1. Guidelines for the Management of Kidney Transplant Recipients

2. “…renal physiologists have abandoned
the sick in order to pursue complicated and
specious theorems in ivory towers …”
-- Homer W. Smith, 1950

3. What are guidelines?

4. “Systematically developed statements to
assist practitioner and patient decisions
about appropriate health care
for specific clinical circumstances.”
--Institute of Medicine

5. Guidelines are not …

6. Commandments

7. Codes of Conduct
Elizabeth: Wait! You have to take me to shore. According to the Code of the Order of the Brethren... Barbossa: First, your return to shore was not part of our negotiations nor our agreement so I must do nothing. And secondly, you must be a pirate for the pirate's code to apply and you're not. And thirdly, the code is more what you'd call "guidelines" than actual rules. Welcome aboard the Black Pearl, Miss Turner .

8. Guidelines Are NOT:
Standards of care
Performance measures

9. Why do we need
guidelines?

10. “If you don't know where you are going, you will wind up somewhere else.”
--Yogi Berra

11. Reasons for Guidelines
The volume of evidence is too great for clinicians to know
Clinicians cannot be expected to judge study quality
Disclosing the lack of evidence can stimulate research

12. What makes a good
guideline good?

13. Characteristics of Good Guidelines
Multidisciplinary development
Systematic review
Graded recommendations
R Grilli, et al. Lancet 2000; 355:103

14. Guideline Controversies

15. Guideline Controversies
Conflicts of interest
Avoid
Full disclosure
Recommendations with little/no evidence

16. Of 192 authors surveyed, 100 (52%) responded
CONTEXT: Increasing contact has been reported between physicians and the pharmaceutical industry, although no data exist in the literature regarding potential financial conflicts of interest for authors of clinical practice guidelines (CPGs). These interactions may be particularly relevant since CPGs are designed to influence the practice of a large number of physicians. OBJECTIVE: To quantify the extent and nature of interactions between authors of CPGs and the pharmaceutical industry. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 192 authors of 44 CPGs endorsed by North American and European societies on common adult diseases published between 1991 and July One hundred authors (52%) provided usable responses representing 37 of 44 different CPGs that we identified. MAIN OUTCOME MEASURES: Nature and extent of interactions of authors with drug manufacturers; disclosure of relationships in published guidelines; prior discussion among authors regarding relationships; beliefs regarding whether authors' own relationships or those of their colleagues influenced treatment recommendations in guidelines. RESULTS: Eighty-seven percent of authors had some form of interaction with the pharmaceutical industry. Fifty-eight percent had received financial support to perform research and 38% had served as employees or consultants for a pharmaceutical company. On average, CPG authors interacted with 10.5 different companies. Overall, an average of 81% (95% confidence interval, 70%-92%) of authors per CPG had interactions. Similarly, all of the CPGs for 7 of the 10 diseases included in our study had at least 1 author who had some interaction. Fifty-nine percent had relationships with companies whose drugs were considered in the guideline they authored, and of these authors, 96% had relationships that predated the guideline creation process. Fifty-five percent of respondents indicated that the guideline process with which they were involved had no formal process for declaring these relationships. In published versions of the CPGs, specific declarations regarding the personal financial interactions of individual authors with the pharmaceutical industry were made in only 2 cases. Seven percent thought that their own relationships with the pharmaceutical industry influenced the recommendations and 19% thought that their coauthors' recommendations were influenced by their relationships. CONCLUSIONS: Although the response rate for this survey was low, there appears to be considerable interaction between CPG authors and the pharmaceutical industry. Our study highlights the need for appropriate disclosure of financial conflicts of interest for authors of CPGs and a formal process for discussing these conflicts prior to CPG development.
44 Guidelines in
Of 192 authors surveyed, (52%) responded

