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Combined Heart-Kidney Transplantation: A Review of Recipient Selection and Patient Outcomes

2009; Elsevier BV; Volume: 16; Issue: 4 Linguagem: Inglês

10.1053/j.ackd.2009.05.003

1548-5609

Barbara Labban, Russell J. Crew, David J. Cohen,

Cardiac Structural Anomalies and Repair

Elevated serum creatinine is a common finding among patients awaiting heart transplantation because of reduced renal perfusion in the setting of severe heart failure as well as overlapping risk factors for chronic kidney disease and heart disease. Patients with significant renal dysfunction preoperatively have worse outcomes with heart transplantation alone compared with those with normal renal function or those with renal dysfunction who undergo combined heart-kidney transplantation. Optimizing organ distribution and patient outcomes after cardiac transplantation requires appropriate recipient selection, including deciding which patients will benefit from combined heart-kidney transplantation. This review focuses on the evaluation of patients with chronic kidney disease awaiting heart transplantation and the outcomes of combined heart-kidney transplantation. Elevated serum creatinine is a common finding among patients awaiting heart transplantation because of reduced renal perfusion in the setting of severe heart failure as well as overlapping risk factors for chronic kidney disease and heart disease. Patients with significant renal dysfunction preoperatively have worse outcomes with heart transplantation alone compared with those with normal renal function or those with renal dysfunction who undergo combined heart-kidney transplantation. Optimizing organ distribution and patient outcomes after cardiac transplantation requires appropriate recipient selection, including deciding which patients will benefit from combined heart-kidney transplantation. This review focuses on the evaluation of patients with chronic kidney disease awaiting heart transplantation and the outcomes of combined heart-kidney transplantation. Chronic kidney disease is present among 15% to 25% of patients awaiting heart transplantation.1Odim J. Wheat J. Laks H. et al.Peri-operative renal function and outcome after orthotopic heart transplantation.J Heart Lung Transplant. 2006; 25: 162-166Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 2Ojo A.O. Held P.J. Port F.K. et al.Chronic renal failure after transplantation of a nonrenal organ.N Engl J Med. 2003; 349: 931-940Crossref PubMed Scopus (1860) Google Scholar Virtually all patients who have cardiac dysfunction severe enough to be suitable candidates for heart transplantation will have reduced renal blood flow leading to some degree of compromise in renal function based on hemodynamic factors. Chronic kidney disease, however, may also be caused by irreversible renal parenchymal damage either related to chronic hypoperfusion or to an unrelated primary renal disease. Many of the patients with ischemic heart disease have underlying conditions such as hypertension and diabetes mellitus, which are also risk factors for chronic kidney disease. Chronic kidney disease is well documented to have an adverse impact on outcomes after cardiac transplantation. Not surprisingly, reduced renal function pretransplantation is a predictor of poor kidney function after transplantation. Elevated serum creatinine and, in particular, the need for dialysis pretransplant is associated with increased early and long-term mortality.3Cipullo R. Finger M.A. Ponce F. et al.Renal failure as a determinant of mortality after cardiac transplantation.Transplant Proc. 2004; 36: 989-990Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 4Hendawy A. Pouteil-Noble C. Villar E. et al.Chronic renal failure and end-stage renal disease are associated with a high rate of mortality after heart transplantation.Transplant Proc. 2005; 37: 1352-1354Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 5Ostermann M.E. Rogers C.A. Saeed I. et al.Pre-existing renal failure doubles 30-day mortality after heart transplantation.J Heart Lung Transplant. 2004; 23: 1231-1237Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Furthermore, renal dysfunction after heart transplantation is associated with increased mortality and graft loss.1Odim J. Wheat J. Laks H. et al.Peri-operative renal function and outcome after orthotopic heart transplantation.J Heart Lung Transplant. 2006; 25: 162-166Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 6Kobashigawa J.A. Starling R.C. Mehra M.R. et al.Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.J Heart Lung Transplant. 2006; 25: 1063-1069Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 7Senechal M. Dorent R. du Montcel S.T. et al.End-stage renal failure and cardiac mortality after heart transplantation.Clin Transplant. 