Abstract
OBJECTIVES
Renal transplantation is an effective treatment for end-stage renal failure. The aim of this study was to evaluate outcomes for these patients undergoing cardiac surgery.
METHODS
A retrospective analysis identified patients with a functioning renal allograft at the time of surgery. A 2:1 propensity matching was performed. Patients were matched on: age, sex, left ventricle function, body mass index, preoperative creatinine, operation priority, operation category and logistic EuroSCORE.
RESULTS
Thirty-eight patients undergoing surgery with a functioning renal allograft were identified. The mean age was 62.4 years and 66% were male. A total of 44.7% underwent coronary artery bypass grafting and 26.3% underwent a single valve procedure. The mean logistic EuroSCORE was 10.65. The control population of 76 patients was well matched. Patients undergoing surgery following renal transplantation had a prolonged length of intensive care unit (3.19 vs 1.02 days, P < 0.001) and hospital stay (10.3 vs 7.17 days, P = 0.05). There was a higher in-hospital mortality (15.8% vs 1.3%, P = 0.0027). Longer-term survival on Kaplan–Meier analysis was also inferior (P < 0.001). One-year survival was 78.9% vs 96.1% and 5-year survival was 63.2% vs 90.8%. A further subpopulation of 11 patients with a failed renal allograft was identified and excluded from the main analysis; we report demographic and outcome data for them.
CONCLUSIONS
Patients with a functioning renal allograft are at higher risk of perioperative mortality and inferior long-term survival following cardiac surgery. Patients in this population should be appropriately informed at the time of consent and should be managed cautiously in the perioperative period with the aim of reducing morbidity and mortality.
Keywords: Renal transplant, Cardiac surgery, Functioning allograft, Outcomes
Renal transplantation remains the most effective treatment for end-stage renal failure.
INTRODUCTION
Renal transplantation remains the most effective treatment for end-stage renal failure. With advances in transplantation and growing donor organ pools, the number of patients with functioning renal allografts continues to grow. In the UK alone, there were 3280 adult renal transplants in 2018–19 with an increasing overall trend over the past 10 years [1].
Solid organ transplant recipients are at higher risk of cardiovascular disease [2, 3]. Renal transplant recipients may have cardiovascular risk factors such as hyperlipidaemia, diabetes and hypertension [4], and cardiovascular disease remains the leading cause of death in these patients [5]. This may be due to the primary renal disease, the effects of receiving a transplant or immunosuppression required post-transplant [4]. As a result of this cardiovascular morbidity, there is a cohort of patients undergoing cardiac surgery with a functioning renal allograft.
Cardiac surgery in this patient population presents challenges. It is recognized that cardiopulmonary bypass adversely effects native organs [6], and the impact on allografts is likely to be even greater. Furthermore, the physiological changes consequent upon long-term steroid use and the risks associated with immunosuppression are likely to impact on the patients’ recovery and outcomes following cardiac surgery.
Several published studies have looked at outcomes of cardiac surgery in recipients of solid abdominal organ allografts [3, 7–14]. Outcomes vary across each study. Short-term mortality rates are in general low, being <5% in most studies with the exception of 2 recent studies, which report short-term mortality rates of 7% [13] and 15.7% [14]. Long-term survival rates are also good in general, with most studies reporting 5-year survival rates >75%. However, most of these studies involve heterogenous patient groups with mixed allograft types. Therefore, the aim of this study was to more specifically examine outcomes for patients undergoing cardiac surgery with a functioning renal allograft.
PATIENTS AND METHODS
Patient population
This was a retrospective observational study conducted at a single institution. The study was approved by the Royal Papworth Hospital Research and Development clinical ethics department. Consent of patients was waived. All patients undergoing cardiac surgery at Royal Papworth Hospital (UK) between January 2012 and December 2019 were included in this study (excluding pulmonary endarterectomy and cardiothoracic transplantation). Demographic, intraoperative and postoperative outcome data were collected prospectively. Acute kidney injury (AKI) grade was calculated using the Acute Kidney Injury Network classification [15]. Creatinine clearance was calculated using Cockcroft–Gault formula [16]. Details of perioperative complications were not available for some patients operated early in the cohort. Mortality information was obtained from the UK national patient administration system and was available for all patients.