17. Relationships of Authors with Pharmaceutical Industry
CONTEXT: Increasing contact has been reported between physicians and the pharmaceutical industry, although no data exist in the literature regarding potential financial conflicts of interest for authors of clinical practice guidelines (CPGs). These interactions may be particularly relevant since CPGs are designed to influence the practice of a large number of physicians. OBJECTIVE: To quantify the extent and nature of interactions between authors of CPGs and the pharmaceutical industry. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 192 authors of 44 CPGs endorsed by North American and European societies on common adult diseases published between 1991 and July One hundred authors (52%) provided usable responses representing 37 of 44 different CPGs that we identified. MAIN OUTCOME MEASURES: Nature and extent of interactions of authors with drug manufacturers; disclosure of relationships in published guidelines; prior discussion among authors regarding relationships; beliefs regarding whether authors' own relationships or those of their colleagues influenced treatment recommendations in guidelines. RESULTS: Eighty-seven percent of authors had some form of interaction with the pharmaceutical industry. Fifty-eight percent had received financial support to perform research and 38% had served as employees or consultants for a pharmaceutical company. On average, CPG authors interacted with 10.5 different companies. Overall, an average of 81% (95% confidence interval, 70%-92%) of authors per CPG had interactions. Similarly, all of the CPGs for 7 of the 10 diseases included in our study had at least 1 author who had some interaction. Fifty-nine percent had relationships with companies whose drugs were considered in the guideline they authored, and of these authors, 96% had relationships that predated the guideline creation process. Fifty-five percent of respondents indicated that the guideline process with which they were involved had no formal process for declaring these relationships. In published versions of the CPGs, specific declarations regarding the personal financial interactions of individual authors with the pharmaceutical industry were made in only 2 cases. Seven percent thought that their own relationships with the pharmaceutical industry influenced the recommendations and 19% thought that their coauthors' recommendations were influenced by their relationships. CONCLUSIONS: Although the response rate for this survey was low, there appears to be considerable interaction between CPG authors and the pharmaceutical industry. Our study highlights the need for appropriate disclosure of financial conflicts of interest for authors of CPGs and a formal process for discussing these conflicts prior to CPG development.
Choudhry, et al, JAMA 2002; 287:612

18. Declarations in 44 Published Clinical Practice Guidelines
CONTEXT: Increasing contact has been reported between physicians and the pharmaceutical industry, although no data exist in the literature regarding potential financial conflicts of interest for authors of clinical practice guidelines (CPGs). These interactions may be particularly relevant since CPGs are designed to influence the practice of a large number of physicians. OBJECTIVE: To quantify the extent and nature of interactions between authors of CPGs and the pharmaceutical industry. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 192 authors of 44 CPGs endorsed by North American and European societies on common adult diseases published between 1991 and July One hundred authors (52%) provided usable responses representing 37 of 44 different CPGs that we identified. MAIN OUTCOME MEASURES: Nature and extent of interactions of authors with drug manufacturers; disclosure of relationships in published guidelines; prior discussion among authors regarding relationships; beliefs regarding whether authors' own relationships or those of their colleagues influenced treatment recommendations in guidelines. RESULTS: Eighty-seven percent of authors had some form of interaction with the pharmaceutical industry. Fifty-eight percent had received financial support to perform research and 38% had served as employees or consultants for a pharmaceutical company. On average, CPG authors interacted with 10.5 different companies. Overall, an average of 81% (95% confidence interval, 70%-92%) of authors per CPG had interactions. Similarly, all of the CPGs for 7 of the 10 diseases included in our study had at least 1 author who had some interaction. Fifty-nine percent had relationships with companies whose drugs were considered in the guideline they authored, and of these authors, 96% had relationships that predated the guideline creation process. Fifty-five percent of respondents indicated that the guideline process with which they were involved had no formal process for declaring these relationships. In published versions of the CPGs, specific declarations regarding the personal financial interactions of individual authors with the pharmaceutical industry were made in only 2 cases. Seven percent thought that their own relationships with the pharmaceutical industry influenced the recommendations and 19% thought that their coauthors' recommendations were influenced by their relationships. CONCLUSIONS: Although the response rate for this survey was low, there appears to be considerable interaction between CPG authors and the pharmaceutical industry. Our study highlights the need for appropriate disclosure of financial conflicts of interest for authors of CPGs and a formal process for discussing these conflicts prior to CPG development.
Choudhry, et al, JAMA 2002; 287:612

