This is the current release of the guideline.

Kidney transplant recipients with hyper-acute rejection, acute humoral or cellular allograft rejection, or chronic allograft dysfunction

A structured literature search is performed for all guidelines but this search is limited to randomised controlled trials and meta-analyses, covering at least the past three years, or up until the date of the latest text update if this exceeds the three-year period. Other excellent sources to include are other high-level evidence, Cochrane review and available high-quality guidelines produced by other expert groups or organizations. If there are no high-level data available, the only option is to include lower-level data. The choice of literature is guided by the expertise and knowledge of the Guidelines Working Group.

Not stated

Level of Evidence

1a Evidence obtained from meta-analysis of randomised trials

1b Evidence obtained from at least one randomised trial

2a Evidence obtained from at least one well-designed controlled study without randomisation

2b Evidence obtained from at least one other type of well-designed quasi-experimental study

3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports

4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities

Not stated

General Methods Used to Formulate the Recommendations

• The first step in the European Association of Urology (EAU) guidelines procedure is to define the main topic.
• The second step is to establish a working group. The working groups comprise about 4 to 8 members, from several countries. Most of the working group members are academic urologists with a special interest in the topic. Specialists from other medical fields (radiotherapy, oncology, gynaecology, anaesthesiology, etc.) are included as full members of the working groups as needed. In general, general practitioners or patient representatives are not part of the working groups. Each member is appointed for a four-year period, renewable once. A chairman leads each group.
• The third step is to collect and evaluate the underlying evidence from the published literature.
• The fourth step is to structure and present the information. All main recommendations are summarised in boxes and the strength of the recommendation is clearly marked in three grades (A–C), depending on the evidence source upon which the recommendation is based. Every possible effort is made to make the linkage between the level of evidence and grade of recommendation as transparent as possible.

Specific Methods Used for This Guideline

As renal transplantation is very much an interdisciplinary field, the Guidelines Group contains not only urologists but also an immunologist and a nephrologist. Besides medical and technical aspects, the Guidelines Group has also considered ethical, social and political aspects. This was necessary because of the still-increasing gap between 'supply' and 'demand' for kidney transplants, and the large differences in organ donation rates between several European countries, suggesting European countries can learn from each other on how to increase organ donation rates.

There are few prospective randomised studies for most sections of the Guidelines, and sometimes none. Thus, the grades of recommendation, which are evidence-based, seldom exceed grade C. Instead, the Guidelines are well supported by a wealth of clinical experience based on several decades of work in renal transplantation, as in, for example, technical aspects of transplantation and explantation.

A level of evidence and/or grade of recommendation have been assigned where possible. The aim of grading recommendations is to provide transparency between the underlying evidence and the recommendation given.

Grade of Recommendation

1. Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial
2. Based on well-conducted clinical studies, but without randomised clinical trials
3. Made despite the absence of directly applicable clinical studies of good quality

A formal cost analysis was not performed and published cost analyses were not reviewed.

There is no formal external review prior to publication.

The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was used to analyse and assess a range of specific attributes contributing to the validity of a specific clinical guideline.

The AGREE instrument, to be used by two to four appraisers, was developed by the AGREE collaboration (www.agreecollaboration.org ) using referenced sources for the evaluation of specific guidelines. (See the "Availability of Companion Documents" field for further methodology information.)

Note from the European Association of Urology (EAU) and the National Guideline Clearinghouse (NGC): The following recommendations were current as of the publication date. However, because EAU updates their guidelines frequently, users may wish to consult the EAU Web site  for the most current version available.

Grades of recommendation (A–C) are defined at the end of the "Major Recommendations" field.

Hyper-acute Rejection (HAR)

• All recipients and donors must be tested for blood group antigens and blood group incompatibility must be avoided, except intentional living-donor ABO-incompatible transplantation. (Grade of recommendation: B)
• All centres practising renal transplantation should have access to elective serological profiling of all potential, and actual, waiting-list recipients to define the percentage and specificity of panel-reactive antibody (PRA) and their isotypes, immunoglobulin G (IgG) or immunoglobulin M (IgM). (Grade of recommendation: B)
• The laboratory service should provide a 24-h donor-recipient cross-matching service to be able to quickly inform a surgeon of the complement-dependent cytotoxicity (CDC) cross-match result before a deceased donor renal transplant (within 5 h). (Grade of recommendation: B)

Acute Allograft Rejection

• Renal transplant practitioners must be continuously aware of the possibility of acute rejection, particularly during the first 6 months after renal transplant. (Grade of recommendation: B)
• During hospitalisation, regular blood and urine samples should be taken for renal and haematological studies in addition to regular ultrasound examinations. (Grade of recommendation: B)
• Rejection should be strongly suspected in any patient who suffers fever, graft tenderness, or reduced urine output. In case of suspected acute rejection, other potential causes of graft dysfunction need to be ruled out immediately. (Grade of recommendation: B)
• All patients with suspected acute rejection episodes should undergo renal biopsy, which should be graded according to the most recent Banff criteria. Only if contraindications to renal biopsy are present, can 'blind' steroid bolus therapy be initiated. Steroid treatment for rejection may start before biopsy is performed. (Grade of recommendation: B)
• There should be routine access to ultrasound-guided biopsy of the transplant and sufficient expertise in the hospital pathology department to allow a clear-cut diagnosis of rejection or other type of allograft dysfunction. (Grade of recommendation: B)
• Staff and facilities on renal transplant units should be sufficiently equipped to admit a patient with acute rejection immediately to allow rapid diagnosis and treatment. (Grade of recommendation: B)
• Patients who suffer acute cellular rejection (ACR) should be tested as soon as possible for anti-human leukocyte antigen (HLA) IgG antibodies reactive with the graft. (Grade of recommendation: B)

