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Graft Survival in Patients With Polycystic Kidney Disease With Nephrectomy of Native Kidney Pretransplant
Graft Survival in Patients With Polycystic Kidney Disease With Nephrectomy of Native Kidney Pretransplant J.H. García-Rubio*, J. Carrasco Valiente, J.P. Campos Hernández, J. Ruiz García, J. Márquez López, J.C. Regueiro López, R. Cano Castiñeira, M.V. Pendón Ruiz de Mier, and M.J. Requena Tapia Hospital Universitario Reina Sofía, Avenida Menendez Pidal s/n, Córdoba, Spain
ABSTRACT Introduction. Autosomal-dominant polycystic disease (ADPKD) represents 5%e10% of cases of end-stage renal failure. However, management of these patients in terms of whether or not to perform a transplant and optimal timing remains controversial. The objective of our analysis was to evaluate graft survival in patients with ADPKD in which we conduct pretransplant nephrectomy. Methods. This retrospective study including renal transplant patients secondary to ADPKD in our hospital between January 2000 and December 2012. Pretransplant native kidney nephrectomy was indicated in cases of need for space or repeated complications (cysts). We compared the initial function and graft survival between groups of transplanted based on whether nephrectomy had been performed or not. Results. Eighty-seven patients underwent a kidney transplant owing to ADPKD; 62% (n ¼ 54) were male, with an average age of 55.22 years. Twenty-seven patients (30%) underwent nephrectomy native kidneys before transplantation. There were no serious postoperative complications. Patients who underwent nephrectomy (group 1) showed values of creatinine of 1.57 and 1.50 mg/dL at 3 and 6 months, respectively. In the no nephrectomy group, these values were 2.03 and 1.83 mg/dL, respectively. Graft survival after the first year was of 98% for group 1 and 95% for group 2. The 5-year implant survival was 95% and 80%, respectively. Conclusions. Native kidney nephrectomy before transplantation in ADPKD is safe in an experienced center, both in terms of surgery-related morbidity and mortality and graft survival and function.
A
UTOSOMAL-DOMINANT polycystic kidney disease (ADPKD) is a monogenic, multisystem illness. It is characterized by the development of cysts in both kidneys, along with other abnormalities in other organs, such as the liver, heart, or digestive system [1,2]. It has a prevalence between 0.1% and 0.25%, and is responsible for 10% the cases of end-stage renal failure. Among these patients, 17% are 29e39 years old, present with cysts, a figure that increases to a 75% for ages 70 [3]. Globally, 50% of individuals with ADPKD develop endstage renal failure [4]. Only 20% of patients suffering from ADPKD require nephrectomy [5]. Cyst-related complications and space concerns for implantation are the main reasons to consider nephrectomy. It has been argued that, globally, the risk of performing the nephrectomy is less than
the potential complications derived from not performing it, including graft loss [6]. Moreover, keeping the polycystic kidneys after implantation could increase the risk of infections owing to the required posttransplant immunosuppression. In addition, mechanical compression could damage the graft, the vasculature, and the urethra [7]. In cases where nephrectomy is needed, there is no consensus with respect to optimal timing. Several alternatives have been proposed: nephrectomy before, after, and even during the transplant. A “sandwich technique” has also
*Address correspondence to José Horacio García-Rubio, C/Pintor Espinosa n 19 5 1, Córdoba (Córdoba), P.C., Spain 14004. E-mail: [email protected]
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.10.009
Transplantation Proceedings, 47, 2615e2617 (2015)
2615
2616
GARCÍA-RUBIO, CARRASCO VALIENTE, CAMPOS HERNÁNDEZ ET AL
been described, which consists of extracting 1 kidney before, and the other kidney after, the transplant [8]. The aim of our study was to analyze graft survival in patients who underwent kidney transplantation owing to ADPKD and pretransplant nephrectomy. METHODS We performed a retrospective study of patients with kidney transplant owing to ADPKD in our unit between January 2000 and December 2012. Pretransplant nephrectomy was performed in patients under dialysis when internal space is needed or after serious or chronic complications involving a cyst. By protocol we extract the right kidney, unless the left kidney was the one presenting complications, or if confronted with an unworkable transplant on the right iliac fosse. The approach was transperitoneal using medium suprainfraumbilical laparotomy incision. We establish early graft function as level of serum creatinine at 3 and 6 months. Delayed graft function is defined as need for dialysis during the first week posttransplantation. Graft failure was defined as return to dialysis; patient dying with a functional graft were not included in this group. We use the Clavien classification to grade surgical complications [9]. The clinical history and demographics of all patients were analyzed, including data related to the pretransplant nephrectomy and patient follow-up. We used the Student unpaired t test to compare the various groups. Patient and graft survivals were analyzed using KaplanMeier estimation. Probability was measured using the c2 test.
