Impact of preoperative occult renal dysfunction on early and late prognosis in elderly patients with coronary artery bypass in China

doi:10.21203/rs.3.rs-2884632/v1

Background

Renal dysfunction is related to the poor outcomes of cardiac surgery. Preoperative occult renal dysfunction (PORD) is defined as patients with normal serum creatinine (Scr) but the glomerular filtration rate (GFR) less than 60 ml/min/1.73m². However, there is no report on prognosis of elderly PORD patients undergoing coronary artery bypass grafting (CABG). This problem deserves further exploration.

Methods

Totally 1103 patients undergoing CABG with normal Scr and age ≥ 70 years old were enrolled. The estimated GFR (eGFR) of each patient was monitored using the Berlin initiative study formula. The patients were divided by eGFR into PORD group and control group. Propensity score matching was used to adjust preoperative characteristics. Univariate and multivariate analyses were performed to identify risk factors for postoperative acute kidney injury (AKI) and postoperative mortality. The Kaplan-Meier method was applied to estimate survival rates. A multivariate cox regression model was used to analyze the impacts of factors on long-term survival.

Results

Elderly patients with normal Scr had high PORD proportion (27.65%). The PORD group had significantly higher preoperative Cr (99.20 ± 12.74 vs. 71.57 ± 11.96), postoperative AKI rates (39.13% vs. 17.75%) and postoperative mortality (5.80% vs. 1.81%) compared with control group. PORD was a significant risk factor for postoperative mortality (OR = 11.648) and postoperative AKI (OR = 2.731). PORD was also a significant risk factor for long-term death after CABG (HR = 1.724).

Conclusions

PORD is a risk factor for postoperative AKI and short- and long-term death in elderly patients undergoing CABG. eGFR shall be used to assess preoperative renal function.

Preoperative occult renal dysfunction

Coronary artery bypass grafting

Elderly patients.

Poor preoperative renal dysfunction is a clear risk factor for death after cardiac operations. The gold standard for assessing renal function is glomerular filtration rate (GFR), but due to the expensive and time-consuming measurement of GFR, renal function is widely assessed using the serum creatinine (Scr) value in clinic. However, the Scr value is affected by many factors such as age, race, muscle mass and dietary intake^[1]. The renal function declines with ageing, and renal function insufficiency is common in the elderly^[2]. In initial stage of renal insufficiency, the filtration rate decreases without a significant increase in Scr. Therefore, patients with normal Scr value may be in a state of impaired renal function, which is a possible clinical problem. The patient who has a normal range of Scr value but abnormal GFR (<60 ml/min/1.73m²) is considered as having preoperative occult renal dysfunction (PORD)^[3].

Coronary artery disease (CAD) is also a common concomitant in elderly patients. Coronary artery bypass grafting (CABG) is one of the most common treatments for severe CAD. Compared with other cardiac surgeries, patients undergoing CABG usually have more underlying diseases, including poor preoperative renal function^[4]. Relevant research mostly focuses on the effect of renal function based on Scr assessment on CABG postoperative outcomes. However, PORD accounts for a high proportion of elderly patient undergoing CABG, which has been rarely studied. As a result, the role of CABG in PORD patients is overlooked constantly, especially in the elderly population, which may result in adverse consequences, including more postoperative acute kidney injury (AKI), early death and poor long-term prognosis. To confirm this hypothesis, we observed the incidence of PORD in patients over 70 years old and its impact on the short-term and long-term prognosis after CABG in this retrospective study.

2.1. Patient Population

This retrospective observational cohort study covered two medical centers, Jiangsu People Hospital (JSPH) and Shanghai Chest Hospital (SHCH), between January 2005 and January 2019. Finally, 1103 of 4339 patients were enrolled according to the exclusion criteria below. Exclusion criteria were (1) age less than 70 years, (2) other cardiac procedure at the same time, (3) absence of medical records, especially Scr, and (4) preoperative Scr above the upper limit of normal value. All patients received preoperative evaluation, surgery and postoperative treatment as required by routine diagnosis and treatment. All data were collected retrospectively from clinical information systems. The criteria and process of patient selection were elaborated in Figure 1.

