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Screening and Follow-Up of Living Kidney Donors: A Systematic Review of Clinical Practice Guidelines

Tong, Allison1,2,5; Chapman, Jeremy R.3; Wong, Germaine1,2,3; de Bruijn, Jeanine1,4; Craig, Jonathan C.1,2

doi: 10.1097/TP.0b013e3182328276
Editorials and Perspectives: Overview
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To minimize the health risks faced by living kidney donors, multiple clinical practice guidelines have been developed on the assessment and care of potential donors. This study aims to compare the quality, scope, and consistency of these guidelines. We searched for guidelines on living kidney donation in electronic databases, guideline registries, and relevant Web sites to February 21, 2011. Methodological quality was assessed using the Appraisal of Guidelines for Research and Education (AGREE) instrument. Textual synthesis was used to compare guideline recommendations. Ten guidelines, published from 1996 to 2010, were identified. Although generally comprehensive, scope varied considerably and mostly appeared to lack methodological rigor. Many recommendations were consistent, but important differences were evident, particularly for thresholds for comorbidities which precluded donation; obesity/overweight (body mass index, 30–35 kg/m2), diabetes/prediabetes (fasting blood glucose level, 6.1–7.0 mmol/L and oral glucose tolerance test, 7.8–11.1 mmol/L), hypertension (130/85 to 140/90 mm Hg), cardiovascular disease, malignancy, and nephrolithiasis. The importance of informed voluntary consent, genuine motivation, support, and psychological health were recognized but difficult to implement as specific tools for conducting psychosocial assessments were not recommended. Multiple major guidelines for living kidney donation have been published recently, resulting in unnecessary duplicative efforts. Most do not meet standard processes for development, and important recommendations about thresholds for exclusion based on comorbidities are contradictory. There is an urgent need for international collaboration and coordination to ensure, where possible, that guidelines for living donation are consistent, evidence based, and comprehensive to promote best outcomes for a precious resource.

1 Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.

2 School of Public Health, The University of Sydney, Sydney, NSW, Australia.

3 Centre for Transplant and Renal Research, Westmead Hospital, NSW, Australia.

4 Faculty of Social and Behavioural Sciences, University of Amsterdam, Amsterdam, Netherlands.

This work was supported by the National Health and Medical Research Council Capacity Building Grant in Population Health ID 457281.

The authors declare no conflicts of interest.

5 Address correspondence to: Allison Tong, Ph.D., Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW 2145, Sydney, Australia.

E-mail: AllisonT@health.usyd.edu.au

A.T. developed the manuscript outline and drafted the manuscript. A.T., G.W., J.R.C., and J.C.C. contributed the study design, provided intellectual input on the manuscript, and contributed to writing the manuscript. A.T. and J.dB. collected and analyzed the data. A.T. is the guarantor.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.transplantjournal.com). A combined file of all SDC is available as SDC 1 (http://links.lww.com/TP/A519).

Received 31 May 2011. Revision requested 22 June 2011.

Accepted 11 August 2011.

Because of the severe shortage of deceased kidney donor organs worldwide, living kidney donation has been accepted in most transplant centers to increase the supply of kidneys for transplantation (1). However, there is variability and lack of consensus in the screening and care of living kidney donors (2, 3).

In some countries such as the United Kingdom, United States, and Australia, live organ donation represents approximately one-half of all kidney transplants (4–6). Although living kidney donation is associated with better recipient outcomes compared with deceased kidney donation, donors face risks including surgical-related complications, death, and potential long-term physical and psychosocial problems (7, 8). Long-term outcomes are largely unknown as the majority of studies are retrospective, have a large loss to follow-up, and a small sample size (9). There are even less data on long-term outcomes of donors who do not meet what are typically high threshold criteria for suitability, including hypertensive or overweight donors (6). Some studies have found that donation may be a potential risk factor for hypertension, proteinuria, and cardiovascular events (10, 11). Although there are no apparent intrinsic clinical benefits for live donors, studies have shown that most donors perceive unchanged or improved psychosocial well-being after donation (12). Such data are problematic because these studies have used a noncomparable control, that is, eligible donors who did not undergo nephrectomy, but rather healthy eligible donors with the normal population (13).

