Objectives: Patients with polycystic kidney disease are candidates for kidney transplant. We report the results of our single center study of 250 first transplant recipients with polycystic kidney disease (autosomal dominant [64%], medullary cystic [16%], autosomal recessive [6%], and nonspecified [14%]).
Materials and Methods: Patient groups were divided and analyzed according to the origin of the graft (deceased donor or living donor). We also analyzed demographic data of donors and recipients, waiting time, duration of dialysis, transfusion, nephrectomy, hospitalization, morbidities, and graft and patient survival. The study was approved by the Ethical Review Committee of the Institute. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration.
Results: The deceased-donor group comprised 79% and the living-donor group comprised 21% of the cases. Nephrectomy was performed on 21% of the recipients. The deceased-donor group showed significantly higher values than the living-donor group regarding rate of hemodialysis (82% vs 68%), duration of dialysis (1571 vs 1002 days), waiting time (1129 vs 33 days), and blood transfusions (45% vs 27%). In deceased-donor versus living-donor transplant recipients, surgical complications included arterial stenosis (1% vs 0%), venous thrombosis (1% vs 0%), urine leakage (0.5% vs 1.9%), ureteral stenosis (0.5% vs 0%), reflux (0% vs 1.9%), lymphocele (11.7% vs 8.1%), and hernia (5.2% vs 8.1%), with no statistically significant differences shown between the groups. The living-donor group had graft and patient survival rates as high as the deceased-donor group.
Conclusions: The low rate of morbidity and excellent survival rates make kidney transplant an excellent option for patients with polycystic kidney disease. Although fear of future appearance of polycystic kidney disease may reduce the rate of related living donors, our study showed that graft and patient survival rates in the living-donor group were as high as in the deceased-donor group.
Key words : Kidney transplantation, Polycystic kidney disease, Follow-up
Polycystic kidney diseases (PKDs) are characterized by the formation of multiple renal cysts, which may arise sporadically as a developmental abnormality or may be acquired in adult life; however, most forms are hereditary.1 Among the acquired forms, dialysis, certain drugs, and hormonal changes can cause multicystic disease. Inherited PKDs, which are due to germline mutations in single genes, are inherited as Mendelian traits. They include mostly autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), and medullary cystic disease (MCD).2-5 The severity of the symptoms, rate of end-stage renal failure, and rate of survival vary widely in these subgroups of PKD.6,7 With approximately 3% of the end-stage renal disease (ESRD) in the United States and as one of the leading causes of it, PKDs are common indications for dialysis or kidney transplant. Kidney transplant is the only option for curative treatment and is a superior treatment choice versus dialysis.1,8-12 Although numerous studies have evaluated the results of kidney transplant in patients with PKD, most of these have only published the results after kidney transplant in patients with ADPKD.13-18 Furthermore, the results have not considered the origin of the graft. Here, we report our single center experience with kidney transplant, providing the largest available single center case series to include all of the PKD types during the last 37 years with a focus on the source of the graft.
Materials and Methods
We reviewed our transplant database for patients who underwent kidney transplant as a result of PKD from 1975 to the end of 2011. We compared the demographic data between living donors and deceased donors and evaluated the family relationship between living donors and recipients. We also evaluated the demographic data of the recipients, comparing them regarding type of PKD (ADPKD, ARPKD, MCD), and recorded the time and rate of nephrectomy. Comorbidities of recipients, duration of waiting time before kidney transplant, type of dialysis, and duration of dialysis were also reviewed. Furthermore, the cold ischemia time, the duration of the surgical procedure, intraoperative blood loss, and transfusion of blood products were evaluated based on the origin of the graft (deceased donor vs living donor). Finally, duration of hospitalization after transplant, morbidity, and graft and patient survival were analyzed. The immunosuppressive agents, changes in the agents, and the consequent effects have been already discussed in our previous study.19
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 17.0, IBM Corporation, Armonk, NY, USA). For quantitative data, medians and ranges were calculated and reported as number and percents. In this study, we used Mann-Whitney U test for variables of interest. P values < .05 were considered as statistically significant.