2004; 18: 1-6Crossref PubMed Scopus (31) Google Scholar Thus, optimizing outcomes involves optimizing kidney function. This requires accurately ascertaining the level of renal function, distinguishing patients with reversible kidney disease from those patients with irreversible renal failure significant enough to compromise transplantation outcomes, and providing those patients with dual-organ transplants. Given the inadequate deceased donor organ supply, this decision is of paramount importance: not impairing heart transplant outcomes in patients who would do better with combined organs and not wasting kidneys in heart transplant recipients who do not need them. This article reviews demographics, patient assessment, indications, outcomes, and management of simultaneous heart-kidney transplantation (HKT). Heart transplantation is the third most common solid organ transplant performed in the United States behind kidney and liver transplants. Annually between 1,700 and 2,200 individuals receive solitary heart transplants. In 1988, 3 cases of combined HKTs were performed in contrast to 1,673 cases of heart transplant alone. In 2008, 53 combined HKTs and 1,748 isolated heart transplants were performed in the United States. There were 2,754 patients on the waiting list for heart transplantation and 105 for HKT in 2008 (Figure 1, Figure 2).Figure 2The numbers of waitlist additions from January 1988 and October 2008 (UNOS data).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Selecting patients who will benefit from combined HKT versus heart transplantation alone is often difficult. This decision is based on the assessment of the degree of renal dysfunction and the amount of reversible kidney function after correction of heart failure (ie, distinguishing potentially reversible renal hypoperfusion from irreversible intrinsic kidney disease). Currently, there are no nationally accepted criteria to identify patients for combined HKT. Patients without significant intrinsic renal disease are likely to recover adequate renal function after heart transplant alone. The past medical history and prior laboratory results are important in determining the likelihood of intrinsic disease, particularly in patients with acute cardiac decompensation. Recent normal serum creatinine levels suggest that renal function will recover once renal blood flow is improved after transplantation, whereas prolonged prior elevations in serum creatinine suggest, but do not prove, irreversibility. Proteinuria and/or hematuria suggest intrinsic renal parenchymal disease. Accurate measurement of renal function may itself be problematic. Serum creatinine levels that are normal or only mildly elevated may be misleading, particularly in patients with severe congestive heart failure, many of whom are malnourished and have experienced significant muscle wasting. In 1 study, formulae that estimate renal function and 24-hour urine creatinine clearance were tested for accuracy compared with isotopically measured glomerular filtration rate (GFR) in heart failure patients.8Smilde T.D.J. van Veldhuisen D.J. Navis G. et al.Drawbacks and prognostic value of formulas estimating renal function in patients with chronic heart failure and systolic dysfunction.Circulation. 2006; 114: 1572-1580Crossref PubMed Scopus (269) Google Scholar In this study, the Cockroft-Gault and Modification of Diet in Renal Disease (MDRD) equations as well as 24-hour urine creatinine clearance, overestimated renal function at low GFR, and underestimated renal function at high GFR. The predictive performance of the formulae was best in severe congestive heart failure (New York Heart Association classes III and IV). Small or severely echogenic kidneys on ultrasound usually indicate chronic disease. However, normal sonographic appearance of the kidneys does not exclude pathology. Screening for renal artery stenosis (RAS) is reasonable in patients with ischemic heart disease and a history of hypertension. Studies using screening abdominal aortography at the time of coronary angiography have detected RAS of 50% or greater in between 5% and 20% of patients.9White C.J. Jaff M.R. Haskal Z.J. et al.Indications for renal arteriography at the time of coronary arteriography: A Science Advisory From the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease.Circulation. 