ACUTE KIDNEY INJURY IN ORTHOPEDIC SURGERY RELATED TO OBESITY AND ANGIOTENSIN AXIS BLOCKADE

Background: Controversy still exists regarding the use of angiotensin axis blockade (AAB) with angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs preoperatively. Multiple studies suggest the AAB results in acute kidney injury (AKI) (1,2), while other studies do not (3,4 ). Some studies suggest that the AKI associated with AAB is due to disruption of the pleiotrophic effects of the angiotensin axis, rather than simply to the effects of hypotension (5). Some studies have identified obesity and its associated oxidative stress as a contributor to AKI after surgery (6). We hypothesize that the contradictory conclusions regarding the use of AAB prior to surgery are due to the failure of recognizing the interacting effects of obesity and AAB. We examined the relationship between AAB and obesity as it relates to AKI following orthopedic surgery.

Methods: We performed a retrospective chart review of 1154 patients who underwent elective spine fusion, total knee arthroplasty (TKA), and total hip arthroplasty (THA) within one calendar year. Of these, 798 patients met the inclusion criteria of being > 21 years old, having had a pre-anesthesia evaluation with documented preoperative medication recommendations, and having documented preoperative and postoperative creatinine values. Postoperative AKI was defined as an increase in serum creatinine >0.3 mg/dL or an increase of 50% from preoperative to postoperative creatinine. Age, gender, body mass index (BMI), co-morbidities, medications, estimated blood loss, induction and intra-operative blood pressures, anesthetics, amount of vasopressors, intravenous fluids, and transfusions were covariates adjusted for in the logistic regression analysis of the effects of AAB on AKI. Serum creatinine and hematocrit <30 day preoperatively and within 24 hours postoperatively were recorded. Since AAB use and BMI remained as independent factors related to AKI, we measured their relationship in the development of AKI.

Results: AAB medications were taken preoperatively in 313 patients.Using multivariate logistic regression analysis, preoperative AAB use was independently associated with greater odds of developing AKI postoperatively (OR 2.68, 95% CI: 1.08, 6.69, p=0.034). For every 5-unit increase in BMI, the odds of developing AKI were 1.53 (95% CI: 1.26, 1.85, p<0.0001). This relationship of greater BMI to AKI was consistent in all three procedures. Categorizing AKI by weight, we found that the significant increase in AKI in AAB patients vs non-AAB patients did not occur until patients had a BMI > 30 (OR 4.91; CI: 1.96,12.31, p=0.0007). We also found that the development of AKI in AAB patients persisted, independent of post-induction or intraoperative hypotension (OR 2.60; CI 1.04,6.51, p=0.042). In fact, the greater the BMI, the less chance of post-induction hypotension (OR 0.85; CI 0.72,1.00, p=0.049).

Conclusions: Perhaps the contradictory conclusions in the literature regarding the use of AAB prior to surgery are due to the failure of recognizing the interacting effects of obesity and AAB. We found that the use of AAB drugs prior to orthopedic surgery did not cause AKI in normal to overweight patients. But we found a significant increase in AKI when AAB was used in obese patients with BMI> 30. We propose that the oxidative stress of obesity combined with the influence of AAB on the pleiotropic effects of the renin-angiotensin-aldosterone system results in AKI during the stress of surgery.