This review and meta-analysis investigated whether CKD has an adverse impact on the outcomes of TJA based on recently published evidence with data of over two million patients. Our analysis determined that patients with baseline moderate to severe CKD had a significantly increased risk of mortality (two-fold or more) compared to those with mild/non-CKD. CKD was also significantly associated with more than twice the increased risk of receiving blood transfusion and was significantly associated with increased risk of re-admission and surgical site infection compared to those without CKD. No significant associations were found between CKD and reoperation or DVT in patients undergoing TJA.
Studies included in the present meta-analysis were selected based on inclusion of patients with a range of severity from stage 3, or “moderate,” to severe, defining CKD as stage >=3 or eGFR < 60 mL/min/1.73 m2. Studies designed only for comparing outcomes between dialysis-dependent versus non-dialysis-dependent patients were excluded. Our selection strategy was to extend the range of investigation to cover patients with less advanced CKD who were more likely to undergo TJA compared to those with end-stage renal disease (ESRD) and/or were on maintenance dialysis who may not be candidates for surgery. Multiple previous studies have examined outcomes of TJA specifically in patients who were either dialysis-dependent or renal transplant recipients, which led to noticeably higher risk of increased length of stay, readmission and mortality in those study populations [45-48]. In one such study [45], the results revealed that kidney transplant increased risk of surgical site infection and wound infections, systemic infection, deep venous thrombosis, acute renal failure, respiratory, and cardiac complications in patients undergoing TJA. And dialysis dependence was found to be independently associated with higher risk for 30-day adverse events [46, 48], ICU care, longer admission, rehabilitation needs [46], and inpatient mortality [47, 48].
Mortality
In the present review and meta-analysis, CKD was associated with a significantly higher risk of mortality than that among non-CKD patients who had undergone THA or TKA. CKD is a known risk factor for mortality in the nonsurgical setting [16-18], and in the setting of noncardiac surgeries, CKD is also predictive of postoperative death as reported in the previous studies [19, 20]. In elective primary total knee and hip arthroplasty, dialysis-dependent patients present with inpatient mortality rates 10-20 times greater than in non-dialysis-dependent patients [47]. Given our findings and those of other studies reporting higher mortality risk among patients with varying stages of CKD, this risk should be of the main concern in the selection of TJA candidates who had underlying CKD, even if not yet considered ESRD.
Reoperation and readmission
Results of the present meta-analysis found no significant differences in the occurrence of re-operation between CKD and non-CKD patients undergoing TJA; however, CKD patients who received TJA had higher any-cause readmission rates than non-CKD patients. Although outcomes of TJA are generally reported to be excellent, implant failure and increased risk of revision surgery continues to be of concern [49-51]. Revision surgery may be the result of infection, dislocation, osteolysis or loosening of the component; after THA, dislocation and mechanical loosening are the main risk factors reported for revision surgery [49]. For TKA, the main etiology reported for re-operation are infection and mechanical loosening [50]. A scoping review determined that risk of revision surgery was associated mainly with demographic factors such as age and African-American ethnicity, as well as surgical factors such as uncemented procedure, implant malalignment and longer operative times [51]. A systematic review evaluating results of 86 studies reported that risk factors for revision surgery included younger age, more comorbidities, avascular necrosis as an indication (rather than osteoarthritis) and larger femoral head size in revision performed due to dislocation [52]. However, in that study, younger age was associated with fewer dislocations. Perhaps not all studies had adjusted for confounders when determining risk factors, and clearly, not enough is known about the causes of revision surgery. Further study is needed to identify modifiable and non-modifiable risk factors related to the need for revision.
As mentioned above, readmission rates after TJA in the present meta-analysis were significantly higher among CKD patients than among those without CKD. Another review and meta-analysis reported that the overall readmission rates after THA were 5.6% at 30 days and 7.7% at 90 days, and for TKA were 3.3% at 30 days and 9.7% at 90 days; the leading reason for readmission were joint-specific for THA and surgical site infection for TKA, followed by DVT, pulmonary embolism, and cardiac dysrhythmia [53]. The early successes commonly associated with TJA are compromised by such postoperative complications, and readmission is often considered an indictment of surgical management; however, no consensus has been reached on the main reasons for readmission after primary TJA [53], and further research is essential to determine trends in readmission rates and reasons for readmission.
Deep vein thrombosis (DVT)
In the present study, no significant differences were found in the presence of DVT between patients with and without CKD who underwent TJA. Although DVT has been shown to occur commonly after joint replacement surgeries, and has been reported to cause unfavorable outcomes after TJA, a recent study of national trends in the United States showed that DVT incidence actually declined for TKA (0.86% to 0.45%) and THA (0.55% to 0.24%) over a 10-year period from 2001 to 2011 [54]. The explanation for this trend is that DVT prophylaxis has been the focus of surgeons performing TJA, along with the recognition of higher risk for DVT among older patients, African Americans and patients with comorbidities [54]. This may, at least in part, explain our result in conjunction with the characteristics of our CKD patient population. A systematic review and meta-analysis conducted in 2015 examined evidence from 54 studies across ten previous years and identified several potential factors associated with venous thromboembolism (VTE) occurring after THA and TKA including older age, female, history of VTE, higher body mass index (BMI), longer surgeries and bilateral surgeries [55]. Decreased kidney function is associated with an increased risk of venous thrombosis and, in particular, in combination with arterial thrombosis, is increased additionally in patients with moderate and severe reduction in kidney function undergoing surgery [56], however, the types of surgical setting were not specified. In the present study, the database lacked information about DVT prophylaxis, therefore, our estimation of associations between CKD and DVT may include bias. Nevertheless, continued focus on DVT prophylaxis and perhaps applying more aggressive management strategies may help to reduce the rate of DVT among those at increased risk [54].
Transfusion
CKD was found significantly associated with perioperative blood transfusion in the present review and meta-analysis. A previous study analyzing a large statewide database from the year 2006 to 2011 reported that overall utilization of blood transfusion in TJA remained high over time, with nearly 25% of their study cohort [57]. It is also found that hip arthroplasty more often required transfusion during surgery than knee arthroplasty, and risk was even greater in bilateral procedures. Transfusion was more common among females, older patients and those with a higher burden of comorbidities [57]. CKD is commonly associated with both lower hemoglobin levels and elevated risks of bleeding, which may explain the greater risk of blood transfusion in CKD after TJA.
Surgical site infection
The result in this review and meta-analysis indicated that CKD patients had higher risk of surgical site infection than non-CKD patients after TJA. Surgical site infection is previously estimated to occur in 1% to 2.5% of cases annually after TJA [58]. It is thought to pose a great challenge on the joint replacement, and also place a substantial burden on the healthcare system. A recent review documented that advances in surgical technique, sterile protocol, and operative procedures have been instrumental in minimizing surgical site infections and may account for the recent plateau in rising rates after TKA and THA [59]. In the present review and meta-analysis, CKD group might contain ESRD patients who are susceptible to infections, thus explains the excess risk of surgical site infection compared to non-CKD. Also, the fact that CKD patients are more prone to surgical site infections might attribute to increased related conditions such as diabetes or poor nutrition.
Cardiovascular complications