2006; 114: 1892-1895Crossref PubMed Scopus (93) Google Scholar Song and others10Song H.Y. Hwang J.H. Noh H. et al.The prevalence and associated risk factors of renal artery stenosis in patients undergoing cardiac catheterization.Yonsei Med J. 2000; 41: 219-225PubMed Google Scholar detected significant (≥50% diameter narrowing) RAS in 24 of 427 patients (5.6%) and insignificant stenosis in 21 patients (4.9%) undergoing routine cardiac catheterization. Uzu and colleagues11Uzu T. Inoue T. Fujii T. et al.Prevalence and predictors of renal artery stenosis in patients with myocardial infarction.Am J Kidney Dis. 1997; 29: 733-738Abstract Full Text PDF PubMed Scopus (103) Google Scholar found that the prevalence of RAS in patients who died from myocardial infarction was 12%. The frequency of RAS appears to be substantially less in those who undergo heart transplantation. Bolad and associates12Bolad I.A. Breen J. Rogers P. et al.Prevalence and significance of renal artery stenosis and abdominal aortic atherosclerosis early after heart transplantation.Transplant Proc. 2002; 34: 3236-3238Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar collected data on screening aortography at a single center on 108 heart recipients transplanted between June 1996 and December 1999. The study population consisted of 77% of the total number of patients transplanted during that time period, having excluded those who suffered early postoperative death and those who refused to give consent to the study. The prevalence of RAS was 5.6% (6/108 patients) but was only considered significant in 1 patient. All screening aortograms were performed within 1 year of the transplant, making de novo disease posttransplant unlikely. The etiologies of heart failure in these patients were as follows: 55 patients (51%) had ischemic cardiomyopathy, 32 (29%) had idiopathic cardiomyopathy, congenital heart disease in 6 patients (6%), and other causes in 15 (14%). It is possible that the low rate of renal artery stenosis in this posttransplant population is related to selection bias because patients with renal dysfunction related to renal arterial disease or those with significant peripheral vascular disease may have been excluded from transplantation or for aortography because of concern for contrast toxicity. Despite thorough noninvasive testing, the etiology of renal dysfunction and the degree of reversibility will remain unclear in many patients. In this group, a renal biopsy may help in identifying patients who have significant renal pathology and therefore would be better served by combined HKT. Our experience at Columbia University Medical Center includes 29 patients who underwent renal biopsy before heart transplantation for an estimated GFR (eGFR) 500 mg/d proteinuria or history of amyloidosis. Based on the biopsy findings, 9 patients were cleared to have heart transplant alone and 8 patients to undergo combined HKT. The rest of the patients were not listed mainly because of other comorbidities. Eight of the 9 patients listed for heart transplant alone underwent transplantation; the last patient was delisted because of worsening overall medical condition. None of the patients who underwent heart transplant alone required postoperative dialysis. One patient with amyloidosis caused by transthyretin mutation received combined liver and kidney transplant 1 year after the heart transplant because of progressive chronic kidney disease related to recurrent urinary tract infections and cyclosporine nephrotoxicity. The other 7 patients had a mean eGFR of 47 mL/min (range, 35-79 mL/min) 3 months after transplant. Of the 8 patients listed for HKT, 2 patients were transplanted and are doing well, 2 patients died while on the waiting list, and 2 remain on the waiting list. The remaining 2 patients were too hemodynamically unstable immediately after heart transplant to proceed with renal transplantation. One patient subsequently received a successful living donor renal transplant. The other patient was initiated on dialysis 1 month before receiving the heart transplant. He remained dialysis dependent posttransplant, and he died 2 years later of humoral rejection. The following pathologic findings were noted: 8 of the 29 patients had ischemic nephropathy, 4 had focal global glomerulosclerosis, 6 patients had diabetic glomerulosclerosis, and 2 patients had hypertensive nephrosclerosis. The findings for the remaining 9 patients were as follows: renal atheroembolic disease, obesity and hypertension-associated focal segmental glomerulosclerosis, membranous glomerulopathy, cyclosporine nephrotoxicity, fibrillary glomerulonephritis, diffuse global glomerulosclerosis secondary to tacrolimus, amyloid light chain (AL) vascular amyloidosis, amyloid associated (AA) amyloidosis in glomeruli and vessels, and 1 patient had a combination of ischemic nephropathy with vascular amyloidosis. There was no correlation between creatinine level or eGFR at the time of evaluation for transplant and the TA/IF (tubular atrophy/interstitial fibrosis) found on biopsy for all of the patients. There is no consensus on what level of renal function precludes heart transplantation alone. In 2006, the International Society of Heart and Lung Transplantation Guidelines for the care of cardiac transplant candidates considered the presence of irreversible renal dysfunction reflected by eGFR of 3 mg/dL was a relative contraindication to transplantation.14Miller L.W. Listing criteria for cardiac transplantation: Results of an American Society of Transplant Physicians–National Institutes of Health Conference.Transplantation. 