Surgical management
No specific adjustments were made to the usual perioperative or intraoperative management of these patients. They all received our unit’s standard antibiotic prophylaxis (flucloxacillin and gentamicin or vancomycin and gentamicin for penicillin allergy).
Immunosuppression and renal allograft monitoring
Immunosuppression was managed in collaboration with our local renal transplant unit. Steroids were administered intravenously until the patient was able to take them orally. Calcineurin inhibitor blood trough levels were taken, and drug dosing advised by the renal transplant physicians daily. Daily creatinine levels were taken whilst an inpatient and the results discussed with the renal transplant physicians who reviewed the patients if necessary. All renal transplant patients were receiving immunosuppression at the time of surgery.
Statistical analysis
Statistical analysis was performed using GraphPad Prism 5.03 (GraphPad Software, Inc., San Diego, CA), SPSS 26 (IBM Corporation, USA) and R 3.4.4 (R Core Team, Vienna, Austria). Propensity matching was performed to identify a 2:1 control population for the patients who underwent cardiac surgery with a functioning renal allograft. This was performed using the ‘nearest-neighbour’ method whereby a control patient whose propensity score is closest to that of a patient undergoing cardiac surgery without a prior renal transplant is identified. Patients were matched on: age, sex, left ventricle function, body mass index, preoperative creatinine, operation priority, operation category and logistic EuroSCORE (Supplementary Material, Table S1). If multiple control patients have propensity scores that are equally close, one of these control subjects is selected at random. Standardized difference of means was calculated for both continuous and categorical variables to ensure that the frequency of a variable was equally balanced between the 2 groups.
The Kaplan–Meier method was used to estimate the patient survival rates, with the log-rank (Mantel–Cox) test used to compare groups. Univariable analyses were performed. For the comparison of groups, continuous variables were analysed with the Mann–Whitney U-test if not normally distributed and with the Student’s t-test if normally distributed. Categorical variables were analysed with either chi-square test or Fisher’s exact test. P ≤ 0.05 was considered statistically significant.
RESULTS
Patient demographics
Over the 8-year period of study, a total of 14 129 patients underwent cardiac surgery. Of this cohort, 49 patients (0.35%) were renal transplant recipients of whom 11 had failed allografts and were dialysis dependent. Demographics of the 38 patients with a functioning renal allograft are summarized in Tables 1–3. The most frequent aetiologies of end-stage renal failure were hypertensive and diabetic nephropathy. Six (15.8%) had received >1 renal transplant. The median time from renal transplant to cardiac surgery was 80.9 months. At the time of surgery, the median age was 63 years. The mean baseline creatinine level was 165.19 μmol/l and the median logistic EuroSCORE of the cohort was 3.74. The majority of patients underwent cardiac surgery on an elective or urgent basis (97.4%). Most frequently, they underwent coronary artery bypass grafting (44.7%). There was no evidence of a different pattern of coronary artery disease in this patient population.
Table 1:
Details of allografts and pretransplant renal pathology in the cohort of 38 patients with functioning allografts at the time of surgery
| Renal transplant cohort (n = 38) | |
|---|---|
| Renal pathology prior to transplant, n (%) | |
| Hypertensive nephropathy | 11 (28.9) |
| Diabetic nephropathy | 6 (15.8) |
| Autosomal dominant polycystic kidney disease | 3 (7.89) |
| Glomerulonephritides* | 4 (7.89) |
| Obstructive uropathy | 3 (7.89) |
| Chronic pyelonephritis | 2 (5.26) |
| Congenital hepatic fibrosis with renal failure | 1 (2.63) |
| Drug induced nephrotoxicity | 1 (2.63) |
| Mercury poisoning | 1 (2.63) |
| Renovascular disease | 1 (2.63) |
| Tubulointerstitial nephritis | 1 (2.63) |
| Not recorded | 4 (10.5) |
| Number of transplants before surgery, n (%) | |
| 1 | 32 (84.2) |
| 2 | 3 (7.89) |
| 3 | 3 (7.89) |
| Age of latest allograft (months), median (IQR) | 80.9 (35.0–157.1) |
IQR: interquartile range.