There were no serious postoperative complications (Clavien > IIIb). The average postoperative stay was 8 days (range, 4e26). After transplantation, 4 patients required nephrectomy, 2 owing to cysts infections and 2 owing to hematuria. Among the patients who have underwent nephrectomy (group 1), we found values of creatinine of 1.57 and 1.50 mg/dL at 3 and 6 months, respectively. In the other group (no nephrectomy; group 2), creatinine values were 2.03 and 1.83 mg/dL at 3 and 6 months, respectively. These differences were not significant (P ¼ .082 and P ¼ .27). We also evaluated the renal function with the Modification of Diet in Renal Disease formula, and found values of 47.62 and 50.31 mL/min/1.73 m2 in group 1 at 3 and 6 months and 46.27 and 48.73 mL/min/1.73 m2 at 3 and 6 months in group 2, respectively. These differences were not significant. Delayed graft function occurred in 3 of 27 patients (11%) in group 1 and 13 of 60 patients (22%) in group 2. Again, this difference was not significant (P ¼ .36). Only 1 of the 27 patients (4%) in group 1 lost the allograft, whereas 11 of 60 patients (19%) in group 2 lost their allograft. However, this difference was not significant (P ¼ .062). Graft survival after the first year was 98% in group 1 and 95% in group 2. The 5year graft survival was 95% and 80%, respectively (P ¼ .117). On multivariate analysis, found delayed graft function to be the only independent predictor of survival (P ¼ .020). DISCUSSION
RESULTS
During the period of study, a total of 87 patients underwent a kidney transplant owing to ADPKD: 62% (n ¼ 54) were male, with an average age of 55.22 years (range, 24e76; Table 1). For all cases, it was a first graft and came from a deceased donor. Posttransplant follow-up ranged from 1 to 169 months, with a mean follow-up period of 64.09 months. Twenty-seven patients (30%) underwent pretransplant nephrectomy of the native kidneys. The causes of the nephrectomy were lack of space for the implant (n ¼ 20; 74%), hematuria (n ¼ 5; 19%), and chronic lumbar pain (n ¼ 2; 7%). Seven patients (26%) experienced postoperative complications, 2 owing to postoperative collection ending in percutaneous puncture (Clavien IIIa), and the rest owing to paralytic ileus ending with conservative measures (Clavien II). Table 1. Patient Characteristics Variable
Nephrectomy (n ¼ 27)
No Nephrectomy (n ¼ 60)
Age (y) 53.3 56.03 Male sex 15/28 (54%) 14/58 (71%) Delayed graft function 3/27 (11%) 13/60 (22%) Modification of Diet in Renal Disease-4 (mL/min/1.73 m2) At 3 months 47.62 46.27 At 6 months 50.31 48.73 Creatinine (mg/dL) At 3 months 1.57 2.06 At 6 months 1.50 1.83 Graft loss 4/27 (3.7%) 11/60 (18.3%)
P
.144 .119 .36 .812 .077 .082 .27 .062
Management of ADPKD patients remains controversial regarding the need for pretransplant nephrectomy. Since the 1970s, treatment of patients with ADPKD has been changing, from most patients undergoing bilateral nephrectomy to present practice, were several protocols exist that differ in timing of nephrectomy (pretransplant, peritransplant, or posttransplant), indication for unilateral or bilateral, and the most appropriate approach (laparoscopic or open procedure). In our hospital, we applied a protocol consisting of open nephrectomy pretransplant via a transperitoneal approach for those patients who have been on dialysis and have repetitive complications, or owing to need for space for the anticipated allograft. Our results show that graft survival is not influenced by pretransplant nephrectomy; we have found better graft survival in the group of patient who underwent nephrectomy, although these differences were not significant. Our results are similar to others series. Like Knispel et al. [10], we did not found a higher rate of complications or graft dysfunction in the patients who were transplanted and went under pretransplant nephrectomy. Optimal Timing and Indications for Nephrectomy
Regarding the best timing and indications we found our results similar to the series from Singh et al. [6], which show no differences in graft survival or complications derived from previous. Unlike Sulikowski et al. [11], in our series only 6% of patients required posttransplant nephrectomy.