1998; 66: 947-951Crossref PubMed Scopus (64) Google Scholar Preoperative renal dysfunction (eGFR 19,000 heart transplant recipients from 1995 to 2005. Using serum creatinine values at the time of listing for heart transplantation, they found that an eGFR <33 mL/min served as the threshold for worse outcomes after heart transplantation alone. To further refine recipient selection, they created a risk score based on pretransplant characteristics of patients with an eGFR <33 mL/min to identify which subset of patients in this group benefits from combined organ transplantation. They used regression analysis to identify clinical predictors of transplant survival and to assign weights to each risk factor according to the relative risks calculated. The preoperative factors that significantly impacted outcomes included a history of peripheral vascular disease with a weight of 4, recipient age older than 65 years and assigned a weight of 3.5, dialysis dependence at the time of transplantation with a weight of 2.5, nonischemic etiology of heart failure with a weight of 2, and bridge to transplantation using a ventricular assist device assigned a weight of 2 as well. The weights were rounded off. The risk score was the total of the weights of the individual risk factors present and was used to categorize the patients as low risk (total risk score of less than 4), medium risk (score of 4 to 6), and high risk (score of 7 or higher). They found that only low-risk patients and an eGFR of less than 33 mL/min gained a survival benefit from HKT. There was a trend toward better survival in the moderate-risk group, but the difference was not significant and there was no survival benefit in the high-risk group. There was no benefit for HKT in patients with eGFR of more than 33 mL/min irrespective of their risk score (Fig 3). They concluded that the use of the eGFR and their risk profile can guide the allocation of heart and kidney organs. This would achieve the maximal benefit from transplantation given the scarcity of donor organs.17Russo M.J. Rana A. Chen J.M. et al.Pretransplantation patient characteristics and survival following combined heart and kidney transplantation.Arch Surg. 2009; 144: 241-246Crossref PubMed Scopus (59) Google Scholar From the nephrologic perspective, the immediate postoperative management of combined HKTs is similar to solitary heart transplant recipients with acute kidney injury (AKI). The main therapeutic goals in the immediate postoperative period are: (1) to maximize renal perfusion, (2) to limit nephrotoxins, and (3) to provide appropriate immunosuppression. Improving renal perfusion requires coordinating inotrope use, vasopressor use, and fluid balance. A Swan-Ganz catheter is essential to measure the intracardiac pressures and cardiac output and hence differentiate the etiology of hypoperfusion. Diagnosing right ventricular failure is particularly important because this accounts for 50% of cardiac complications and is a frequent cause of early death.18Bacal F. Vieira Pires P. Moreira L.F. et al.Normalization of right ventricular performance and remodeling evaluated by magnetic resonance imaging at late follow-up of heart transplantation: Relationship between function, exercise capacity and pulmonary vascular resistance.J Heart Lung Transplant. 2005; 24: 2031-2036Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar The use of inhaled nitric oxide, inhaled prostacyclin iloprost (Ventavis, Actelion Pharmaceuticals US, Inc., South San Francisco, CA), intravenous prostaglandins, and milrinone may help by reducing the pulmonary vascular resistance.19Von Scheidt W. Costard-Jaeckle A. Stempfle H.U. et al.Prostaglandin E1 testing in heart failure-associated pulmonary hypertension enables transplantation: The PROPHET Study.J Heart Lung Transplant. 2006; 25: 1070-1076Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar In these cases, maintaining a negative fluid balance is frequently essential to decrease right-heart pressures and may require the initiation of continuous venovenous hemodiafiltration in patients with inadequate diuresis from the renal allograft. Limiting nephrotoxins may be a challenge because complicated patients may require imaging studies with intravenous contrast or nephrotoxic antibiotics in the setting of increasingly resistant hospital acquired infections. Finding alternative imaging strategies and using careful antibiotic dosing with close following of blood levels becomes paramount. Most studies show a significant increase in early mortality in patients requiring renal replacement therapy immediately after heart transplantation.5Ostermann M.E. Rogers C.A. Saeed I. et al.Pre-existing renal failure doubles 30-day mortality after heart transplantation.J Heart Lung Transplant. 