Glomerulonephritides include Goodpasture disease [2 (5.26%)], focal segmental glomerulosclerosis [1 (2.63%)] and nephrotic syndrome of an unrecorded aetiology [1 (2.63%)].
Propensity matching was performed, and 76 matched control patients were identified on a 2:1 basis. A comparison between the demographics of the renal transplant recipients and the controls is summarized in Tables 2 and 3. The patient groups were well matched for demographic and operative parameters. The only variable significantly different on univariable analysis was that a greater proportion of the renal transplant group was hypertensive (80.6% vs 54.8%; P = 0.02).
Table 2:
Baseline characteristics of patients
| Renal transplant (n = 38) | Matched controls (n = 76) | P-value | Standardized difference | |
|---|---|---|---|---|
| Age (years), median (IQR) | 63.00 (56.3, 67.0) | 63.00 (53.8, 70.0) | 0.91a | 0.03 |
| Sex, male, n (%) | 25 (65.8) | 55 (72.4) | 0.52b | 0.14 |
| BMI, median (IQR) | 26.43 (24.0, 30.7) | 26.20 (23.4, 28.1) | 0.39a | 0.16 |
| Preop serum creatinine (μmol/l), mean (SD) | 165.19 (127.6) | 138.39 (144.3) | 0.35c | 0.19 |
| Preop creatinine clearance (ml/min), median (IQR) | 40.8 [28.7, 58.3] | 83.2 [64.2, 99.8] | <0.001 a | |
| Hypertension, n (%) | 29 (80.6) | 40 (54.8) | 0.02 b | |
| Peripheral vascular disease, n (%) | 10 (28.6) | 12 (16.2) | 0.21b | |
| Diabetes, n (%) | 11 (28.9) | 15 (19.7) | 0.34b | |
| Smoker, n (%) | 0.67b | |||
| Current smoker | 3 (7.9) | 8 (10.5) | ||
| Ex-smoker | 16 (42.1) | 37 (48.7) | ||
| Never smoked | 19 (50.0) | 30 (39.5) | ||
| Not recorded | 0 (0.0) | 1 (1.3) | ||
| Pulmonary disease, n (%) | 0.96b | |||
| Asthma | 3 (7.9) | 6 (7.9) | ||
| COPD/emphysema | 5 (13.2) | 9 (11.8) | ||
| No pulmonary disease | 29 (76.3) | 60 (78.9) | ||
| Not recorded | 1 (2.6) | 1 (1.3) | ||
| NYHA class, n (%) | 0.64b | |||
| I | 5 (13.2) | 17 (22.4) | ||
| II | 18 (47.4) | 36 (47.4) | ||
| III | 10 (26.3) | 17 (22.4) | ||
| IV | 3 (7.9) | 2 (2.6) | ||
| Not recorded | 2 (5.3) | 4 (5.3) | ||
| Heart rhythm, n (%) | 0.32b | |||
| Sinus | 35 (92.1) | 62 (81.6) | ||
| AF | 3 (7.9) | 8 (10.5) | ||
| Others | 0 (0.0) | 3 (3.9) | ||
| Not recorded | 0 (0.0) | 3 (3.9) | ||
| Left ventricular function, n (%) | 0.45b | 0.31 | ||
| Good | 24 (63.2) | 52 (68.4) | ||
| Moderate | 9 (23.7) | 19 (25.0) | ||
| Poor | 5 (13.2) | 4 (5.3) | ||
| EuroSCORE, median (IQR) | 5.00 (3.25, 7.00) | 4.00 (2.00, 6.00) | 0.06a | |
| Logistic EuroSCORE, median (IQR) | 3.74 (2.55, 8.91) | 2.96 (1.70, 6.30) | 0.11a | 0.35 |
AF: atrial fibrillation; BMI: body mass index; COPD: chronic obstructive pulmonary disease, IQR: interquartile range; NYHA: New York Heart Association; SD: standard deviation.
Statistical analysis: Mann–Whitney U-test.
Statistical analysis: chi-square test.
Statistical analysis: unpaired Student’s t-test.
Bold represents a statistically significant P-value <0.05.