Clinical practice guidelines and consensus statements provide explicit recommendations to influence clinical decision making, (14) to minimize acute surgical morbidity, mortality, and psychosocial harms in living kidney donors. This study aims to compare the quality, scope, and consistency of these guidelines.

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Search and Characteristics of Guidelines and Consensus Statements

The search yielded 922 articles. Of these, 870 were excluded after title and abstract review for ineligibility. Of the remaining 52 potentially eligible articles, 42 were excluded because they were review articles, editorials/opinions, primary research, or guidelines replaced by more recent guidelines. Nine clinical practice guidelines (15–23) and one consensus statement (24) were included (see SDC 2, http://links.lww.com/TP/A520).

The characteristics and process of the guidelines and consensus statements are provided in Tables 1 and 2. They were published between 1996 and 2010, from Australia, United Kingdom, United States, Continental Europe, and Canada. Three guidelines covered living organ donation broadly (17, 19, 21) and seven included recommendations specifically for living kidney donors (15, 16, 18, 20, 22–24). Four reported undertaking a structured review and appraisal of the evidence and were explicit about the level of evidence underpinning the recommendations (16, 18, 19, 23) and one graded their recommendations (18).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

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Appraisal of Guidelines and Consensus Statements

Interrater assessment for each guideline and consensus statement ranged from slight κ=0.30 (95% CI: 0.00–0.60) to substantial agreement κ=0.78 (95% CI: 0.61–0.94) (25, 26). Interrater agreement for across all guideline and consensus statement was good, with an overall weighted kappa coefficient of 0.60 (95% CI: 0.51–0.68) (25, 26).

Table 3 indicates the domain scores for each guideline according to the six Appraisal of Guidelines for Research and Education (AGREE) domains. The mean score (and range) for the domain scope and purpose across all guidelines was 77.5% (44%–100%). On average, 53.2% (17%–96%) of the criteria in the domain for stakeholder involvement were met. For rigor of development, the overall mean score was 43.4% (14%–86%), six scoring less than 50%. The overall mean score for clarity and presentation was 71.0% (29%–92%), two scoring less than 50%. Applicability had a mean score of 27.3% (0%–56%). The overall mean score for editorial independence was 44.2% (17%–100%).

TABLE 3

TABLE 3

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Textual Descriptive Synthesis

Screening

Assessment Team

To minimize conflict of interest, guidelines recommended an independent assessment of the potential donor by healthcare providers not involved in the recipient's care and in the absence of the potential recipient and their family (15–18, 20, 23). However, this was not mandated due to possible resource constraints. Nephrologists should assess the medical suitability, and surgeons should be responsible for assessing surgical risk in potential donors (15, 20). Additional specialist opinion should be sought if the donor has a history of significant non-nephrological health problems (15, 20). Psychological assessments should be completed by an experienced and trained mental health professional (15, 17–22). A decision to proceed or to reject live donor transplant should reflect general agreement between members of the transplant assessment team, and any conflict should be resolved with additional independent assessment of suitability (16).

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Donor Characteristics

Four guidelines explicitly stated that minors (younger than 18 years of age) should not donate (18, 20, 23, 24). However, three stated that minor donors could be considered under “exceptional” circumstances—if permissible by law, the recipient had no donor alternative, and the minor underwent an intensive process of informed consent (15, 17, 21). Guidelines suggested that older donors (i.e., >70 years) should be evaluated on an individual basis and may be considered for recipients older than 60 years (18). There were few specific guidelines on the evaluation of women especially of child-bearing age, apart from recommending that they should be considered but should undergo a beta-hCG test; guidelines advised against nephrectomy during pregnancy (16, 22, 24). One guideline specified the right kidney is preferred for nephrectomy in women of child-bearing age as the left kidney is protected from the hydronephrosis of pregnancy (22). Two guidelines stated that ABO incompatible transplantation should only be permitted if there were mechanisms in place to support the management of the recipient, and recipients should be counseled about the potential risks (15, 18).

