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Therapeutic Apheresis and Dialysis 15(3):245249 doi: 10.1111/j.1744-9987.2011.00945.x 2011 The Authors Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

Dialysis Patients Refusing Kidney Transplantation: Data From the Slovenian Renal Replacement Therapy Registry
Jadranka Buturovic-Ponikvar, Jakob Gubenek, Miha Arnol, Andrej Bren, Aljoa Kandus, and Rafael Ponikvar
Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia

Abstract: Kidney transplantation is considered the best renal replacement therapy (RRT) for patients with endstage renal disease; nevertheless, some dialysis patients refuse to be transplanted. The aim of our registry-based, cross-sectional study was to compare kidney transplant candidates to dialysis patients refusing transplantation. Data were collected from the Slovenian Renal Replacement Therapy Registry database, as of 31 December 2008. Demographic and some RRT data were compared between the groups. There were 1448 dialysis patients, of whom 1343 were treated by hemodialysis and 105 by peritoneal dialysis (PD); 132 (9%) were on the waiting list for transplantation, 208 (14%) were preparing for enrollment (altogether 340 [23%] dialysis patients were kidney transplant candidates); 200 (13.7%) patients were reported to refuse transplantation, all 65 years of age; 345 (24%)

were not enrolled due to medical contraindications, 482 (33%) due to age, and 82 (6%) due to other or unknown reasons. No signicant difference was found in age, gender, or presence of diabetes between kidney transplant candidates vs. patients refusing transplantation (mean age 50.5 13.9 vs. 51.3 9.6 years, males 61% vs. 63%, diabetics 18% vs. 17%). The proportion of patients 65 years old who were refusing transplantation was 28% (187/661) for hemodialysis and 17% (13/79) for PD patients (P = 0.03). There is a considerable group of dialysis patients in Slovenia refusing kidney transplantation. Compared to the kidney transplant candidates, they are similar in age, gender and prevalence of diabetes. Patients treated by peritoneal dialysis refuse kidney transplantation less often than hemodialysis patients. Key Words: Dialysis, Hemodialysis, Kidney transplantation, Peritoneal dialysis, Refusal.

Kidney transplantation is widely promoted as the best renal replacement therapy (RRT) for end-stage renal disease. It is claimed to prolong life and improve its quality compared to maintenance hemodialysis (1,2); nevertheless, a number of dialysis patients refuse to be transplanted. This topic is rarely mentioned in the literature (3,4), with patients refusing to be transplanted reported as anecdotal (3). Kidney transplantation has made signicant progress in past decades. One-year graft survival exceeds 90% in many centers.The number of patients with a functioning kidney graft worldwide is increasing and exceeds half a million (5); however, long-term
Received March 2011. Address correspondence and reprint requests to Professor Jadranka Buturovic-Ponikvar, Department of Nephrology, Univer sity Medical Center Ljubljana, Zaloka cesta 7, 1525 Ljubljana, Slovenia. Email: jadranka.buturovic@mf.uni-lj.si Presented in part at the Symposium Celebrating the 40th Anniversary of Chronic Dialysis and Kidney Transplantation in Slovenia held 45 November 2010 in Bled, Slovenia.

survival has not improved signicantly (6). The complications of immunosuppressive therapy still represent a major problem, both in the short and long term, causing signicant morbidity or mortality and jeopardizing compliance with therapy, especially in younger patients (7). In parallel to transplantation development, longterm dialysis survivors (>30 or >40 years of dialysis treatment) are accumulating across the world (8,9) and in Slovenia (10) as living evidence of dialysis potential and achievements. The existence of such patients may have an important impact on a subgroup of dialysis patients already reluctant to enroll for kidney transplantation. In Slovenia, the chronic dialysis and kidney transplantation programs were both started in 1970. On 1 January 2000, Slovenia joined Eurotransplant. The majority of kidney transplantations in Slovenia are performed using kidneys from deceased donors, with graft and patient survival above the Eurotransplant average (11). The Slovenian Renal Replacement 245

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J Buturovic-Ponikvar et al. weekly duration of hemodialysis procedures, and dry body weight. Pediatric data are included. Continuous variables were expressed as mean SD. The differences between the patient groups were compared using an unpaired Students t-test. Categorical variables were compared using the c2-test. A two-sided P value <0.05 was used as the criterion for statistical signicance. All analyses were performed using the Statistica statistical software (version 7.0; StatSoft, Tulsa, OK, USA). RESULTS PATIENTS AND METHODS

Therapy Registry was founded in 2004. It collects numerous data on individual patients, including data on the dialysis patients enrollment as kidney transplant candidates. Information on the reasons for not being enrolled are also collected. The refusing transplantation option is included in the questionnaire (11). The aim of our cross-sectional, registry-based study was to compare some demographic and treatment data between dialysis patients refusing kidney transplantation and kidney transplant candidates.