Table 3:
Perioperative demographics
| Renal transplant (n = 38) | Matched controls (n = 76) | P-value | Standardized difference | |
|---|---|---|---|---|
| Priority, n (%) | 0.28a | 0.18 | ||
| Elective | 28 (73.7) | 50 (65.8) | ||
| Urgent | 9 (23.7) | 23 (30.3) | ||
| Emergency | 1 (2.6) | 3 (3.9) | ||
| Surgery category, n (%) | 0.76a | 0.43 | ||
| Aorta surgery | 2 (5.3) | 1 (1.3) | ||
| CABG | 17 (44.7) | 49 (64.5) | ||
| CABG + valve | 7 (18.4) | 9 (11.8) | ||
| Major cardiac* | 2 (5.3) | 3 (3.9) | ||
| Valve | 10 (26.3) | 14 (18.4) | ||
| CPB time, median (IQR) | 86.0 (68.0, 114.0) | 89.5 (61.5, 108.8) | 0.81b | |
| Cross-clamp time, median (IQR) | 54.0 (44.0, 79.0) | 51.5 (39.5, 68.0) | 0.42b |
CABG: coronary artery bypass grafting; CPB: cardiopulmonary bypass; IQR: interquartile range.
Statistical analysis: chi-square test.
Statistical analysis: Mann–Whitney U-test.
Major cardiac = atrial septal defect closure or atrial myxoma.
Perioperative complications
Overall, patients with a functioning renal allograft experienced a significantly greater number of complications compared to matched controls (Table 4). In particular, there was a significantly greater incidence of AKI (73.7% vs 38.2%; P < 0.001). In addition to a higher overall rate of patients suffering complications (90.9% vs 66.0%; P < 0.01), renal transplant patients had higher rates of non-respiratory/non-wound infections (21.2% vs 3.8%; P = 0.02), which included urinary tract infections, oral candidiasis and endocarditis.
Table 4:
Postoperative outcomes including incidence of acute kidney injury and other complications in renal transplant patients and in matched controls
| Acute kidney injury, n (%) | Renal transplant (n = 38) | Matched controls (n = 76) | P-value |
|---|---|---|---|
| AKI | 28 (73.7) | 29 (38.2) | <0.001 a |
| Stage 1 | 14 (36.8) | 26 (34.2) | |
| Stage 2 | 2 (5.3) | 0 | |
| Stage 3 | 12 (31.6) | 3 (3.9) | |
| Postoperative complications | Renal transplant (n = 33) | Matched controls (n = 53) | |
| Patients experiencing complications, n (%) | 30 (90.9) | 35 (66.0) | <0.01 b |
| Bleeding, n (%) | |||
| Re-exploration for bleeding | 2 (6.1) | 0 | 0.144a |
| Tamponade without re-exploration | 1 (3.0) | 1 (1.9) | 1.0a |
| Bleeding (others) | 0 | 1 (1.9) | 1.0a |
| Cardiac, n (%) | |||
| Atrial fibrillation | 7 (21.2) | 15 (28.3) | 0.46b |
| Cardiac arrest | 2 (6.1) | 1 (1.9) | 0.56a |
| Required IABP or inotrope support | 2 (6.1) | 2 (3.8) | 0.64a |
| Infections | 12 (36.4) | 14 (26.4) | 0.33b |
| Lower respiratory infection | 6 (18.2) | 9 (17.0) | 0.89b |
| Infections (others)* | 7 (21.2) | 2 (3.8) | 0.02 a |
| Wound infection** | 0 | 3 (5.7) | 0.28a |
| Neurological, n (%) | |||
| Stroke | 2 (6.1) | 0 | 0.14a |
| Seizures | 1 (3.0) | 2 (3.8) | 1.0a |
| DVT, n (%) | 0 | 1 (1.9) | 1.0a |
| Multi-organ failure, n (%) | 1 (3.0) | 0 | 0.38a |
| Redo surgery, n (%) | 1 (3.0) | 1 (1.9) | 1.0a |
AKI stages are defined by applying the serum creatinine criteria as described in [15]. Five renal transplant patients and 23 matched controls did not have recorded postoperative inpatient notes and were thus excluded from the complication analysis.
AKI: acute kidney injury; DVT: deep venous thrombosis; IABP: intra-aortic balloon pump.
Statistical analysis: Fisher’s exact test.
Statistical analysis: chi-square test.
Infections (others) indicate all non-respiratory or wound infections. These include urinary tract infections, oral candidiasis, septicaemia and endocarditis.