GRAFT SURVIVAL IN PCKD
Therefore, unless there is a clear need, nephrectomy before transplantation should not be performed routinely. Complications and Mortality
Nephrectomy of polycystic kidneys could be a complex surgery with a high rate of morbidity and mortality [12,13]. Nevertheless, our results showed low complications rates, and no major complications (Clavien > IIIb) or mortality. In conclusion, based on these results, pretransplant native kidney nephrectomy is a safe option, in an experienced center, both in terms of surgery-related morbidity and mortality and graft survival and function. REFERENCES [1] Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007;369:1287e301. [2] Banos GJ, Martin PJ, Diego BR, et al. Renal graft outcome in patients with associated liver transplant. Actas Urol Esp 2008;32: 220e4. [3] Parfrey PS, Bear JC, Morgan J, et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med 1990;323:1085e90. [4] Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 2002;13:2384e98.
2617 [5] Patel P, Horsfield C, Compton F, et al. Native nephrectomy in transplant patients with autosomal dominant polycystic kidney disease. Ann R Coll Surg Engl 2011;93:391e5. [6] Singh S, Hariharan S. Renal replacement therapy in autosomal dominant polycystic kidney disease. Nephron 1991;57:40e4. [7] Rayner BL, Cassidy MJ, Jacobsen JE, et al. Is preliminary binephrectomy necessary in patients with autosomal dominant polycystic kidney disease undergoing renal transplantation? Clin Nephrol 1990;34:122e4. [8] Cassuto-Viguier E, Quintens H, Chevallier D, et al. Transplantation and nephrectomy in autosomal dominant polycystic disease. Clin Nephrol 1991;36:105e6. [9] Clavien PA, Barkun J, de Oliveira ML, et al. The ClavienDindo classification of surgical complications: five-year experience. Ann Surg 2009;250:187e96. [10] Knispel HH, Klan R, Offermann G, et al. Transplantation in autosomal dominant polycystic kidney disease without nephrectomy. Urol Int 1996;56:75e8. [11] Sulikowski T, Tejchman K, Zietek Z, et al. Experience with autosomal dominant polycystic kidney disease in patients before and after renal transplantation: a 7-year observation. Transplant Proc 2009;41:177e80. [12] Yarimizu SN, Susan LP, Straffon RA, et al. Mortality and morbidity in pretransplant bilateral nephrectomy: analysis of 305 cases. Urology 1978;12:55e8. [13] Kirkman MA, van Dellen D, Mehra S, et al. Native nephrectomy for autosomal dominant polycystic kidney disease: Before or after kidney transplantation? BJU Int 2011;108:590e4.
ABSTRACT Introduction. Autosomal-dominant polycystic disease (ADPKD) represents 5%e10% of cases of end-stage renal failure. However, management of these patients in terms of whether or not to perform a transplant and optimal timing remains controversial. The objective of our analysis was to evaluate graft survival in patients with ADPKD in which we conduct pretransplant nephrectomy. Methods. This retrospective study including renal transplant patients secondary to ADPKD in our hospital between January 2000 and December 2012. Pretransplant native kidney nephrectomy was indicated in cases of need for space or repeated complications (cysts). We compared the initial function and graft survival between groups of transplanted based on whether nephrectomy had been performed or not. Results. Eighty-seven patients underwent a kidney transplant owing to ADPKD; 62% (n ¼ 54) were male, with an average age of 55.22 years. Twenty-seven patients (30%) underwent nephrectomy native kidneys before transplantation. There were no serious postoperative complications. Patients who underwent nephrectomy (group 1) showed values of creatinine of 1.57 and 1.50 mg/dL at 3 and 6 months, respectively. In the no nephrectomy group, these values were 2.03 and 1.83 mg/dL, respectively. Graft survival after the first year was of 98% for group 1 and 95% for group 2. The 5-year implant survival was 95% and 80%, respectively. Conclusions. Native kidney nephrectomy before transplantation in ADPKD is safe in an experienced center, both in terms of surgery-related morbidity and mortality and graft survival and function.
