Abstract
Importance
Pyometra is a common reproductive disorder in intact female dogs and can progress to sepsis and multi-organ dysfunction. Accurate prognostic indicators are needed to guide clinical management. The blood urea nitrogen-to-albumin ratio (BUN/ALB) has been reported as a prognostic marker in human sepsis but has not been evaluated in canine pyometra.
Objective
To evaluate the prognostic value of the BUN/ALB in canine pyometra before and after surgery.
Methods
In this retrospective study, BUN/ALB was compared among survivors, non-survivors, and healthy dogs. The BUN/ALB was calculated as blood urea nitrogen (mg/dL) ÷ albumin (g/dL). Analyses included one-way analysis of variance with the Holm-Sidak post hoc test, Mann–Whitney tests, Jonckheere–Terpstra trend analysis, and receiver operating characteristic (ROC) curve analysis.
Results
Preoperative BUN/ALB was higher in dogs with pyometra than in healthy dogs, with the highest values in non-survivors. ROC analysis showed an area under the curve (AUC) of 0.86 and an optimal cut-off of 8.935 (sensitivity of 73.08%, specificity of 90.91%). Postoperatively, the BUN/ALB remained higher in non-survivors (AUC, 0.81; cut-off, 8.445; sensitivity, 68.28%, specificity, 83.33%).
Conclusions and Relevance
The BUN/ALB was significantly associated with mortality in dogs with pyometra both pre- and postoperatively. The BUN/ALB may serve as a simple, inexpensive, and readily available prognostic marker to support clinical decision-making in canine pyometra.
Keywords: Albumin, blood urea nitrogen, dog, pyometra
INTRODUCTION
Pyometra, which is the most common reproductive disorder in dogs, is characterized by the accumulation of purulent exudate within the uterine lumen [1]. The disease typically arises during the luteal phase, with progesterone playing a pivotal role in predisposing the uterus to ascending infections caused by opportunistic bacteria [2]. Clinical manifestations often begin insidiously, with signs such as polydipsia, polyuria, and vaginal discharge. Without timely treatment, it can progress to peritonitis, sepsis, and multiple organ dysfunction [1,3]. Due to systemic consequences, canine pyometra is considered a natural model of sepsis [4].
Although the diagnosis is generally straightforward, it can be complicated in dogs lacking vaginal discharge or presenting with nonspecific signs. Moreover, canine pyometra is commonly accompanied by hematologic and biochemical abnormalities, such as leukocytosis, neutrophilia with a left shift, anemia, monocytosis, and hypoalbuminemia [5]. The standard and most effective treatment is ovariohysterectomy (OHE); however, despite advances in perioperative management, mortality rates of until 3% are still reported [6,7]. Notably, most affected bitches develop systemic inflammatory response syndrome, which is linked to increased hospitalization and mortality [8]. Accurate prediction of clinical outcomes in dogs with pyometra is therefore crucial but remains challenging in veterinary clinical practice. Consequently, simple and potentially useful prognostic indicators, including physical examination and laboratory findings, are needed as objective parameters that can be used to predict prognosis and guide clinical decisions.
Among potential indicators, blood urea nitrogen (BUN) and serum albumin (ALB) have long been used to assess metabolic and systemic status. BUN provides valuable information regarding renal function, protein metabolism, and nutritional balance, while also reflecting intravascular volume status and the early response to fluid resuscitation [9]. Serum ALB is another critical parameter that contributes to osmotic regulation, molecular transport, antioxidative defense, anti-inflammatory activity, and endothelial stability [10,11]. ALB concentrations, however, are susceptible to variation and are influenced by nutritional condition, hepatic synthesis, and catabolic processes [12]. In dogs with pyometra, hypoalbuminemia and elevated BUN levels are frequently observed [13]. The blood urea nitrogen-to-albumin ratio (BUN/ALB) represents an easily obtainable composite index that simultaneously reflects nutritional, inflammatory, metabolic, and renal status. In human medicine, the BUN/ALB has been validated as a reliable prognostic marker for mortality in conditions such as pancreatitis, coronary artery disease, and sepsis [9,14,15]. The BUN/ALB provides an integrated index of renal, metabolic, nutritional, and inflammatory statuses and can be rapidly calculated from routine laboratory tests.