19. Of All Recommendations: 314 of 2711 (12%) were “Evidence A”
Of Class 1* Recommendations:
245 of 1305 (19%) were “Evidence A”
CONTEXT: The joint cardiovascular practice guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) have become important documents for guiding cardiology practice and establishing benchmarks for quality of care. OBJECTIVE: To describe the evolution of recommendations in ACC/AHA cardiovascular guidelines and the distribution of recommendations across classes of recommendations and levels of evidence. DATA SOURCES AND STUDY SELECTION: Data from all ACC/AHA practice guidelines issued from 1984 to September 2008 were abstracted by personnel in the ACC Science and Quality Division. Fifty-three guidelines on 22 topics, including a total of 7196 recommendations, were abstracted. DATA EXTRACTION: The number of recommendations and the distribution of classes of recommendation (I, II, and III) and levels of evidence (A, B, and C) were determined. The subset of guidelines that were current as of September 2008 was evaluated to describe changes in recommendations between the first and current versions as well as patterns in levels of evidence used in the current versions. RESULTS: Among guidelines with at least 1 revision or update by September 2008, the number of recommendations increased from 1330 to 1973 (+48%) from the first to the current version, with the largest increase observed in use of class II recommendations. Considering the 16 current guidelines reporting levels of evidence, only 314 recommendations of 2711 total are classified as level of evidence A (median, 11%), whereas 1246 (median, 48%) are level of evidence C. Level of evidence significantly varies across categories of guidelines (disease, intervention, or diagnostic) and across individual guidelines. Recommendations with level of evidence A are mostly concentrated in class I, but only 245 of 1305 class I recommendations have level of evidence A (median, 19%). CONCLUSIONS: Recommendations issued in current ACC/AHA clinical practice guidelines are largely developed from lower levels of evidence or expert opinion. The proportion of recommendations for which there is no conclusive evidence is also growing. These findings highlight the need to improve the process of writing guidelines and to expand the evidence base from which clinical practice guidelines are derived.
*Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective