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Medical Contraindications

The recommendations for the medical screening are provided in Tables 4 and 5. The guidelines recommended an assessment of kidney function, usually on the basis of serum creatinine (CG formula, modification of diet in renal disease) or direct evaluation (nuclear glomerular filtration rate [GFR]); and anatomical suitability for all potential donors. The suggested GFR cut-off was 80 mL/min/1.73 m2 or a GFR below normal for the person's age, some indicated that lower GFR cut-offs could be considered for older donors. Guidelines indicated that proteinuria (24-hr urine >300 mg/day) (15, 16, 18, 20, 22, 24) and microalbuminuria (cut-off range, 20–30 mg/day) (16, 18, 22, 24) could be contraindications for live donation. No absolute recommendations were made for microscopic hematuria except that underlying urological or kidney disease should be investigated.

TABLE 4

TABLE 4

TABLE 4

TABLE 4

TABLE 5

TABLE 5

There were variations in the coverage and thresholds for comorbidities including obesity (body mass index [BMI], 30–35 kg/m2), impaired glucose tolerance (fasting blood glucose level, 6.1–7.0 mmol/L), hypertension (130/85 to 140/90 mm Hg), cardiovascular disease, and malignancy. The guidelines indicated that obesity was associated with an increased risk of surgical complications though it may not affect graft quality. Current diabetes was a contraindication but a person with a risk of developing type 2 diabetes (based on age, family history, obesity, ethnicity, and smoking status) could be considered. Some guidelines recommended that a 2-hr oral glucose tolerance test should be performed for individuals with impaired fasting blood glucose greater or equal to 6.1 mmol/L on two or more occasions. However, the 2-hr oral glucose tolerance test threshold for absolute contraindication ranged from 7.8 to 11.1 mmol/L. Some guidelines stated that specific populations including Southern Asian, Caribbean, African Americans, Native Americans Hispanic, Aboriginal, and Torres Strait Islanders were at an increased risk for diabetes and progressive complications (15, 16, 20, 22). Gestational diabetes was indicated as a risk factor for diabetes mellitus (20, 22) and one guideline recommended that it should be an absolute contraindication for living kidney donation (16). Potential donors with poorly controlled blood pressure should be excluded; with a stricter threshold applied to younger donors. Cardiovascular disease or having risk factors for cardiovascular disease (elevated cholesterol and family history) was indicated as an absolute contraindication (15–18, 20, 24).

Recent or current malignancy was indicated as an absolute contraindication to nephrectomy; except for low-grade nonmelanoma skin cancer and carcinoma in situ of the uterine cervix (15, 18, 20, 22, 24). Exclusion from nephrectomy was recommended for patients with a history of malignancy (especially cancers with long times to recurrence) unless the treatment of the malignancy will not decrease kidney function or increase the risk of end-stage kidney disease or surgical risk of nephrectomy. Recommendations for cancer screening were provided in three guidelines (15, 20, 23). Except for Papanicolaou test recommended for all women, screening for cancer was deemed necessary only on the basis of cancer history, family risk and age. Prostate-specific antigen was recommended for potential donors older than 50 years, mammogram for women older than 40 years, and colonoscopy for individuals older than 50 years.

Across guidelines, a wide range in scope and recommendations for other medical considerations including infectious disease and nephrolithiasis were apparent. Five provided recommendations for screening for infectious disease (15, 20, 22–24). Standard screening for cytomegalovirus, Epstein-Barr virus, Herpes Simplex virus, human immunodeficiency virus, human T-lymphotropic virus, Hepatitis B and C, and tuberculosis were recommended, whereas decisions to screen for other infectious diseases such as malaria should be based on geographical risk. Nephrolithiasis was not an absolute contraindication for living donation; however, five guidelines recommended that patients with nephrocalcinosis or bilateral stone disease, metabolic conditions, obstructions, multiple stones, or have kidney stones that have potentially high recurrence rates should not donate (15, 18, 22–24).

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Psychosocial Assessment

The importance of a thorough psychosocial assessment was recognized, however most guidelines did not offer detailed guidance on how to operationalize key principles of ensuring genuine altruistic motivations, safeguarding voluntary consent, and evaluating mental suitability. Only two included specific questions for conducting a psychological assessment (17, 20). The domains covered by guidelines on the psychosocial assessment and screening are illustrated in SDC 4 (http://links.lww.com/TP/A522).