During a 37-year period, 250 patients underwent a first kidney transplant due to PKD. The demographic data of the donors are summarized in Table 1. For our patient group, 79% of the grafts were from deceased donors and 21% of the grafts were from living donors. The deceased donors were mostly men (62%), and the living donors were mostly women (58%). Table 2 shows the family relationships in the living-donor group and details about the PKD subgroups. Overall, most of the living donors were spouses or partners of the recipients. Most of the recipients of living-donor kidney transplant had ADPKD. The median age in the ARPKD subgroup was lower than in the other subgroups. Demographic characteristics of the recipients by type of PKD are summarized in Table 3. In all subgroups, most recipients were male patients. As shown in Table 4, hypertension (95%), renal anemia (60%), and hyperparathyroidism (49%) were the most prevalent comorbidities.
Table 5 shows that more patients underwent hemodialysis than peritoneal dialysis (80% vs 20%). The proportion of patients who had hemodialysis was also significantly higher in the deceased-donor transplant group than in the living-donor transplant group (82% vs 68%). The median duration of dialysis in the deceased-donor transplant group was 1571 days (range, 19-5385 d), which was significantly longer than the median duration of 1002 days in the living-donor transplant group (range, 1-4089 d). The median waiting list time for deceased-donor transplant recipients was 1129 days (range, 4-3637 d), which was significantly longer than the median waiting list time of 33 days (range, 0-1878 d) for living-donor transplant recipients . The median cold ischemia time for grafts from deceased donors was 1200 minutes (range, 390-2380 min), which was also significantly longer than the median cold ischemia time of 200 minutes (range, 72-270) for grafts from living donors. During the surgical procedure, deceased-donor transplant recipients had a median blood loss of 300 mL (range, 0-5000 mL), whereas living-donor transplant recipients had a median blood loss of 200 mL (range, 50-1000 mL). More patients in the deceased-donor group received blood products than in the living-donor group (45% vs 27%). For deceased-donor transplant recipients, the surgical procedure lasted 190 minutes (range, 70-360 min), whereas the duration was 180 minutes (range, 78-370 min) for living-donor transplant recipients. In total, 21% of the patients underwent nephrectomy, 3% simultaneously with kidney transplant and 18% not simultaneously with kidney transplant. In the deceased-donor group, 22% of the patients underwent nephrectomy (17% simultaneously with kidney transplant, 83% not simultaneously with kidney transplant), whereas 19% of living-donor transplant recipients underwent nephrectomy (12% simul-taneously with kidney transplant, 88% not simultaneously with kidney transplant). Most of the nephrectomies in both groups that did not occur simultaneously were performed before kidney transplant and unilaterally.
Complications after transplant were also categorized and compared between deceased-donor and living-donor transplant recipients (Table 6). Although vascular complications were higher in the deceased-donor group, there were no significant differences between groups. Ureteral leakage, reflux, and hernia occurred, but rates of occurrence were not significantly higher than in the living-donor group. Lymphocele and surgical site infection also occurred at a higher rate in the deceased-donor group; however, results were not significant higher than in the living-donor group. The median duration of hospitalization after initial transplant surgery was 16 days in the living-donor group (range, 6-62) and 18 days in the deceased-donor group (range, 6-90).
The cumulative graft survival (death-censored) and patient survival rates are shown in Figure 1 and Figure 2. For deceased-donor transplant recipients, the 1-year, 3-year, 5-year, and 10-year graft survival rates were 97%, 96%, 95%, and 85%. In addition, this group had 1-year, 3-year, 5-year, and 10-year patient survival rates of 98%, 98%, 97%, and 97%. For living-donor transplant recipients, the cumulative 1-year, 3-year, 5-year, and 10-year graft survival rates were 100%, 100%, 100%, and 75%. This group had cumulative 1-year, 3-year, 5-year, and 10-year patient survival rates of 97%. There were no significant differences between both groups regarding graft and patient survival rates. In the living-donor group, there was only 1 death. The patient had received a combined liver and kidney transplant and died from liver failure.