Despite this evidence, the prognostic value of the BUN/ALB has not been investigated in canine pyometra. Therefore, the aim of this study was to evaluate the prognostic value of the BUN/ALB in dogs with pyometra both before and after surgery.
METHODS
Study population
This study was designed as a retrospective study. Clinical data were collected from electronic medical records of dogs with pyometra at Forev Animal Medical Center between 2018 and 2024. Owner consent for clinical examination and treatment was obtained at the time of hospital admission, and all data were anonymized prior to analysis. No animals were subjected to additional procedures for research purposes. A total of 92 client-owned intact female dogs of various breeds, weights, and ages were enrolled. In total, 92 dogs were included; 63 had pyometra, and 29 were healthy. The diagnosis of pyometra was established according to previously proposed definitions [16,17]. Healthy client-owned female dogs undergoing elective OHE during routine health examination or at owner’s request were included as controls. Surgery was performed in a standardized manner for all dogs. Dogs with other underlying systemic diseases that could affect the analysis, including cases with concurrent mammary gland tumor, were excluded from the study.
Blood sampling
Blood samples were collected both before and after surgery. Postoperative blood samples were available for a subset of dogs with pyometra (28/63). Postoperative blood sampling was not standardized and was performed only when follow-up samples were available in the medical records according to clinical monitoring needs, hospitalization duration, or owner compliance. Dogs without postoperative blood samples were excluded from postoperative analyses. Preoperative samples were obtained at the time of presentation, whereas postoperative samples were collected within a maximum of three days: on postoperative day 1 (n = 15), day 2 (n = 9), and day 3 (n = 4). All samples were obtained via venipuncture and stored in tubes containing ethylenediaminetetraacetic acid (EDTA) and plain tubes with gel separators. EDTA-preserved blood was immediately analyzed using an automated hematology analyzer. The plain tubes with gel separators were allowed to clot for 30 min and centrifuged within 1 h after collection. The serum was harvested and analyzed immediately.
Hematological analysis
Complete blood counts (CBCs) were obtained using a ProCyte Dx hematology analyzer (IDEXX Laboratories, USA), which provides measurements of red blood cell (RBC) counts, hematocrit (HCT), hemoglobin (HGB) levels, and white blood cell (WBC), neutrophil (NEU), lymphocyte (LYM), monocyte (MONO), eosinophil (EOS), basophil (BASO), and platelet (PLT) counts.
Serum biochemical parameters, including blood glucose, BUN, creatinine, phosphorus, total calcium, total protein, ALB, globulin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and total cholesterol, were assessed with the IDEXX Catalyst Dx analyzer (IDEXX Laboratories).
The BUN/ALB was selected as the primary variable of interest and was calculated using the following formula: BUN (mg/dL) ÷ ALB (g/dL).
For postoperative comparisons of hematological analysis, samples obtained on postoperative days 1–3 were pooled and analyzed as early postoperative values, because the purpose of the analysis was to assess short-term postoperative changes rather than day-specific trends. Given the limited number of cases on each postoperative day, separate analyses by postoperative day were not performed.
Statistical analysis
All experimental data were analyzed in SPSS version 25 (IBM, USA) and GraphPad Prism 10.0 (GraphPad Software, USA). All graphs were plotted using GraphPad Prism 10.0. Prior to performing the statistical analysis, data normality was assessed using Shapiro–Wilk tests and Q–Q plots. The statistical differences among the dog groups were estimated by one-way analysis of variance with Holm-Sidak’s post hoc test (GraphPad Prism) for normally distributed variables, whereas non-normally distributed variables were analyzed using Mann–Whitney test and Kruskal-Wallis test with Dunn’s post hoc test (GraphPad Prism). The Jonckheere–Terpstra test (SPSS) was performed to evaluate the presence of a significant ordered trend among the three groups. Receiver operating characteristic (ROC) curves were generated using GraphPad Prism to compare sensitivity and specificity. Optimal ROC cut-offs were determined using the Youden index. Data are presented as the mean ± standard deviation, and p < 0.05 was considered significant.