20. What will make
guidelines better?

21. Seven Recommendations to Improve Guidelines
Multidisciplinary
Change/rotate authors
Record dissenting views
Independent public review
Independent scientific review
Financial disclosure
Joint codes-no industry money
Why Guideline-Making Requires Reform Allan D. Sniderman, MD; Curt D. Furberg, MD
JAMA. 2009;301(4):
Guidelines are a constructive response to the reality that the practicing physician requires assistance to assimilate and apply the exponentially expanding, often contradictory, body of medical knowledge. Guidelines are widely perceived as evidence based, not authority based, and therefore as unbiased and valid. Because they are sponsored by organizations, staffed by experts, and conducted according to apparently formal processes, the products of the exercise—the guidelines—are generally assumed to have the same level of certainty and security as conclusions generated by the conventional scientific method. For many clinicians, guidelines have become the final arbiters of care.
Guidelines have taken hold and multiplied. The National Guideline Clearinghouse has registered 2373 guidelines produced by 285 organizations.1 Indeed, any group of individuals can designate itself a guideline group and different guideline groups have reviewed the same disease and reached different conclusions.2-3 If the process is so secure, how is this possible? After all, replication is the distinguishing characteristic of scientific knowledge and an essential test of the validity of any scientific statement.
Given the influence of guidelines on clinical practice and given the fact that the process has been, and remains, essentially unregulated, the guideline process deserves review. In this Commentary, we examine the sources of guideline authority; identify major limitations of the present process; briefly address the issue of conflict of interest, both for the individuals who staff the committees and the organizations that govern them; and provide suggestions for reform that may help improve the conduct of the process. Examples are principally selected from lipid guidelines because many clinicians are familiar with them and they illustrate issues that apply to many other guidelines.
Sources of Authority for the Guideline Process The anchoring authority of the guideline process is the belief that guidelines are evidence based, not opinion based, and therefore their conclusions flow directly from the conclusions of studies. Accordingly, the outcome is perceived to be impersonal and inevitable. Guidelines are issued under the imprimatur of the organization that sponsored them. This immersion of a specific product within the aura and prestige of an overall organization is another source of their authority. Guidelines also acquire authority from the prestige of the journals in which they are published. Moreover, guideline decisions are characteristically unanimous and the single voice in which guidelines are expressed undoubtedly adds enormously to their influence.
Limitations of the Guideline Process Governance and Composition of the Guideline Committee
Typically, guideline committees are created by professional organizations committed to the care of patients with one disease or group of diseases. These organizations establish the mandate for the guideline group, select its members, and provide powerful mechanisms for the dissemination of the products of the process. Once issued, the sponsoring associations become promoters and defenders of the guideline that has been produced. Few associations submit the final products of the guideline process for external review before they are accepted and, therefore, in a limited but real sense, the committee, which is a creation of the organization, becomes the final arbiter of its process.
Foundational principles and operating procedures have been suggested for the guideline process.4-5 Nevertheless, most committees have considerable latitude to establish their own working rules. For example, there do not appear to be explicit rules as to the range of expertise that must be included within the committee. Epidemiologists and economists are often minimally represented. Different topics require different repertoires of talents. Importantly, even when it is known that areas of legitimate controversy will be covered, there is often no attempt to ensure that all sides will have reasonable opportunity to present their evaluation of the evidence and participate in the decision-making process.
Although guidelines strive to be evidence based, they cannot be derived strictly, solely, and incontestably from the evidence. On many, if not most, issues the evidence, no matter how extensive, remains incomplete. For example, even though the general conclusion that statins reduce the risk of vascular events is incontestable, many specifics remain debatable, such as how intensive therapy should be, when therapy should be started for different clinical situations, and which markers should be used to monitor therapy. Because gaps in the evidence are inevitable, they must be filled in with judgments, and judgments tend to preserve previous positions. Thus, what is to be decided is often already decided with the selection of the deciders.
