Workload generated by a living donor programme for renal transplantation

Richard N. Saunders, Rosemary Elwell, Gavin J. Murphy, Terry Horsburgh, Susan J. Carr and Michael L. Nicholson

Leicester General Hospital, Leicester, UK



   Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. The ethical and medical implications of live kidney donation result in a comprehensive work-up process. The aim of this study was to determine the magnitude of the workload and the yield of renal transplants generated by a live donor programme.

Methods. Referrals to the Leicester live donor programme over the five-year period 1994–1998 were retrospectively assessed. These were initiated by nephrology referral and subsequently investigated in a stepwise manner. Patients were counselled and baseline tests performed prior to consultant surgeon review and assessment of donor renal function/anatomy.

Results. One hundred and fifty referrals consisting of 150 recipients with 269 potential donors were originally made. This resulted in 32/120 (27%) related and 3/30 (10%) unrelated recipients (P=0.06) and 32/220 (15%) related and 3/49 (6%) unrelated donors proceeding to live donor transplantation, with a mean work-up time (±SD) of 9 (±7) months. One hundred and fifteen recipients (77%) and 234 (87%) donors failed to proceed at various stages of assessment, for a variety of immunological, medical and social reasons. A large number of expensive immunological investigations were required for potential donors, the majority of which did not proceed to transplantation. However as a result of performing these in the early stages of assessment the number of more invasive tests is kept to a minimum.

Conclusions. There is a relatively low yield of transplants from live donor referrals, particularly those between unrelated individuals. The vast majority of referrals fail to proceed for legitimate reasons, but as a result, create a significant workload with notable staffing and financial implications.

Keywords: live organ donor; renal transplant; workload



   Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Renal transplant programmes throughout the UK are suffering from an increasing shortage of cadaveric kidneys. In 1998 there were 4635 patients on the UKTSS waiting list but only 1373 transplants were performed from cadaveric donors, a fall of 11% from the previous year. In order to compensate for this shrinking pool of organ donors many units run a live donor programme and in 1998 there were 240 such renal transplants, an increase of 38% from the previous year. Recipients of these organs have consistently been shown to have longer graft survival than those receiving cadaveric organs [13].

There are a number of principles that govern the approach to live organ donation. First, to protect the donor from harm; secondly, to protect the recipient from harm and ensure as good an outcome as possible; whilst thirdly, avoiding unnecessary investigations and procedures. Three specific objectives stem from these principles: (i) to identify contraindications early, (ii) to identify and avoid unreasonable risks and (iii) to obtain good quality consent [4]. An important aspect of live organ donation that has not been emphasized is that, because of these considerations, a significant proportion of live donor referrals will not result in transplantation. This creates a large additional workload for transplant units, frequently with an unsuccessful outcome. The aim of this study was to determine the magnitude of this workload over a 5-year period and to investigate why referrals for live kidney donation result in a relatively low yield of renal transplants. This should allow for more efficient use of both staff and resources in the future.



   Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The work-up process for live organ donation in Leicester has evolved into a stepwise process, with a clear sequence of events. Referrals can be found to be inappropriate at any stage.

Work-up process for live kidney donors, Leicester 1994–1998

  1. Nephrology referral
  2. Co-ordinator counselling and ABO Group/Virology
  3. Tissue typing
  4. Consultant surgeon opinion and counselling
  5. Cytotoxic cross match (including flow cytometry)
  6. Donor glomerular filtration rate (GFR)
  7. Donor IVU and renal arteriogram or spiral abdominal CT
  8. Repeat pre-operative cytotoxic cross matching/ULTRA application
All potential renal transplant recipients in Leicester are asked to attend a monthly information meeting, in order to educate them about what to expect before, during and after transplantation. Live donor transplants are mentioned at this meeting, but a formal referral from a consultant nephrologist to a designated transplant co-ordinator is required before work-up is initiated. A proactive attitude was adopted by nephrologists in suggesting both related and unrelated living donation as an option to patients and their families.