RESULTS
Characterization of dogs
The 63 dogs with pyometra that were enrolled in this study included 18 different breeds including Maltese (n = 19), mixed breeds (n = 9), Poodles (n = 6), Yorkshire Terriers (n = 5), Pomeranians (n = 4), Spitz (n = 3), Golden Retrievers (n = 3), Shih Tzus (n = 2), Miniature Pinschers (n = 2), Dachshunds (n = 2), a Shetland Sheepdog (n = 1), a Sapsali (n = 1), a Pekingese (n = 1), a Labrador Retriever (n = 1), a Jindo (n = 1), a Cocker Spaniel (n = 1), a Chihuahua (n =1), and a Cane Corso (n = 1). The dogs with pyometra were 8.76 ± 3.30 years old and weighed 6.04 ± 5.21 kg. The 29 healthy dogs, consisting of 10 different breeds, including mixed breeds (n = 13), Pomeranians (n = 5), Maltese (n = 4), a Shih Tzu (n = 1), a Pungsan (n = 1), a Poodle (n = 1), a French Bulldog (n = 1), a Dachshund (n = 1), a Chihuahua (n = 1), and a Bichon Frise (n = 1) were 4.93 ± 3.45 years old and weighed 3.36 ± 2.19 kg.
Preoperative blood profile comparisons
The clinical data, including hematologic and biochemical data, showed significant differences among pyometra survivors, pyometra non-survivors, and healthy dogs (Table 1). Both the pyometra survivors and non-survivors showed significantly lower RBC counts, HCTs, and HGB levels than healthy dogs, with the lowest values observed in the pyometra non-survivors. WBC and NEU counts were significantly elevated in both pyometra survivors and non-survivors, with the highest values observed in pyometra non-survivors. Biochemistry analyses revealed that BUN and creatinine levels were significantly increased in pyometra non-survivors compared with both pyometra survivors and healthy dogs. Pyometra non-survivors exhibited the lowest ALB levels, while globulin levels were lowest in healthy dogs. Pyometra survivors showed significantly lower glucose levels than healthy dogs, while pyometra non-survivors exhibited the lowest values, which were not significantly different from either group.
Table 1. Mean preoperative clinical data from dogs with pyometra and healthy dogs.
| Variables | Healthy dogs (n = 29) | Pyometra survivors (n = 51) | Pyometra non-survivors (n = 12) | Reference range |
|---|---|---|---|---|
| RBC (M/μL) | 7.57 ± 0.86a | 6.38 ± 1.34b | 5.85 ± 1.77b | 5.65–8.87 |
| HCT (%) | 48.87 ± 4.64a | 41.18 ± 8.54b | 37.90 ± 11.03b | 37.30–61.70 |
| HGB (g/dL) | 17.83 ± 1.73a | 15.19 ± 2.99b | 13.96 ± 3.87b | 13.10–20.50 |
| WBC (K/μL) | 12.27 ± 7.03a | 26.56 ± 18.25b | 39.60 ± 28.89c | 5.05–16.76 |
| NEU (K/μL) | 5.86 ± 1.81a | 20.66 ± 15.45b | 31.30 ± 24.31c | 2.95–11.64 |
| LYM (K/μL) | 4.01 ± 1.23 | 3.50 ± 1.90 | 4.96 ± 4.47 | 1.05–5.10 |
| MONO (K/μL) | 1.33 ± 2.35a | 2.63 ± 2.35a,b | 3.34 ± 3.27b | 0.16–1.32 |
| EOS (K/μL) | 0.38 ± 0.38 | 0.18 ± 0.74 | 0.01 ± 0.01 | 0.06–1.23 |
| BASO (K/μL) | 0.05 ± 0.23 | 0.01 ± 0.02 | 0.01 ± 0.01 | 0–0.10 |
| PLT (K/μL) | 281.90 ± 137.10 | 273.50 ± 173.40 | 223.00 ± 155.70 | 148.00–484.00 |
