Baseline Study Population Characteristics
The mean age of the cohort was 66±11 years, with a male majority of 80%. Among the 1112 patients with multivessel CAD included in the registry, 126 (11.3%) had significant renal impairment (GFR ≤60mL/min per 1.73m2) according to all five formulas (MDRD, Mayo, CKD-EPI, CG, and IB formulas), and 783 (70.4%) had non-significant renal impairment (GFR >60mL/min per 1.73m2) according to all five formulas. Of the remaining 203 patients (18.3%), the eGFR was discordant and shifted between <60 mL/min per 1.73m2 and >60 mL/min per 1.73m2 depending on the formula used. "Discordant eGFR" was used when a patient was considered to have normal renal function by at least one formula and abnormal renal function by at least one formula. Patients with normal renal function tended to be younger with fewer cardiovascular risk factors such as diabetes, hypertension, history of stroke, history of congestive heart failure, atrial fibrillation and lower SYNTAX scores (Table 1).
CABG was used as the revascularization strategy in 50% of the significant renal impairment group, 51% of the discordant group and 54% of the non-significant renal impairment group. Compared with PCI patients, those who underwent CABG were more likely to be male (83% vs. 77%, p=0.013), had a higher frequency of diabetes (49% vs. 42%, p=0.026), and were more likely to have had a prior stroke (12% vs. 7%, p=0.014). Those who underwent CABG also had higher mean SYNTAX scores (27±9 vs. 18±8, p<0.001), reflective of more complex CAD. However, PCI-treated patients were more likely to have had prior PCI (40% vs. 30%, p=0.001), prior myocardial infarction (32% vs. 25%, p=0.007) and a history of congestive heart failure (12% vs. 8%, p=0.046), than those treated with CABG.
Estimated Glomerular Filtration Rate
With all five formulas, only a minority of patients had severe renal impairment or kidney failure. The prevalence of patients with renal failure (eGFR <60 ml/min/1.73m2) at baseline was 12.9% by the Mayo equation, 20.9% by MDRD, 22.8% by CG, 22.9% by IB and 24.6% by the CKD-EPI equation.
The mean eGFR values on admission were in the mild renal dysfunction range for both CABG and PCI patients with no differences in eGFR between the two groups (Fig. S2). For both CABG and PCI patients, the Mayo formula yielded the highest mean value (89.8±27.1 and 90.6±25.4 mL/min per 1.73m2, p=0.623; respectively) and CKD-EPI the lowest (75.4±24.7 and 76.6±23.4 mL/min per 1.73m2, p=0.402; respectively). Notably, the Mayo included more patients with normal renal function (N=625, 56%) and thus fewer with mild (N=343, 31%) and moderate renal dysfunction (N=103, 9%) (Fig. S2, Table 2). This finding was consistent in both the CABG and PCI subgroups.
In order to determine whether the CG method, as the reference formula, and the Mayo, CKD-EPI, MDRD, and IB formulas yielded the same results, we calculated the correlation coefficient, and found a strong correlation between the CG formula and each of the other four formulas (Mayo: r=0.80, p<0.001; CKD-EPI: r=0.87, p<0.001; MDRD: r=0.84, p<0.001; IB: r=0.99, p<0.001). Furthermore, in order to assess the agreement between the values obtained from the CG formula and those from each of the other formulas we used the Bland and Altman analyses, which showed good agreement with all formulas used (Fig. 1 A-D). The mean±SD of the eGFR difference between the CG formula (reference) and the Mayo, CKD-EPI, MDRD, and IB formulas were: 2±21.7, 12.2±19.2, 5.4±19.9, and 1.8±4.1 mL/min per 1.73m2, respectively.
Mortality by Renal function and Post-procedural Acute Kidney Injury
Post-procedural acute kidney injury was more prevalent in the CABG than the PCI group (5.8% vs. 0.9%, p<0.001), and more in the eGFR ≤60 mL/min per 1.73m2 than the discordant and eGFR >60 groups (9.7% vs. 3.9% vs. 1.7%, p<0.001). Patients with eGFR ≤60 mL/min per 1.73m2 by all five methods had significantly higher 30-day, 1-year and 3-year mortality compared to patients with discordant eGFR, and compared to patients with eGFR >60 mL/min per 1.73m2 by all five methods (5.8% vs. 2.6% vs. 0%, p<0.001; 18.8% vs. 8.2% vs. 2.1%, p<0.001; and 27% vs. 12.3% vs. 4.7%, p<0.001, respectively) (Fig. 2 and Fig. S3). Furthermore, the severity of renal impairment correlated with increased mortality (Fig. 3). All five models predicted similar mortality trends, which plateaued at eGFR <30 mL/min per 1.73m2 (Fig. 3). Multivariable analysis demonstrated that worse renal function is an independent predictor of 3-year mortality for all five formulas (Table 3). Mortality risk was increased by 16-28% for each 10-unit decrease in eGFR, using all five formulas. Other independent predictors of 3-year mortality were older age, chronic obstructive pulmonary disease, previous stroke, history of atrial fibrillation and diabetes.
There were no significant differences in 3-year mortality rates between patients who underwent either CABG or PCI in all three eGFR categories (consistently low eGFR 25% vs. 29%, log-rank p=0.879; discordant eGFR 11% vs. 14%, log-rank p=0.714; consistently high eGFR 3% vs. 6%, log-rank p=0.121; respectively). Furthermore, the overall 30-day and 3-year mortality rates were not significantly different between the CABG and PCI groups (1.6% and 7.4% for CABG; 0.7% and 9.7% for PCI, respectively).
The ability of the five formulas to predict 3-year mortality risk was highest with the Mayo (AUC 0.78 [0.73-0.83]) and lowest with the MDRD formula (AUC 0.75 [0.70-0.80]) (p=0.004). The p-value of Hosmer-Lemeshow test was >0.05 for all models, indicating that they were suitable. The NRI results showed that addition of a GFR formula to the baseline model correctly reclassified approximately one-sixth of patients to a higher predicted risk group (Table 4). IDI analysis demonstrated that, when added to the basic logistic regression model, each of the five formulas improved mortality risk prediction. Among the five formulas, the Mayo had the highest additive effect on mortality prediction (Mayo: rIDI=26.4%, p=0.001; CG: rIDI=16.6%, p=0.009; IB: rIDI=15.2%, p=0.012; CKD-EPI: rIDI=22.8%, p=0.003; and MDRD: rIDI=11.7%, p=0.035) (Table 4).