After referral, donors and recipients are counselled by the transplant co-ordinator and blood is taken to determine blood group compatibility, viral serology and tissue type. If after this they are still candidates to proceed, the donor and recipient receive an appointment to see the consultant surgeon. Both are counselled further by the surgeon, before a detailed donor history and examination is undertaken. Routine urinalysis, urine culture, serum haematology/biochemistry, ECG and CXR are performed with the aim of excluding donors that are medically unfit for surgery at a relatively early stage. A cytotoxic and flow cytometric cross match are also requested at this stage. Renal function is assessed using a single shot radioisotope (Cr-51 labelled EDTA) GFR measurement. Assuming that the results from these investigations are satisfactory, further tests are performed to establish the excretory, arterial and venous anatomy of the donor kidneys. This was originally the function of the IVU and renal arteriogram but in the latter part of 1998 contrast-enhanced spiral abdominal CT scans have superseded these. Immediately before proceeding to transplantation it is mandatory to repeat the cytotoxic cross match to ensure that the potential recipient has not generated new antibodies over the work-up period. If the donor and recipient are unrelated, then a formal ULTRA application is completed and approval awaited before transplantation can occur.

A retrospective review of the referrals received over the 5-year period between 1994 and 1998 was performed. The stage in assessment reached, the reason for failure to proceed beyond this, and the specific investigations performed, were documented in each case.



   Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Between January 1994 and December 1998 a total of 150 potential recipients were referred to the programme. There were 269 potential donors assessed, with a median of two donors per recipient (range 1–8). One hundred and twenty (80%) potential recipients were referred with related donors (n=220) and 30 (20%) were referred with unrelated donors (n=49). Two recipients had both related (n=3) and unrelated (n=2) potential donors. Only 35 live donor–recipient pairs resulted in successful transplantation. Therefore only 35/150 (23%) potential recipients and 35/269 (13%) potential donors proceeded to this stage, the vast majority of these being related to one another (Table 1Go). Despite the low yield, live donor allografts constituted 16.4% of the total number of renal transplants performed in Leicester over this time period, comparing favourably with the UK figure of 11.9% (UKTSS 1994–1998). These successful live donor transplants had a mean work-up time (±SD) of 9.3 (±6.5) months, with the range varying between 3 and 39 months.


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Table 1. Live donor renal transplants (Leicester 1994–1998)

 
Sixty-two (41%) recipients of whom 51/120 (43%) had related and 11/30 (37%) unrelated donors, were lost or held between initial interview with a transplant co-ordinator and consultant surgeon counselling (Figure 1Go). There were three main reasons for this. First, 27/62 recipients withdrew for various socio-economic reasons after a discussion about the pros and cons of live organ donation between the potential recipient, donor(s) and transplant co-ordinator. Secondly, in 20/62 cases, blood group incompatibility between potential donor and recipient led to withdrawal. Thirdly, 8/62 recipients had ongoing medical problems identified during routine nephrology review.



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Fig. 1. Recipients excluded before consultant surgeon review, n=62/150 (41%).

 
Two out of three potential donors (n=181) did not proceed beyond an early stage; most frequently because another potential donor had a better HLA tissue match with the recipient (n=74), or because of ABO incompatibility (n=48) (Table 2Go). Related donors were more likely than unrelated donors to be excluded because another donor had a better tissue match with the recipient (P<0.05, Fisher's exact test). A greater proportion of unrelated compared to related donors withdrew for socio-economic reasons (P<0.05, Fisher's exact test). The grounds for this were diverse, but commonly included reasons such as the potential donor was the major financial contributor to the family income, had significant commitments to dependent family members, or was concerned about future children developing chronic renal failure when there was a hereditary component to this, e.g. Alports syndrome.


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Table 2. A comparison of the reasons that donors are excluded from further assessment prior to consultant surgeon review

 
Eighty-eight (58.7%) referrals consisting of one donor per recipient saw a consultant surgeon. Sixty-nine (78%) were related and 19 (22%) unrelated. Only 35 (40%) proceeded to surgery, 32 related and three unrelated referrals. Therefore 53 (60%) were lost or remained in the follow-up process. Although the number of unrelated referrals reaching this stage was relatively small, there was a lower probability that they would proceed to transplantation when compared to related referrals (P<0.05, Fisher's exact test). The reasons for failure to proceed to operation following consultant surgeon review are considered below (Figures 2Go and 3Go).



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Fig. 2. Donor/recipient referrals excluded after consultant surgeon review, n=53/150 (36%).

 


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Fig. 3. A comparison of related and unrelated referrals that did not produce a live donor transplant after consultant surgeon review. *Fisher's exact test.