In the literature, only a few case series have reported outcomes of patients with PKD after kidney transplant. Table 7 provides an overview of the main published studies in this regard. Our single center study sought to evaluate the results of our 37-year experience as one of the largest single center studies of patients with different types of PKD who underwent kidney transplant. As expected, most of our study patients had ADPKD. Medullary cystic disease, for which limited published studies on kidney transplant exist,16,17,20 was the second most frequent primary renal disease requiring kidney transplant. Although MCD is normally clinically milder and typically appears first in adulthood,5 the average age of ADPKD patients at our center was higher at the time of transplant, probably because these patients usually reach end-stage renal disease at an advanced age. Overall, male patients comprised most of our study population, even in the ADPKD subgroup. This could be because of a more aggressive course of the disease in male patients.21-23
Hypertension is one of the most common early manifestations of PKD. Even when renal function is still normal, hypertension is seen in 50% to 75% of patients with ADPKD.24,25 In our study, we also observed a high rate of hypertension, and this was the leading comorbidity of the recipients before transplant. This was expected as most of our patients had ADPKD, and hypertension is extremely frequent among patients with ADPKD before transplant.26 In our population, renal anemia was the second most prevalent comorbidity. As suggested by Masunaga and associates, this could be from a erythropoietin production disorder caused by the progressive polycystic formation in kidneys.27
It has been reported many times that the results of kidney transplant from living donors are more satisfactory than from deceased donors.28-34 Because most of the PKD subtypes are genetic diseases, living relatives may avoid donating a kidney because of fear of a future appearance of polycystic disease. The rate of kidney transplants from living donors in patients with PKD was lower than the total rate of living-donor kidney transplant in our kidney transplant program (21% vs 36%). Because of a lack of early symptoms and absence of clear diagnostic criteria, selection of donor candidates among family members can be difficult and sometimes impossible.35 For example, in the MCD subgroup, we excluded brothers and sisters of the patients and accepted only 1 of the parents (the 1 without the disease). However, the genes for PKD can now be detected in the clinic.36 Interested family members over 30 years old can safely donate a kidney without any fear of developing this disease, absent the offending genes.37 In our center, we safely rule out donors over 30 years old through magnetic resonance imaging and sonography and exclude donors under 30 years old with potential risks of PKD, as the genetic control has only an 85% hit rate.
Residual renal function is an important predictor of survival in the early years of renal replacement therapy, and strategies to preserve it may add years of benefit to patients.38 The preservation of residual renal function may in fact confer an important survival benefit in peritoneal dialysis, as patients who have peritoneal dialysis have a slower rate of decline of residual renal function than patients who have hemodialysis. For example, Wang and colleagues reported that for every 1 mL/min/1.73 m2 increase in residual glomerular filtration rate, there was a 50% reduction in all-cause mortality and cardiovascular death among their cohort of patients who received peritoneal dialysis.39 Once there is no residual renal function, it is more difficult to achieve absolute clearance with peritoneal dialysis than with hemodialysis. Therefore, peritoneal dialysis is used at the beginning of renal replacement therapy up to exhaustion, thus delaying the use of hemodialysis and preserving the upper extremities for vascular access. In our study, all PKD patients underwent peritoneal dialysis for initial renal replacement therapy without any significant differences between the deceased-donor and living-donor transplant recipients. However, in the deceased-donor group, because duration of dialysis and waiting time for transplant were longer, hemodialysis was significantly more frequently used before kidney transplant.
Clinicians treating symptomatic patients with PKD are often confronted with the question of when to perform native nephrectomy regarding kidney transplant. Today, there is a general consensus that pretransplant native nephrectomy, especially bilateral nephrectomy, should be avoided, if possible.40-42 Initial experiences with concomitant bilateral nephrectomy and kidney transplant have resulted in unfavorable results, likely due to complex fluid shifts, peritonitis from infected cyst fluid, and graft compromise secondary to hemorrhage-induced hypotension, which was attributable to the nephrectomy portion of the procedure.43 Although the general opinion among nephrologists and surgeons was that this combined approach involves too much surgery and might likely lead to poor outcomes,44-47 there are some studies in the literatures that support it in decreasing the postoperative mortalities.12,48-50 Recently, the transcatheter arterial embolization technique has shown promising results as an alternative.51 Thus, the removal of polycystic kidneys at renal grafting is still controversial. Because the presence of PKD confers an increased risk for development of renal cell carcinoma, the survival rate of recipients can be influenced without native nephrectomy. This has been also mentioned as an indication of native nephrectomy.52,53 In our study, one-fifth of the patients in the deceased-donor group and one-fifth of the patients in the living-donor group underwent native nephrectomy. There was no significant difference between the groups regarding the time of nephrectomy, with most of the nephrectomies that did not occur simultaneously performed unilaterally before kidney transplant. Simultaneous nephrectomy was avoided as much as possible to prevent longer operation time and higher complication rate. The few simultaneously nephrectomies were performed in children.
