Abstract
Background
Arthroplasty literature describes preoperative hypoalbuminemia as a risk factor for perioperative complications. A correlation between low postoperative albumin levels and acute infection–related complications has been studied in cardiothoracic and abdominal surgery. We aim to further characterize postoperative hypoalbuminemia, independent of preoperative albumin level, as a risk factor for long-term complications in arthroplasty, specifically knee and hip periprosthetic joint infections (PJIs).
Methods
The TriNetX database was queried for patients undergoing primary or revision hip or knee arthroplasty from January 1, 2000 to January 1, 2024. Cohorts were defined as patients with normal postoperative albumin levels (≥3.5 g/dL) and those with postoperative hypoalbuminemia (<3.5 g/dL) on postoperative days 1-3. These cohorts were propensity matched based on demographics, comorbidities, and preoperative albumin level. PJI rates at 3 months, 1 year, and 5 year were compared between cohorts.
Results
Low postoperative albumin level following hip arthroplasty was associated with approximately 2.5 times increased risk of PJI within 3 months, and a 2.3 times increased risk at later time points. In patients who underwent knee arthroplasty, postoperative hypoalbuminemia was associated with a lesser but significant PJI risk of 1.4- to 1.5-fold at all time points.
Conclusions
Risk for PJI in patients with low postoperative albumin, independent of preoperative albumin level, is substantial, up to 2.5 times in those undergoing hip arthroplasty. This risk is also elevated for knee arthroplasty patients. This likely represents an acute marker of the surgical “hit,” underscoring the importance of better defining the underlying mechanisms and associated biomarkers to improve acute care, complications surveillance, and identify therapeutic interventions.
Keywords: Hypoalbuminemia, Prosthetic joint infection, Total hip arthroplasty, Total knee arthroplasty, Malnutrition, Arthroplasty complications
Introduction
Malnutrition has been widely recognized as a significant contributor to postoperative complications. Malnutrition affects serum protein synthesis, and thus, a low albumin level can be used as a proxy for undernourishment [1]. Preoperative hypoalbuminemia, defined as a serum albumin level below 3.5 g/dL, has been associated with a higher risk of poor postoperative outcomes, including a 3-fold increased risk of prosthetic joint infection (PJI), prolonged hospital stays, and greater likelihood of complications following surgery [[2], [3], [4], [5], [6]]. Given its correlation with nutritional status and inflammatory responses, albumin measurement is a valuable tool for identifying patients at elevated risk for adverse surgical outcomes. In addition to reflecting baseline nutritional status, perioperative changes in serum albumin may reflect the physiologic “hit” of surgery itself. Major operations are associated with acute inflammatory and stress responses that can downregulate albumin synthesis and promote capillary leak, leading to a rapid postoperative decline in serum albumin independent of preoperative nutrition [7]. As a result, postoperative hypoalbuminemia may serve as a marker of surgical stress and host response rather than undernourishment alone. Disruption of the intestinal barrier during periods of acute physiologic stress may also facilitate hematogenous translocation of enteric pathogens, providing a potential link between surgical stress, postoperative hypoalbuminemia, and infection risk [8].
PJIs following total hip arthroplasty (THA) and total knee arthroplasty (TKA) pose substantial risks to patients and place a significant burden on the health care system. Recent data highlight the rising prevalence of hip and knee arthroplasties among older adults [[9], [10], [11], [12]]. Current literature shows that infection rates in prosthetic joints following THA or TKA are approximately 1%-2% [13,14]. While postoperative infection occurs at a relatively low rate, infected patients are 5.6 times more likely to undergo revision THA, and infected patients account for 15% of revision surgeries [12,15]. This correlates with increased health care costs: annual hospital expenses for managing PJIs are projected to reach $1.85 billion by 2030 [13]. Given the escalating health care risks and costs, identifying measures that better predict complications is crucial.
Existing literature shows preoperative hypoalbuminemia as a risk factor for perioperative complications across specialties. Less is known about the prognostic value of acute postoperative serum albumin levels. This study aims to evaluate if postoperative hypoalbuminemia, irrespective of preoperative albumin level, is a risk factor for long-term complications in arthroplasty, specifically peri-PJIs of the hip and knee. We hypothesize that postoperative hypoalbuminemia is associated with adverse arthroplasty outcomes, when controlling preoperative nutritional markers (such as preoperative albumin) and relevant comorbidities.
