Renal Transplantation after Transcatheter Aortic Valve Replacement: Case Report

Abstract

Patients with chronic kidney disease (CKD) have an increased likelihood of developing calcific aortic stenosis (AS). These patients also often suffer from multiple comorbidities, potentially making them high-risk surgical candidates and limiting their treatment options. Transcatheter aortic valve replacement (TAVR) is the recommended therapeutic approach for severe AS in patients who are not suitable candidates for surgical aortic valve replacement (SAVR). TAVR is being increasingly considered as a viable alternative to SAVR. As such, its applications in patients with CKD and other chronic diseases, as well as methods to optimize peri- and postoperative results are of great interest and significance. We present the case of a successful renal transplant procedure, performed within a year following a TAVR, in a 52-year-old man who suffered from multiple comorbidities.

Introduction

Chronic kidney disease (CKD) is known to be associated with an increased cardiovascular risk, and the onset of CKD in the setting of a pre-existing cardiovascular disease often serves to accelerate the latter's course. Valvular abnormalities are among the commonly observed cardiovascular conditions in patients with CKD. Among these, aortic stenosis (AS) is found to be associated with both higher morbidity as well as mortality rates. ¹ The proinflammatory milieu and predominance of factors favoring calcification against those that prevent it, lead to an increased risk of arterial and valvular calcification in patients with CKD.

The prevalence of severe AS in subjects undergoing hemodialysis is estimated to be around 6 to 13%. ² This number is significantly higher when compared with the general population, where the prevalence of aortic sclerosis is ∼25% in people over 65 years of age, and that of severe AS is ∼3% in the subjects over 75 years of age. ³ With the increasing age of patients undergoing dialysis, the prevalence of co-existing aortic valve stenosis is on a parallel rise. ⁴

Transcatheter aortic valve replacement (TAVR), first performed in 2002, has emerged as a viable alternative to the traditional open-heart surgical aortic valve replacement (SAVR). Patients undergoing TAVR are usually candidates, who are otherwise deemed unfit for an open-heart SAVR. ⁵ The most common reasons for this include advanced age and comorbid conditions, which place these patients at an increased risk for peri- and postoperative complications.

The functional status of the kidney is of prime significance in the patient undergoing TAVR, both pre- and post procedure. As per one study review, CKD is one of the independent predictors of mortality in the immediate year following the procedure. ⁶ TAVR is also known to be associated with an increased risk of acute kidney injury (AKI). However, literature regarding the risk of acute kidney injury in patients undergoing TAVR with CKD show varied results. ⁷

We present the first reported case of a patient who had a successful renal transplantation (RT) within a year of undergoing TAVR.

Case Report

A 52-year-old Caucasian male presented with end-stage renal disease (ESRD) due to type 2 diabetes mellitus and hypertension. At the time of presentation, he had diabetes for over 30 years and hypertension for 10 years. He had been on renal replacement therapy with hemodialysis for the past 4 years. His cardiovascular history was also notable for an episode of myocardial infarction, a coronary artery bypass graft, and paroxysmal atrial fibrillation for which he was placed on an anticoagulant regimen. After an initial risk–benefit analysis, he was considered a potential candidate for kidney transplantation.

During the pretransplant cardiac risk evaluation, he was found to have severe aortic valve stenosis. Taking into account his comorbidities, he was selected for TAVR. The procedure was soon performed, along with which he also had a permanent pacemaker implanted. The postoperative period was uneventful, and he did not experience any symptoms of ischemia, congestive heart failure, or arrhythmias in the subsequent months.

After 6 months following the TAVR, he received a live donor kidney transplant, after risk stratification and approval for surgery by the transplant team. In the immediate postoperative period, he experienced an episode of ventricular tachycardia, which required cardioversion. Immunosuppressive therapy consisted of thymoglobulin induction and maintenance regimen that included tacrolimus and mycophenolate mofetil (MMF). The tacrolimus dose was adjusted to meet therapeutic levels. Following the surgery, he had immediate allograft function, and the serum creatinine levels showed a steady decline.