| Glucose (mg/dL)c | 125.50 (112.50–136.00)a | 105.00 (90.00–126.00)b | 109.00 (96.25–133.30)a,b | 75.00–128.00 |
| BUN (mg/dL) | 18.77 ± 4.34a | 24.75 ± 20.16a | 50.94 ± 39.42b | 9.20–29.20 |
| Creatinine (mg/dL) | 0.58 ± 0.16a | 0.74 ± 0.53a | 1.22 ± 0.79b | 0.40–1.40 |
| Phosphorus (mg/dL) | 3.75 ± 0.64a | 4.12 ± 1.56a | 8.58 ± 5.06b | 1.90–5.00 |
| Total Ca (mg/dL) | 10.90 ± 2.12 | 12.13 ± 4.24 | 10.12 ± 1.31 | 9.30–12.10 |
| Total protein (g/dL) | 6.09 ± 0.41a | 7.45 ± 0.98b | 7.61 ± 2.19b | 5.00–7.20 |
| ALB (g/dL) | 3.61 ± 0.31a | 3.21 ± 0.63a | 2.62 ± 0.81b | 2.60–4.00 |
| Globulin (g/dL) | 2.43 ± 0.39a | 4.44 ± 1.14b | 4.94 ± 1.33b | 2.80–4.20 |
| ALT (U/L) | 44.74 ± 15.82 | 37.04 ± 23.07 | 45.06 ± 26.85 | 17.00–78.00 |
| ALP (U/L) | 293.70 ± 190.90a | 405.20 ± 295.10a | 646.00 ± 402.10b | 47.00–254.00 |
| Total bilirubin (mg/dL)c | 0.40 (0.13–0.75) | 0.20 (0.10–0.38) | 0.60 (0.35–0.75) | 0.10–0.50 |
| Cholesterol (mg/dL) | 280.00 ± 53.74 | 275.70 ± 94.48 | 345.00 ± 97.75 | 111.00–312.00 |
Differences were assessed by one-way analysis of variance with Holm–Sidak post hoc tests for normally distributed variables and the Kruskal-Wallis with Dunn’s post hoc test for non-normally distributed variables. Values are presented as mean ± standard deviation or median (Q1–Q3).
RBC, red blood cell; HCT, hematocrit; HGB, hemoglobin; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; MONO, monocyte; EOS, eosinophil; BASO, basophil; PLT, platelet; BUN, blood urea nitrogen; ALB, albumin; ALT, alanine aminotransferase; ALP, alkaline phosphatase.
a,bLettered subscripts indicate statistical differences between groups (p < 0.05). cIndicates variables analyzed using non-parametric test due to non-normal distributions.
Preoperative BUN/ALB analysis
The BUN/ALB values among pyometra survivors, pyometra non-survivors, and healthy dogs are presented in Fig. 1A. The BUN/ALB values were significantly elevated in both pyometra survivors and non-survivors compared with healthy dogs. Compared with pyometra survivors, the BUN/ALB values were significantly increased in pyometra non-survivors. To evaluate the presence of a significant ordered trend, the Jonckheere–Terpstra test was performed. The Jonckheere–Terpstra test demonstrated a significant monotonic trend in BUN/ALB values across healthy dogs, pyometra survivors, and pyometra non-survivors. The mean BUN/ALB increased progressively from healthy dogs to pyometra survivors and non-survivors, indicating stepwise elevation of the BUN/ALB (Table 2). To compare the sensitivity and specificity with pyometra survivors and non-survivors, ROC curve analysis was used (Fig. 1B) and revealed an area under the curve (AUC) of 0.86. The most appropriate BUN/ALB cut-off value obtained from the ROC curve analysis was 8.935 with a combined sensitivity of 73.08% and a specificity of 90.91% (Table 3).