All included patients or their legal representatives signed a written informed consent for all surgical procedures. With the approval and consent of the Ethics Committees, all enrolled patients were exempted from informed consent for their participation. This study was approved by the Ethics Committees of both hospitals (ID: 2022-SR-209 and ID: IS22026) and was registered with the number of ChiCTR1800020130 (http://www.chictr.org.cn/).

Scr values of the enrolled patients before operation (within 48 hours before CABG) and within 7 days after surgery were obtained from the hospital information systems. As stated in the inclusion criteria, the preoperative Scr values of all enrolled patients were within the normal range. Since the “gold standard” of GFR determination is cumbersome and expensive and all patients were older than 70 years, the BIS formula [^5] was used to calculate eGFR instead of GFR. According to the definition of PORD, patients were divided into a PORD group and a control group.

Postoperative AKI was defined as per the definition of AKI in the guideline for Kidney Disease: Improving Global Outcomes (KDIGO)[^6]. However, due to the frequent use of diuretics during treatment and the difficulty of accurate urine output to hours, only Scr was used for evaluation. AKI was diagnosed when a patient had one of the following three conditions after operation: 1. Scr increase ≥26.5 μmol/L within two days or 1.5-1.9 times of baseline within seven days; 2. Scr 2.0-2.9 times of baseline within seven days; 3. Scr more than 3 times of baseline within seven days or using renal replacement therapy (RRT) during hospitalization.

2.2. Endpoints

The primary endpoint was the occurrence of postoperative AKI and mortality. The secondary endpoint was medium and long-term all-cause death.

2.3. Follow-Up

According to the regulations on follow-up after CABG, patients who survived and were discharged from hospitals were followed up by outpatient clinic services or telephone in the first and third months after operation. Subsequent follow-up was every six months, with patient survival status and cause of death being the main follow-up goals. The latest follow-up date was 8 March 2022.

2.4. Statistical Analysis

Continuous variables were presented as mean± standard deviation (SD) and tested for normal distribution using the Shapiro-Wilk test. Unpaired Student’s t-test was used to compare between groups when the distribution was normal, and the Mann-Whitney U test was used otherwise. Dichotomous variables were presented as numbers and percentages and compared between groups using the Pearson or Fisher exact test.

Univariate analysis was performed to identify risk factors for postoperative AKI and postoperative mortality. Factors at P<0.1 were included into a multivariate analysis, including age, gender, number of diseased vessels, cerebrovascular disease, New York heart association (NYHA) classification, PORD, European system for cardiac operative risk evaluation II (EuroSCORE II), emergency operation, intra-aortic balloon pump (IABP) implantation, left ventricular ejection fraction (LVEF), peripheral vascular disease, chronic obstructive pulmonary disease (COPD), preoperative atrial fibrillation (AF) and pulmonary hypertension. Odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of each variable's association with these outcomes.

The Kaplan-Meier (K-M) method was applied to estimate survival rates between groups. A multivariate cox regression model was used to analyze the impacts of numerous factors on long-term survival, including age, gender, BMI, CAD classification, NYHA, hypertension, diabetes, PORD, number of diseased vessels, valvular disease, COPD, pulmonary hypertension, peripheral vascular disease, PCI history, number of bypass vessels, preoperative AF and EuroSCORE II. Hazard ratio (HR) with 95%CI was calculated to estimate the strength of each variable's association with long-term mortality.

To avoid the interference of baseline differences on the analysis conclusions, we used propensity score matching (PSM) to adjust some preoperative characteristics of the patients. Each PORD patient was matched to one patient without PORD by using the following variables: age, CAD classification, hypertension, cerebrovascular disease, preoperative LVEF, pulmonary hypertension and EuroSCORE II. The closed propensity score on the logit scale with a closer was 0.05. Univariate and multivariate logistic regression analyses were still used to identify the factors associated with the endpoints.

