Acute kidney injury (AKI) occurs in up to one third of all patients who undergo cardiac surgery, with 1% requiring hemodialysis. The development of acute renal failure is associated with a high mortality and a more complicated postoperative recovery.1 Surgical aortic valve replacement is the criterion standard for the treatment of severe aortic stenosis (AS). However, transcatheter aortic valve implantation (TAVI) is now considered as the standard of care in patients deemed at extreme or prohibitive surgical risk and as an acceptable alternative to surgery in those deemed at high risk.2,3 Acute kidney injury after TAVI has been reported in up to 28% of patients and has been associated with increased mortality.4–6 The pathogenesis of AKI after TAVI is multifactorial, including hemodynamic, inflammatory, and nephrotoxic factors. The administration of contrast media, renal hypoperfusion during rapid pacing and periods of hypotension, and cholesterol atheroembolization from catheter manipulation are all potential risk factors of AKI after TAVI. One study has reported that AKI after TAVI occurred in 19% of patients and red blood cell transfusion was found to be an independent factor of AKI, which was associated with a high mortality.7 Sinning and colleagues8 have reported that the development of AKI after TAVI was related to peripheral artery disease, moderate to severe paraprosthetic regurgitation, and the development of systematic inflammatory response syndrome (SIRS). Identifying the risk factors of AKI is important because high-risk patients can then be targeted for renal protective protocols.
The objectives of this study were to determine the incidence and persistence of AKI after TAVI, to identify patients who are at higher risk for developing AKI, and to investigate the prognostic effects of AKI on 1-year mortality after TAVI.
PATIENTS AND METHODS
Between December 2007 and March 2011, a total of 79 patients with symptomatic severe AS underwent 81 TAVI procedures with either the Medtronic CoreValve (Medtronic CoreValve Inc, Irvine, CA USA) or the Edwards SAPIEN (Edwards Lifesciences Inc, Irvine, CA USA). The decision for a TAVI procedure was discussed in multidisciplinary meetings that consisted of at least two cardiac surgeons, one interventional cardiologist, one noninterventional cardiologist, one cardiac anesthetist-intensivist, one stroke neurologist, and one pulmonary physician. The decision of the access route was determined by the multidisciplinary team, with the transfemoral approach as the first choice.
All patients underwent a systematic process of clinical evaluation and angiographic and echocardiographic assessments. The TAVI imaging consisted of peripheral angiography, detailed measurement of the aortic root using transthoracic and transoesophageal echocardiography, aortography, and coronary angiography. Where indicated, computed tomographic scan and magnetic resonance imaging and lung function tests were also performed. Two patients were excluded because creatinine levels after the procedure were not available, and both died within the first year.
Our standard protocol for preprocedure optimization of patients with renal impairment preoperatively is to hydrate with 0.5 normal saline or 5% dextrose, intravenously, for 8 hours before the procedure (1 mL/kg/h) if the creatinine level was greater than 120 μmol/L. All patients were hydrated for 18 hours after TAVI, with the same solution at the same rate. The patients with baseline creatinine levels of less than 120 μmol/L received intravenous fluids during the procedure and afterward until normal oral intake was re-established. Prophylactic administration of N-acetylcysteine was considered in the high-risk patients.
Hospital mortality, transient ischemic attack or stroke, peripheral vessel complications, wound infection, renal replacement therapy requiring hemofiltration, myocardial infarction, pacemaker implantation, blood transfusion, platelet transfusion, prolonged ventilation defined as longer than 24 hours, and intensive care and hospital stay were recorded. Within 72 hours after TAVI, serum creatinine, glomerular filtration rate (GFR), hemoglobin, platelet, C-reactive protein (CRP), and white cell count were recorded. Serum creatinine and GFR before hospital discharge were also measured.
The patients underwent transfemoral, transaortic, or subclavian CoreValve or transapical SAPIEN valve insertion. All procedures were performed under general anesthesia.
Follow-up was completed using data from outpatient clinics, referral hospitals, and general practitioners. Follow-up was completed in all patients.