2004; 23: 1231-1237Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 20Canver C.C. Heisey D.M. Nichols R.D. Acute renal failure requiring hemodialysis immediately after heart transplantation portends a poor outcome.J Cardiovasc Surg (Torino). 2000; 41: 203-206PubMed Google Scholar, 21De Maria R. Minoli L. Parolini M. et al.Prognostic determinants of six-month morbidity and mortality in heart transplant recipients. The Italian Study Group on Infection in Heart Transplantation.J Heart Lung Transplant. 1996; 15: 124-135PubMed Google Scholar, 22Ouseph R. Brier M.E. Jacobs A.A. et al.Continuous venovenous hemofiltration and hemodialysis after orthotopic heart transplantation.Am J Kidney Dis. 1998; 32: 290-294Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar The increased mortality appears to be mostly from the increased risk of infections.23Zuckermann A.O. Ofner P. Holzinger C. et al.Pre- and early postoperative risk factors for death after cardiac transplantation: A single center analysis.Transpl Int. 2000; 13: 28-34Crossref PubMed Scopus (32) Google Scholar This may be related to the need for central venous catheters for dialysis access as well as the added immunosuppressive effect of uremia on an immune system that is already undergoing intense immunosuppression. Despite the increased risk of early death, those patients who required dialysis perioperatively and survived the first month have similar 5-year survival rates as patients without perioperative renal failure.23Zuckermann A.O. Ofner P. Holzinger C. et al.Pre- and early postoperative risk factors for death after cardiac transplantation: A single center analysis.Transpl Int. 2000; 13: 28-34Crossref PubMed Scopus (32) Google Scholar The use of induction therapy is controversial in heart transplant alone but is used in the majority of kidney transplant recipients.24Sulemanjee N. Merla R. Lick S. et al.The first year post-heart transplantation: Use of immunosuppressive drugs and early complications.J Cardiovasc Pharmacol Ther. 2008; 13: 13-31Crossref PubMed Scopus (7) Google Scholar In the setting of renal failure, modification of the immunosuppressive regimen should be considered. This could consist of using antibody induction therapy, allowing the delayed initiation of a calcineurin inhibitor (CNI) including cyclosporine or tacrolimus.25Delgado D.H. Miriuka S.G. Cusimano R.J. et al.Use of basiliximab and cyclosporine in heart transplant patients with pre-operative renal dysfunction.J Heart Lung Transplant. 2005; 24: 166-169Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar Although it would seem intuitive that a CNI, which is known to be nephrotoxic, should be minimized or avoided in the setting of acute renal failure, data from randomized trials in kidney transplantation suggest that early CNI use causes little delay in renal recovery.26Kamar N. Garrigue V. Karras A. et al.Impact of early or delayed cyclosporine on delayed graft function in renal transplant recipients: A randomized, multicenter study.Am J Transplant. 2006; 6: 1042-1048Crossref PubMed Scopus (63) Google Scholar, 27Kasiske B.L. Johnson H.J. Goerdt P.J. et al.A randomized trial comparing cyclosporine induction with sequential therapy in renal transplant recipients.Am J Kidney Dis. 1997; 30: 639-645Abstract Full Text PDF PubMed Scopus (20) Google Scholar In patients with prolonged AKI, the added infectious risk and hematologic complications of antithymocyte sera must be balanced against the potential for prolonging the duration of AKI with early CNI initiation. Sirolimus (Rapamune, Wyeth Pharmaceuticals, Philadelphia, PA), a target of rapamycin (TOR) inhibitor does not share the same nephrotoxic effect of CNIs. It has been used successfully in heart transplant patients with chronic kidney disease as a replacement to CNI and has been tried as primary immunosuppression immediately after heart transplantation.28Vazquez de Prada J.A. Vilchez F.G. Cobo M. et al.Sirolimus in de novo heart transplant recipients with severe renal impairment.Transpl Int. 2006; 19: 245-248Crossref PubMed Scopus (11) Google Scholar Higher rates of rejection, however, have been observed with a CNI-free regimen based on the use of sirolimus in the early postoperative period. The Heart Save the Nephron clinical trial had to be terminated prematurely when 4 of 7 patients randomized to sirolimus experienced a grade IIIA rejection episode.29Hunt J. Bedanova H. Starling R.C. et al.Premature termination of a prospective, open label, randomized, multicenter study of sirolimus to replace calcineurin inhibitors (CNI) in a standard care regimen of CNI, MMF and corticosteroids early after heart transplantation.J Heart Lung Transplant. 