All analyses were two sided, with the significant level at P≤ 0.05. SPSS 22.0 (IBM, USA) was used for data processing.

3.1. Baseline demographics and clinical characteristics

Of the 1103 included patients, 305 (27.65%) patients were diagnosed as PORD. The patients in the PORD group showed higher prevalence rates of hypertension (76.72% vs. 69.67%, P=0.020), cerebrovascular disease (27.21% vs. 17.54%, P=0.001) and preoperative Scr (98.88±12.73 vs. 71.24±12.66, P<0.001). The incidence rates of postoperative AKI (37.70% vs. 18.42%, P<0.001) and postoperative mortality (5.57% vs. 2.26%, P=0.005) were also relatively higher in the PORD group.

After one-to-one PSM, 276 patients were enrolled in each of the two groups. The PORD group also had higher preoperative Cr (99.20±12.74 vs. 71.57±11.96, P<0.001), higher postoperative AKI rates (39.13% vs. 17.75%, P<0.001) and higher postoperative mortality (5.80% vs. 1.81%, P=0.014). Detailed perioperative characteristics of the total cohort and after PSM were presented in Table 1.

Table 1 the baseline clinical characteristic of PORD and control group before and after propensity score matching

	Before PSM			After PSM
	PORD (n=305)	Control group (n=798)	P value	PORD (n=276)	Control group (n=276)	P value
Age(y)	75.03±3.74	73.16±3.20	<0.001	74.67±3.43	74.35±3.73	0.283
Male sex (n, %)	225(73.77)	602(75.44)	0.568	212(76.81)	206(74.64)	0.572
Weight (kg)	67.53±10.57	66.16±9.69	0.048	67.63±10.38	67.85±10.40	0.800
Height (cm)	165.29±7.78	165.21±7.82	0.887	165.36±7.82	164.36±8.27	0.138
BMI (kg/m²)	24.68±3.27	24.21±2.96	0.027	24.70±3.21	25.08±3.21	0.153
BSA (m²)	1.84±0.16	1.82±0.15	0.103	1.84±0.16	1.83±0.16	0.806
BMI classification			0.002			0.178
Normal weight	116(38.03)	366(45.86)		108(39.13)	88(31.88)
Lean	8(2.62)	18(2.26)		7(2.54)	8(2.90)
Overweight	130(42.62)	335(41.98)		123(44.57)	140(50.72)
Obesity	30(9.84)	52(6.52)		29(10.51)	32(11.59)
Severe obesity	21(6.89)	27(3.38)		19(6.88)	18(6.52)
CAD classification			0.827			0.087
Stable angina pectoris (n, %)	95(31.15)	242(30.33)		90(32.61)	67(24.28)
Unstable angina pectoris (n, %)	177(58.03)	469(58.77)		168(60.87)	190(68.84)
Acute myocardial infarction (n, %)	33(10.82)	87(10.90)		28(10.14)	29(10.51)
Hypertension (n, %)	234(76.72)	556(69.67)	0.020	219(79.35)	23(8.33)	0.264
Diabetes mellitus (n, %)	99(32.46)	249(31.20)	0.688	92(33.33)	95(34.42)	0.790
Cerebrovascular disease			0.001			0.690
Stroke (n, %)	26(8.52)	46(5.76)		23(8.33)	24(8.70)
Lacunar infarction (n, %)	57(18.69)	94(11.78)		52(18.84)	56(20.29)
Peripheral vascular disease (n, %)	33(10.82)	73(9.15)	0.400	30(10.87)	13(4.71)	0.007
NYHA classification			0.065			0.001
I (n, %)	14(4.59)	39(4.89)		13(4.71)	19(6.88)
II (n, %)	171(56.07)	472(59.15)		160(57.97)	189(68.48)
III (n, %)	102(33.44)	272(34.09)		96(34.78)	72(26.09)
