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Combined heart and kidney transplantation
Combined Heart and Kidney Transplantation M.G. Crespo-Leiro, J.A. Rodriguez, M.J. Paniagua, L.F. Hermida, J.J. Cuenca, A. Juffe´-Stein, F. Go´mez-Veiga, A. Alonso, D. Vilela, and A. Castro-Beiras
I
RREVERSIBLE severe renal dysfunction is a contraindication for heart transplantation (HT) unless HT is accompanied by kidney transplant. Combined heart and kidney transplantation (HKT) has had varying success.1–3 We report here the results of retrospective analyses of the immunosuppressive protocols and outcomes of HKT cases in our center since 1995. PATIENTS AND METHODS Between 1995 and 1998, eight patients, all males, underwent HKT in our institution. Seven, all with end-stage heart and kidney disease and aged between 43 and 67 years (mean 52 years), received the heart and kidney from a single donor in a single operation; the eighth underwent kidney transplant at age 49 years and heart transplant for ischemic cardiopathy 2 years later. In all cases, patients and donors were ABO-compatible but HLA matching was not investigated. Immunosuppressive therapy consisted of induction with OKT3 (mean 4 days) followed by cyclosporine (CyA), prednisone, and either mofetil-micofenolate (seven patients) or azathioprine (one patient, the first operated on in 1995). Routine endomyocardial biopsies were performed every 7 to 10 days during the first 2 months, every 15 to 20 days during the third and fourth months, at the end of months 5, 6, 8, 10, and 12, and upon any suspicion of rejection; biopsy specimens were graded in accordance with the classification of the International Society for Heart and Lung Transplantation Classification.4 Kidney biopsies were performed only upon suspicion of kidney rejection based on decline of renal function. We reviewed the following variables: patient and transplant characteristics, immunosuppressive regimen, and outcome.
RESULTS AND DISCUSSION
The cardiopathy motivating HT was dilated cardiomyopathy in four patients (50%), ischemic cardiomyopathy in three (37.5%), and graft vasculopathy of a previously transplanted heart in one patient (12.5%). The nephropathy motivating kidney transplant was nephroangioesclerosis in two cases (25%), Wegener granulomatosis in one (12.5%), CyA nephrotoxicity in the patient who underwent a second HT (12.5%), and end-stage kidney disease of unknown origin in the remaining four cases (50%). The transplanted hearts were ischemic for between 64 and 280 minutes (mean 162 minutes), and the cold ischemic times of the kidneys ranged from 180 to 480 minutes (mean 353 minutes). At the time of writing this report, the patients
have been followed for between 67 and 1331 days (median 390 days). The survival rate to date is 100%. Two patients contracted pneumonia during the first postoperative month, and there was one case of urinary infection. At the latest check-up, creatinine level was in all cases ⬍1.3 mg/dL. There have been no cases of malignancy, diabetes, or cardiac or renal rejection. All eight patients have normal heart and kidney function and are in NYHA class I. In a multi-institutional study of 82 HKT patients who were followed for 26 ⫾ 24 months, Narula et al1 observed survival rates of 92%, 79%, 76%, and 67% at, respectively, 1, 6, 12, and 24 months posttransplant, and 48% of the patients suffered no organ rejection. The striking difference with respect to the 100% survival and nonrejection rates among our patients may have been due to differences in immunosuppressive regimen; evaluation of this possibility is hampered by the wide variety of protocols used at the centers involved in the Narula study, but it seems possible that our patients may have been more immunosuppressed than the patients of Narula et al. because they all received mofetil-micofenolate and underwent induction with OKT3. A 100% survival rate was also reported by Laufer2 for a group of six HKT patients followed for 33 ⫾ 21 months. It must, of course, be noted that both Laufer’s series and ours are very much smaller than that of Narula et al. Clinical experience and experimental studies have shown that heart rejection rates can be lower following multiorgan transplant than when only the heart is transplanted.5 This appears to be the case when the heart is transplanted together with an organ with higher MHC-related antigenicity. Because MHC class I and class II antigens are, respectively, 14 and 18 times more numerous in the kidney than in the heart,6 the absence of heart rejection episodes among our HKT patients may also be due in part to this effect of the second organ. The absence of kidney rejection episodes (despite patients and donors probably not being matched for HLA) may be due to the immunosuppressive therapy
From the Heart Transplant and Kidney Transplant Program, Hospital Juan Canalejo, La Corun˜a, Spain. Address reprint requests to M.G. Crespo-Leiro, Heart Transplant Program, Hospital Juan Canalejo, Xubias 84, 15006, La Corun˜a, Spain.