2007; 26: 398Google Scholar In another study, this regimen led to the restoration of renal function in patients with significant pretransplant renal failure but was also associated with a higher rate of rejection.30Gonzalez-Vilchez F. Vasquez de Prada J.A. Exposito V. et al.Avoidance of calcineurin inhibitors with use of proliferation signal inhibitors in de novo heart transplantation with renal failure.J Heart Lung Transplant. 2008; 27: 1135-1141Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Experience from kidney transplantation though suggests that sirolimus, because of its potent antiproliferative effect, may prolong recovery from AKI as well as impair wound healing.31Stallone G. Di Paolo S. Schena A. et al.Addition of sirolimus to cyclosporine delays the recovery from delayed graft function but does not affect 1-year graft function.J Am Soc Nephrol. 2004; 15: 228-233Crossref PubMed Scopus (77) Google Scholar There are several single-center studies reporting outcomes of small numbers of combined HKTs. The largest is from the University of Wisconsin, where 19 patients underwent HKT between 1987 and 2006. Hermsen and colleagues32Hermsen J.L. Nath D.S. Del Rio A.M. et al.Combined heart-kidney transplantation: The University of Wisconsin experience.J Heart Lung Transplant. 2007; 26: 1119-1126Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar found no difference in 1- and 5- year patient survival between recipients of HKTs (89.5% and 82%, respectively) and heart transplants alone (88.3% and 74.9%, respectively). Reasons for death in HKT patients included sepsis in 2 patients, squamous cell lung cancer in 1 patient, cardiac amyloidosis in 1 patient, and 1 patient had a prolonged postoperative course complicated by multiple infectious problems. Leeser and associates33Leeser D.B. Jeevanandam V. Furukawa S. et al.Simultaneous heart and kidney transplantation in patients with end-stage heart and renal failure.Am J Transplant. 2001; 1: 89-92Crossref PubMed Scopus (32) Google Scholar reported 13 heart-kidney recipients between 1990 and 1999 at Temple University Hospital. Kaplan-Meier survival rates for heart kidney transplant recipients in this series were 77% ± 12% at 1 year and 60% ± 14% at 2 and 5 years. Blacks were more likely to have worse outcome. Notably, there was significant in-hospital mortality (21%), primarily because of sepsis. Blanche and others34Blanche C. Kamlot A. Blanche D.A. et al.Combined heart-kidney transplantation with single-donor allografts.J Thorac Cardiovasc Surg. 2001; 122: 495-500Abstract Full Text PDF PubMed Scopus (48) Google Scholar reported 10 heart-kidney recipients transplanted at Cedars Sinai Medical Center. Survival rates were 100%, 88%, and 55% at 1, 2, and 5 years, respectively, compared with 169 patients who underwent heart transplantation alone whose survival rates were 92%, 84%, and 71%. Bruschi and colleagues35Bruschi G. Busnach G. Colombo T. et al.Long-term follow-up of simultaneous heart and kidney transplantation with single donor allografts: Report of nine cases.Ann Thorac Surg. 2007; 84: 522-527Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar reported on 9 HKTs performed between 1989 and 2006, with patient survival rates of 88.9% at 1 year and 77.8 % at 5 years. Four patients died of multiorgan failure postoperatively, 1 patient of lung cancer, 1 patient of cerebral stroke, and 1 patient of infection (Table 1).Table 1Single Center Outcomes for Combined Heart Kidney TransplantationStudyType of TransplantNo. of Patients1-Year Survival (%)5-Year Survival (%)P ValueHermsen et al32Hermsen J.L. Nath D.S. Del Rio A.M. et al.Combined heart-kidney transplantation: The University of Wisconsin experience.J Heart Lung Transplant. 2007; 26: 1119-1126Abstract Full Text Full Text PDF PubMed Scopus (37) Google ScholarHKT1989.582NSOHT51588.374.9Leeser et al33Leeser D.B. Jeevanandam V. Furukawa S. et al.Simultaneous heart and kidney transplantation in patients with end-stage heart and renal failure.Am J Transplant. 2001; 1: 89-92Crossref PubMed Scopus (32) Google ScholarHKT1377∗Kaplan-Meier survival rates.60∗Kaplan-Meier survival rates.NSOHT60080∗Kaplan-Meier survival rates.67∗Kaplan-Meier survival rates.Blanche et al34Blanche C. Kamlot A. Blanche D.A. et al.Combined heart-kidney transplantation with single-donor allografts.J Thorac Cardiovasc Surg. 2001; 122: 495-500Abstract Full Text PDF PubMed Scopus (48) Google ScholarHKT1010055NSOHT1699271Brushi et al35Bruschi G. Busnach G. Colombo T. et al.Long-term follow-up of simultaneous heart and kidney transplantation with single donor allografts: Report of nine cases.Ann Thorac Surg. 2007; 84: 522-527Abstract Full Text Full Text PDF PubMed Scopus (26) Google ScholarHKT988.977.8NSOHT7118778OHT = orthotopic heart transplant alone; NS = not significant.