Prior to discharge, he underwent an electrophysiological study, which did not show any inducible arrhythmias. An echocardiogram was also performed, which showed preserved ejection fraction. His cardiac enzyme levels were not elevated. He was discharged with LifeVest, wearable defibrillator, which had been continued for 1 month. He had since been on regular follow-up at the transplant clinic. At the time of the report, serum creatinine was 1.5 mg/dL, and he had no proteinuria. He remained on metoprolol 25 mg twice daily and amlodipine 10 mg daily for blood pressure control. His maintenance immunosuppressive regimen consisted of tacrolimus with a therapeutic target of 4 to 7 ng/mL, MMF 500 mg twice daily, and prednisone 5 mg once a day.

Discussion

CKD plays a facilitatory role on cardiovascular diseases (CVD). The risk of CVD in patients with impaired renal function increases by almost two to four fold. ⁸ Estimated 45 to 50% of deaths in patients with ESRD can be attributed to CV causes. ^{9 10 11}

In addition to being an independent risk factor for CVD, CKD also amplifies the impact of other traditional cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes mellitus. ^{8 9} Moreover, cardiovascular disease burden is found to be substantially higher in patients who are undergoing dialysis, as was first pointed out in 1974, by Lindner et al. ¹² About one-third of hospitalizations in patients undergoing dialysis is reported to result from CV causes. ¹¹

Atherosclerosis, left ventricular hypertrophy, and arteriosclerosis constitute the three most prevalent pathological forms of CVD in patients with CKD. Apart from these, cardiac valvular disorders are also emerging as significant contributors to CV morbidity and mortality in these patients. The aortic and mitral valves most commonly undergo thickening and calcification, in the setting of ESRD, leading to complications such as stenosis or regurgitation of affected valves.

Drawing particular attention is AS, which is associated with higher morbidity and mortality rates and is being observed at an increased frequency in the recent years. This trend could be attributed to the increasing age of patients undergoing dialysis. The incidence of AS increases proportionately with age and is a condition predominantly seen in the elderly. Moreover, the hemodynamic and metabolic derangements associated with CKD, such as increased cardiac output (due to anemia or arteriovenous fistula), dysregulation of calcium, and phosphate metabolism and increased stress on the valves created secondary to hypertension, provide the perfect setting to accelerate the progression of AS. Up till recently, the primary modality of treatment for AS has been with SAVR.

However, up to 30% patients with severe symptomatic AS are unable to undergo valve replacement by the traditional open-heart technique, owing to factors such as increased age, multiple comorbidities, severe left ventricular dysfunction, etc. Medical treatment alone is associated with a very poor prognosis in patients with severe symptomatic AS.

The advent of TAVR has now enabled many high-risk patients who were otherwise ineligible for an open-heart surgery to undergo valve replacement. Ever since the first-in-man TAVR performed by Dr. Cribier in Rouen (year 2002), >50,000 patients, worldwide, have benefited from this procedure.

TAVR, however, is associated with an increased risk of AKI, which is observed in up to 30% of patients. ¹³ Multiple mechanisms are implicated, including renal ischemia, cholesterol emboli, oxidative stress, hemolysis, and inflammation, which act synergistically leading to AKI. As such, it is prudent to proceed with the valve replacement prior to the renal transplant procedure to avoid the potential ischemic insult to the newly transplanted kidney and also avoid the adverse effects of immunosuppression.

In addition, there is growing evidence, which suggests that the renal function is an important predictor of mortality in patients, after undergoing TAVR. Many of the known long-term complications post-TAVR, such as stroke, ¹⁴ myocardial infarction and bleeding could be potentially exacerbated by ongoing dialysis. Patients on dialysis who undergo TAVR have been found to have significantly lower survival rates at 1 year as compared with the TAVR candidates who are not on dialysis. ¹⁵ This risk could be brought down substantially post RT. In our patient, who suffered from multiple co-existing illnesses, the prospect of renal transplantation offered significant survival benefits and improvement in the quality of life.

Conclusion

There is a relative paucity of literature reporting the challenges and outcomes faced by similar patients. The article published by Cheungpasitporn et al ⁷ present an extensive review of current literature on the various nephrology aspects of the TAVR procedure. Our aim with this report is to present the postoperative outcome observed in our patient to shed light on the impact of TAVR with particular emphasis on the cohort of patients who need to undergo renal transplantation. The anticipated rise in the number of patients with coexisting AS and ESRD would warrant further reports and studies in an effort to improve upon current management practices.