Unanimity in Guidelines
Unanimity is not a natural component of science. Given the number and complexity of issues reviewed and given that scientific knowledge is at any moment incomplete, unanimity is obviously a tactic, not a necessary result. Debate may have been brisk within the committee but usually all evidence has been expunged from the final document. Contrast the guidelines with the decisions of any court of appeal in which some judgments are issued unanimously but most are not. Most decisions are divided, with reasoned argument recorded by those on either side, often with different analyses by different dissenters. These minority opinions, not infrequently, provide the legal scaffolding for future reversal of the majority decision they opposed.
Although unanimity is the rule in individual guidelines, it can be strikingly absent when different guidelines are compared. The debate as to whether low-density lipoprotein cholesterol (LDL-C) or apolipoprotein B (apoB) is a more powerful marker of the risk of vascular disease illustrates that guideline groups may not just disagree—they actually may contradict each other. For instance, in the past 6 months, 4 reports have compared LDL-C and apoB, with 2 supporting LDL-C over apoB6-7 and 2 in favor of apoB for predicting cardiovascular risk.8-9 The 2 reports that favor LDL-C state categorically that there is no published evidence allowing apoB treatment targets to be established. The 2 that chose apoB cite multiple studies supporting their position in favor of an apoB target. Only one9 presents a complete, detailed, organized review and analysis of the evidence including the technical accuracy and reproducibility of the 2 measures. The discordance between the views on apoB vs LDL-C is disconcerting, but not surprising given the failure to even agree on what constitutes evidence or how that evidence should be graded.
Lack of Independent Review
Guidelines generally are outside the accepted procedures of scientific publication in which acceptance for publication is the independent decision of the editorial staff of the journal and that decision must include fair independent review. Not only do the scientific organizations that commission guidelines usually not subject the guideline reports to independent review before they issue them, the journals that those organizations control often must publish their guidelines essentially as is. Thus, one of the core processes of science—the necessity to submit any analysis to the independent review of others—is bypassed. The process can be bypassed, but not the consequences, because review is an essential and constructive element in the never-ending effort to root out error.
Conflict of Interest and Guidelines
By favoring one test over another, or one therapy over another, guidelines often create commercial winners and losers, who cannot be disinterested in the result and who therefore must be separated from the process. While the groups that finance medical care do not automatically accept these recommendations, they undoubtedly have a major influence on their decisions. Accordingly, those who write the guidelines and those who issue them should be free from significant conflict of interest. This issue has received attention in the past,10-11 but attention has not ensured coherent, comprehensive action.
There have been constructive, legitimate relationships between industry and academic medicine, both with regard to education and research. However, there also have been inappropriate and intolerable relationships, which escaped attention for much too long Currently, simple declaration of all relationships with industry is considered sufficient, although to be meaningful, disclosure must be complete. Present and recent past direct monetary relationships must be divulged in detail, along with any independent investment or contractual relationship conferring potential future financial benefit.14 Moreover, the prominence gained from participation in a guideline process can translate into sizeable speaking fees. Therefore, disclosure cannot stop just with publication of the guidelines because payment in the future can be the reward for actions in the past.
It is not the number of entanglements with industry—it is their size, individually and in toto. Therefore, the sums should be reported. The argument has been made that ethical equipoise can be achieved by accepting rewards from all the competitors in a field.15 However, accepting financial reward from everyone does not equal being beholden to no one. Indeed, once the sum of the benefits is large enough, no matter how it is partitioned, the presumption that physicians are unaffected is not credible.