Material and methods
The TriNetX Research Network database was queried for patients undergoing hip arthroplasty (THA, hip hemiarthroplasty, or revision THA) or knee arthroplasty (TKA, unicompartmental arthroplasty, or revision TKA) from January 1, 2000 to January 1, 2024. TriNetX is a global database that includes data from over 250 million patients across 30 countries and 830 health care organizations. Variables captured include patient demographics, laboratory values, medications, diagnoses, and procedures. Current Procedural Terminology and International Classification of Diseases, 10th Revision diagnosis codes are utilized within the TriNetX database to conduct the retrospective analysis and are included in the appendix (Appendix Tables 1-3). The dataset includes aggregated counts and statistical summaries of deidentified information and thus is institutional review board exempt [16].
Cohorts were defined as patients with normal postoperative albumin levels (>3.5 g/dL) and those with postoperative hypoalbuminemia (<3.5 g/dL) measured on postoperative days 1-3 (Fig. 1). These cohorts were propensity matched based on demographic data and comorbidities. Propensity score matching was performed based on age, gender (man, woman, or unknown), race, and ethnicity. The cohorts were subsequently matched based on the preoperative comorbidities based on parameters that are considered when optimizing patients preoperatively, including preoperative albumin level and hemoglobin (Appendix Table 4). The rate of PJI within various time frames was compared between patients with normal or low postoperative albumin. TriNetX completes logistical regression using scikit-learn software to generate propensity scores.
Figure 1.
Cohort propensity matched for comorbidities and demographic data and divided based on postoperative albumin level between postoperative day 1-3.
An outcomes analysis of the matched cohorts was conducted using TriNetX, evaluating the rate of peri-PJI at various time points up to 5 years postoperatively. Infection rates were reported as both the total number of patients and as a percentage of each cohort. The risk ratio, defined as rate of complication in the low albumin cohort divided by the rate of complication in the normal albumin cohort, was reported with a 95% confidence interval, a P value of .05, and an Z-test to assess the statistical significance of differences between proportions of the presence of outcomes in patients in each cohort. All statistical analyses were performed using the TriNetX analytics platform, which employs Java 11.0.16, R 4.0.2, and Python 3.7 [17].
Results
Low postoperative albumin levels, independent of preoperative albumin levels, were associated with a greater than 2-fold increased risk (2.6% absolute risk) of PJI within 90-day, 1-year, and 5-year postoperative time points following major hip surgery (relative risk 2.48, 2.33, 2.27, respectively) (Figs. 2 and 3). This effect was most pronounced in patients who underwent hip arthroplasty as their index procedure. In patients who underwent knee arthroplasty as their index procedure, low postoperative albumin levels were also associated with increased risk for PJI at their corresponding time points (Figs. 2 and 3) but to a lesser degree (relative risk 1.44, 1.45, 1.45 respectively). While the increase in risk for PJI was statistically significant when comparing low vs normal postoperative albumin cohorts for patients undergoing TKA, propensity matching of the cohorts decreased the clinical impact. However, risk remained elevated in patients undergoing THA who had low postoperative albumin levels, suggesting that these patients sustain a more notable hit to their reserve during THA. Importantly, these patients remain at an elevated risk of infection up to 5 years postoperatively.
Figure 2.
Magnitude of increased risk at postoperative time points up to 5 years for patients with low postoperative albumin levels who underwent either major hip or major knee surgery as their index procedure.
Figure 3.
Risk of PJI at 3 months, 1 year, and 5 years after hip and knee arthroplasty, comparing patients with normal vs low postoperative albumin levels. Error bars represent a 95% confidence interval between normal and hypoalbuminemia conditions. P values comparing normal to hypo albumin for both hip and knee were significant at all time points (Table 1).
Discussion
Historically, arthroplasty literature has focused on preoperative albumin level as a marker for nutritional status and predictor of perioperative complications. Many have published these risks [4,5,18], and while outside the scope of this article, Golladay et al. [19] and Cross et al. [4] provide guidelines on preoperative correction of malnutrition in elective arthroplasty patients. A study by Holbert et al. [3] examined malnutrition in patients with a body mass index over 35, finding that preoperative hypoalbuminemia in obese patients increased the risk of postoperative complications and health care resource utilization following total joint arthroplasty. Similarly, Hur et al. [20] demonstrated that patients undergoing unicompartmental knee arthroplasty with preoperative albumin levels below 3.5 g/dL had over twice the probability of experiencing complications. Low preoperative albumin has also been linked to cardiopulmonary issues, systemic infections, and general surgical complications in both elective spine surgeries and total joint arthroplasty [4,5].
