Preoperative hidden renal dysfunction add an age dependent risk of progressive chronic kidney disease after cardiac surgery

Preoperative renal dysfunction is a high risk factor for outcomes in cardiac surgery, not only for postoperative acute kidney injury (AKI), but also for in-hospital mortality and even long-term outcomes [1‐3]. Renal dysfunction is mostly evaluated by serum creatinine (SCr), but scholars have noted that patients with normal SCr had estimated glomerular filtration rate (eGFR) values < 60 mL/min and called it “occult renal dysfunction”, which significantly increased the risk of renal replacement therapy (RRT), inpatient death and prolonged hospitalization after coronary artery bypass grafting (CABG) surgery [4, 5]. In the study of Volkmann et al., patients with plasma creatinine (PCr) ≤ 1.5 mg/dL who underwent CABG were divided into 2 groups, estimated creatinine clearance (eCrCl) ≥ 60 mL/min (normal renal function) or eCrCl < 60 mL/min (reduced renal function), respectively. The results showed that reduced renal function had a double risk of death, a longer total hospital stay and post-surgical hospital stay than those patients with normal renal function [6]. However, a considerable fraction of cardiac surgery patients may have normal SCr values and an eGFR under 90 mL/min/1.73 m², but above 60 mL/min/1.73 m², particularly since eGFR declines with age [7]. In the present retrospective, observational, single center study we analyzed whether patients with “normal” SCr and “hidden renal dysfunction” (60 ≤ eGFR < 90 mL/min) have an enhanced risk of complications after cardiac surgery especially focusing on age-related eGFR decline.

It is commonly accepted that preoperative renal dysfunction is a risk factor for AKI, in-hospital mortality or even long-term outcomes after cardiac surgery [12]. Also “occult renal insufficiency” defined as SCr ≤ 100 μm with CrCl ≤  60 mL/min with an incidence rate of up to 13% has been shown to be associated with RRT [13], which is in accordance with our findings, that for patients with normal SCr under the age of 65 years, preoperative eGFR < 60 mL/min/1.73 m² was an independent risk factor for AKI. However, interestingly for patients over the age of 65 years, preoperative eGFR< 60 ml/min/1.73 m² was not an independent risk factor for AKI in our study, but was still a risk factor for 3-year death and progressive CKD. The senescent kidney already shares morphological features of CKD [7], and the weighing of aging was heavier than eGFR in a multivariate regression analysis, which may explain the result.

However, most studies about preoperative renal dysfunction usually studied patients with eGFR < 60 mL/min /1.73 m² [6, 14], but the risk of patients with mild decreased eGFR (60~90 mL/min /1.73 m²) and normal SCr is less evaluated. In the study by Howell et al. including 7621 consecutive patients who underwent CABG, valve surgery or combined procedures, eGFR ≥  90 mL/min /1.73 m² were considered normal renal function (reference group), eGFR 60–90 mL/min/1.73 m² were mild renal dysfunction (group 2), eGFR 30–59 mL/min/ 1.73 m² were moderate renal dysfunction (group 3) and eGFR 15–29 mL/min/1.73 m² were severe renal dysfunction (group 4) and the results showed that eGFR of 60–90 mL/min/1.73 m² (mild renal dysfunction) was an independent predictor of in-hospital and late mortality as well as cardiovascular complications [15], which is in line with our results, which revealed that for patients with normal SCr under the age of 65 years preoperative 60 ≤ eGFR< 90 mL/min/1.73 m² values became a risk factor for 3-year progressive CKD.

The mechanism why mild renal dysfunction contributes to poor outcomes is not clear. A possible explanation is that patients with impaired eGFR may have a more advanced cardiovascular disease and a reduced cardiac output before surgery. Along with aging, inflammatory mediators, endothelial dysfunction, left ventricular hypertrophy, all factors may contribute to the poor outcomes [16] and when eGFR values decreased to 60~90 mL/min/1.73 m², it may be not obvious yet for the kidney to develop AKI, but the kidneys may be less able to recover from the injurious event of surgery.

The cause of preoperative decreased eGFR is complicated and different for eGFR 60~90 mL/min/1.73 m² and eGFR < 60 mL/min/1.73 m² cases. For patients with eGFR 60~90 mL/min/1.73 m², aging and increased BMI may be the main causes for decreased eGFR [7, 17, 18]. In patients over the age of 65 years, the proportion of hidden renal dysfunction was up to 67.0% in our study. It is considered that intimal thickening and decreased compliance of the renal vasculature contribute to observed 10% decreases in renal blood flow (RBF) per decade of life [19] and a decline in eGFR has been observed in patients without histological evidence of nephrosclerosis [20]. Also our results showed that though the rate of abnormalities in urinalysis and renal ultrasound was significantly higher in the eGFR < 60 mL/min/1.73 m² group, there was no statistical difference between 60 ≤ eGFR < 90 mL/min/1.73 m² and no renal dysfunction cases, which confirmed that most patients with eGFR 60–90 mL/min/1.73 m² have no substantial damage. However, 44.0% of our patients < 65 years old had hidden renal dysfunctions. Besides age-dependent changes in kidney structure and function, increased exposure to comorbidities including cardiac-renal syndrome (type II, IV), hypertension, diabetes and nephrotoxic drugs may together increase the susceptibility of the kidney to develop AKI. The main cause may be the hemodynamic instability caused by cardiac-renal syndrome, since in our study, the proportion of New York Heart Association (NYHA) > II of the other three groups were significantly higher than in the no renal dysfunction group. Proportions of hypertension and diabetes also increased along with the decreased eGFR. Thus non-age dependent hidden renal dysfunction may be functional and reversible, and efforts could be made for better prevention of AKI.

Our study has some limitations. First, it was an observational and retrospective study in a single center, possibly not able to identify all potential confounding factors. Furthermore, mild renal dysfunction is always poorly defined. Our study used the cut-off of SCr ≤ 1.2 mg/dL (female)/1.5 mg/dL (male) which was arbitrarily chosen from the normal value of our hospital. We chose it because our aim was to raise the awareness of surgeons to concern about patients with conventionally regarded normal SCr but decreased eGFR,

Known renal dysfunction (eGFR < 60 mL/min/1.73 m²) was a significant risk factor of progressive CKD for both ≥65 and < 65 year old patients. However, hidden renal dysfunction (60 ≤ eGFR < 90 mL/min/1.73 m²) correlated with progressive CKD only in < 65 year old patients. Awareness should be raised for these patient group.