The patient and treatment data from the Slovenian Renal Replacement Therapy Registry database, as of 31 December 2008, were analyzed. A special part of the dialysis patient questionnaire relates to transplantation status and includes the following options: (i) enrolled on waiting list; (ii) work-up for enrollment; (iii) refusing transplantation; (iv) not a transplant candidate because of age; (v) medical contraindications for transplantation; and (vi) other. Although there is no formal upper age limit for transplantation from 2005, patients >65 years, if not reported as having medical contraindications, were counted as not being enrolled for transplantation because of age. Patients referred as refusing transplantation and being >65 years of age were also counted as not being transplant candidates because of age. So, for the purposes of the registry and our study, only those patients of 65 years old and younger, who had refused kidney transplantation, were counted as patients refusing transplantation. The response rate to the individual patient questionnaire was 100%. We compared these patients to the kidney transplant candidates (patients already on the waiting list and in the work-up for enrollment) with respect to demographic and treatment data: age, gender, duration and type of RRT, previous transplantation, presence of diabetes, vascular access for hemodialysis,

At the end of 2008, there were 1448 dialysis patients in Slovenia, of whom 1343 were treated by hemodialysis and 105 by peritoneal dialysis (PD). A total of 132 (9%) were reported as being enrolled for transplantation, and another 208 (14%) were preparing for enrollment; altogether 340 (23%) patients were considered as kidney transplant candidates (Fig. 1).Two hundred patients (13.7%) were reported as refusing renal transplantation, with no signicant difference between the patients treated with hemodialysis or PD (187/1343 = 13.9% vs. 13/105 = 12.3%, P = 0.66). However, if the number of patients refusing transplantation (all being 65 years) is calculated as the proportion of dialysis patients 65 years, more hemodialysis patients were reported as refusing kidney transplantation compared to PD patients (187/661 = 28% vs. 13/79 = 17%, P = 0.03). No signicant differences were found between patients refusing kidney transplantation and kidney transplant candidates in terms of age (median age 53 years in both groups), gender, dry body weight, presence of diabetes, or previous transplantation. Expectedly, the duration of RRT therapy was signicantly longer in patients refusing transplantation. Such patients were less often treated by PD. The weekly duration of hemodialysis was signicantly longer in patients refusing transplantation. Both groups had a very high proportion of arteriovenous

FIG. 1. Prevalent dialysis patients (N = 1448) and their waiting list status as kidney transplant candidates (on 31 December 2008).

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2011 The Authors Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

Patients Refusing Kidney Transplantation

TABLE 1. Demographic and renal replacement therapy data for kidney transplant candidates compared to dialysis patients refusing transplantation
Parameter N Age (years) Male gender Diabetes mellitus Dry weight (kg) Treated with hemodialysis Total RRT time (years) AV stula or graft (in HD patients) Weekly time on dialysis (in HD patients) (h) Previous Tx Kidney Tx candidates 50.8 340 14.1 (377) 61% 18% 70.9 15.9 87% 5.1 6.2 92% 13.1 2.1 5% Refusing Tx 51.3 200 9.6 (2265) 63% 17% 69.5 15.5 94% 10.9 8.3 97% 14.1 2.4 7% P value 0.62 0.81 0.72 0.36 0.02 <0.001 0.04 <0.001 0.42

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AV, arteriovenous; HD, hemodialysis; RRT, renal replacement therapy; Tx, transplantation.

stula or graft as the vascular access, 97% vs. 92%, with a signicantly higher proportion in patients refusing transplantation (Table 1). Both the number as well as the proportion of dialysis patients 65 years reported as refusing kidney transplantation decreased in the period from 2006 to 2008 from a maximum of 239 patients reported in 2006 to 200 patients reported in 2008 (Fig. 2). The special group of dialysis patients includes those patients with a failed graft. There were 49 such patients alive on 31 December 2008, of whom 59% were males aged 51 11 years, 6% had diabetes, being treated by RRT for 21.6 8.2 years. More than a third of these patients (37%) are candidates for a new transplantation, and less than a third (28%) are reported as refusing transplantation (Fig. 3). DISCUSSION Our study has shown that an important proportion of dialysis patients, 65 years old or younger, refuse to

be transplanted. The patients treated by PD refuse kidney transplantation less often than hemodialysis patients. According to our best knowledge, this is one of the very few, if any, systematic reports on this topic. The interpretation of these data is demanding and should be performed with caution. The study is retrospective, cross-sectional, and registry based. Referral of the patients attitudes towards kidney transplantation was made by medical staff (nephrologists or dialysis nurses), and not by the patients themselves. The reasons for refusing kidney transplantation were not reported. Some of the patients may already have had signicant comorbidities and were not suitable for transplantation anyway. The decision to refuse transplantation may not be nal and may change during the course of RRT. A longitudinal study would be needed to address this issue. Nevertheless, as transplantation is generally viewed as the best RRT, it is important to know that this view is not shared by all dialysis patients. In reality, this view is not shared by a signicant number and proportion of dialysis patients, a number that is much higher than anecdotal. The quality of kidney transplantation in Slovenia is high, with graft and patient survival signicantly

FIG. 2. Percentage of dialysis patients refusing transplantation (Tx) in Slovenia from 20052008.
2011 The Authors Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

FIG. 3. Prevalent hemodialysis patients after kidney graft failure (31 December 2008) and their waiting list status (N = 49).