While preoperative malnutrition has been shown to increase infection risks, our study emphasizes the importance of considering postoperative albumin levels as a surrogate marker for the overall impact of surgery on the patient's risk for complications, particularly in the context of PJIs. While much of the existing research has focused on preoperative factors, our data support the hypothesis that postoperative hypoalbuminemia is not only a marker of immediate risk but also associated with complication risk at delayed time points. We observed that low postoperative albumin levels were strongly associated with an increased risk of infection at 90 days, 1 year, and 5 years following major hip and knee surgeries. As noted above, low postoperative albumin in the acute postoperative period is associated with more than a 2-fold increase in risk for PJI at 3-month, 1-year, and 5-year time points. There is a minimal increase in the risk of PJI in patients with low albumin in the acute postoperative period after TKA, which is statistically significant, but has less clinical relevance.
It is an important consideration that major hip surgery may unveil fragile nutritional states, which could be identified by surrogate markers such as postoperative hypoalbuminemia. A study by Redelmeier [7] showed that 20%-40% of postoperative patients experience a rapid decline in albumin levels following elective surgery. In addition, Wu et al. [16] found that 37.7% of patients who underwent THA developed postoperative hypoalbuminemia, which was associated with prolonged intraoperative times. However, this study did not correlate hypoalbuminemia with surgical outcomes. A study by Ryan et al [18], examining day 1 postoperative albumin levels found, preoperative hypoalbuminemia to be a better predictor of surgical outcome compared with other factors.
Beyond baseline nutritional status, postoperative hypoalbuminemia may reflect the physiologic impact of surgery itself. The cortisol-driven stress response during surgery is well documented and suggests that major surgeries may induce a hyperinflammatory state, which can disrupt endothelial integrity and promote capillary leak, including within the gastrointestinal tract, resulting in loss of intravascular proteins, such as albumin [7,17,21]. In this context, postoperative hypoalbuminemia may represent a marker of the surgical “hit” and host response rather than isolated undernourishment. Patients with greater physiologic vulnerability or frailty may be less able to compensate for this acute insult, potentially predisposing them to sustained hypoalbuminemia and downstream complications. This framework supports the interpretation of postoperative albumin as an integrated marker of surgical stress, inflammatory burden, and patient reserve.
Our results highlight the predictive value of postoperative hypoalbuminemia on patient outcomes, extending beyond the perioperative period. Notably, the varying infection rates between hip and knee surgeries suggest that the type of surgical procedure or impact of the surgical hit may influence the infection risk. Variance between procedures may be a result of longer operative times, increased blood loss, and greater inflammatory response in hip compared with knee arthroplasty, which may help explain the stronger association observed in hips. This disparity warrants further investigation into how surgical invasiveness and physiological stress—including acute inflammatory responses and capillary leak—impact patient outcomes, for which postoperative hypoalbuminemia may serve as a surrogate. The sustained risk of infection observed over several years following surgery suggests that monitoring markers in the postoperative phase could help identify patients at higher risk for long-term adverse outcomes. While no causation can be drawn from the design of this study, the findings suggest utility in albumin as a marker for postoperative outcomes at various time points. Further research is needed to identify interventions to combat this postoperative state.
Limitations
While retrospective use of the TriNetX databases provides large patient populations, variations in coding and reporting of medical conditions provide limited details and data outside the codes used to report PJI. Patients are seen across a variety of health care systems, leading to differences in care and coding practices. Such variation may affect absolute rates but is unlikely to meaningfully bias comparisons between groups. In addition, sicker patients may be more likely to have postoperative laboratory studies obtained, introducing potential selection bias into the albumin-defined cohorts. Finally, PJI is multifactorial in nature, and our data only provide insight on limited time points across 5 years.
Conclusions
The elevated risk of PJI in patients with low postoperative albumin levels (<3.5 g/dL) undergoing THA is most pronounced within the 3-month time frame following major hip surgery, compared with the 1-year and 5-year time points. For patients undergoing knee arthroplasty, the increased risk of PJI is similarly significant at all time points. These findings underscore the importance of further investigation into how postoperative nutrition contributes to infection-related complications, as the risk of PJI in patients with acutely low albumin levels remains elevated even in the long term. A better understanding of this connection could inform improvements in postsurgical monitoring and targeted interventions aimed at reducing infection risk in vulnerable patients.