∗ Kaplan-Meier survival rates. Open table in a new tab OHT = orthotopic heart transplant alone; NS = not significant. Based on the Organ Procurement and Transplantation Network data as of January 21, 2009, patients who underwent combined HKTs between 2002 and 2007 had survival rates of 87.92% and 78.77 % at 1 and 5 years, respectively. Infections, specifically bacterial septicemia, followed by cardiovascular disease accounted for most of the causes of death among the reported cases. Patients who received heart transplants alone had a similar 1-year survival of 87.74%, but the 5-year survival was 73.11%. However, in this group, cardiovascular complications including graft failure from acute rejection and cardiac arrest were more common than infections. Kidney allograft survival rates were 86.08% and 72.92% at 1 and 5 years, respectively, compared with 91.98% and 72.60% in patients who received kidney transplants alone. Hermsen and others32Hermsen J.L. Nath D.S. Del Rio A.M. et al.Combined heart-kidney transplantation: The University of Wisconsin experience.J Heart Lung Transplant. 2007; 26: 1119-1126Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar determined that the time to the first heart graft rejection was significantly prolonged for heart-kidney recipients compared with heart-alone recipients. Similarly, rejection-free survival time for the kidney grafts was also significantly prolonged when compared with recipients of deceased donor kidneys. In the series published by Narula and associates,15Narula J. Bennett L. DiSalvo T. et al.Outcomes in survival of combined heart-kidney transplantation: Multiorgan, same-donor transplant study of the International Society of Heart and Lung Transplantation/United Network for Organ Sharing Scientific Registry.Transplantation. 1997; 63: 861-867Crossref PubMed Scopus (114) Google Scholar combined transplants had a lower incidence of treated cardiac allograft rejection. A recent analysis of data from the UNOS of patients transplanted between January 1, 1994, and October 6, 2005, showed that heart, liver, and kidney allografts are themselves protected from rejection and protect the other organ when transplanted simultaneously. Among the cardiac allograft recipients, combined heart-kidney allograft recipients experienced cardiac rejection episodes at 1 year only half as often as those who received cardiac transplant alone (26% v 52%, P < .001). Among kidney allograft recipients, combined kidney-heart and kidney-liver allograft recipients had significantly reduced 1-year incidence of renal allograft rejection compared with kidney allograft alone (17% and 15%, respectively, v 24%, P = .032 and P < .001). This effect was also present in interval transplants (from 2 different donors) of heart and kidney when the sequential allografts shared 1 or more HLA- matched antigen.36Rana A. Robles S. Russo M.J. et al.The combined organ effect: Protection against rejection?.Ann Surg. 2008; 248: 871-879Crossref PubMed Scopus (100) Google Scholar Various hypotheses have been proposed to explain the protective effect of 1 organ on another in combined transplants including closer follow-up in recipients of dual-organ transplants; different regimens of immunosuppression; higher degrees of microchimerism, defined as the presence and persistence of passenger donor leukocytes in the peripheral blood of the host leading to induction of tolerance37Starzl T.E. Demetris A.J. Murase N. et al.Chimerism after organ transplantation. 1997; 6: 292-298Google Scholar, 38Perico N. Remuzzi G. Acquired transplant tolerance.Int J Clin Lab Res. 1997; 27: 165-177Crossref PubMed Google Scholar, 39Schlitt H.J. Hundrieser J. Ringe B. et al.Donor-type microchimerism associated with graft rejection eight years after liver transplantation.N Engl J Med. 1994; 30: 646-647Crossref Scopus (128) Google Scholar, 40Löffeler S. Meyer D. Otto C. et al.Different kinetics of donor cell populations after isolated liver and combined liver/small bowel transplantation.Transpl Int. 2000; 13: S537-S540Crossref PubMed Scopus (12) Google Scholar; enhanced induction of regulatory/suppressor T cells; high antigen loads leading to immune paralysis15Narula J. Bennett L. DiSalvo T. et al.Outcomes in survival of combined heart-kidney transplantation: Multiorgan, same-donor transplant study of the International Society of Heart and Lung Transplantation/United Network for Organ Sharing Scientific Registry.Transplantation. 