To our knowledge, this is the first study investigated the prognosis of the kidney function change in patients with DM and/or HTN undergoing TAVR procedure. We found that 1). Declined kidney function patients were associated with higher mortality significantly in hospital and at 30 days; 2). Improved kidney function is ubiquitous in baseline diabetic and/or hypertensive patients, with a higher STS score, lower LVEF, and smaller aortic valve area, though the prevalence of improved population was lower than no diabetic or hypertensive population; 3). The STS score, LVEF, baseline eGFR, and bleeding are the independent predictors of improved versus declined kidney function after TAVR.
Prevalence
In the present study, 38.4% of diabetic and/or hypertensive patients had an improvement in kidney function which was lower than 49.0% in no diabetic or hypertensive patients. The previous study observed the 52% incidence of improved kidney function in baseline renal dysfunction patients after TAVR [20, 21]. Though the procedure itself may bring some risk to renal injury by the usage of contrast, nearly half of patients benefited more from the procedure. This phenomenon reveals that the release of pressure afterload by TAVR plays a more prominent role in the recovery of type 2 chronic cardiorenal syndrome whose cause may be multifactorial like reduced cardiac output, elevated venous pressure, renin-angiotensin-aldosterone system activation [23]. In our study, the observed rate of recovery kidney function was lower in diabetic and/or hypertensive patients. The phenome revealed that even in diabetic and/or hypertensive patients, whose comorbidities may influence the recovery of the kidney function benefited from TAVR procedure.
The presence of diabetes mellitus and/or hypertension has been associated with impaired kidney autoregulation, which was consistent with the previously reported study [24][25]. The pathophysiology mechanism may be related to the negative influence of DM and/or HTN on kidney autoregulation [26]. Aortic stenosis patients with uncontrolled hypertension or controlled hypertension by medication may have irreversible renal damage due to excessive activation of the renin-angiotensin-aldosterone system and decreased afferent arteriolar resistance [27][28]. Moreover, AS patients with DM came up, not only with more pronounced metabolic syndrome, but also with increased incidence of generalized atherosclerosis [29]. Though previously study by D. Schewel et al. couldn’t find any evidence for influence of DM on the incidence of AKI, their data showed the numerically increased rate in AKI among those diabetic patients with severe renal failure (eGFR < 30 ml/min/1.86 m2) [25]. A meta-analysis by Mina et al. showed DM was associated with increased AKI and 1-year mortality after TAVR [30]. Over all, it is reasonable that the rate of recovery kidney function was lower in diabetic and/or hypertensive patients when compared with previous studies.
Independent predictors of kidney function change
Alexis et al. found that female gender, baseline liver dysfunction, and preoperative left ventricular ejection fraction was associated with an immediately declining or improving kidney function in baseline renal dysfunction patients [20]. Data from the PARTNER 1 Trial and registry reported by Boehar et al. showed that female gender and baseline left ventricular mass are predictors of declined or improved kidney function [21]. Multivariable logistic regression in previous study by Azarbal et al found moderate to severe lung disease, eGFR < 50 ml/min, and previous aortic valve surgery were the independent predictors of acute kidney recovery, while patients with diabetes mellitus, baseline anemia, and STS > 6.1 were likely to develop acute kidney injury [19]. Though the included population were different, our study identified four independent predictors of improved versus declined eGFR in diabetic and hypertensive patients. We had found lower STS, LVEF, baseline eGFR, and less unplanned CPB may give the potential improvement of kidney function.
Our study identified the patients with lower LVEF may be likely to improve kidney function after TAVR. This finding supports the concept that after the release of the pressure afterload, the LVEF recovered, and the low perfusion state in the kidney was eliminated. Therefore, it can be observed that lower LVEF patients had more prevalence of improved kidney function. Our findings are similar to previous results. Lower eGFR patients were more likely to develop kidney function improvement and higher STS scores may increase the risk of kidney function injury [19]. Thus, clinical avoidance of TAVR in these severe kidney dysfunction patients may not be reasonable given the enormous potential for improvement in this high-risk group. Moreover, it was reasonable that less unplanned CPB during the TAVR procedure may help the recovery of the kidney function. Unplanned cardiopulmonary bypass was one of the severe peri-procedural complications that was associated with acute kidney injury after cardiac surgery [31, 32]. The exposure of blood to non-endothelial lined surfaces during cardiopulmonary bypass can induce a systemic inflammatory response, coagulopathy, hemodilution, generation of thrombin, inflammatory reaction, and postoperative bleeding leading to declined kidney function [33].
Mortality
Findings from the present study showed the relationship between declined kidney function change and higher mortality in diabetic and/or patients who underwent TAVR. The previous study by Okoh et al. showed that in-hospital, 30-day and 1-year mortality was associated with declined kidney function change significantly [20]. All these results confirm the adverse effects of declined kidney function on mortality after TAVR [34–38]. Our study confirmed that the detrimental effect on all-cause and cardiovascular mortality persisted in diabetic and/or hypertensive patients.
Limitations
This study is a retrospective single-center study with a small number of patients and therefore there are still some limitations inherently present in such study. Patients with baseline eGFR < 15 ml/min and those on dialysis were excluded from the present study because the fluctuations in eGFR of these diabetic and/or hypertensive patients were not accurate. The present study only considered an immediate improvement change as improved or declined kidney function change in eGFR defined by pre-discharge value. Long-term follow-up was not considered in our study, which would have been valuable to be further studied whether it would persist in the long term as well. The study is likely not adequately powered to detect differences in some clinical endpoints in improved or declined kidney function group compared with the group who experienced no change for the limited number of patients. We used a clinically meaningful definition of improved or declined eGFR, but the other definition like absolute increase or decrease of serum creatinine of 0.3 mg/dl could also be used as the Valve Academic Research Consortium definition [22].