Informed voluntary consent: All guidelines and statements agreed on the importance of obtaining voluntary, informed consent. Risks associated with nephrectomy, mortality, short- and long-term complications; and potential impact on employment and financial status should be discussed (15–17, 19, 20, 23). Also, donors had to be willing, able to withdraw at any time, and free from coercion. Some emphasized that donors needed to have a realistic expectation of the recipient outcomes (15–17, 19–21, 23). One guideline recommended a “cooling off period” between consent and donation (19).

Motivation: Guidelines recommended that the assessment team should be sure that the donor would not be receiving payment for donating a kidney. Direct payment was not recommended, however, some discussed donor reimbursement for donation-related expenses (15, 17–19, 21, 22). One guideline specifically addressed altruistic, nondirected living kidney donors, and recommended that nondirected donation should only proceed if there was no active recruitment or incentives involved, and any unrealistic expectation or ill-motivations should be identified (19).

Mental illness: All guidelines recommended an evaluation of the donor's psychological status and history including depression, anxiety, medication dependency, self-harming behavior, and impaired cognitive capacity. Potential donors had to be carefully considered if they had current or former psychiatric illness or a history of substance abuse (15, 17, 19, 20, 22, 23).

Support: Most guidelines recommended that donors should have adequate social support and coping mechanisms (15–17, 19, 20, 22). The relationship between the potential donor and their recipient should be evaluated to address imbalance of power, conflict, and expectations (15–17, 19–22, 24). Three recommended that donors have health insurance (15, 17, 20).

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Surgical Techniques

Three guidelines (15, 16, 18) discussed the surgical techniques in living donor nephrectomy. The guidelines stated that recipient outcomes are equivalent with laparoscopic and open live donor nephrectomy, although, laparoscopic surgery can offer benefits to the donor including reduced analgesic requirements, earlier return to normal activities, less postoperative pain and in-patient stays. It was strongly advised that trained and experienced surgeons should perform laparoscopic surgery.

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Follow-Up

Postsurgical Care

There was some variability in the scope of recommendations for postsurgical care. Some guidelines covered the management of surgical pain (15, 16, 18, 20, 22) infections (16, 17, 24). Abstinence of smoking and alcohol was recommended by two guidelines/consensus statements (20, 24).

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Medical Assessment

All guidelines and the consensus statement recommended follow-up assessment of kidney function (15–18, 20, 24), hypertension and diabetes (15–17, 20, 24), and obesity (15, 16, 20, 24). Three advised that pregnancy should only occur at least 2 months after nephrectomy (15, 16, 24). For patients with a history of stone disease, long-term follow-up for early detection of urinary sepsis, metabolic abnormalities, or recurrent strong formation was recommended (15). Guidelines suggested that donors should be actively followed for at least 12 months (17) or 24 months (20) by the transplant center, then life-long follow-up for example in local general practice (15, 17, 20).

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Psychosocial Follow-Up

Most guidelines recommended follow-up psychosocial assessment (15–17, 19, 20). One guideline recommended extensive psychological support for donors whose recipient had a poor outcome (16) and recommended follow-up assessment of donor-recipient relationship (15, 19). The SF-36 Health Survey was suggested by one guideline (19), and another guideline provided a question schedule to assess the donor's psychosocial status (20).

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CONCLUSION

Current guidelines are generally comprehensive, but scope varied considerably and mostly seemed to lack methodological rigor. Many recommendations were consistent but important differences were evident, particularly for thresholds for comorbidities which precluded donation; obesity/overweight, diabetes, hypertension, cardiovascular disease, malignancy, and nephrolithiasis. The recommendations were underpinned by expert opinion or sparse evidence. A discrepancy across guidelines concerned the acceptance of minor (<18 years) kidney donors. In the United States, minors could be considered only if no alternative donor or opportunities for transplant exists; and the donor is approved by a court, completes a rigorous psychosocial evaluation, and gives informed consent (27–29). The importance of informed voluntary consent, genuine motivation, support, and psychological health were recognized but difficult to implement as specific tools for psychosocial assessments were not recommended.