A
UTOSOMAL-DOMINANT polycystic kidney disease (ADPKD) is a monogenic, multisystem illness. It is characterized by the development of cysts in both kidneys, along with other abnormalities in other organs, such as the liver, heart, or digestive system [1,2]. It has a prevalence between 0.1% and 0.25%, and is responsible for 10% the cases of end-stage renal failure. Among these patients, 17% are 29e39 years old, present with cysts, a figure that increases to a 75% for ages 70 [3]. Globally, 50% of individuals with ADPKD develop endstage renal failure [4]. Only 20% of patients suffering from ADPKD require nephrectomy [5]. Cyst-related complications and space concerns for implantation are the main reasons to consider nephrectomy. It has been argued that, globally, the risk of performing the nephrectomy is less than
the potential complications derived from not performing it, including graft loss [6]. Moreover, keeping the polycystic kidneys after implantation could increase the risk of infections owing to the required posttransplant immunosuppression. In addition, mechanical compression could damage the graft, the vasculature, and the urethra [7]. In cases where nephrectomy is needed, there is no consensus with respect to optimal timing. Several alternatives have been proposed: nephrectomy before, after, and even during the transplant. A “sandwich technique” has also
*Address correspondence to José Horacio García-Rubio, C/Pintor Espinosa n 19 5 1, Córdoba (Córdoba), P.C., Spain 14004. E-mail: [email protected]
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.10.009
Transplantation Proceedings, 47, 2615e2617 (2015)
2615
2616
GARCÍA-RUBIO, CARRASCO VALIENTE, CAMPOS HERNÁNDEZ ET AL
been described, which consists of extracting 1 kidney before, and the other kidney after, the transplant [8]. The aim of our study was to analyze graft survival in patients who underwent kidney transplantation owing to ADPKD and pretransplant nephrectomy. METHODS We performed a retrospective study of patients with kidney transplant owing to ADPKD in our unit between January 2000 and December 2012. Pretransplant nephrectomy was performed in patients under dialysis when internal space is needed or after serious or chronic complications involving a cyst. By protocol we extract the right kidney, unless the left kidney was the one presenting complications, or if confronted with an unworkable transplant on the right iliac fosse. The approach was transperitoneal using medium suprainfraumbilical laparotomy incision. We establish early graft function as level of serum creatinine at 3 and 6 months. Delayed graft function is defined as need for dialysis during the first week posttransplantation. Graft failure was defined as return to dialysis; patient dying with a functional graft were not included in this group. We use the Clavien classification to grade surgical complications [9]. The clinical history and demographics of all patients were analyzed, including data related to the pretransplant nephrectomy and patient follow-up. We used the Student unpaired t test to compare the various groups. Patient and graft survivals were analyzed using KaplanMeier estimation. Probability was measured using the c2 test.
There were no serious postoperative complications (Clavien > IIIb). The average postoperative stay was 8 days (range, 4e26). After transplantation, 4 patients required nephrectomy, 2 owing to cysts infections and 2 owing to hematuria. Among the patients who have underwent nephrectomy (group 1), we found values of creatinine of 1.57 and 1.50 mg/dL at 3 and 6 months, respectively. In the other group (no nephrectomy; group 2), creatinine values were 2.03 and 1.83 mg/dL at 3 and 6 months, respectively. These differences were not significant (P ¼ .082 and P ¼ .27). We also evaluated the renal function with the Modification of Diet in Renal Disease formula, and found values of 47.62 and 50.31 mL/min/1.73 m2 in group 1 at 3 and 6 months and 46.27 and 48.73 mL/min/1.73 m2 at 3 and 6 months in group 2, respectively. These differences were not significant. Delayed graft function occurred in 3 of 27 patients (11%) in group 1 and 13 of 60 patients (22%) in group 2. Again, this difference was not significant (P ¼ .36). Only 1 of the 27 patients (4%) in group 1 lost the allograft, whereas 11 of 60 patients (19%) in group 2 lost their allograft. However, this difference was not significant (P ¼ .062). Graft survival after the first year was 98% in group 1 and 95% in group 2. The 5year graft survival was 95% and 80%, respectively (P ¼ .117). On multivariate analysis, found delayed graft function to be the only independent predictor of survival (P ¼ .020). DISCUSSION
RESULTS