Wound infections indicate either sternal or drain site wound infections.
Bold represents a statistically significant P-value <0.05.
Postoperative outcomes and survival
Patient outcomes are summarized in Table 5. Patients undergoing cardiac surgery with a functioning renal allograft experienced a significantly greater length of intensive care unit (ICU) stay (3.2 vs 1.0 days; P < 0.001). This was largely attributed to a significantly greater proportion requiring haemofiltration in the postoperative period (44.7% vs 5.3%; P < 0.001). This also resulted in a significantly prolonged hospital length of stay (10.3 vs 7.2 days; P < 0.001).
Table 5:
Postoperative outcomes compared between renal transplant patients and matched controls
| Outcome | Renal transplant (n = 38) | Matched controls (n = 76) | P-value |
|---|---|---|---|
| ICU length of stay (days), median (IQR) | 3.19 (1.08, 9.35) | 1.02 (0.88, 1.82) | <0.001 a |
| Patients needing haemofiltration, n (%) | 17 (44.7) | 4 (5.3) | <0.001 b |
| Twelve-hour blood loss post-surgery (ml), median (IQR) | 453.4 (212.5, 475.0) | 463.7 (225.0, 625.0) | 0.34a |
| Hospital length of stay (days), median (IQR) | 10.3 (6.18, 15.3) | 7.17 (5.35, 10.3) | 0.03 a |
| In-hospital mortality, n (%) | 6 (15.8) | 1 (1.3) | <0.01 b |
| Survival | <0.001 c | ||
| One-year survival (%) | 78.9 | 96.1 | |
| Five-year survival (%) | 63.2 | 90.8 |
ICU: intensive care unit; IQR: interquartile range.
Statistical analysis: Mann–Whitney U-test.
Statistical analysis: chi-square test.
Statistical analysis: log-rank test Mantel–Cox.
Bold represents a statistically significant P-value <0.05.
Patients with a functioning renal allografted experienced a significantly greater in-hospital mortality (15.8% vs 1.3%; P < 0.01). Furthermore, 1-year survival was significantly inferior (78.9% vs 96.1%; P < 0.001). Longer-term survival on Kaplan–Meier analysis was also significantly inferior (P < 0.001; Fig. 1).
Figure 1:
Kaplan–Meier survival plot of renal transplant patients compared to matched controls post-surgery, along with numbers at risk for both groups at each year post-surgery. Patients with a functioning renal allograft had poorer survival in the long term compared to matched controls.
Patients with a failed renal allograft
Eleven patients had failed allografts at the time of surgery requiring renal replacement therapy, and this subpopulation was excluded from the main analysis. Demographic and outcome details for these 11 patients with a failed renal allograft are summarized in Table 6. These patients had a mean age of 55.4 years. The mean logistic EuroSCORE of this cohort was 6.62. These patients similarly suffered a high incidence of postoperative complications. Two patients (18.2%) died in the postoperative period. One-year survival was only 54.5%.