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J Buturovic-Ponikvar et al. patients) has been steadily increasing for years, with a further increase expected in future. Patients refusing transplantation are not preventing this increase. Although the waiting list for kidney transplantation is relatively small, it is constantly being replaced by new patients. The cohort of patients refusing kidney transplantation is more stable, without such patient turnover as on the waiting list. Moreover, a decrease in the number and proportion of dialysis patients refusing kidney transplantation has been observed in past years. It is not very likely that dialysis patients refusing transplantation are not well-informed on kidney transplantation. Living with chronic dialysis is not an easy life, and it may be expected that dialysis patients will have explored and thoroughly analyzed the alternatives, specically kidney transplantation. Because it is the patients themselves who will carry the consequences of their choices, it is probable that they have weighed the pros and cons carefully. For an individual dialysis patient, the short- and longterm transplantation outcome is difcult to predict. It may not be surprising that some patients who are well-adapted to dialysis, working full-time, are active in sports, and have been living a stable and predictable life for decades, may be reluctant to take a risk with kidney transplantation. Riis et al. have shown, in a study measuring patients moods in real time and in real life, that hemodialysis patients are not less happy than healthy non-patients, emphasizing their adaptation to dialysis (14). After speaking with a number of these patients, our impression was that their decision to stay on dialysis rather than choose a kidney transplant was careful, well-informed, and not necessarily nal. Some patients are waiting for a breakthrough in immunosuppressive therapy. Some are waiting for their children to grow up, or their business plans to be realized. Some have disappointing experiences with previous transplants or immunosuppressive drugs during treatment of their original kidney disease. The reasons may vary and are certainly worthy of further study. It also seems that dialysis patients are not so afraid of the standard complications of immunosuppressive therapy, such as infection, malignancy, and diabetes, but more specic ones: reduction in physical capability, mobility, changes in physical appearance, and eye problems, complications that are frequently neglected in many studies. The concerns may be different in different age groups (15). More in-depth studies of patients refusing kidney transplantation are necessary. Transplant medicine should be aware of the concerns and fears of patients, and attempt to address them in clinical practice.
2011 The Authors Therapeutic Apheresis and Dialysis 2011 International Society for Apheresis

above the Eurotransplant average (11). All kidney transplant recipients are transplanted and treated at the same center, and the preparations for transplantation enrollment are very thorough and detailed. Thus, the quality of transplantation in Slovenia is probably not a reason for the patients concerns over transplantation. More probable reasons are the limitations of kidney transplantation itself, and the side effects of immunosuppressive therapy. The quality and accessibility of dialysis may also have an impact on motivation to have a transplant. Slovenia has a good dialysis center network with easy access. High-quality hemodialysis is offered to all patients. Re-use was never practiced, and the duration of hemodialysis procedures is relatively long (12). Almost half of hemodialysis patients are treated by on-line hemodialtration, and almost three-quarters have ultrapure dialysis uid (11). The patients may choose between in-hospital or private centers, all providing a good quality of dialysis. Transport to dialysis is organized, as well as meals during and/or after hemodialysis. A nocturnal hemodialysis program is available. The majority of patients have a timely constructed arteriovenous stula due to the long tradition of interventional nephrology in Slovenia (13). The salvage of thrombosed arteriovenous stulas and grafts is well organized, thus increasing the sense of safety related to vascular access function. Some specics in Slovenia may also play a role. Living in a small country, many patients know each other. Dialysis patients are often aware of the transplant outcome and complications in their former dialysis fellows. They may compare a patients appearance and mobility before and after transplantation more easily than patients in a large country with several big transplant centers. Patient outcomes after transplantation, sometimes tragic, may inuence the attitude towards transplantation. Of course, the same is true for successful transplantation stories. Patients on PD refuse kidney transplantation less often than patients on hemodialysis, which is not surprising.As PD is performed for a limited time, usually less than 10 years, the patient in soon faced with the need to transfer to another RRT modality, either hemodialysis or kidney transplantation. Kidney transplantation, besides other advantages, is much more compatible with the lifestyle of the PD patient, with relative independence from the dialysis center. So it is not surprising that PD patients, already preferring PD to hemodialysis in the past, prefer transplantation to hemodialysis in the future. The proportion of patients with a functioning kidney graft in Slovenia (out of all prevalent RRT

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Patients Refusing Kidney Transplantation CONCLUSION There is a considerable group of dialysis patients in Slovenia refusing kidney transplantation. Compared to the kidney transplant candidates, they are similar in age, gender, and prevalence of diabetes. Patients treated by peritoneal dialysis refuse kidney transplantation less often than hemodialysis patients.
Acknowledgments: We would like to thank all the members of the Slovenian Renal Replacement Therapy Registry Group for providing data to the Registry.

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