Fig. 1. Preoperative BUN/ALB as a prognostic indicator in canine pyometra. (A) Comparison of the preoperative BUN/ALB in healthy dogs, pyometra survivors, and pyometra non-survivors. Data are presented as the mean ± standard deviation. Statistical significance was determined using one-way analysis of variance with Holm-Sidak’s post hoc test. (B) ROC curves of the BUN/ALB values of dogs with pyometra. The AUC was estimated to be 0.86.
BUN/ALB, blood urea nitrogen-to-albumin ratio; ROC, receiver operating characteristic; AUC, area under the curve.
a,b,cLettered subscripts indicate statistical differences between groups (p < 0.05).
Table 2. Jonckheere–Terpstra test for ordered trend and pairwise preoperative comparisons between groups.
| Comparison | Test statistics (T) | Standard error | Standard test statistic | Adjusted p value |
|---|---|---|---|---|
| Jonckheere-Terpstra (overall trend) | 2,009.50 | 132.76 | 5.80 | < 0.001 |
| Healthy dogs vs. pyometra survivors | 1,164.50 | 98.32 | 4.47 | < 0.001 |
| Healthy dogs vs. pyometra non-survivors | 347.00 | 36.75 | 4.31 | < 0.001 |
| Pyometra survivors vs. pyometra non-survivors | 498.00 | 58.88 | 2.94 | 0.005 |
Adjusted p value was calculated with Bonferroni correction.
Table 3. Clinical sensitivity and specificity of the BUN/ALB.
| BUN/ALB | AUC | Cut-off value | Sensitivity (%) | Specificity (%) |
|---|---|---|---|---|
| Preoperative | 0.86 (95% CI, 0.75–0.96) | 8.935 | 73.08 | 90.91 |
| Postoperative | 0.81 (95% CI, 0.64–0.98) | 8.445 | 68.18 | 83.33 |
BUN/ALB, blood urea nitrogen-to-albumin ratio; AUC, area under the curve; CI, confidence interval.
Postoperative blood profile comparisons between pyometra survivors and non-survivors
Postoperative blood test data were available for a subset of dogs with pyometra (28/63), including 22 survivors and 6 non-survivors. The CBC and biochemistry data showed significant differences between postoperative pyometra survivors and postoperative pyometra non-survivors (Table 4). The postoperative pyometra survivors showed significantly lower WBC counts, LYM counts, BUN levels, and ALP levels than postoperative pyometra non-survivors.
Table 4. Mean postoperative clinical data in pyometra survivors and non-survivors.