CRediT authorship contribution statement
Kyle Sterns: Writing – review & editing, Writing – original draft, Investigation, Formal analysis, Data curation. Indigo Milne: Writing – review & editing, Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation. Kirstin Humble: Writing – review & editing, Supervision. Nikkole Haines: Writing – review & editing, Writing – original draft, Supervision.
Conflicts of interest
The authors declare there are no conflicts of interest. For full disclosure statements, refer to https://doi.org/10.1016/j.artd.2026.101960.
Table 1.
Rate of PJI at various time points in patients undergoing either major hip or knee surgery with normal vs low postoperative albumin levels.
| Time | Operation (N) | Albumin level | Patients with PJI (n) | Rate (%) | Risk ratio | Absolute risk difference (%) | 95% Confidence interval | P-value |
|---|---|---|---|---|---|---|---|---|
| 3 mo | Knee (5522) | Normal | 239 | 4.33 | 1.44 | 1.92 | 1.229-1.695 | <.0001 |
| Low | 345 | 6.25 | ||||||
| Hip (2124) | Normal | 42 | 1.98 | 2.48 | 2.91 | 1.739-3.525 | <.0001 | |
| Low | 104 | 4.89 | ||||||
| 1 y | Knee (7212) | Normal | 329 | 4.56 | 1.45 | 2.05 | 1.265-1.662 | <.0001 |
| Low | 477 | 6.61 | ||||||
| Hip (2270) | Normal | 45 | 1.98 | 2.33 | 2.65 | 1.654-3.292 | <.0001 | |
| Low | 105 | 4.63 | ||||||
| 5 y | Knee (6209) | Normal | 378 | 6.10 | 1.45 | 2.74 | 1.280-1.648 | <.0001 |
| Low | 549 | 8.84 | ||||||
| Hip (2358) | Normal | 49 | 2.08 | 2.27 | 2.63 | 1.626-3.155 | <.0001 | |
| Low | 111 | 4.71 |
Appendix A. Supplementary data
Appendix.
Table S1.
CPT of ICD-10 codes for index hip procedures.
| CPT or ICD-10 code | Procedure | |
|---|---|---|
| Total arthroplasty | CPT 27130 | Arthroplasty acetabular and proximal femoral prosthetic replacement (THA), with or without autograft or allograft |
| ICD-10 OSR90JA | Replacement of R hip joint with synthetic substitute, uncemented, open approach | |
| ICD-10 OSR90JZ | Replacement of R hip joint with synthetic substitute, open approach | |
| ICD-10 0SRBOJA | Replacement of left hip joint with synthetic substitute, uncemented, open approach | |
| ICD-10 0SRBOJZ | Replacement of left hip joint with synthetic substitute, open approach | |
| Revision | CPT 1004910 | Revision of THA |
| CPT 27134 | Revision of THA; both components with or without allograft or autograft | |
| CPT 27138 | Revision of THA; femoral component only, with or without allograft | |
| CPT 27137 | Revision of THA; acetabular component only, with or without autograft or allograft | |
| Conversion | CPT 27132 | Conversion of previous hip surgery to THA, with or without autograft or allograft |
| Hemiarthroplasty | ICD-10 0SUA0BZ | Supplement right hip joint, acetabular surface with resurfacing device, open approach |
| ICD-10 0SUR0BZ | Supplement right hip joint, femoral surface with resurfacing device, open approach | |
| ICD-10 0SUA09Z | Supplement right hip joint, acetabular surface with liner, open approach | |
| ICD-10 0SUR09Z | Supplement right hip joint, femoral surface with liner, open approach | |
| ICD-10 0SUE0BZ | Supplement left hip joint, acetabular surface with resurfacing device, open approach | |
| ICD-10 0SUS0BZ | Supplement left hip joint, femoral surface with resurfacing device, open approach | |
| ICD-10 0SUE09Z | Supplement left hip joint, acetabular surface with liner, open approach | |
| ICD-10 0SUS09Z | Supplement left hip joint, femoral surface with liner, open approach |
CPT, Current Procedural Terminology; ICD-10, International Classification of Diseases, 10th Revision.
Table S2.