IV (n, %)	18(5.90)	15(1.88)		17(6.16)	6(2.17)
Preoperative LVEF (%)	59.83±8.70	60.17±7.99	0.549	59.82±8.83	61.74±7.59	0.005
Preoperative Cr (umol)	98.88±12.73	71.24±12.66	<0.001	99.20±12.74	71.57±11.96	<0.001
Valvular disease (n, %)	35(11.48)	126(15.79)	0.070	32(11.59)	34(12.32)	0.794
COPD (n, %)	19(6.23)	55(6.89)	0.694	18(6.52)	8(2.90)	0.045
Preoperative AF (n, %)	18(5.90)	31(3.88)	0.146	15(5.43)	4(1.45)	0.010
Pulmonary hypertension (n, %)	84(27.54)	224(28.07)	0.780	75(27.17)	43(15.58)	0.009
Previous PCI (n, %)	25(8.20)	80(10.03)	0.355	23(8.33)	26(9.42)	0.655
Diseased Coronary arteries (n)	2.82±0.46	2.80±0.50	0.592	2.83±0.45	2.77±0.54	0.178
EuroSCORE II	3.22±2.63	2.30±1.83	<0.001	3.05±2.40	2.91±2.58	0.498
Emergency operation			0.223			0.140
Emergency operation (n, %)	6(1.97)	22(2.76)		5(1.81)	6(2.17)
Salvage (n, %)	0(0.00)	3(0.38)		0(0.00)	3(1.09)
Coronary artery bypass grafts (n)	3.29±0.95	3.35±0.97	0.337	3.31±0.94	3.23±0.92	0.303
Cardiopulmonary bypass (n, %)	19(6.23)	46(5.76)	0.769	19(6.88)	8(2.90)	0.030
Postoperative Cr (umol)
1 day	113.39±42.27	83.31±23.38	<0.001	114.21±42.99	85.04±22.77	<0.001
2 days	121.37±51.19	84.80±29.23	<0.001	121.86±52.10	84.80±26.61	<0.001
3 days	121.19±55.20	84.57±32.80	<0.001	121.10±55.74	82.97±26.36	<0.001
4 days	118.31±57.81	83.39±39.30	<0.001	117.30±57.07	79.75±23.39	<0.001
5 days	123.37±82.23	81.85±37.03	<0.001	121.60±79.95	79.24±24.62	<0.001
6 days	116.69±73.78	79.96±37.55	<0.001	116.57±75.66	76.91±25.26	<0.001
7 days	120.37±74.61	83.85±52.09	<0.001	120.10±75.38	79.68±43.98	<0.001
Postoperative AKI (n, %)	115(37.70)	147(18.42)	<0.001	108(39.13)	49(17.75)	<0.001
IABP implantation (n, %)	4(1.31)	12(1.50)	0.017	3(1.09)	8(2.90)	0.843
30-day postoperative mortality (n, %)	17(5.57)	18(2.26)	0.005	16(5.80)	5(1.81)	0.014

PORD, preoperative occult renal dysfunction; PSM, propensity score matching; BMI, body mass index; BSA, body surface area; CAD, coronary artery disease; NYHA, New York heart association; LVEF, left ventricular ejection fraction; Cr, creatinine; COPD, chronic obstructive pulmonary disease; AF, atrial fibrillation; PCI, percutaneous coronary intervention; EuroSCORE II, European system for cardiac operative risk evaluation II; AKI, acute renal failure.

3.2. Trends of Scr in perioperative period

At the 8 points during the CABG, Scr generally increased at the first day after operation and then decreased gradually. The Scr values of the PORD group were significantly higher than those of the control group at each point. After PSM, the Scr values of the two groups were still significantly different. Interestingly, the Scr values in the PORD group increased continuously for two days after surgery and then fluctuated severely, while the Scr values in the control group only increased on the first postoperative day and then decreased slightly (Figure 2).