The lack of high-quality outcome data for living kidney donors and uncertainties in estimating risks in live donation may explain the variability in the “strictness” of medical criteria indicated in current guidelines. The recommended GFR threshold was consistent. However, estimated GFR is usually used in the CKD population, less reliable for GFRs greater than 60 mL/min (30), and serum creatinine is affected by age, race, and muscle mass (31). Direct measurements of GFR are usually expensive, time consuming, and not readily available. The “normal” decline of GFR meant a lower GFR may be deemed acceptable in older donors. Long term, direct data on outcomes of patients with impaired glucose tolerance, hypertension, obesity, or nephrolithiasis (or a combination of these risk factors) who have donated a kidney is sparse (32). People with diabetes or impaired glucose tolerance are generally excluded due to the risk of developing metabolic disease such as hypertension, vascular, and CKD. Hypertension was indicated as a relative contraindication to donation but the associated long-term risk of hypertensive cardiomyopathy and cardiac failure is uncertain. As a risk factor for perioperative complications, type 2 diabetes, hypertension and cardiovascular disease, and obesity (30 kg/m2) were relative contraindications for living kidney donation; morbidly obese (BMI greater than 35 kg/m2) was an absolute contraindication. Again, there is little evidence to support an absolute BMI threshold. Individuals with current or a history of malignancy with a long time to recurrence should be generally precluded from live donation. Recipient malignancy from a donor organ is rare but detrimental (33), and data on cancer transmission from donors to recipients are limited to case reports and case series.

Psychosocial assessment and follow-up of living kidney donors was recommended to protect ethical standards underpinning living kidney donation. However, specific guidance and implementation tools for evaluating the psychosocial status of living kidney donors were lacking. The development or the inclusion of standardized or validated tools may improve the applicability and implementation of the recommendations in clinical practice. Quality of life of living donors have been assessed with generic instruments including the Medical Outcomes Study Short Form (SF-36) (34, 35) and WHO quality of life questionnaire (36). No QOL tool has been derived specifically for living organ donors.

Patient involvement in the development of clinical practice guidelines has been advocated (37, 38). Only one guideline was explicit about patient involvement (15). Living kidney donors should be actively involved in guideline development, for example, through participating in interactive, facilitated patient feedback workshops (39, 40), to ensure that their medical and quality of life concerns are incorporated in guideline recommendations. For example, the efficiency of health service delivery received little attention in guidelines, yet unnecessary delays can instigate undue stress and worry for donors, particularly if their recipient's kidney function is deteriorating (41). Despite reports of donor depression and suicide after the death of the donor's recipient (42, 43), few guidelines provide recommendations on supporting donors in the event of recipient death. Paired kidney exchange, in which a live kidney donor donates to a compatible recipient in order for another donor to donate to the original donor's recipient (44) has particular logistical, legal and ethical challenges, and more complex psychosocial implications. Such programs are expanding; therefore, guidelines addressing psychosocial and ethical issues for “newer” types of living kidney donation are needed. In 2002, a discussion forum on nondirected living donors covered topics unique nondirected donors including the following: motivations (altruism, religious beliefs, and reciprocate to society), compensation, acceptance of prisoners, anonymity, and media involvement (45).

In our study, we used a validated and reliable instrument to appraise the guidelines and consensus statement and there was fair agreement between reviewers. But, our study has limitations. Our assessment was based on what the guideline organizations reported, and we did not confirm with guideline developers whether they met AGREE criteria in practice. However, contacting guideline developers is not standard practice when using the AGREE instrument as the instrument specifically aims to provide a framework for assessing the quality of reporting and the quality of some aspects of recommendations. The inter-rater variability may be due to the differences in interpretation of AGREE items where the instructions for assessing each item were broad, vague, or included multiple domains; which has also been observed in other studies (46). Another limitation of the study was the exclusion of non-English guidelines due to translation restrictions, and therefore the transferability of our findings to other settings is uncertain.

Suitability for living kidney donation is usually made under the discretion of the transplantation team. Given the lack of high quality evidence (8, 32) and variability in the scope and content of guidelines, decisions are often implicitly made; resulting in inconsistencies and variability in practice. Long-term, prospective cohort studies are needed in the living kidney donor population to assess physical and psychosocial outcomes after nephrectomy, and we suggest that living donor registry data be mandated. We also recommend longer term follow-up and monitoring by healthcare providers, education and support to maintain a healthy lifestyle, and early detection and management of potentially modifiable risk factors.