During the period of study, a total of 87 patients underwent a kidney transplant owing to ADPKD: 62% (n ¼ 54) were male, with an average age of 55.22 years (range, 24e76; Table 1). For all cases, it was a first graft and came from a deceased donor. Posttransplant follow-up ranged from 1 to 169 months, with a mean follow-up period of 64.09 months. Twenty-seven patients (30%) underwent pretransplant nephrectomy of the native kidneys. The causes of the nephrectomy were lack of space for the implant (n ¼ 20; 74%), hematuria (n ¼ 5; 19%), and chronic lumbar pain (n ¼ 2; 7%). Seven patients (26%) experienced postoperative complications, 2 owing to postoperative collection ending in percutaneous puncture (Clavien IIIa), and the rest owing to paralytic ileus ending with conservative measures (Clavien II). Table 1. Patient Characteristics Variable
Nephrectomy (n ¼ 27)
No Nephrectomy (n ¼ 60)
Age (y) 53.3 56.03 Male sex 15/28 (54%) 14/58 (71%) Delayed graft function 3/27 (11%) 13/60 (22%) Modification of Diet in Renal Disease-4 (mL/min/1.73 m2) At 3 months 47.62 46.27 At 6 months 50.31 48.73 Creatinine (mg/dL) At 3 months 1.57 2.06 At 6 months 1.50 1.83 Graft loss 4/27 (3.7%) 11/60 (18.3%)
P
.144 .119 .36 .812 .077 .082 .27 .062
Management of ADPKD patients remains controversial regarding the need for pretransplant nephrectomy. Since the 1970s, treatment of patients with ADPKD has been changing, from most patients undergoing bilateral nephrectomy to present practice, were several protocols exist that differ in timing of nephrectomy (pretransplant, peritransplant, or posttransplant), indication for unilateral or bilateral, and the most appropriate approach (laparoscopic or open procedure). In our hospital, we applied a protocol consisting of open nephrectomy pretransplant via a transperitoneal approach for those patients who have been on dialysis and have repetitive complications, or owing to need for space for the anticipated allograft. Our results show that graft survival is not influenced by pretransplant nephrectomy; we have found better graft survival in the group of patient who underwent nephrectomy, although these differences were not significant. Our results are similar to others series. Like Knispel et al. [10], we did not found a higher rate of complications or graft dysfunction in the patients who were transplanted and went under pretransplant nephrectomy. Optimal Timing and Indications for Nephrectomy
Regarding the best timing and indications we found our results similar to the series from Singh et al. [6], which show no differences in graft survival or complications derived from previous. Unlike Sulikowski et al. [11], in our series only 6% of patients required posttransplant nephrectomy.
GRAFT SURVIVAL IN PCKD
Therefore, unless there is a clear need, nephrectomy before transplantation should not be performed routinely. Complications and Mortality
Nephrectomy of polycystic kidneys could be a complex surgery with a high rate of morbidity and mortality [12,13]. Nevertheless, our results showed low complications rates, and no major complications (Clavien > IIIb) or mortality. In conclusion, based on these results, pretransplant native kidney nephrectomy is a safe option, in an experienced center, both in terms of surgery-related morbidity and mortality and graft survival and function. REFERENCES [1] Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007;369:1287e301. [2] Banos GJ, Martin PJ, Diego BR, et al. Renal graft outcome in patients with associated liver transplant. Actas Urol Esp 2008;32: 220e4. [3] Parfrey PS, Bear JC, Morgan J, et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med 1990;323:1085e90. [4] Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 2002;13:2384e98.
2617 [5] Patel P, Horsfield C, Compton F, et al. Native nephrectomy in transplant patients with autosomal dominant polycystic kidney disease. Ann R Coll Surg Engl 2011;93:391e5. [6] Singh S, Hariharan S. Renal replacement therapy in autosomal dominant polycystic kidney disease. Nephron 1991;57:40e4. [7] Rayner BL, Cassidy MJ, Jacobsen JE, et al. Is preliminary binephrectomy necessary in patients with autosomal dominant polycystic kidney disease undergoing renal transplantation? Clin Nephrol 1990;34:122e4. [8] Cassuto-Viguier E, Quintens H, Chevallier D, et al. Transplantation and nephrectomy in autosomal dominant polycystic disease. Clin Nephrol 1991;36:105e6. [9] Clavien PA, Barkun J, de Oliveira ML, et al. The ClavienDindo classification of surgical complications: five-year experience. Ann Surg 2009;250:187e96. [10] Knispel HH, Klan R, Offermann G, et al. Transplantation in autosomal dominant polycystic kidney disease without nephrectomy. Urol Int 1996;56:75e8. [11] Sulikowski T, Tejchman K, Zietek Z, et al. Experience with autosomal dominant polycystic kidney disease in patients before and after renal transplantation: a 7-year observation. Transplant Proc 2009;41:177e80. [12] Yarimizu SN, Susan LP, Straffon RA, et al. Mortality and morbidity in pretransplant bilateral nephrectomy: analysis of 305 cases. Urology 1978;12:55e8. [13] Kirkman MA, van Dellen D, Mehra S, et al. Native nephrectomy for autosomal dominant polycystic kidney disease: Before or after kidney transplantation? BJU Int 2011;108:590e4.