 
Twenty-two referrals remained in the work-up system for living related donation at the end of 1998. Thirteen had a positive cytotoxic cross match and nine were awaiting completion of investigations. Sixteen referrals were ruled out as the donor was found to be unsuitable for kidney donation. Five followed a positive cytotoxic cross match, three had inadequate GFR (<80 mls/min/1.73m2), two had renal calculi, two had cardiac problems, one was hypertensive, one was morbidly obese, one had impaired glucose tolerance and one was injured in a road traffic accident. Five referrals withdrew from work-up, three for social reasons and two following the recipient's decision to wait for a cadaveric kidney. Significantly more unrelated than related referrals (P=0.025, Fisher's exact test) decided to withdraw at a late stage, despite having a complete work-up. The transplant team withdrew two referrals. This included a donor who was being coerced at knifepoint to donate and a case where the recipient was deemed unsuitable for transplantation due to the discovery of metastatic cancer. Eight referrals failed to proceed as the recipient received a cadaveric kidney.

In view of the high referral dropout rate throughout the assessment process, the number of investigations and the cost of each of these excluding labour was examined (Table 3Go). This shows a plethora of investigations particularly in the early stages of work-up. The most frequent are the costly immunological tests such as tissue typing that are performed on a large number of individuals in order to ensure the best matched donor is worked up. In addition, flow cytometry and cytotoxic cross matching are often repeated throughout the work-up of referrals, particularly if these have been positive in the past, there is prolonged work-up, or patients have had blood transfusions/blood products over this period. More interventional investigations occurring later in work-up are only performed in donors with a significant chance of proceeding and are thus limited in frequency.


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Table 3. Number and cost of investigations performed by the live donor programme 1994–1998

 



   Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Over the 5-year period from January 1994 to December 1998, despite a concerted effort, only 23% of potential recipients and 13% of potential donors successfully completed the work-up process resulting in 35 live donor kidney transplants. The only similar study in the literature by a team from The Netherlands reported that 34% of donors assessed produced successful live donor transplantation [5]. This study had very few referrals that withdrew for personal or socio-economic reasons, in contrast to our findings, and this may account for the difference observed.

In order to achieve these results, 269 donors were assessed; the vast majority of whom did not proceed to transplantation. It is clear that the number of investigations performed vastly exceeds the number of referrals that proceed to transplantation, particularly in the early stages of work-up where the greatest dropout occurs. This has significant implications for the staff required to organize, perform and follow these up. In addition, immunological tests undertaken early in the work-up process on a large number of referrals have significant cost implications. The financial issues and extra workload need to be considered when funding and staff are allocated to run live kidney donor programmes. These factors may help to explain the lack of enthusiasm for this source of organs in the UK compared with Europe and the US [67], despite the well-documented benefits for recipients [13] and communities alike [8].

There is considerable variation in the organization of live kidney donor evaluation and the methods of assessment used [9]. In Leicester, a clearly defined stepwise process with a clear sequence of events has been developed. This allows for efficient use of resources and also protects the potential donor from more invasive procedures e.g. arteriography, until there is a reasonable chance that donation will occur [10]. The live donor programme is organized by a transplant co-ordinator who also maintains a regular commitment to routine duties. Therefore the assessment of referrals can take a reasonable length of time (mean=9.3 months). A significant number of referrals are lost after co-ordinator counselling or because of blood group incompatibility. Referrals were not excluded on the basis of HLA mismatch between donor and recipient but if there were multiple potential donors then they all underwent blood grouping and tissue typing in order to identify the best match. Although uneconomical this is undertaken to optimize the outcome for the potential recipient and thus to maximize the benefits from the donated organ.

Several recommendations can be made to increase the efficiency of the assessment in the early stages, reducing the delay between referral and potential surgery and thus allowing pre-dialysis transplantation and limiting the complications associated with long-term dialysis. Assessment of donor/recipient blood group could be performed in the nephrology clinic and only those who were ABO compatible referred. This could be extended so that nephrologists arrange the tissue typing of potential referrals and choose the best HLA matched donor for further assessment, thus discarding mismatched donors prior to the formal referral and allowing the co-ordinator to concentrate on a smaller number of potential donors. In addition a full-time live-donor co-ordinator would be completely focused on the programme, therefore providing a more rapid and efficient assessment of referrals. Over the last 2 years in Leicester this has allowed the co-ordinator to organize cross matches on donor–recipient pairs prior to the consultant surgeon review, thus preventing referrals with a positive cross match from making an unnecessary visit to a transplant surgeon.

About 40% of referrals that see a consultant surgeon are excluded on immunological or medical grounds, thus justifying a thorough clinical work-up. There is an almost universal acceptance that this is necessary in order to ensure good donor and recipient outcome [10,11]. Beekman et al. [5] implicate medical and immunological reasons for failing to proceed in 65% of referrals. Although this is an issue in Leicester, other factors such as withdrawal for socio-economic reasons were also important.

