortality.

There are also several limitations of this study. This retrospective observational study was conducted in a single center and the sample size was small. Because the number of researchers is limited, and the medical records of patients admitted to our hospital long time ago may be lost or inaccurate. Therefore, only 307 patients were included in this retrospective study. There were many kinds of inevitable biases which may affect the validity of the results. There may be admission rate bias in the selection of patients, and confounding bias and observational bias in the subsequent process. Although we attempted to use PSM and IPTW to adjust the impact of confounding factors and reduce bias, it is still impossible to completely eliminate unknown bias. In addition, this study collected a single HRR value in the early postoperative period rather than dynamic monitoring. Dynamic monitoring values may predict AKI more accurately. We did not dynamically monitor the HRR values because of the limitation of time and condition of this study and the restriction of clinical pathway. Dynamic monitoring of HRR can exhibit the variation tendency of HRR. Continuous decrease of postoperative HRR means the risk of AKI is increasing, while the increasing tendency of HRR may reflect that the patients have lower risk of AKI and are recovering from the trauma of fracture and surgery. Moreover, we did not further explore the relationship between the HRR and the stage or prognosis of AKI due to the limited sample size. And we did not elucidate the underlying mechanism of the effect of decreased postoperative HRR on AKI. HRR value is related to the value of Hb and RDW, which are associated with several abnormal physical conditions, such as inflammation, stress, and malnutrition. Unveiling the association between HRR and these abnormal physical conditions may be the specific aspects of our future research. It is necessary to conduct a large sample prospective cohort study to further confirm the association between the HRR and AKI, and unveil the underlying mechanism.

Conclusion

In conclusion, postoperative HRR is an effective predictor for postoperative AKI in elderly patients with femoral intertrochanteric fracture who received surgical treatment. As a simple, effective and economical blood parameter, the HRR may help clinicians stratify the risk of AKI, identify high-risk patients and intervene in a timely manner, reduce the medical burden, and improve the prognosis of patients.

Data availability

All the data and materials concerning this research are included in the published article.

Abbreviations

HRR:

Hemoglobin-to-red blood cell distribution width ratio

AKI:

Acute kidney injury

ROC:

Receiver operating characteristic

PSM:

Propensity score matching

IPTW:

Inverse probability of treating weighting

MODS:

Multiple organ dysfunction syndrome

CBC:

Complete blood count

BMI:

Body mass index

RDW:

Red blood cell distribution width

eGFR:

Estimated glomerular filtration rate

OR:

Odds ratio

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Acknowledgements

We sincerely appreciate the support we received from all staffs of the center for joint surgery.

Funding

The authors received no funding for this work.

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Author notes

  1. Xin Yuan and Wang Zeng contributed equally to this work.

Authors and Affiliations

  1. Center for Joint Surgery, Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Linjiang road No.76, Yuzhong District, Chongqing, 400010, China

    Xin Yuan, Wang Zeng, Hao Wang, Guoyin Shu, Chen Wu, Ming Nie, Jiao Wang & Shirong Chen

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  1. Xin Yuan
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  2. Wang Zeng
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Contributions

X.Y., G.S., H.W., C.W. and M.N. collected all the data and conducted statistical analysis. W.Z. and H.W. drafted the manuscript. J.W. and S.C. designed this study and revised the manuscript. All authors have read and approved the final submitted manuscript.

Corresponding authors

Correspondence to Jiao Wang or Shirong Chen.

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Ethics approval and consent to participate

This retrospective study was approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University (Approval Number: 2023-80). Written informed consent to participate were obtained from all patients.

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Not applicable.

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The authors declare no competing interests.

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Yuan, X., Zeng, W., Wang, H. et al. Predictive value of the early postoperative hemoglobin-to-red blood cell distribution width ratio for acute kidney injury in elderly intertrochanteric fracture patients. BMC Musculoskelet Disord 25, 630 (2024). https://doi.org/10.1186/s12891-024-07745-y

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Keywords

BMC Musculoskeletal Disorders

ISSN: 1471-2474

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