Suggestions for Reform The following reforms of the guideline process are suggested. First, the requisite membership of guideline groups should be defined and include the expertise relevant to that discipline plus epidemiologists, statisticians, and experts in health care policy. Second, the largest part of the guideline committee membership, and in particular the leaders, should be changed from one edition to the next and each edition of the guideline should include an expiration date. Third, reports should not be issued unanimously unless all members fully agree to all sections. Alternate interpretations and viewpoints should be recorded and issued along with the majority opinions. Fourth, posting an almost final version on the Internet and inviting commentary is an attractive model. This helps ensure that where legitimate differences of scientific opinion exist, there is an opportunity for exchange before final decisions are taken. Fifth, before publication, guidelines should undergo independent scientific review. The journal editor should present the criticisms and suggestions that result from the reviewers to the panel for its responses, and may require revision of the guideline document, as appropriate. The editor also should consider co-publishing alternate points of view as necessary.
Sixth, all financial relationships with industry should be disclosed in detail, including amounts received, and should be publicly available. Receipt of substantial benefits from any company or series of companies whose products might be under consideration should disqualify that individual from participation in any guideline decision-making process. Potential and actual financial benefits gained by the authors for the next 2 years should also be limited and disclosed to the association that sponsored the guideline process.
Seventh, associations that sponsor and promote guidelines should create joint codes to govern conflict of interest both on the part of participants in the guideline process and the associations. Associations should not accept money from industry to sponsor, underwrite, or promote guidelines.
In summary, evidence is complex and incomplete. Therefore, when the evidence warrants, guidelines should respect diversity of views. Guidelines must be directed only to the interests of patients and not to those who profit from them. Failure to reform the guideline process risks replacing one authority-based system with another, whereas the core objective should be to strengthen an evidence-based approach to improve clinical care.
AUTHOR INFORMATION Corresponding Author: Allan D. Sniderman, MD, Mike Rosenbloom Laboratory for Cardiovascular Research, Room H7.22, Royal Victoria Hospital, 687 Pine Ave W, Montreal, QC H3A 1A1, Canada ).
Financial Disclosures: Dr Sniderman reports receiving speakers' honoraria from Merck and AstraZeneca, serving as a consultant to Merck Schering, and receiving a research grant from AstraZeneca. Dr Furberg reported no disclosures.
Author Affiliations: Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, McGill University, Montreal, Canada (Dr Sniderman); and Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina (Dr Furberg).
REFERENCES 1. National Guideline Clearinghouse Web site. Updated January 5, Accessed January 6, Burgers JS, Bailey JV, Klazinga NS, Van Der Bij AK, Grol R, Feder G, AGREE Collaboration. Inside guidelines: comparative analysis of recommendations and evidence in diabetes guidelines from 13 countries. Diabetes Care. 2002;25(11): FREE FULL TEXT 3. McAlister FA, van Diepen S, Padwal RS, Johnson JA, Majumdar SR. How evidence-based are the recommendations in evidence-based guidelines? PLoS Med. 2007;4(8): Committee to Advise the Public Health Service on Clinical Practice Guidelines, Institute of Medicine. Clinical Practice Guidelines: Directions of a New Program. Washington, DC: National Academy Press; American Medical Association Office of Quality Assurance. Attributes to Guide the Development and Evaluation of Practice Parameters. Chicago, IL: American Medical Association; Leiter LA, Genest J, Harris SB; et al. Dyslipidemia. Can J Diabetes. 2008;32:S107-S Rosenzweig JL, Ferrannini E, Grundy SM; et al, Endocrine Society. Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(10): FREE FULL TEXT 8. Brunzell JD, Davidson M, Furberg C; et al, American Diabetes Association; American College of Cardiology Foundation. Lipoprotein management in patients with cardiometabolic risk. Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008;31(4): FREE FULL TEXT 9. Contois JH, McConnell JP, Sethi AA; et al. Apolipoprotein B and cardiovascular disease risk: a position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on best practices. Clin Chem. In press Choudhry NK, Stelfox HT, Detsky AS. Relationships between authors of clinical practice guidelines and the pharmaceutical industry. JAMA. 2002;287(5): FREE FULL TEXT 11. Psaty BM, Furberg C. British guidelines on managing hypertension provide evidence, progress, and an occasional missed opportunity. BMJ. 1999;319(7210): FREE FULL TEXT 12. Lenzer J. Alteplase for stroke: money and optimistic claims buttress the "brain attack" campaign. BMJ. 2002;324(7339): FREE FULL TEXT 13. Lenzer J. US consumer body calls for review of cholesterol guidelines. BMJ. 2004;329(7469):759. PUBMED 14. DeAngelis CD, Fontanarosa PB. Impugning the integrity of medical science: the adverse effects of industry influence. JAMA. 2008;299(15): FREE FULL TEXT 15. Kassirer JP. On the Take: How Medicine's Complicity With Big Business Can Endanger Your Health. New York, NY: Oxford University Press; 2005:97-99.
AD Sniderman, CD Furberg JAMA 2009; 301:429