3.3. Risk factors for postoperative mortality

In multivariate analysis, number of diseased vessels (OR=0.247, P=0.037), NYHA classification (OR=1.752, P=0.045), PORD (OR 2.718, P=0.011), emergency operation (OR=5.371, P=0.002) and IABP implantation (OR 3.065, P < 0.001) were identified as significant risk factors for postoperative mortality (Table 2). However, after PSM, PORD (OR = 11.648, P=0.031), emergency operation (OR=6.256, P=0.010) and IABP implantation (OR=2.987, P < 0.001) were still risk factors for postoperative mortality (Table 2).

Table 2 risk factors of postoperative mortality by univariate and multivariate logistic regression analysis before and after propensity score matching

	Before PSM						After PSM
	Univariate logistic regression			Multivariate logistic regression			Univariate logistic regression			Multivariate logistic regression
	OR	95% CI	P value	OR	95% CI	P value	OR	95% CI	P value	OR	95% CI	P value
Age	1.048	0.957-1.148	0.311	1.004	0.902-1.117	0.944	1.009	0.894-1.139	0.884	0.972	0.836-1.130	0.711
Gender	1.206	0.572-2.544	0.623	1.190	0.516-2.744	0.684	0.843	0.304-2.342	0.743	0.702	0.198-2.491	0.584
BMI	0.911	0.812-1.021	0.107				0.934	0.814-1.071	0.328
BSA	0.252	0.029-2.200	0.212				2.201	0.148-32.815	0.567
CAD classification	1.072	0.620-1.854	0.804				1.271	0.605-2.671	0.526
Number of diseased vessels	0.569	0.338-0.959	0.034	0.247	0.066-0.920	0.037	0.421	0.231-0.766	0.005	0.516	0.186-1.430	0.203
Hypertension	0.661	0.329-1.329	0.245				0.533	0.210-1.352	0.185
Diabetes mellitus	1.655	0.837-3.274	0.147				1.279	0.521-3.141	0.592
Cerebrovascular disease	0.271	0.074-0.993	0.049	0.722	0.387-1.350	0.308	0.306	0.082-1.148	0.079	0.354	0.095-1.320	0.122
eGFR	0.991	0.966-1.018	0.520				0.964	0.923-1.006	0.094	1.039	0.955-1.130	0.372
NYHA classification	2.022	1.206-3.389	0.008	1.752	1.012-3.032	0.045	2.214	1.188-4.126	0.012	1.663	0.820-3.372	0.159
Peripheral vascular disease	0.562	0.133-2.375	0.433				0.606	0.079-4.627	0.629
Valvular disease	0.974	0.372-2.549	0.958				1.291	0.370-4.506	0.689
COPD	0.838	0.197-3.564	0.811				<0.001	<0.001	0.998
Preoperative AF	1.317	0.307-5.652	0.711				3.307	0.712-15.346	0.127
Pulmonary hypertension	1.340	0.813-2.209	0.251				1.937	1.106-3.391	0.021	1.178	0.528-2.631	0.689
PORD	2.558	1.300-5.031	0.007	2.718	1.261-5.859	0.011	3.330	1.203-9.217	0.021	11.648	1.258-107.862	0.031
Previous PCI	1.235	0.427-3.570	0.696				1.129	0.255-4.995	0.873
EuroSCORE II	1.145	1.052-1.245	0.002	0.976	0.865-1.103	0.702	1.146	1.043-1.259	0.004	1.018	0.863-1.201	0.830
Emergency operation	5.916	2.603-13.449	<0.001	5.371	1.897-15.205	0.002	5.950	2.238-15.818	<0.001	6.256	1.559-25.100	0.010
IABP implantation	3.373	2.208-3.152	<0.001	3.065	1.827-5.141	<0.001	3.101	1.948-4.935	<0.001	2.987	1.626-5.485	<0.001
Bypass graft number	0.812	0.576-1.144	0.234				0.657	0.421-1.026	0.065	0.915	0.480-1.744	0.787

PSM, propensity score matching; BMI, body mass index; BSA, body surface area; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate; NYHA, New York heart association; COPD, chronic obstructive pulmonary disease; AF, atrial fibrillation; PORD, preoperative occult renal dysfunction; PCI, percutaneous coronary intervention; EuroSCORE II, European system for cardiac operative risk evaluation II.