CPT or ICD-10 code for index knee procedures.
| CPT or ICD-10 code | Procedure | |
|---|---|---|
| Total arthroplasty | CPT 27447 | Arthroplasty, knee, condyle and plateau; medial and lateral compartments with or without patella resurfacing (TKA) |
| ICD-10-PCS 0SRD0JZ | Replacement of L knee joint with synthetic substitute, open approach | |
| ICD-10-PCS 0SRW0JZ | Replacement of L knee joint, tibial surface with synthetic substitute, open approach | |
| ICD-10-PCS 0SRD0KZ | Replacement of L knee joint with nonautologous tissue substitute, open approach | |
| ICD-10 PCS 0SRD07Z | Replacement of L knee joint with autologous tissue substitute, open approach | |
| ICD-10-PCS 0SRU07Z | Replacement of L knee, femoral surface with autologous tissue substitute, open approach | |
| ICD-10 PCS 0SRU0KZ | Replacement of L knee joint, femoral surface with nonautologous tissue substitute, open approach | |
| ICD-10-PCS 0SRW07Z | Replacement of L knee joint, tibial surface with autologous tissue substitute, open approach | |
| ICD-10-PCS 0SRT0JZ | Replacement of R knee joint, femoral surface with synthetic substitute, open approach | |
| ICD-10-PCS 0SR0JZ | Replacement of R knee joint, tibial surface with synthetic substitute, open approach | |
| ICD-10-PCS 0SRC0KZ | Replacement of R knee joint with nonautologous tissue substitute, open approach | |
| ICD-10-PCS 0SRT07Z | Replacement of R knee joint, femoral surface with autologous tissue substitute, open approach | |
| ICD-10-PCS 0SRC07Z | Replacement of R knee joint with autologous tissue substitute, open approach | |
| Revision | CPT 1005095 | Revision of TKA, with or without allograft |
| CPT 27487 | Revision of TKA, with or without allograft; femoral and entire tibial component | |
| CPT 27486 | Revision of TKA, with or without allograft; 1 component |
CPT, Current Procedural Terminology; ICD-10, International Classification of Diseases, 10th Revision.
Table S3.
ICD-10 code for outcome: PJI.
| Code | Procedure or diagnosis | |
|---|---|---|
| Infection | ||
| PJI | ICD-10 T84.50XA | Infection and inflammatory reaction because of unspecified internal joint prosthesis, initial encounter |
ICD-10, International Classification of Diseases, 10th Revision.
Table S4.
ICD-10 codes for preoperative comorbidities and laboratory values.
| Comorbidities | ICD-10 code |
|---|---|
| Essential primary hypertension | I10 |
| Hyperlipidemia | E78.5 |
| Pure hypercholesterolemia | E78.0 |
| Overweight, obese | E66 |
| Type 2 diabetes | E11 |
| Chronic ischemic heart disease | I25 |
| Acute kidney injury | N17 |
| Chronic kidney disease | N18 |
| End-stage renal disease | N18.6 |
| Heart failure | I50 |
| Atrial fibrillation | I48 |
| Pacemaker | Z95.0 |
| Chronic obstructive pulmonary disease | J44 |
| Asthma | J45 |
| Prior venous thromboembolism | Z86.71 |
| Chemotherapy-induced anemia | I63 |
| Transient cerebral ischemic attacks | G45 |
| Myocardial infarction | I21 |
| Fibrosis and cirrhosis of the liver | K74 |
| Chronic viral hepatitis | B18 |
| Acute hepatitis A | B15 |
| Acute hepatitis B | B16 |
| Acute hepatitis C | B17.1 |
| Alcoholic liver disease | K70 |
| Acute and subacute hepatic failure | K72.0 |
| Protein-calorie nutrition, mild to moderate | E44 |
| Severe protein-calorie nutrition | E43 |
| Cachexia | R64 |
| Nutritional marasmus | E41 |
| Kwashiorkor | E40 |
| Aplastic anemia | D60-D64 |
| Disorders of blood and blood-forming organs | D70-D77 |
| Nutritional anemias | D50-D53 |
| Coagulation defects | D65-D69 |
| Disorders involving the immune mechanism | D80-D89 |
| Intraoperative and postprocedural complications of the spleen | D78 |
| Hemolytic anemias | D55-D59 |
| Other disorders of plasma-protein metabolism | E88.09 |
| Preoperative albumin level | TNX curated lab value 9045 albumin (mass/volume) |
| Hemoglobin level | TNX curated lab value 9014 hemoglobin (mass/volume) |
ICD-10, International Classification of Diseases, 10th Revision.
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