Table 6:
Demographic details and outcomes of patients excluded from main analysis due to renal allograft failure
| Demographics | Patients with failed allografts (n = 11) |
|---|---|
| Age (years), mean (SD) | 55.4 (14.4) |
| Sex, male, n (%) | 7 (63.6) |
| BMI, mean (SD) | 28.17 (3.41) |
| Hypertension, n (%) | 9 (81.8) |
| Diabetes, n (%) | 5 (45.4) |
| Pulmonary disease, n (%) | 1 (9.1) |
| Smoking, n (%) | |
| Current smoker | 2 (18.2) |
| Ex-smoker | 6 (54.6) |
| Never smoked | 3 (27.3) |
| Renal pathology prior to transplant, n (%) | |
| Alport syndrome | 1 (9.09) |
| Diabetic nephropathy | 2 (18.2) |
| Haemolytic uraemic syndrome | 1 (9.09) |
| Henoch Schoenlein purpura | 1 (9.09) |
| Hypertensive and diabetic nephropathy | 1 (9.09) |
| Obstructive nephropathy | 3 (27.3) |
| Polycystic kidney disease | 1 (9.09) |
| Not recorded | 1 (9.09) |
| Time from latest renal transplant to surgery (months), mean (SD) | 116.9 (85.1) |
| Left ventricular function, n (%) | |
| Good | 7 (63.6) |
| Moderate | 2 (18.2) |
| Poor | 2 (18.2) |
| Preoperative creatinine, mean (SD) | 495.8 (179.9) |
| Preoperative heart rhythm, n (%) | |
| Sinus | 11 (100) |
| Priority, n (%) | |
| Elective | 6 (54.5) |
| Urgent | 3 (27.3) |
| Emergency | 2 (18.2) |
| Surgery category, n (%) | |
| Aorta surgery | 1 (9.09) |
| CABG | 4 (36.4) |
| Major cardiac | 1 (9.09) |
| Valve | 5 (45. 5) |
| EuroSCORE, mean (SD) | 6.09 (2.66) |
| Logistic EuroSCORE, mean (SD) | 6.62 (3.98) |
| Outcomes, n (%) | |
| Patients experiencing complications | 6 (54.5) |
| Atrial fibrillation | 1 (9.1) |
| Cardiac arrest | 1 (9.1) |
| Infections, n (%) | |
| Infection (others)* | 1 (9.1) |
| Wound infection | 1 (9.1) |
| Lower respiratory infection | 2 (18.2) |
| Readmission to theatre, n (%) | |
| Re-exploration for bleeding | 1 (9.1) |
| Reoperation** | 1 (9.1) |
| Multi-organ failure, n (%) | 1 (9.1) |
| In-hospital mortality, n (%) | 2 (18.2) |
| Long-term survival (%) | |
| 1-Year survival | 54.5 |
| 5-Year survival | 45.5 |
BMI: body mass index; CABG: coronary artery bypass grafting; SD: standard deviation.
*Infections (others) indicate all non-respiratory or wound infections. These include urinary tract infections, oral candidiasis, septicaemia and endocarditis.
**Wound infections indicate either sternal or drain site wound infections.
DISCUSSION
In this propensity-matched study, we have been able to demonstrate that patients undergoing cardiac surgery with a functioning renal allograft have inferior outcomes compared to matched control patients. Specifically, they experience a greater incidence of complications, resulting in prolonged ICU and ward lengths of stay and they suffer increased perioperative and longer-term mortality.
The renal transplant and control groups were well matched, despite the former having a higher incidence of hypertension. It is well known that there is a complex relationship between hypertension and renal disease, with the former being both a cause and consequence of the latter. In these patients, it is likely that the hypertension is a result of volume overload due to abnormal sodium homeostasis, systemic vasoconstriction due to activation of the renin–angiotensin–aldosterone system and increased sympathetic activity [17]. Systemic arteriosclerosis also progresses with the severity of chronic kidney disease [18] and may contribute to this hypertension, although it is difficult to quantify the relative contributions of both phenomena (non-arteriosclerotic versus arteriosclerotic). In addition, this finding may be accounted for by prior studies that demonstrate post-transplant patients to be at higher risk of hypertension, which may be attributable to the immunosuppressive agents, tacrolimus and cyclosporine A [19]. A notable difference in outcome between the groups was the incidence of AKI, which was almost double in the renal transplant cohort. It is recognized that non-pulsatile flow during cardiopulmonary bypass (CPB) adversely affects native organs. Specifically relating to the kidneys, AKI can occur in up to 5% of patients undergoing CPB [20]. The mechanisms underlying this increased morbidity are poorly understood, although it is suggested that activation of inflammatory and clotting cascades due to non-physiological flow in the circuit may play a role [6]. In addition, there will be mechanical blood cell trauma attributed to roller pumps in the circuit as well as cell saver suction techniques [4, 6]. There is also evidence of direct damage to renal tubules due to circulating cell fragments, which will be a consequence of the above [21]. The impact of CPB on transplanted organs, however, is poorly represented in the literature. Allografts will already be experiencing some degree of inflammation despite immunosuppression; therefore, it is plausible that an additional inflammatory burden imparted by the CPB circuit may cause a cumulative pro-inflammatory impact on transplanted organs. Here, we show that patients with a functioning renal allograft experience a high incidence of AKI and requiring renal replacement therapy in the postoperative period. To attempt to preserve renal allograft function during and after cardiac surgery, it is suggested that high CPB perfusion pressures and pulsatility are maintained during surgery and this is our practice, but clearly this is insufficient to prevent some renal allograft injury [4].