3.4. Risk factors for postoperative AKI

Multivariate logistic regression analysis showed that age (OR=1.069, P=0.002), PORD (OR=2.339, P < 0.001) and IABP implantation (OR=1.914, P=0.002) were risk factors of postoperative AKI (Table 3). However, after PSM, body surface area (BSA) (OR=4.322, P=0.046), PORD (OR=2.731, P < 0.001) and IABP implantation (OR=2.102, P = 0.002) were independent risk factors of postoperative AKI (Table 3)

Table 3 risk factors of postoperative acute kidney injury by univariate and multivariate logistic regression analysis before and after propensity score matching

	Before PSM						After PSM
	Univariate logistic regression			Multivariate logistic regression			Univariate logistic regression			Multivariate logistic regression
	OR	95% CI	P value	OR	95% CI	P value	OR	95% CI	P value	OR	95% CI	P value
Age	1.103	1.061-1.146	<0.001	1.069	1.024-1.115	0.002	1.061	1.008-1.116	0.023	1.049	0.991-1.111	0.101
Gender	0.724	0.517-1.013	<0.001	0.697	0.484-1.004	0.052	0.680	0.440-1.050	0.082	0.838	0.490-1.433	0.518
BMI	1.022	0.977-1.069	0.345				1.029	0.972-1.090	0.325
BSA	2.098	0.857-5.136	0.105				3.254	1.032-10.261	0.044	4.322	1.027-18.192	0.046
CAD classification	1.091	0.870-1.368	0.450				1.012	0.739-1.384	0.943
Number of diseased vessels	0.926	0.701-1.225	0.590				0.866	0.606-1.239	0.432
Hypertension	1.301	0.946-1.789	0.105				1.097	0.698-1.725	0.688
Diabetes mellitus	1.182	0.881-1.587	0.264				0.987	0.667-1.461	0.948
Cerebrovascular disease	1.224	0.972-1.540	0.086				1.058	0.792-1.413	0.702
LVEF	0.978	0.962-0.994	0.006	0.990	0.971-1.008	0.265	0.970	0.950-0.991	0.004	0.991	0.967-1.016	0.494
NYHA classification	1.313	1.051-1.640	0.016	1.076	0.841-1.377	0.558	1.593	1.197-2.120	0.001	1.210	0.874-1.675	0.250
Peripheral vascular disease	1.840	1.202-2.817	0.005	1.474	0.914-2.376	0.112	1.460	0.758-2.813	0.258
Valvular disease	1.158	0.790-1.698	0.452				1.485	0.862-2.557	0.154
COPD	1.705	1.031-2.820	0.038	1.223	0.700-2.137	0.479	1.424	0.621-3.264	0.404
Preoperative AF	2.114	1.169-3.822	0.013	1.622	0.850-3.094	0.142	3.833	1.512-9.716	0.005	2.419	0.891-6.569	0.083
Pulmonary hypertension	1.517	1.222-1.884	<0.001	1.259	0.978-1.622	0.074	1.773	1.320-2.382	<0.001	1.397	0.995-1.962	0.054
PORD	2.680	2.000-3.592	<0.001	2.339	1.709-3.200	<0.001	2.935	1.988-4.333	<0.001	2.731	1.811-4.118	<0.001
Previous PCI	0.946	0.587-1.526	0.821				1.184	0.626-2.239	0.604
EuroSCORE II	1.110	1.045-1.179	0.001	1.000	0.932-1.072	0.990	1.085	1.012-1.163	0.021	1.031	0.947-1.122	0.481
Emergency operation	0.719	0.312-1.654	0.438				0.855	0.321-2.279	0.754
IABP implantation	2.022	1.383-2.955	<0.001	1.914	1.267-2.891	0.002	2.053	1.340-3.145	0.001	2.102	1.317-3.355	0.002
Bypass graft number	0.987	0.855-1.140	0.859				0.989	0.812-1.204	0.912

PSM, propensity score matching; BMI, body mass index; BSA, body surface area; CAD, coronary artery disease; LVEF, left ventricular ejection fraction; NYHA, New York heart association; COPD, chronic obstructive pulmonary disease; AF, atrial fibrillation; PORD, preoperative occult renal dysfunction; PCI, percutaneous coronary intervention; EuroSCORE II, European system for cardiac operative risk evaluation II.