Acute Kidney Injury Definition
Acute kidney injury was defined according to the Valve Academic Research Consortium (VARC) based on change in serum creatinine (up to 72 hours) compared with baseline.9 The VARC categorizes three stages of AKI: stage 1, increase in serum creatinine to 150% to 200% (1.5–2.0 × increase compared with baseline) or increase of ≥0.3 mg/dL (≥26.4 mmol/L); stage 2, increase in serum creatinine to 200% to 300% (2.0–3.0 × increase compared with baseline) or increase between >0.3 mg/dL (>26.4 mmol/L) and <4.0 mg/dL (<354 mmol/L); stage 3, increase in serum creatinine to ≥300% (>3 × increase compared with baseline) or serum creatinine of ≥4.0 mg/dL (≥354 mmol/L) with an acute increase of at least 0.5 mg/dL (44 mmol/L). The patients receiving renal replacement therapy were considered to meet stage 3 criteria, irrespective of other criteria.
Continuous data are presented as mean ± SD. The Student t test was used to compare the mean values for the continuous variables. Multiple groups were compared using analysis of variance. The χ2 or the Fisher exact test was used to find significant associations among the categorical variables. The data were analyzed using the SPSS software package, and statistical significance was taken as P < 0.05. The Kaplan-Meier survival curve was used to determine the relationship between AKI and 1-year mortality. Forward stepwise logistic regression was carried out, with presence of AKI as the dependent variable, to determine predictive factors. Variables included: age, gender, smoking, diabetes, MI, COPD, asthma, neurological disease, prior AF, prior heart block, prior cardiac surgery, previous PCI, NYHA, PA pressure >60, LV function, CAD, rout of access, vascular injury and serum creatinine.
A total of 79 patients with severe AS who underwent 81 TAVI procedures were included. In two patients, a second TAVI was performed as a valve-in-valve procedure at a later date. Patients with chronic renal failure on regular dialysis were excluded from this study. The baseline characteristics and the risk factors are shown in Table 1.
The transfemoral approach was used in 81% of the patients. A total of 71 patients (88%) had the CoreValve prosthesis, and 10 patients (12%) had the Edwards SAPIEN valves. Significant concomitant coronary artery disease and previous cardiac surgery were present in 25 (30.8%) and 33 (40.7%) patients, respectively.
Periprocedural outcomes are shown in Table 2. One patient had cardiac arrest due to left coronary occlusion immediately after the implantation of the valve and was converted to surgical aortic valve replacement. She had a very good outcome and was discharged home at day 10 after surgery. Two patients required a second TAVI at a later date to the original implantation to successfully correct severe paravalvar regurgitation. The incidence of vascular injury, stroke, and permanent pacemaker implantation was 3.7%, 4.9%, and 18.5%, respectively.
Acute kidney injury occurred in 10 patients (12.3%), and none required dialysis during hospitalization. Nine patients (90%) experienced mild AKI (stage 1) and only one patient (10%) had moderate AKI (stage 2) according to VARC definitions. No patients had stage 3 AKI.
Acute kidney injury had completely resolved in nine patients before hospital discharge. The length of stay in the hospital was not affected by the transient AKI after the procedure. The correlation between GFR before and after TAVI is shown in Figure 1.
The predictive factors of AKI after TAVI were history of diabetes (odds ratio, 6.722; P = 0.004) and preoperative creatinine greater than 104 μmol/L (odds ratio, 1.024; P = 0.02). The probability of AKI after TAVI is shown in Figure 2. Blood transfusion was not a predictive factor of AKI. There was no significant difference in CRP or white cell count between patients with or without AKI after TAVI (P = 0.46 and P = 0.96, respectively).
Preoperative serum creatinine level greater than 104 μmol/L was found to be associated with AKI (P = 0.02). The sensitivity and the specificity of the creatinine cutoff point of 104 were 80% and 59%, respectively.
The mean contrast volume used in this study was 170 mL. The amount of contrast media was the most significant cause of creatinine rise after the procedure (P = 0.08). However, low osmolar contrast agents were used in all patients, and the amount of contrast was limited in the high-risk patients.
The all-cause 1-year mortality was 16.4% (13 patients). Three of the nonsurvivors (3.7%) developed AKI, which had completely resolved before hospital discharge. The causes of death in the patients with AKI were cardiac failure, bronchopneumonia, and sepsis. Acute kidney injury was not an independent predictor of 1-year mortality (P = 0.92; Fig. 2).