22. What is KDIGO?

23. Pronounced: Kay · Dee´· Go
KDIGO
Pronounced: Kay · Dee´· Go
Not: Kay · Die´· Go

24. Kidney Disease Improving Global Outcomes (KDIGO)

25. KDIGO Mission Statement
To improve the care and outcomes of kidney disease patients worldwide by promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines.

26. KDIGO Guideline Process
KDIGO Board of Directors
Public Review
& Comment
Work
Group
Evidence
Review Team
KDIGO Guideline
Local / National Application

27. Core Principles of KDIGO Guideline Development
Evidence-based methods
Grade evidence
Grade recommendations
Multidisciplinary work groups
Appropriate expertise
International representation
Independent work groups
Openness & transparency
Public review
Guiding principles for the KDIGO guideline development process include:
Scientific and methodological rigor: The process will be evidence-based. The grading of the evidence and recommendations will be guided by the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines.
Interdisciplinary approach: Work Group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO.
Independence of Work Groups: The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry
Openness of the guideline development process: Following their initial review by KDIGO Executive Committee and Board of Directors the draft guideline will be subjected to an organizational and peer review process that invites comment from international groups and professionals whom the guideline will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guideline.

28. transplant guidelines?
Why do we need KDIGO
transplant guidelines?

29. Kidney Transplant Guidelines
CMV Disease
Outpatient
Surveillance
Immunosuppressive
Therapy
Posttransplant
Care
AST 2000
EBP 2000
Standards
for SOT
Dyslipidemia
EBPG

30. Rationale Encourage transplant worldwide by:
Defining minimum standards
Removing misconceptions and barriers
Improve patient care by encouraging:
Evidence-based practice
Research, when evidence is poor

31. Scope Post-transplant Aspects unique to transplant
Does not include pre-transplant
Does not include donor issues
Aspects unique to transplant
Immunosuppressive medications
Focus on prevention

32. Target Audience
Caregivers
Physicians
Nurses
Coordinators
Pharmacists

33. Guidelines Work Group Co-Chairs Liaison Members Bertram Kasiske, MD
Minneapolis, USA
Martin Zeier, MD
Heidelberg, GERMANY
Jonathan Craig, MD
Westmead, AUSTRALIA
Cathy Garvey, RN, BA, CCTC
St. Paul, USA
Michael D. Green, MD
Pittsburgh, USA
Vivekanand Jha, MD
Chandigarh, INDIA
Michelle Josephson, MD
Chicago, USA
Bryce Kiberd, MD
Halifax, CANADA
Henrik Ekberg, MD
Malmö, SWEDEN
Henri Kreis, MD
Paris, FRANCE
Ruth McDonald, MD
Seattle, USA
John Newmann, PhD, MPH
Reston, USA
Gregorio Tomas Obrador, MD
Mexico City, MEXICO
Liaison Members
American Society Transplantation
Flavio Vincenti, MD
San Francisco, USA
Global Alliance of Transplantation
Jeremy Chapman, MD
Westmead, AUSTRALIA

34. Where's the Evidence?

35. Tufts-New England Medical Center Evidence-Based Practice Center
Evidence Review Team
Tufts-New England Medical Center
Evidence-Based Practice Center
Boston, MA
Joseph Lau, MD, Director
Ethan Balk, MD, MPH, Associate Director
Katrin Uhlig, MD, MS, Program Director, Nephrology
Martin Wagner, MD, Fellow
Gowri Raman, MD, Research Associate
Samuel Abariga, MD, MS, Research Associate
Amy Earley, BS, Research Assistant

36. Uhlig K, et al. Kidney Int 2006; 70: 2058
KDIGO Recommendation
Grading
Uhlig K, et al. Kidney Int 2006; 70: 2058

37. Grades of Recommendation Assessment, Development, and Evaluation (GRADE)
Guyatt GH, et al. BMJ 2008; 336:924

38. KDIGO-GRADE*: Strength of Evidence
*Grades of Recommendation, Assessment, Development, and Evaluation

39. KDIGO-GRADE: Strength of Recommendations

40. KDIGO-GRADE: Recommendations Not Graded
“Motherhood and apple pie”
Not sufficiently specific to allow application of evidence
Not subjected to formal review

41. KDIGO Graded Transplant Recommendations
198 (80.5%)
Not Graded
45 (19.5%)
Grades of Recommendation Assessment, Development, and Evaluation (GRADE)
Grade   N       %       1A      3       1.2%    1B      16      6.5%    1C      17      6.9%    1D      13      5.3%    2A      1       0.4%    2B      11      4.5%    2C      59      24%     2D      77      31%     Not graded      49      20%     (1X)    1              

42. Strength of Evidence
C (38.9%)
B (13.6%)
A (2.0%)
D (45.5%)

43. Strength of Recommendation1
50 (25.3%) 2
148 (74.7%)

44. KDIGO Graded Transplant Recommendations
1B (8.1%)
1C (9.1%)
1D (6.6%)
2A (0.5%)
2B (5.6%)
2C (29.8.%)

46. Guideline Statements 27 guideline subject areas Major content areas:
Immunosuppression
Graft monitoring and infections
Cardiovascular disease
Malignancies
Other complications