3.5. Risk factors for long-term survival

The K-M survival curve showed the 1-, 3-, 5- and 10-year survival rates were 96.2%, 92.2%, 87.5% and 68.1% respectively in the PORD group, which were significantly lower than those of the control group (97.0%, 93.9%, 92.3% and 79.8% respectively).

The medium duration of follow-up was 50.9 months, ranging from 1.0 to 176.8 months. The K-M method explained a worse long-term prognosis in the PORD group (Figure 3A), and the difference was still significant after PSM (Figure 3B). The cox regression showed obesity (HR=0.758, P=0.006) and PORD (HR=1.724, P=0.037) impacted long-term survival in the overall cohort. After PSM, NYHA (HR=1.889, P=0.019) and PORD (HR=1.874, P=0.047) were risk factors for long-term survival (Figure 4).

PORD is very common in Chinese elder patients undergoing CABG. More than a quarter (27.65%) of the patients with normal Scr in this study was diagnosed as PORD. This observation clinical study shows that PORD is a clear factor of postoperative AKI and postoperative mortality for elderly patients, regardless PSM. Long-term survival of PORD patients was significantly lower either before or after PSM. Cardiac function and PORD were risk factors for long-term death in elderly CABG patients.

It is well-known that preoperative renal function is an important factor affecting the prognosis of patients undergoing cardiac surgery^[7]. Thus, preoperative evaluation of renal function becomes meaningful, especially for elderly patients. GFR is the standard method for evaluating renal function. It measures the renal clearance of some exogenous substances such as iohexol, inulin, and Cr-EDTA^[8]. The tedious and expensive detection of GFR offsets its high evaluation accuracy. Thus, Scr is still the most commonly-used clinical marker of renal function. Patients with abnormal Scr had a higher incidence of postoperative AKI and worse short- or long-term survival outcomes after CABG^[9,10]. The determination of Scr is convenient and cheap, but the Scr value is affected by many factors^[11], which lead to the conflict of normal Scr value and impaired renal function. When the Scr concentration increases, secretion in the renal tubules will improve, resulting in GFR overestimation in these patients^[12]. Reportedly, up to 65% patients with normal Scr had 24-hour urinary creatiniue clearance (UrCrCl)<60 mls/min ^[13]. Therefore, the use of Scr alone to evaluate renal function will lay a hidden danger for the prognosis of patients.

Given the convenience and accuracy of renal function evaluation methods, several correction formulas are commonly used for renal function evaluation in adults, such as the Cockroft-Gault formula ^[14], the Modifification of Diet in Renal Disease formula ^[15], the CKD epidemiology collaboration formula ^[16], the BIS formula ^[17] and the full age spectrum formula ^[18]. The BIS formula was specially designed for patients aged 70 years and above. Reportedly, its application in elderly is better than other formulas^[19]. Patients enrolled in the present study were all older than or equal to 70 years old, so the BIS formula was selected to calculate the eGFR of each patient.

Our team previously studied the impact of PORD on the short- and long-term prognosis of patients under off-pump CABG. Due to the limited number of patients, the elderly patients were not well analyzed, and only the situation of the whole age group (35-86 years old) was observed and analyzed^[20]. Atherosclerosis, a systematic disease, occurs more frequently with age. CAD is a manifestation of atherosclerosis in the heart. GFR gradually decreases with age, which occurs after the age of 20 and is called the physiological decrease in GFR^[21]. Although the reason is not completely clear, it is a fact that the GFR of elderly patients decreases. Elderly patients undergoing CABG are also accompanied by systemic atherosclerosis, especially renal artery atherosclerosis^[22]. Hence, renal insufficiency and CAD often occur in elderly patients at the same time. Therefore, attention shall be paid to the impact of renal function (especially PORD) on elderly patients with CABG. According to the existing literature and logical reasoning, PORD will increase the poor prognosis of elderly patients undergoing CABG. However, after carefully searching relevant studies, we found no specific data to support this view.

