EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Combined heart-kidney transplant has become an alternative for heart transplant candidates with significant chronic kidney disease. However, it is not clear which patients will benefit most from such intervention, and in whom cardiac transplant alone will be sufficient to restore adequate renal function. We report the case of a man with ischemic cardiomyopathy and chronic kidney disease who was wait-listed for heart-kidney transplant after acute decompensated heart failure and renal failure requiring hemodialysis. Because of unexpected circumstances, the kidney transplant was cancelled, and only a heart transplant was performed. Nonetheless, the kidney function rapidly improved beyond the levels before hospitalization and remains stable months after transplant.

This case illustrates the difficulties in assessing the reversibility of kidney damage in the context of heart failure requiring transplant. This issue is primordial to improve selection of patients who will benefit most from combined heart-kidney transplant in a context of scarce organ allocation resources.

Key words : Transplantation, Kidney transplantation, Heart transplantation

The first combined heart-kidney transplant (HKT) was performed in 1978,¹ and thereafter, the incidence of HKT has slowly increased, but remains marginal compared with heart or kidney transplant alone.²As advanced chronic kidney disease (CKD) is considered a relative contraindication to heart transplant alone (HTA),³ HKT has become a viable therapeutic option for patients with heart failure and CKD. Patient survival in HKT appears to be similar to HTA,^4,5 but a survival advantage seems to be present in patients requiring pretransplant dialysis.⁴ In the context of scarce organ allocation resources, it is important to adequately identify patients with irreversible renal impairment, important enough to warrant concomitant kidney transplant. Here, we report a case illustrating the difficulties inherent to patient selection in this context.

Case Presentation

The patient was a 57-year-old white man known for severe dilated ischemic cardiomyopathy with a left ventricular ejection fraction estimated at 25% and atrial fibrillation. The patient also had CKD attributed to arterial renal embolization that occurred in 2006, with a serum creatinine stable at 180 μmol/L, and an estimated glomerular filtration rate⁶ (eGFR) of 34 mL/min/1.73 m². In January 2012, the patient presented to our institution with heart failure exacerbation with acute renal failure (creatinine level, 210 μmol/L). His cardiac function was stabilized with inotropic, but his kidney function deteriorated with the use of high-dose diuretics. Serum creatinine levels from admission to the last follow-up are shown in Figure 1.

Because the patient remained dependent of intravenous inotropic support, he was judged eligible for heart transplant at the end of February. The Nephrology Department was consulted to evaluate the indication for HKT. At that moment, the serum creatinine levels oscillated between 200 and 250 μmol/L (eGFR 23 to 30 mL/min/1.73 m²).

A 24-hour urine collection revealed a creatinine clearance level at 17.5 mL/min/1.73 m², and a proteinuria, level of 570 mg in 24 hours. A renal ultrasound showed that the right and left kidneys measured 11.6 and 10.1 cm, with multiple focal areas of cortical atrophy. A kidney biopsy was not done because of this important renal atrophy. While a diagnosis of cardiorenal syndrome with some element of prerenal state induced by diuretic use was suspected, the degree of kidney failure reversibility was difficult to assess. Thus, considering the pre-existing moderate CKD, the lack of improvement with inotropic therapy, the echographic appearance of the kidneys, and the risk of progression to end-stage renal failure with the use of calcineurin inhibitors after transplant, this patient was listed for HKT at the beginning of March. Five Kidney Transplant Programs out of 6 in the Province of Quebec agreed with this decision, as required for listing a patient for any combined solid-organ transplant.

While waiting for HKT, the patient’s kidney function worsened, and hemodialysis was initiated on April 3, and was continued until heart transplant, which was done on April 13th. A renal transplant from the same donor was scheduled after the first surgery, but 2 hepatic lesions of 2.0 cm and 0.5 cm were discovered after the heart recovery. Because adenocarcinoma of the liver could not be excluded, the kidney transplant was cancelled. The patient received immunosuppressive therapy consisting of rabbit antithymocyte globulin followed by basiliximab for induction therapy, and corticosteroids, tacrolimus, and mycophenolate for maintenance. After the heart transplant, the kidney function rapidly improved, with no further need of dialysis, and the patient left the hospital on May 14, with a serum creatinine level of 123 μmol/L. Follow-up was uneventful, and the serum creatinine level 5 months after transplant remained stable (117 μmol/L).

The above case shows the difficulties associated with selecting patients who will benefit the most from HKT. Our patient had acute exacerbation of a chronic cardio-renal syndrome, and was evaluated by several nephrologists and all the kidney transplant programs in the province, which considered that his renal dysfunction was severe and irreversible enough to warrant HKT. This decision was based on the presence of long-term CKD, multiple bilateral areas of atrophy on renal ultrasound, deterioration of kidney function, despite treatment of heart failure and the need for hemodialysis before heart transplant.