| Variables | Postoperative survivors (n = 22) | Postoperative non-survivors (n = 6) | p value | Reference range |
|---|---|---|---|---|
| RBC (M/μL) | 6.15 ± 3.89 | 4.63 ± 1.22 | 0.3283 | 5.65–8.87 |
| HCT (%) | 34.82 ± 9.36 | 31.17 ± 8.45 | 0.6916 | 37.30–61.70 |
| HGB (g/dL) | 14.44 ± 6.78 | 11.15 ± 2.73 | 0.1784 | 13.10–20.50 |
| WBC (K/μL) | 40.87 ± 31.27 | 72.40 ± 31.81 | 0.0283 | 5.05–16.76 |
| NEU (K/μL) | 36.52 ± 27.76 | 53.90 ± 24.65 | 0.0680 | 2.95–11.64 |
| LYM (K/μL) | 5.04 ± 5.22 | 7.47 ± 2.74 | 0.0307 | 1.05–5.10 |
| MONO (K/μL) | 4.15 ± 3.30 | 5.13 ± 2.33 | 0.2085 | 0.16–1.32 |
| EOS (K/μL) | 0.15 ± 0.29 | 5.90 ± 11.01 | 0.9387 | 0.06–1.23 |
| BASO (K/μL) | 0.28 ± 0.60 | 0.08 ± 0.11 | 0.9156 | 0–0.10 |
| PLT (K/μL) | 243.30 ± 133.20 | 238.70 ± 120.00 | 0.9999 | 148.00–484.00 |
| Glucose (mg/dL) | 85.12 ± 46.06 | 116.40 ± 50.24 | 0.6110 | 75.00–128.00 |
| BUN (mg/dL) | 16.54 ± 7.76 | 23.93 ± 4.58 | 0.0187 | 9.20–29.20 |
| Creatinine (mg/dL) | 0.58 ± 0.53 | 0.71 ± 0.57 | 0.2788 | 0.40–1.40 |
| Phosphorus (mg/dL) | 3.85 ± 1.34 | 7.73 ± 6.34 | 0.5476 | 1.90–5.00 |
| Total Ca (mg/dL) | 6.35 ± 3.48 | 6.90 ± 2.70 | 0.9643 | 9.30–12.10 |
| Total protein (g/dL) | 6.00 ± 1.58 | 6.87 ± 0.72 | 0.1217 | 5.00–7.20 |
| ALB (g/dL) | 2.28 ± 0.44 | 2.25 ± 0.58 | 0.8429 | 2.60–4.00 |
| Globulin (g/dL) | 3.93 ± 0.75 | 4.60 ± 0.36 | 0.0602 | 2.80–4.20 |
| ALT (U/L) | 78.05 ± 84.77 | 79.60 ± 75.85 | 0.9044 | 17.00–78.00 |
| ALP (U/L) | 517.10 ± 281.40 | 1231.00 ± 683.90 | 0.0093 | 47.00–254.00 |
| Total bilirubin (mg/dL) | 0.49 ± 0.70 | 0.83 ± 0.84 | 0.3091 | 0.10–0.50 |
| Cholesterol (mg/dL) | 170.70 ± 99.80 | 262.00 ± 24.04 | 0.9999 | 111.00–312.00 |
Statistically significant differences among dog groups were estimated by the Mann-Whitney test.
RBC, red blood cell; HCT, hematocrit; HGB, hemoglobin; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; MONO, monocyte; EOS, eosinophil; BASO, basophil; PLT, platelet; BUN, blood urea nitrogen; ALB, albumin; ALT, alanine aminotransferase; ALP, alkaline phosphatase.
Postoperative BUN/ALB analysis
Differences in the BUN/ALBs were compared between postoperative pyometra survivors and non-survivors. In postoperative pyometra survivors, the BUN/ALB was significantly lower than in postoperative pyometra non-survivors (Fig. 2A). To estimate sensitivity and specificity, ROC curve analysis was performed (Fig. 2B). ROC curve analysis revealed a cut-off value of 8.445 with a combined sensitivity of 68.18%, a specificity of 83.33%, and an AUC of 0.81 (Table 3).
Fig. 2. Evaluation of the postoperative BUN/ALB in dogs with pyometra. (A) BUN/ALB values after surgical treatment in postoperative survivors and non-survivors. Data are presented as the mean ± standard deviation. The significance of differences was determined using the Mann-Whitney test. (B) ROC curves of the BUN/ALB values of dogs with pyometra. The AUC was estimated to be 0.81.
BUN/ALB, blood urea nitrogen-to-albumin ratio; ROC, receiver operating characteristic; AUC, area under the curve.
a,bLettered subscripts indicate statistically significant differences between groups (p < 0.05).
DISCUSSION
This study demonstrated that the BUN/ALB was significantly associated with outcome in dogs with pyometra both before and after surgery. Non-survivors consistently exhibited higher BUN/ALB values than survivors, and a clear overall increasing trend was confirmed from healthy controls to survivors and non-survivors. These findings indicate that the BUN/ALB reflects the severity of systemic illness in pyometra and retains prognostic relevance even after OHE.