Immunosuppression regimens may also have an impact on postoperative outcomes and mortality and must be considered as a contributor to the inferior outcomes. We may draw inferences from studies involving cardiac surgery in patients with chronic inflammatory conditions such as rheumatoid arthritis (RA) who may be on long-term immunosuppressive therapy. Patients with RA undergoing cardiac surgery have been shown to experience poorer survival [22]. Specifically, RA patients receiving high dose glucocorticoid therapy are seen to be at an increased risk of poorer outcomes post-surgery [23]. It is worth noting that, in many of these patients, the immunosuppression will have been discontinued prior to surgery unlike in the transplant cohort where the impact on outcomes will likely be even greater. Although inpatient compliance with immunosuppressive therapy was 100% as the medication was administered by healthcare staff, we cannot comment on post-discharge compliance as we did not have access to these data. Thus, the effects of poor compliance to immunosuppressive regimes cannot be excluded as a cause of long-term morbidity and mortality in these patients.
In the short term, in-hospital mortality of our renal transplant patients was higher than matched non-transplant controls (15.8% vs 1.3%, respectively). Although this is a poor outcome compared to the majority of previously published studies that report early or in-hospitality mortality rates ranging from 0% to 7% [3, 7, 8, 10–13], the results from the present study are comparable with 1 recently published pair-matched study that looked at renal and hepatic transplant patients and showed a 30-day mortality rate of 15.7% in these patients [14]. Perhaps this could be due to the fact that patients might have a worse underlying substrate in some studies compared to others; alternatively, publication bias may lead to only favourable series being submitted for publication. Despite this, our study is a sobering reminder that cardiac surgery remains a high-risk endeavour with these complex patients, although we note that the overwhelming majority of published studies show positive results. Thus, there remains scope for future efforts, possibly with the formation of multicentre cohort registries of transplant patients, which will shed light on best practices and risk profiles in these patients.
In the long term, survival of patients after renal transplant is significantly greater than that of patients with end-stage renal failure but remains inferior to the general population, despite significant improvements in short-term graft survival and treatment of rejection [5]. Patients with renal allografts have an increased risk of cardiac death due to myocardial infarction and sudden cardiac death even with a normally functioning graft [24, 25]. Therefore, it is expected that longer-term survival in our renal transplant cohort will be poorer compared to matched controls as was observed. Hence, 1-year survival and 5-year survival are better comparisons between these groups compared to longer-term survival. In the present study, renal transplant patients had a 1-year survival of 78.9% compared to matched controls who had 96.1% survival at 1 year, and 63.2% vs 90.8% at 5 years after surgery. Other studies report 1-year survival ranging from 89% to 93%, and 5-year survival ranging from 50% to 89% in recipients of solid abdominal organs (Table 7), although the data from these studies represent more heterogeneous patient populations both in terms of type of transplanted organ and renal allograft function at the time of surgery. It is also worth noting the very poor 1-year survival for patients with a failed renal allograft undergoing cardiac surgery—54% 1-year survival. Prior studies that try to identify possible predictors of mortality fall short because of variations in sample size, definitions of outcomes and choice of statistical testing. In addition, patient cohorts are heterogenous between studies that make formulating a generalizable score or algorithm difficult [4]. This is also a limitation in the present study.