Acute kidney injury occurred in 12.3% of the patients undergoing TAVI, none of whom required renal replacement therapy. In most of the cases in our series, the AKI was mild. Diabetes and preoperative serum creatinine level greater than 104 μmol/L were the independent predictive factors. Acute kidney injury had completely resolved in 90% of the patients before hospital discharge and was not associated with 1-year mortality.
In our study, two patients had a baseline creatinine of greater than 200 μmol/L. Acute kidney injury was stage 1 according to VARC definition in all but one patient.
Several studies have shown that underlying chronic kidney disease (CKD) increases the risk for AKI from interventional procedures involving contrast agents and that the risk increases proportional to the CKD stage.10–13 It is unclear whether patients with AKI and previous CKD experience a different disease course and outcomes than those without previous CKD.14–16 The risk12 for clinically important nephrotoxicity attributable to contrast material for patients with both diabetes and preexisting renal insufficiency is approximately 9%. Sinning et al8 observed the occurrence of SIRS in patients with AKI after TAVI. They found that 60% of their patients with AKI fulfilled the criteria of SIRS. In our study, there was no significant difference between leukocyte counts and CRP levels before and at 48 hours after TAVI.
Previous studies have highlighted the relationship between AKI and in-hospital mortality.17,5 Acute kidney injury ranged between 11.7% and 19.6%, and the in-hospital mortality was four times higher in the AKI group. Sinning et al8 found AKI in 20 of 77 patients after TAVI, which was a strong predictor of 30-day mortality, independent of whether renal function returned to baseline. Acute kidney injury episodes are associated with a cumulative risk for developing advanced CKD in patients with diabetes, independent of other major risk factors of progression.17
In our study, mild AKI was not a predictor of 1-year mortality. The 30-day mortality in our patients was 3.7%, and the patients who died did not have AKI. One-year mortality was 16.4%. Causes of death were variable and were both of cardiac and noncardiac origin. Three of the nonsurvivors had AKI after TAVI. The fact that AKI was mainly in stage 1 of the VARC definitions and was completely resolved in most patients might explain the lack of an association.
The high-risk patients with diabetes and elevated baseline creatinine should be targeted for renal protective strategies including prehydration, omitting nephrotoxic medications, pretreatment with acetylcysteine, contrast dilution, and using less nephrotoxic contrast media. Adequate intravenous rehydration may prevent contrast-induced nephropathy after TAVI. Furthermore, AKI after TAVI seems to be mild and transient and not associated with increased 1-year mortality.
This is a single-center observational experience and has the inherent limitations of a retrospective study. The number of patients treated is small. Renal hypoperfusion and embolization were not examined and could not be excluded as potential causes of AKI.
Stage 1 AKI is not associated with increased 1-year mortality after TAVI. Patients with diabetes with elevated baseline creatinine are at higher risk and should be targeted for renal protective protocols mainly to reduce the risk for contrast nephropathy. Careful patient selection as well as good preoperative, perioperative, and postoperative management are essential to reduce the risk for AKI after TAVI.
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This case series from St. George’s Hospital at the University of London examined the incidence of acute kidney injury after transcatheter aortic valve replacement. This retrospective study looked at 79 patients treated between 2007 and 2011. Their mean age was 84 years. Ten patients developed acute kidney injury, which completely resolved in nine patients before discharge. The predictive factors for acute kidney injury were diabetes and an elevated preoperative creatinine. Acute kidney injury was not found to be a predictive factor of 1-year mortality.
This is a timely study looking at a complication that has not received much attention in the transcatheter valve literature. Considering the age and the comorbidities of this patient population, the incidence of kidney injury was acceptable and the great majority of the cases were mild. This is an encouraging finding. However, it should be pointed out that this is a small, retrospective, single-center experience and further studies are needed in this area. This well-written report does suggest that, in high-risk patients, renal protective strategies such as prehydration, avoiding nephrotoxic drug pretreatment, pretreatment with acetylcysteine, and avoiding excessive contrast during the procedure should be used.