The outcomes for living kidney donors from ethnic population sub-groups and donors with health risk factors are largely unknown. We suggest that clinical practice guidelines be developed and implemented with careful consideration of the differences in potential benefits, side effects, risks, and complications between different populations, settings and healthcare contexts. In cases where a donor is from an ethnic minority group, it may be necessary to refer to clinical practice guideline developed locally in the donor's country of origin.

Multiple major guidelines for living kidney donation have been published resulting in unnecessary duplicative efforts. Most do not meet standard processes for development, the recommendations are predominantly based on expert opinion or weak evidence, and important recommendations about thresholds for exclusion based on comorbidities are contradictory. There is an urgent need for international collaboration and coordination to ensure, where possible, that guidelines for living donation are consistent, evidence-based and comprehensive, to promote best outcomes for a precious resource.

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MATERIALS AND METHODS

Selection Criteria

Evidence-based clinical practice guidelines (“systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances” [47]) and consensus statements (documents containing clinically relevant suggestions or recommendations based on the collective opinion of an expert panel) that focused on screening and follow-up of living kidney donors were included. Non-English publications were excluded to prevent cultural and linguistic bias in translations. Draft unpublished guidelines, conference or discussion papers, opinions, and guidelines replaced by updated recommendations were excluded.

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Search for Guidelines and Consensus Statements

MeSH terms and text words for living kidney donor were combined with terms relating to clinical practice guidelines and consensus statements (see SDC 3, http://links.lww.com/TP/A521). The searches were carried out in Medline (1948 to February Week 2, 2011), EMBASE (1980 to Week 11, 2011), and PsycINFO (1906 to Week 3, 2011). We also searched guideline databases and organizations including the National Guideline Clearinghouse, Guidelines International Network, Guidelines Finder, Centre for Reviews and Dissemination, National Institute for Clinical Excellence, Centre for Reviews and Dissemination; and professional nephrology and transplantation organizations. JdD/AT independently screened the titles and abstracts and discarded those that did not meet the inclusion criteria. Full texts for potentially relevant guidelines or consensus statements were retrieved, and their complete versions were examined for eligibility.

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Appraisal of Guidelines and Consensus Statements

Methodological quality was assessed independently by JdB/AT using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument (48). The AGREE tool has also been used to assess consensus statements (49). AGREE is an internationally validated, rigorously developed 23-item tool used to evaluate independent domains of guideline development including the following: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence (50) (see SDC 5, http://links.lww.com/TP/A523). Each item is rated on a four-point likert scale of agreement. The score for each domain is obtained by summing all the scores of the individual items in a domain and then standardizing the total as a percentage of the maximum possible score for that domain:

The minimum possible score for each domain would be the number of questions multiplied by the number of reviewers and multiplied by 1 (strongly disagree). The maximum score for a domain would be the number of questions multiplied by the number of reviewers and multiplied by 4 (strongly agree). We used a quadratic-weighted kappa (κ) as a measure of interrater agreement for the two reviewers' ordinal four-item assessment (1=strongly disagree to 4=strongly agree). The weighted kappa takes into account the degree of disagreement between two reviewers, whereas the standard kappa treats all disagreement equally as a “total” disagreement (25, 26). We calculated a weighted kappa for every guideline appraised by AGREE and calculated an overall weighted kappa between the 10 guidelines.

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Textual Descriptive Synthesis

To analyze the scope, content and consistency of the recommendations in the included guidelines and consensus statements, we conducted a textual descriptive synthesis. All the text from each guideline was extracted by JdB and entered into HyperRESEARCH (version 3.0; ResearchWare Inc., Randolph, Massachusetts), software for storing, coding, and searching textual data. JdB/AT coded the text and recorded concepts (criteria or domains) that broadly focused on screening (kidney assessment, comorbid contraindications, other medical contraindications, and psychosocial considerations) and follow-up care (postsurgical recovery, medical assessment, and psychosocial follow-up). The codes were derived inductively from the guidelines; therefore, specific domains or criteria were not predetermined. We compared the guideline recommendations within each concept to identify differences and similarities.

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Keywords:

Living donor; Clinical practice guidelines; Kidney transplantation

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