© 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/99/$–see front matter PII S0041-1345(99)00441-8
Transplantation Proceedings, 31, 2513–2514 (1999)
2513
2514
having been more intense than is usual for kidney transplant and/or to renal ischemic time having been shorter and kidney damage accordingly less.7,8 Patients requiring a second HT not infrequently suffer simultaneous renal dysfunction induced by the administration of CyA following the first HT and aggravated by low cardiac output. Kidney transplantation in conjunction with second HT has previously been reported by Smith and colleagues.9 Our second HT plus kidney transplant patient, whose heart and kidney came from the same donor, is currently doing well 13 months after HKT. CONCLUSIONS
The eight patients who since 1995 have received both heart and kidney grafts in our center are alive and in good condition and have suffered no heart or kidney rejection episodes. Combined heart and kidney transplant is a viable option for patients with terminal cardiac and renal diseases.
CRESPO-LEIRO, RODRIGUEZ, PANIAGUA ET AL
REFERENCES 1. Narula J, Bennett L, Disalvo T, et al: Transplantation 63:861, 1997 2. Laufer G, Kocher A, Grabenwoger M, et al: Transplantation 64:1120, 1997 3. Seydoux C, Berguer D, Wauters J, et al: Schweiz Med Wochenschr 126:2181, 1996 4. Billingham ME, Cary NR, Hammond ME, et al: J Heart Transplant 9:587, 1990 5. Glanville A, Imoto E, Baldwin J: J Heart Transplant 6:357, 1987 6. Williams K, Hart D, Fabre J, et al: Transplantation 29:274, 1980 7. Goes N, Urmson J, Ramasar V, et al: Transplantation 59:565, 1995 8. Shoskes D, Halloran PF.: Transplant Proc 23:599, 1991 9. Smith J, Rivakove G, Hunt S, et al: J Heart Lung Transplant 14:832, 1995
I
RREVERSIBLE severe renal dysfunction is a contraindication for heart transplantation (HT) unless HT is accompanied by kidney transplant. Combined heart and kidney transplantation (HKT) has had varying success.1–3 We report here the results of retrospective analyses of the immunosuppressive protocols and outcomes of HKT cases in our center since 1995. PATIENTS AND METHODS Between 1995 and 1998, eight patients, all males, underwent HKT in our institution. Seven, all with end-stage heart and kidney disease and aged between 43 and 67 years (mean 52 years), received the heart and kidney from a single donor in a single operation; the eighth underwent kidney transplant at age 49 years and heart transplant for ischemic cardiopathy 2 years later. In all cases, patients and donors were ABO-compatible but HLA matching was not investigated. Immunosuppressive therapy consisted of induction with OKT3 (mean 4 days) followed by cyclosporine (CyA), prednisone, and either mofetil-micofenolate (seven patients) or azathioprine (one patient, the first operated on in 1995). Routine endomyocardial biopsies were performed every 7 to 10 days during the first 2 months, every 15 to 20 days during the third and fourth months, at the end of months 5, 6, 8, 10, and 12, and upon any suspicion of rejection; biopsy specimens were graded in accordance with the classification of the International Society for Heart and Lung Transplantation Classification.4 Kidney biopsies were performed only upon suspicion of kidney rejection based on decline of renal function. We reviewed the following variables: patient and transplant characteristics, immunosuppressive regimen, and outcome.