47. Should we use “induction” with a biological agent?

48. 1: Induction Therapy
1.2: We recommend including induction therapy with a biologic agent as part of the initial immunosuppressive regimen in KTRs. (1A)
1.2.1: We recommend that an IL-2 RA be the first-line induction therapy. (1B)
1.2.2: We suggest using a lymphocyte depleting agent, rather than an IL-2 RA, for KTR at high immunological risk. (2B)

49. What is the best maintenance immunosuppressive medication regimen?

50. 2: Initial Maintenance Immuno-suppressive Medications
2.1: We recommend using a combination of immunosuppressive medications as
maintenance therapy, including a CNI and an anti-proliferative agent, with or without corticosteroids. (1B)

51. 2: Initial Maintenance Immuno-suppressive Medications
2.2: We suggest that tacrolimus be the first line CNI used. (2A)
2.2.1: We suggest that tacrolimus or CsA be started before or at the time of transplantation, rather than delayed until the onset of graft function. (2D tacrolimus; 2B CsA)
2.3: We suggest that MMF be the first-line anti-proliferative agent. (2B)

52. 2: Initial Maintenance Immuno-suppressive Medications
2.4: We suggest that, in patients who are low immunological risk and who receive induction therapy, corticosteroids could be discontinued during the first week after transplantation. (2B)
2.5: We recommend that if mTORi are used, they not be started until graft function is established and surgical wounds are healed. (1B)

53. 3: Long-Term Maintenance Immuno-suppressive Medications
3.1: We suggest using the lowest planned doses of maintenance immunosuppressive medications by 2-4 months after transplant-ation if there has been no acute rejection. (2C)
3.2: We suggest that CNIs be continued rather than withdrawn. (2B)
3.3: If prednisone is being used beyond the first week, we suggest prednisone be continued rather than withdrawn. (2C)

54. Can we perform more transplants by reducing
medication cost?

55. 4: Strategies to Reduce Cost
4.1: If drug costs block access to transplantation, a strategy to minimize drug costs is appropriate, even if use of inferior drugs is necessary to obtain the improved survival and quality of life benefits of transplantation compared with dialysis. (Not Graded)

56. 4: Strategies to Reduce Cost
4.1.1: We suggest strategies that may reduce costs include:
• limiting the use of a biologic agent for induction to patients who are high-risk for acute rejection (2C)
• using ketoconazole to minimize CNI dose (2D)
• using a nondihydropyridine CCB to minimize CNI dose (2C)
• using azathioprine rather than MMF (2B)
• using adequately-tested bioequivalent generic drugs (2C)
using prednisone long-term (2C)

57. 13.2: CMV Prophylaxis
13.2.1: CMV prophylaxis: We recommend that KTRs (except when donor and recip-ient both have negative CMV serologies) receive chemoprophylaxis for CMV infection with oral ganciclovir or valganciclovir for at least 3 months after transplantation, (1B) and for 6 weeks after treatment with a T-cell-depleting antibody.(1C)

58. 13.3: EBV and PTLD
13.3.1: We suggest monitoring high-risk (donor EBV seropositive/recipient seronegative) KTRs for EBV by NAT (2C): …
13.3.2: We suggest that EBV-seronegative patients with an increaseing EBV load have immunosuppressive medication reduced.(2D)

59. 13.3: EBV and PTLD
13.3.3: We recommend that patients with EBV disease, including PTLD, have a reduction or cessation of immunosuppressive medication.(2D)

60. KDIGO® Guidelines: Care of the Kidney Transplant Recipient

61. “We’re All Individuals!”
Brian: You've got to think for yourselves! You're all individuals! Crowd: Yes! We're all individuals!
Brian: You're all different! Crowd: Yes! We're all different! Man in Crowd: I'm not...