1997; 63: 861-867Crossref PubMed Scopus (114) Google Scholar; and immune diversion in which 1 organ diverts the immune attack from the second organ. Little if any experimental evidence exists to lend support to any of these theories. The need for a crossmatch pretransplant could explain some of the benefit in survival of heart or liver transplants of combined organs but would not explain the reduced rejection rates of renal allograft in this setting. Despite the benefits associated with combined heart and kidney transplantations in patients with low GFR, there are complicating features. Renal transplantation requires a crossmatch (a test for preformed antidonor antibodies in the serum of the potential recipient) before surgery. The additional time needed to complete the crossmatch limits the acceptable geographic area from which the donor organs can be retrieved. Also, patients after cardiac surgery may be too unstable to safely proceed with the renal transplant (although this can usually be delayed without problem for 24 to 48 hours if necessary). Acute renal failure requiring dialysis occurs in 5% to 15% of patients after heart transplantation alone.6Kobashigawa J.A. Starling R.C. Mehra M.R. et al.Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.J Heart Lung Transplant. 2006; 25: 1063-1069Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 20Canver C.C. Heisey D.M. Nichols R.D. Acute renal failure requiring hemodialysis immediately after heart transplantation portends a poor outcome.J Cardiovasc Surg (Torino). 2000; 41: 203-206PubMed Google Scholar, 22Ouseph R. Brier M.E. Jacobs A.A. et al.Continuous venovenous hemofiltration and hemodialysis after orthotopic heart transplantation.Am J Kidney Dis. 1998; 32: 290-294Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 41Stevens L.M. el Hamamsy I. Leblanc M. et al.Continuous renal replacement therapy after heart transplantation.Can J Cardiol. 2004; 20: 619-623PubMed Google Scholar Hypotension and the frequent need for pressor and inotrope support after heart transplantation may increase the risk of tubular injury in a transplanted kidney. Ischemia remains one of the most frequent causes of postoperative acute kidney injury. Prerenal azotemia from hypoperfusion is also common immediately after transplantation. It can occur as a result of left ventricular failure caused by donor organ dysfunction, cardiac tamponade, hypovolemia because of bleeding, and right ventricular failure in the setting of elevated pulmonary vascular resistance and central venous pressures. Temporary vasopressin deficiency after cardiopulmonary bypass, sepsis, and drug reaction in the case of some induction therapies (cytokine release syndrome with depleting antibody induction) can all cause vasodilatory shock and hypoperfusion. The hemodynamic effects of CNI may also contribute to the incidence of AKI. Other causes of AKI postoperatively include rhabdomyolysis, thrombotic microangiopathy because of CNI, osmotic nephrosis because of starch containing oncotic fluids used during resuscitation, obstruction because of a malfunctioning Foley catheter in the bladder, and other drug toxicities. Based on Organ Procurement and Transplantation Network data as of April 3, 2009, delayed graft function rates for recipients with a cold ischemia time less than 24 hours was 17% for kidney transplant alone compared to 25% for recipients of HKTs. As for other complications after transplantation, including recipients from January 1, 1989, to December 31, 2007, 40% of HKT recipients were hospitalized for an infectious complication within the first year of transplantation versus 36% for heart transplant recipients alone. Additionally, 14.7% of heart-kidney recipients were diagnosed with malignancy compared with 17.4% of heart recipients and 5.6% of recipients of kidney transplant alone. Chronic kidney disease constitutes a major clinical challenge in the care of heart transplant candidates and recipients. Reduced cardiac output associated with end-stage heart failure frequently leads to chronic kidney disease because of poor renal perfusion, which if severe or prolonged enough can lead to irreversible renal injury. Differentiating reversible kidney disease from intrinsic parenchymal damage is crucial in determining who will benefit from heart transplantation alone versus HKT. With the use of nephrotoxic immunosuppressive medications and because long-term survival rates after heart transplant continue to improve, increasing numbers of patients with intrinsic kidney disease will likely reach end-stage renal failure. Those patients with fixed GFR <40 mL/min may benefit from combined HKT. For those patients currently selected to receive combined HKT, outcomes are excellent, with no compromise in the survival of either organ. Increased understanding of the factors leading to irreversible renal damage in those on the waiting list is essential in the management of these patients and will hopefully minimize the number of patients experiencing progressive chronic kidney disease.