Potential recipients with related donors are more likely to proceed to transplantation after consultant surgeon review than those from unrelated donors. An explanation may be that 25% of unrelated referrals intentionally withdrew during the later stages of the work-up process compared to 3% of related referrals. Although the number of referrals is small, this may reflect a lesser commitment on the part of unrelated donors and recipients to live kidney donation. Further support for this can be found in the early stages of work-up where a greater proportion of unrelated compared to related donors withdrew from assessment for personal/socio-economic reasons. If a transplant unit is to encourage unrelated organ donation, a more thorough initial counselling session may be necessary for this type of referral in order to wean out those less enthusiastic donors at an earlier stage.

A significant proportion of donors (42%) remain in the work-up system after consultant surgeon review. These can be divided into a group undergoing prolonged work-up (13/22) and those with a routine work-up (9/22). The individuals with prolonged work-up have had a previously positive cytotoxic cross match/flow cytometer cross match (FACS) that prevented transplantation. However, they remained as potential donors having this repeated regularly to see if it changed over time. It is well documented that serum antibody levels can vary [12] and therefore could theoretically be low enough at some stage to allow safe transplantation. Despite this, a live donor transplant has not been performed in such circumstances and therefore it would seem sensible to limit the number of repeat cross matches/FACS on these referrals in future.

A small group (15%) of donors is extensively investigated following consultant surgeon review only for the recipient to receive a cadaveric transplant. This not only exposes the potential donor to unnecessary risk but is also an inefficient use of resources. Therefore, a suggestion would be to remove recipients from the cadaveric waiting list once the potential donor has had a negative cytotoxic cross match, and thus has a reasonable chance of live kidney donation.

In conclusion, despite a concerted effort to encourage live organ donation over a 5-year period, there was a relatively low yield of actual transplants from such donors. The vast majority of referrals failed to proceed for legitimate reasons and their work-up was conducted in a safe and efficient manner. Several changes to current practice are recommended to increase the efficiency of work-up. These include blood grouping and tissue typing of candidates in nephrology clinics, employment of a full time live donor co-ordinator, earlier initial cross match, limitation of repeat cross matches, more in-depth counselling of unrelated referrals and removal of recipients from the cadaveric waiting list at an appropriate time. These changes should allow the workload generated by the live donor programme to be streamlined thus allowing efforts to be focused on the recruitment of donors and recipients for the future.



   Notes
 
Correspondence and offprint requests to: Mr R. N. Saunders, Transplant Fellow, University Department of Surgery, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. Back



   References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Jones J, Payne WD, Matas AJ. The living related donor-risks, benefits and related concerns. Transplant Rev1993; 7: 115–128
  2. Cecka JM, Terasaki PI. The UNOS scientific renal transplant registry. Los Angeles, UCLA Tissue Typing Laboratory. Clin Transplant1993: 1
  3. Cecka JM, Terasaki PI. The UNOS scientific renal transplant registry. Los Angeles, UCLA Tissue Typing Laboratory. Clin Transplant1992: 1
  4. Nicholson ML. Meeting the challenges of live donation—donor assessment. J R Col Phys Lond1998; 32: 479–481
  5. Beekman GM, Van Dorp WT, van Es LA, van Bockel JH, van Saase JL, van der Woude FJ. Analysis of donor selection procedure in 139 living related kidney donors and analysis of the results for donors and recipients. Nephrol Dial Transplant1994; 9: 163–168[Abstract]
  6. Price DP. The Eurotold project. Ann Transplant1998; 3: 34–37
  7. Shapiro R, Simmons RL, Starzl TE. The living donor. Renal Transplantation1997, Appleton & Lange, Stamford, USA. Chapter 3: 87
  8. de Charro F, de Wit A. An appraisal of living donor kidney transplantation. Trans Proc1996; 28: 3559–3561[ISI]
  9. Lumsdaine JA, Wigmore SJ, Forsythe JLR. Live kidney donor assessment in the UK and Ireland. Br J Surg1999; 86: 877–881[ISI][Medline]
  10. Veitch PS. Evaluation of the potential living kidney donor. Trans Proc1996; 28: 3553–3555[ISI]
  11. Kasiske BL. The evaluation of potential renal transplant recipients and living donors. Surg Clin North Am1998; 78: 27–39[ISI][Medline]
  12. Taube DA, Williams DG, Cameron JS et al. Renal transplantation after removal and prevention of resynthesis of HLA antibodies. Lancet1984; 1: 824–826[Medline]
Received for publication: 17.12.99
Revision received 4. 5.00.