The time of nephrectomy in the deceased-donor group is a challenging issue because of trying to use the residual function of the kidney up to transplant time. In the living-donor group, it is easier and can be planned in a 3-month interval to transplant. The indications were mostly lack of enough places for implant, pressure on the other organs, infection, hypertension, and function disorders or pain. The patients in the deceased-donor group received significantly more blood transfusions than patients in the living-donor group. The higher amount of received blood products in the deceased-donor group can be explained by the greater erythropoietin deficiency and shortened erythrocyte half-life as a complication of end-stage renal disease.54 In addition, because no significant difference between both groups regarding the amount of intraoperative blood loss was shown, this can be explained as a consequence of a more pronounced renal anemia due to the longer time on dialysis. However, among patients with end-stage renal disease, patients with ADPKD have the lowest severity of renal anemia.
The most frequent complications of kidney transplant include perirenal fluid collection (lym-phoceles, hematomas, seromas, urinomas), impaired renal function, and abnormalities of the vasculature and collecting system.55,56 Our data showed that lymphocele was the leading complications after kidney transplant in PKD patients. Vascular complications have been documented in 10% of recipients of renal transplant and are an important cause of graft dysfunction.57 In our case series, vascular complications occurred only in the deceased-donor group with a low rate (arterial stenosis rate of 0.8% and venous thrombosis rate of 0.8%). Urologic complications were higher in the living-donor group, shown as urinary leakage and reflux, but these were not significantly higher. There was no ureteral stenosis in the living-donor group. As expected, lymphocele was the most common complication after kidney transplant, higher in the deceased-donor group but not significantly versus the living-donor group, followed by hernia and surgical site infection. However, no significant differences were shown between groups for any of the complications. Because patients with ARPKD benefit from the rest function of the kidney, receive erythropoietin, and have no recurrence, they enter the transplant program with a better condition and consequently have higher survival rates after kidney transplant. Our high rate of graft survival is also comparable with other studies.
In conclusion, kidney transplant is a safe method of renal replacement therapy in patients with PKD, with low morbidity and high graft and patient survival rates. Although fear of future appearance of PKD may reduce the rate of donations from living relatives, we showed that kidney transplant from living donors for PKD patients is an option supported by a high rate of graft and patient survival.
Volume : 13
Issue : 5
Pages : 413 - 420
DOI : 10.6002/ect.2014.0041
From the 1Department of General, Visceral and Transplantation Surgery; the 2Department of Nephrology; and the 3University Children's Hospital, University of Heidelberg, Heidelberg, Germany
Acknowledgements: The authors declare that they have no sources of funding, and they have no conflicts of interest to declare. AM and MG participated in the design of the study and reviewed articles. JM, HF, CG, and NF participated in data collection. AM and MG drafted the manuscript. MH, AF, and NR performed the statistical analysis. MW, MM, and CM were involved in revising the manuscript critically for important intellectual content. MWB, BT, MZ, JSC, and PT gave the final approval of the version to be published. All authors read and approved the final manuscript. Arianeb Mehrabi and Mohammad Golriz contributed equally to this study.
Corresponding author: Arianeb Mehrabi, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
Phone: +49 6221 56 36223
Fax: +49 6221 56 7470
Table 1. Demographic Characteristics of Deceased Donors and Living Donors
Table 2. Relationship Between Living Donors and Recipients Based on Type of PKD
Table 3. Demographic Characteristics of Recipients Categorized by Type of PKD
Table 4. Most Prevalent Comorbidities in Recipients With PKD and Kidney Transplant
Table 5. Surgical Data of Kidney Transplant Recipients With PKD Categorized by Origin of the Graft
Table 6. Surgical Complications After Kidney Transplant in PKD Patients By Donor Groups
Figure 1. Cumulative Graft Survival in Both Patient Groups
Figure 2. Cumulative Patient Survival in Both Patient Groups
Table 7. Overview of Primary Published Case Series on Kidney Transplant and PKD