Table 7:
Results from prior studies that investigated outcomes in solid abdominal organ transplant patients undergoing cardiac surgery
| Reference | Type of transplant | Short-term mortality (%) |
Long-term survival (%) |
Renal allograft function | |||
|---|---|---|---|---|---|---|---|
| In-hospital mortality | 30-Day mortality | 1-Year survival | 5-Year survival | 15-Year survival | |||
| Kohmoto et al. [3] | Renal (n = 82); renal and pancreatic (n = 15); hepatic (n = 18) | – | 4 | – | – | 43 | Only functioning grafts |
| Farag et al. [14] | Renal (n = 49); hepatic (n = 21) | – | 15.7 | – | 66.1 | – | Mixed |
| Vargo et al. [13] | Renal; hepatic; pancreatic | 7 | – | – | – | – | Mixed |
| Sharma et al. [12] | Renal (n = 30); hepatic (n = 6) | 0 | – | – | 80 | – | Mixed |
| Rahmanian et al. [11] | Renal (n = 29) | 3.4 | – | 89 | 50 | – | Mixed |
| John et al. [10] | Renal (n = 58); renal and pancreatic (n = 12) | – | 1.4 | – | – | – | Mixed |
| Deb et al. [9] | Renal (n = 34); hepatic (n = 13) | – | 2 | 93 | 76 | – | Only functioning grafts |
| Ono et al. [8] | Renal (n = 46); hepatic (n = 5); renal and pancreatic (n = 9) | – | 5 | – | 66.8 | – | Mixed |
| Mitruka et al. [7] | Renal (n = 40); hepatic (n = 16); renal and hepatic (n = 1); heart (n = 5); lung (n = 8) | – | 3 | – | 89 | – | Mixed |
Other groups have investigated interventional cardiology approaches to treat coronary artery disease and aortic stenosis through percutaneous coronary intervention (PCI) or transcatheter aortic valve replacement (TAVR) in renal transplant recipients. A 2018 paper by Lang et al. [26] demonstrated reduced incidence of AKI with PCI relative to CABG; however, PCI versus CABG has no impact on 1-year graft survival, in-hospital mortality or 4-year survival. TAVR may also be considered in aortic valve stenosis, and there is limited evidence from observational and retrospective studies showing reduced mortality compared to surgical aortic valve replacement [27, 28]; nevertheless, TAVR is still associated with the significant risk of post-procedure AKI in renal transplant recipients compared to non-transplant controls [29]. Therefore, these may be presented as alternatives to patients when consenting for surgery, although a balanced discussion is required.
Despite this challenging patient population, we suggest a few strategies to manage risk and improve outcomes. Preoperatively, surgical units should liaise early with the renal physicians, which will help optimize allograft function before and after surgery. Intraoperatively, utilizing pulsatile and high-pressure flow in the CPB circuit may have a reno-protective effect [30]. Ultimately, these strategies aim to reduce the incidence of postoperative AKI and, therefore, reduce the need for haemofiltration, which would allow for the early mobilization of patients post-surgery and reduce the risk of complications relating to prolonged stays in ICU.
Limitations and future directions
This work is a retrospective analysis of outcomes from a relatively small number of patients from a single centre, which limits the potential generalizability of the results. Whilst propensity matching affords an opportunity to identify a well-matched control group, there are limitations with this technique. Nevertheless, since all published studies on this topic so far have been case series or retrospective case–control studies, high-quality prospective studies would be beneficial in the future. Perhaps setting up registries of transplant patient cohorts and linking multiple centres would generate useful risk predictions using real-life data.
CONCLUSION
Patients undergoing cardiac surgery with a functioning renal allograft experience inferior outcomes compared with matched controls. In particular, we observed a high incidence of AKI and requirement for renal replacement therapy. They additionally experience greater morbidity in the postoperative period and have inferior short- and longer-term survival. Those with a failed renal allograft are at even more risk of postoperative morbidity and mortality. It is therefore important to recognize that risk scoring systems will significantly underestimate risk in this population and to counsel patients appropriately and approach their post-surgical care with caution.
SUPPLEMENTARY MATERIAL
Supplementary material is available at ICVTS online.
Funding
No funding was used for the purpose of this study.
Conflict of interest: none declared.
Author contributions
Ibrahim T. Fazmin: Data curation; Formal analysis; Investigation; Methodology; Visualization; Writing—original draft; Writing—review and editing. Muhammad U. Rafiq: Conceptualization; Data curation; Supervision; Writing—original draft; Writing—review and editing. Samer Nashef: Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Supervision; Writing—original draft; Writing—review and editing. Jason M. Ali: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Supervision; Validation; Visualization; Writing—original draft; Writing—review and editing.
Reviewer information
Interactive CardioVascular and Thoracic Surgery thanks Ari Mennander and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.
Supplementary Material
ABBREVIATIONS
- AKI
Acute kidney injury
- ICU
Intensive care unit
- PCI
Percutaneous coronary intervention
- RA
Rheumatoid arthritis
- TAVR
Transcatheter aortic valve replacement
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