RESULTS AND DISCUSSION
The cardiopathy motivating HT was dilated cardiomyopathy in four patients (50%), ischemic cardiomyopathy in three (37.5%), and graft vasculopathy of a previously transplanted heart in one patient (12.5%). The nephropathy motivating kidney transplant was nephroangioesclerosis in two cases (25%), Wegener granulomatosis in one (12.5%), CyA nephrotoxicity in the patient who underwent a second HT (12.5%), and end-stage kidney disease of unknown origin in the remaining four cases (50%). The transplanted hearts were ischemic for between 64 and 280 minutes (mean 162 minutes), and the cold ischemic times of the kidneys ranged from 180 to 480 minutes (mean 353 minutes). At the time of writing this report, the patients
have been followed for between 67 and 1331 days (median 390 days). The survival rate to date is 100%. Two patients contracted pneumonia during the first postoperative month, and there was one case of urinary infection. At the latest check-up, creatinine level was in all cases ⬍1.3 mg/dL. There have been no cases of malignancy, diabetes, or cardiac or renal rejection. All eight patients have normal heart and kidney function and are in NYHA class I. In a multi-institutional study of 82 HKT patients who were followed for 26 ⫾ 24 months, Narula et al1 observed survival rates of 92%, 79%, 76%, and 67% at, respectively, 1, 6, 12, and 24 months posttransplant, and 48% of the patients suffered no organ rejection. The striking difference with respect to the 100% survival and nonrejection rates among our patients may have been due to differences in immunosuppressive regimen; evaluation of this possibility is hampered by the wide variety of protocols used at the centers involved in the Narula study, but it seems possible that our patients may have been more immunosuppressed than the patients of Narula et al. because they all received mofetil-micofenolate and underwent induction with OKT3. A 100% survival rate was also reported by Laufer2 for a group of six HKT patients followed for 33 ⫾ 21 months. It must, of course, be noted that both Laufer’s series and ours are very much smaller than that of Narula et al. Clinical experience and experimental studies have shown that heart rejection rates can be lower following multiorgan transplant than when only the heart is transplanted.5 This appears to be the case when the heart is transplanted together with an organ with higher MHC-related antigenicity. Because MHC class I and class II antigens are, respectively, 14 and 18 times more numerous in the kidney than in the heart,6 the absence of heart rejection episodes among our HKT patients may also be due in part to this effect of the second organ. The absence of kidney rejection episodes (despite patients and donors probably not being matched for HLA) may be due to the immunosuppressive therapy
From the Heart Transplant and Kidney Transplant Program, Hospital Juan Canalejo, La Corun˜a, Spain. Address reprint requests to M.G. Crespo-Leiro, Heart Transplant Program, Hospital Juan Canalejo, Xubias 84, 15006, La Corun˜a, Spain.
© 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/99/$–see front matter PII S0041-1345(99)00441-8
Transplantation Proceedings, 31, 2513–2514 (1999)
2513
2514
having been more intense than is usual for kidney transplant and/or to renal ischemic time having been shorter and kidney damage accordingly less.7,8 Patients requiring a second HT not infrequently suffer simultaneous renal dysfunction induced by the administration of CyA following the first HT and aggravated by low cardiac output. Kidney transplantation in conjunction with second HT has previously been reported by Smith and colleagues.9 Our second HT plus kidney transplant patient, whose heart and kidney came from the same donor, is currently doing well 13 months after HKT. CONCLUSIONS
The eight patients who since 1995 have received both heart and kidney grafts in our center are alive and in good condition and have suffered no heart or kidney rejection episodes. Combined heart and kidney transplant is a viable option for patients with terminal cardiac and renal diseases.
CRESPO-LEIRO, RODRIGUEZ, PANIAGUA ET AL
REFERENCES 1. Narula J, Bennett L, Disalvo T, et al: Transplantation 63:861, 1997 2. Laufer G, Kocher A, Grabenwoger M, et al: Transplantation 64:1120, 1997 3. Seydoux C, Berguer D, Wauters J, et al: Schweiz Med Wochenschr 126:2181, 1996 4. Billingham ME, Cary NR, Hammond ME, et al: J Heart Transplant 9:587, 1990 5. Glanville A, Imoto E, Baldwin J: J Heart Transplant 6:357, 1987 6. Williams K, Hart D, Fabre J, et al: Transplantation 29:274, 1980 7. Goes N, Urmson J, Ramasar V, et al: Transplantation 59:565, 1995 8. Shoskes D, Halloran PF.: Transplant Proc 23:599, 1991 9. Smith J, Rivakove G, Hunt S, et al: J Heart Lung Transplant 14:832, 1995