Because pyometra primarily occurs in middle age intact dogs, intact adult female dogs were used as controls in this study. The clinical data such as CBC and biochemical parameters in dogs were investigated before and after surgical treatment. Preoperatively, pyometra survivors and non-survivors showed significantly lower RBC counts, HCT, and HGB levels than healthy dogs, with the lowest values in pyometra non-survivors. In addition, WBC and NEU counts were significantly elevated in both pyometra survivors and non-survivors, with the highest values observed in pyometra non-survivors. Overall, these results suggested that hematological evidence of anemia, leukocytosis, and neutrophilia, combined with biochemical indicators of renal dysfunction (elevated BUN, creatinine, and phosphorus) and hypoalbuminemia, were more pronounced in pyometra non-survivors and may be associated with a poor prognosis. Although statistically significant differences in glucose levels were observed, the glucose levels remained within the reference range. These findings suggest that the observed glucose variation is unlikely to reflect disease severity or have meaningful prognostic relevance in canine pyometra. Postoperative pyometra non-survivors showed significantly higher WBC counts, LYM counts, BUN levels, and ALP levels than postoperative pyometra survivors. Collectively, these findings indicate that dogs with pyometra, particularly those that did not survive, exhibited pronounced hematologic and biochemical alterations reflecting systemic inflammation, impaired renal function, and altered metabolism. These findings are consistent with previous studies regarding the poor prognosis of dogs with pyometra [13,18,19].
Several conventional markers have been suggested as prognostic indicators in canine pyometra. An increasing lactate concentration and hematologic abnormalities such as leukocytosis and the presence of band neutrophils have been reported to exceed normal ranges in dogs with pyometra, and these variables have been proposed to play roles as prognostic indicators in previous studies [5,20,21]. Increased lactate concentrations may not always serve as a reliable prognostic indicator, and one previous study failed to find an association between elevated lactate levels and mortality [22]. Hematologic abnormalities such as leukocytosis or neutrophilia are frequently observed, but they lack specificity and may be present in a wide range of inflammatory conditions [19]. C-reactive protein, a widely recognized acute-phase protein, has also been investigated in canine pyometra, but its role as a prognostic indicator remains controversial [8]. Compared with these markers, the BUN/ALB has the advantage of being derived from two parameters (BUN and ALB) that are universally measured in routine biochemical panels. Therefore, the BUN/ALB provides an easily accessible and integrative index of systemic dysfunction, making it potentially more practical for clinical applications.
The BUN/ALB functions as an easily accessible index that integrates nutritional state, systemic inflammation, metabolic activity, and renal function. As a ratio derived from both the BUN and serum ALB, the BUN/ALB could be a comprehensive marker of overall body reserves [14]. By encompassing multiple organ functions, it might demonstrate improved utility in assessing disease severity [23]. The BUN/ALB has been validated as a reliable prognostic marker for mortality in some diseases [9,14,15]. However, it should be considered that both BUN and ALB levels could be influenced by dog healthy conditions including breed, body weight, and age. Such physiological variability may influence the BUN/ALB ratio independently of disease severity, and these factors should be considered when interpreting its clinical significance. In this study, the prognostic value of BUN/ALB in dogs with pyometra was investigated. In addition, it was demonstrated that the BUN/ALB was significantly elevated in dogs with pyometra compared with healthy dogs, with the highest value observed in pyometra non-survivors under preoperative conditions. This ordered trend was statistically significant. This finding is consistent with previous studies in human medicine that reported a significant positive association between the BUN/ALB and all-cause mortality among patients with sepsis [15]. Given that canine pyometra is considered a natural model of sepsis [4], the present results supported the translational value of the BUN/ALB as a prognostic marker across species. Moreover, it has been demonstrated that the preoperative BUN/ALB is a simple, rapid, and potentially useful prognostic indicator of postoperative in-hospital mortality in humans [24]. Consequently, the BUN/ALB has potential as an indicator for prognostic evaluation in pyometra, as it not only reflects the systemic impact of sepsis in humans but also mirrors the severity of canine pyometra.