This is an observational study with the largest number of cases in China at present. Results showed PORD was a risk factor of AKI and short- and long-term postoperative death in elderly patients undergoing CABG. After PSM, patients with PORD developed AKI 2.73 times more frequently and the risk of postoperative death increased by 10.65 times than those in the control group.

Patients with PORD showed more NYHA Ⅲ and Ⅳ, lower preoperative LVEF and higher occurrence of preoperative AF. The more NYHA Ⅲ and Ⅳ and lower preoperative LVEF after PSM can consistently characterize cardiac function^[23], and usually imply worse systolic work and tend to result in insufficient renal perfusion^[24]. Reportedly, GFR changes were closely related to effective renal plasma flow in heart failure patients with reduced ejection fraction^[25], which confirm that renal hypoperfusion after cardiac function decline is the direct cause of PORD. In addition, the effect of AF on renal function is also significant. After patients received cryoballoon ablation to curve AF, their eGFR were significantly improved^[26]. Interestingly, correction of AF also improved hemodynamics and postoperative LVEF in patients, suggesting that AF probably causes PORD by affecting LVEF.

Due to the defects of Scr and aging of the body, PORD is relatively high in elder patients. In clinical practice, it is better to use GFR and a suitable eGFR formula to evaluate preoperative renal function. PORD shall be found in time in order to improve the diagnosis and treatment abilities.

There are some limitations in this study. First, it is a retrospective study. Some bias cannot be avoided, although PSM was applied. Second, the study included cases from two medical centers and the time span of the inclusion was long, which may be confounding factors.

More than one in four elderly patients with normal Scr suffered renal dysfunction before CABG. PORD was easily ignored through Scr detection and had an unfavorable impact on postoperative AKI, and early and late outcomes after CABG. Sustainable eGFR formula shall be recommended instead of Scr in elderly patients to evaluate preoperative renal function.

Ethics approval and consent to participate

This study was approved by the Ethics Committees of Jiangsu People Hospital and Shanghai Chest Hospital (ID: 2022-SR-209 and ID: IS22026) and was registered with the number of ChiCTR1800020130 (http://www.chictr.org.cn/).

Patients provided informed consent to undergo treatment, but the requirement for informed consent for participation in the current study was exempted by the Ethics Committee of Jiangsu People Hospital and Shanghai Chest Hospital (ID: 2022-SR-209 and ID: IS22026), due to its retrospective nature.

All methods were carried out in accordance with relevant guidelines and regulations.

The requirement for informed consent was waived by the Ethics Committee of Jiangsu People Hospital and Shanghai Chest Hospital (ID: 2022-SR-209 and ID: IS22026) because of the retrospective nature of the study.

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated and/or analysed during the current study are available from corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding

This study was supported by grants from the Shanghai Jing'an District Discipline Construction Project (2021PY03).

Authors' contributions

Z.L., C.Z. and L.Z. analyzed data and wrote the paper. Y.Z., Z.L., and L.J. designed the research. Y.S., Y.P., and L.H. contributed to data collection and data correction. Y.Z., Z.L., and L.J. are responsible for the overall content as guarantors. All authors contributed to processed and edited the manuscript. All authors provided critical revisions of the manuscript and approved the final manuscript.

Acknowledgements

Not applicable

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No competing interests reported.

Impact of preoperative occult renal dysfunction on early and late prognosis in elderly patients with coronary artery bypass in China

Status:

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Abstract

Background

Methods

Results

Conclusions

Figures

1. Introduction

2. Materials and Methods

3. Results

4. Discussion

5. Limitations

6. Conclusions

Declarations

References

Additional Declarations

Status:

Version 1