A kidney transplant did not take place because of an unexpected event of discovering 2 hepatic lesions. However, the rapid kidney function improvement after restoration of cardiac function suggested that this patient would not have benefited from a renal allograft, which would have deprived another patient on the kidney transplant waiting list. Furthermore, kidney function after heart transplant was better than baseline function, illustrating that even stable CKD can improve after heart transplant.

Studies have shown that preoperative renal dysfunction is associated with higher mortality following HTA.^7,8 Moreover, the postoperative need for dialysis is associated with an early death rate exceeding 40%, regardless of pretransplant kidney function.⁷ Renal function loss after HTA is common, and usually presents early in the first year. A cohort study showed the average loss of eGFR was 24% during the first year, and at 3 years, 23% of patients had at least 50% eGFR loss.⁹ In the Registry of the International Society of Heart and Lung Transplant, severe renal failure (creatinine > 221 μmol/L, need for dialysis or kidney transplant) was present in 7% of recipients 1 year posttransplant.² Also, the prevalence of end-stage renal disease, and subsequent kidney transplant was estimated at 4.4% and 0.9% at 8 years’ follow-up.¹⁰ Mortality in HTA patients with end-stage renal disease is higher than matched HTA patients without end-stage renal disease, and end-stage renal disease patients without HTA.¹¹

No serum creatinine level, as a continuous variable, was associated with an unacceptable risk of HTA.¹² However, the presence of irreversible renal impairment (eGFR < 40 cc/min) is associated with a worse prognosis, and is considered a relative contraindication for HTA.^3,7 In this setting, HKT is proposed as an acceptable solution for patients with CKD and end-stage cardiac failure. Patient outcomes of HKT appear similar to HTA.^4,5,13-16 Although still marginal, HKT is increasingly performed despite the lack of good evidence regarding patient selection.

A recent analysis of registry data showed that patients with HKT had a lower adjusted risk of death compared with HTA patients if pretransplant dialysis only was required, while nearly half of HKT reported were performed in patients who did not need renal replacement therapy before the procedure.⁴

Another study compared patient and dialysis-free survival in HTA patients with or without significant renal impairment (creatinine ≤ 177 μmol/L) and HKT.¹⁶ In this study, survival was better in HTA without significant renal failure, but similar when comparing HTA with renal dysfunction and HKT. Interestingly, almost all HKT patients needed dialysis before transplant, suggesting that combined transplant could reduce mortality in patients requiring renal replacement therapy to the level of HTA with less severe kidney disease.

Fear of progressive renal failure after transplant also can influence patient selection. In the 2005 International Society of Heart and Lung Transplant report, survival for HKT and HTA were similar, but survival of kidney transplant after heart transplant patients was lower than HTA.¹⁷ However, a recent UNOS registry study showed that renal allograft survival was similar between kidney after HTA and combined HKT recipients, regardless of graft quality.¹⁸

Predicting reversibility of kidney impairment also can be a challenge. Renal function estimation formulas tend to overestimate kidney function in heart failure patients with low glomerular filtration rate.¹⁹ Moreover, fluid overload, diuretic therapy, low blood perfusion, and cachexia can influence kidney function evaluation in heart transplant candidates. Ultrasound is only useful if the kidneys are atrophic or highly echogenic, which can indicate chronic disease. Renal biopsy can be used to help guide patient selection,²⁰ but clinical outcome studies are lacking. Pretransplant patient characteristics associated with poor survival (history of peripheral vascular disease, age > 65 years old, nonischemic heart failure, use of ventricular assist device, and dialysis dependence at time of transplant) can be used to categorize patients into risk score strata.²¹ Using this information, only low-risk patients with decreased eGFR (< 33 cc/min) had improved survival with HKT compared with HTA.

In conclusion, the above case illustrates the challenge in selecting patients who will benefit more from HKT than from HTA. The difficulty lies with determining the reversibility of renal dysfunction in a patient with CKD and acute cardio-renal syndrome. Recent data help identify such patients, but more studies are needed. Patients already on dialysis at the time of heart transplant appear to have a survival benefit, but other factors must be considered. As an increasing number of centers now perform HKT, it is crucial to carefully assess recipients in a context of scarce organ resources. As outcomes of kidney transplant after a HTA appear favorable, this approach may be acceptable for patients who have renal impairment not severe enough to warrant dialysis before heart transplant or in whom renal impairment might improve after HTA.

Volume: 12 Issue: 3 June 2014

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