In the postoperative BUN/ALB analysis, it was observed that the BUN/ALB remained significantly elevated postoperatively in non-survivors compared with survivors, suggesting that the systemic impact of sepsis remained even after removal of the primary source of infection. In particular, the remaining elevation of BUN levels and reduction of ALB levels may reflect residual renal impairment, systemic inflammation, and metabolic dysfunction, all of which could contribute to an increased risk of death [18,25]. The ROC curve analysis identified an optimal cut-off value of 8.935, with a combined sensitivity of 73.08% and a specificity of 90.91% for preoperatively predicting mortality, and 8.445, with an acceptable sensitivity of 68.18% and a specificity of 83.33% for postoperatively predicting mortality. Although the sensitivity and specificity were slightly lower than those observed preoperatively, the BUN/ALB remained a clinically relevant indicator for pyometra mortality following surgery. The persistence of an elevated BUN/ALB after surgery in non-survivors was consistent with the findings from previous human studies demonstrating that the postoperative BUN/ALB was a predictor associated with mortality [26]. This finding indicates that postoperative monitoring of the BUN/ALB can provide valuable information to guide the intensity of supportive care and to identify dogs at higher risk of adverse outcomes.
From a clinical perspective, the identified BUN/ALB thresholds in this study could provide practical guidance for risk stratification in canine pyometra. A preoperative BUN/ALB above 8.9 could suggest a higher risk of mortality and might justify intensive perioperative management, including aggressive fluid therapy, careful monitoring, and closer postoperative observation. In addition, a postoperative BUN/ALB remaining above 8.4 could suggest a poor prognosis despite effective treatment and indicate the need for more intensive supportive care. Although these thresholds should not yet be applied for definitive clinical decision-making, they support the potential of the BUN/ALB as a simple, inexpensive, and practical clinical tool for dogs with pyometra.
Due to the characteristics of this retrospective study, postoperative blood samples were not available for all dogs, either because the dogs were discharged early or the owners declined further sampling, which limited the completeness of the analysis. Although dogs with comorbidities were excluded, the small number of non-survivors reduced the statistical power and may have limited the analyses. Another important limitation is the heterogeneity between the healthy control and pyometra groups. The 63 dogs with pyometra and the 29 healthy controls differed in age, body weight, and breed composition, and the healthy controls were significantly younger and lighter than the dogs with pyometra. Because BUN and albumin concentrations may be influenced by factors such as age and body condition, these differences may have acted as confounding variables. To verify the advantages of the BUN/ALB, further studies based on a large number of cases are necessary.
Given that canine pyometra is recognized as a natural model of sepsis, the BUN/ALB may be a translational indicator in veterinary critical care. Therefore, the BUN/ALB is proposed as a simple, inexpensive, and readily available prognostic indicator in dogs with pyometra.
Footnotes
Funding: This study was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry (IPET) through the Agriculture and Food Convergence Technologies Program for Research Manpower Development (RS-2024-00398561), and the HBION (2024-2107-01).
Conflict of Interest: The authors declare no conflicts of interest.
Data Availability Statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
- Conceptualization: Baek M, Lee SY, Son YB.
- Data curation: Baek M.
- Formal analysis: Lee SY.
- Funding acquisition: Son YB.
- Investigation: Baek M, Son YB.
- Methodology: Lee SY.
- Project administration: Son YB.
- Resources: Baek M.
- Software: Lee SY.
- Supervision: Son YB.
- Validation: Baek M, Lee SY, Son YB.
- Visualization: Lee SY.
- Writing - original draft: Baek M, Lee SY, Son YB.
- Writing - review & editing: Baek M, Lee SY, Son YB.
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