Treatment of T-cell Mediated Acute Rejection

• Treatment with steroid bolus therapy is recommended. (Grade of recommendation: B)
• In severe or steroid-resistant rejection, consider intensified immunosuppression, including high-dose steroid treatment, conversion to tacrolimus, and T-cell depleting agents. (Grade of recommendation: B)

Treatment of Acute Humoral Rejection (AHR)

• Treatment of AHR should include early antibody elimination. (Grade of recommendation: B)
• In addition, steroid bolus therapy, conversion to tacrolimus, T-cell depleting agents and intravenous immunoglobulin treatment are used frequently. (Grade of recommendation: B)
• Anti-CD20 (rituximab) may be efficacious. However, firm evidence on efficacy and side-effects is lacking. (Grade of recommendation: B)

Chronic Allograft Dysfunction/Interstitial Fibrosis and Tubular Atrophy (IF/TA)

• During the years of follow-up after renal transplantation, regularly monitor serum creatinine, creatinine clearance, blood pressure and urinary protein excretion. (Grade of recommendation: A)
• Changes in these parameters over time should trigger hospital admission for renal biopsy and further diagnostic work-up including a search for infectious causes and anti-HLA antibodies. An ultrasound of the graft should rule out obstruction and renal artery stenosis. (Grade of recommendation: A)
• If a specific cause for deteriorating renal function can be identified, appropriate treatment should be instituted. (Grade of recommendation: A)
• If unspecific IF/TA is confirmed, begin appropriate medical treatment (e.g., control of hypertension, proteinuria). (Grade of recommendation: A)
• Supportive measures should aim to adequately treat the consequences of chronic kidney disease (e.g., anaemia, acidosis, bone disease) and cardiovascular risk factors (e.g., hyperlipidaemia, diabetes). (Grade of recommendation: A)
• In patients with IF/TA under current calcineurin inhibitor (CNI) therapy and/or with histological signs suggestive for CNI toxicity (e.g., arteriolar hyalinosis, striped fibrosis) without significant proteinuria (<800 mg/day), conversion to an m-TOR inhibitor or substantial CNI reduction under mycophenolic acid (MPA) protection may be indicated. In chronic maintenance patients beyond 5 years, post-transplant CNI withdrawal under MPA and steroids is another safe option. (Grade of recommendation: A)

Definitions:

Grades of Recommendation

1. Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial
2. Based on well-conducted clinical studies, but without randomised clinical trials
3. Made despite the absence of directly applicable clinical studies of good quality

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Side effects of anti-rejection therapy

As attitudes and practice to renal transplantation vary significantly, these guidelines provide general guidance only.

The European Association of Urology (EAU) Guidelines long version (containing all 19 guidelines) is reprinted annually in one book. Each text is dated. This means that if the latest edition of the book is read, one will know that this is the most updated version available. The same text is also made available on a CD (with hyperlinks to PubMed for most references) and posted on the EAU websites Uroweb and Urosource (http://www.uroweb.org/guidelines/online-guidelines/  and http://www.urosource.com/diseases/ ).

Condensed pocket versions, containing mainly flow-charts and summaries, are also printed annually. All these publications are distributed free of charge to all (more than 10,000) members of the association. Abridged versions of the guidelines are published in European Urology as original papers. Furthermore, many important websites list links to the relevant EAU guidelines sections on the association websites and all, or individual, guidelines have been translated to some 15 languages.

Not applicable: The guideline was not adapted from another source.

European Association of Urology

Renal Transplantation Guidelines Writing Panel

Primary Authors: T. Kälble; A. Alcaraz; K. Budde; U. Humke; G. Karam; M. Lucan; G. Nicita; C. Süsal

All members of the Renal Transplantation Guidelines writing panel have provided disclosure statements on all relationships that they have and that might be perceived to be a potential source of conflict of interest. This information is kept on file in the European Association of Urology (EAU) Central Office database. This guidelines document was developed with the financial support of the EAU. No external sources of funding and support have been involved. The EAU is a non-profit organisation and funding is limited to administrative assistance and travel and meeting expenses. No honoraria or other reimbursements have been provided.

This is the current release of the guideline.

Electronic copies: Available in Portable Document Format (PDF) from the European Association of Urology Web site .

Print copies: Available from the European Association of Urology, PO Box 30016, NL-6803, AA ARNHEM, The Netherlands.

The following are available:

• EAU guidelines office template. Arnhem, The Netherlands: European Association of Urology; 2007. 4 p.
• The European Association of Urology (EAU) guidelines methodology: a critical evaluation. Arnhem, The Netherlands: European Association of Urology; 18 p.

The following is also available:

• Guidelines on renal transplantation. 2009, Pocket guidelines. Arnhem, The Netherlands: European Association of Urology; 2009 Mar. 12 p. Electronic copies: Available in Portable Document Format (PDF) in English  and Russian  from the European Association of Urology Web site. Also available as an e-book from the EAU Web site .

Print copies: Available from the European Association of Urology, PO Box 30016, NL-6803, AA ARNHEM, The Netherlands.

None available

This NGC summary was completed by ECRI Institute on April 19, 2010. The information was verified by the guideline developer on May 21, 2010.

This summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Downloads are restricted to one download and print per user, no commercial usage or dissemination by third parties is allowed.