Guideline Statements  27 guideline statements  Major content areas:  Immunosuppression  Graft monitoring and infections  Cardiovascular disease risk  Malignancies  Other complications

Immunosuppression 1)Induction 2)Maintenance: initial 3)Maintenance: long-term 4)Strategies to reduce cost 5)Monitoring medications 6)Treatment of acute rejection 7)Chronic allograft nephropathy

Graft Monitoring and Infections 8)Monitoring kidney function 9) Kidney biopsy 10) Recurrent disease 11) Non-adnherence 12) Vaccination 13) Viral diseases 14) Other infections

Cardiovascular Disease Risk 15)Diabetes mellitus 16) Hypertension, dyslipidemia, tobacco use and obesity 17) Cardiovascular disease management

Malignancies 18)Cancer of the skin and lip 19) Non-skin malignancies 20) Immunosuppressive medication reduction

Other Complications 21)Bone disease 22) Hematologic complications 23) Hyperuricemia and gout 24) Growth and development 25) Sexual function and fertility 26) Life style 27) Mental health

Initial Maintenance Immunosuppressive Medications Recommendations: A combination of immunosuppressive medications as maintenance therapy including a CNI and an antiproliferative agent, with or without corticosteroids. (1B) Tacrolimus be the first-line CNI used. (2A) 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) Mycophenolate be the first-line antiproliferative agent. (2B) CNI, calcineurin inhibitor; CsA, cyclosporine A; mTORi, mammalian target of rapamycin inhibitor(s).

Initial Maintenance Immunosuppressive Medications (Contd..) Recommendations: In patients who are at low immunological risk and who receive induction therapy, corticosteroids could be discontinued during the first week after transplantation. (2B) If mTORi are used, they should not be started until graft function is established and surgical wounds are healed. (1B)

Rationale Used in combination and at reduced doses, drugs that have different mechanisms of action may achieve additive efficacy with limited toxicity. The earlier that therapeutic blood levels of a CNI can be attained, the more effective the CNI will be in preventing acute rejection. There is no reason to delay the initiation of a CNI, and no evidence that delaying the CNI prevents or ameliorates DGF. Compared to CsA, tacrolimus reduces the risk of acute rejection and improves graft survival during the first year of transplantation.

Rationale Low-dose tacrolimus minimizes the risk of new-onset diabetes after transplantation (NODAT) compared to higher doses of tacrolimus. Compared with placebo and azathioprine, mycophenolate reduces the risk of acute rejection; there is some evidence thatmycophenolate improves long-term graft survival compared with azathioprine. Avoiding the use of maintenance corticosteroids beyond the first week after kidney transplantation reduces adverse effects without affecting graft survival. Mammalian target of rapamycin inhibitors (mTORi) have not been shown to improve patient outcomes when used either as replacement for antiproliferative agents or CNIs, or as add-on therapy, and they have important short- and long-term adverse effects

Long-Term Maintenance Immunosuppressive Medications Recommendations: Using lowest planned doses of maintenance immunosuppressive medications by 2– 4months after transplantation, if there has been no acute rejection. (2C) CNIs be continued rather than withdrawn. (2B) If prednisone is being used beyond the first week after transplantation, we suggest prednisone be continued rather than withdrawn. (2C)

Rationale If low-dose CNI was not implemented at the time of transplantation, CNI dose reduction >2–4months after transplantation may reduce toxicity yet prevent acute rejection. RCTs show that CNI withdrawal leads to increased acute rejection, without altering graft survival. RCTs show that steroid withdrawal more than 3 months after transplantation increases the risk of acute rejection. Different immunosuppressive medications have different toxicity profiles and patients vary in their susceptibility to adverse effects.

Topic Selection and Prioritization Process For Clinical Practice Guidelines and Conferences

Prioritization of CPG Development*  Consistency with the mission of the organization.  Feasibility of implementation.  Efficiency and utility of the results. * Recommendations of the Institute of Medicine

WHO Guidelines for Guidelines.  Stage 1. Maximum potential benefit to individual or group of patients if resources were unlimited.  Stage 2. Assess tradeoffs between cost of applying intervention on a population basis and its health impact (very limited vs. unlimited resources).  Stage 3. Provide evidentiary basis and assistance necessary for local Guideline Development Groups in adopting and grading the recommendations for regional implementation considering available resources.

KDIGO Criteria for CPG Topic Selection  Prevalence of clinical problem.  Burden of illness imposed by the problem.  Variability in practice  Potential of guidelines to improve health outcomes.

International Evidence Review Team Grading Evidence and Recommendations for Clinical Practice Guidelines. A Position Statement from KDIGO Kidney Int 70: , 2006

KDIGO Clinical Practice Guidelines  Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in Chronic Kidney Disease Workgroup co-chairs: Michel Jadoul (Belgium) and David Roth (USA). Published – April 2008, Kidney Int  Diagnosis, Evaluation, Prevention and Treatment of Chronic Kidney Disease Related Mineral and Bone Disorders (CKD-MBD) Workgroup co-chairs: Tilman Drüeke (France) and Sharon Moe (USA). Anticipated Publication – Fall 2008, Kidney Int  Care of the Kidney Transplant Recipient Workgroup co-chairs: Bertram Kasiske (USA) and Martin Zeier (Germany). Anticipated Publication – Winter 2008, Kidney Int  Acute Kidney Injury, Workgroup co-chairs: Norbert Lameire (Belgium) and John Kellum (USA). Anticipated Publication – 2009

Guideline Coordination Initiative  Joint effort of leaders of five English- language guideline development groups  Exploring the feasibility of a collaborative and integrated international approach to the development of new guidelines and the updating of existing guidelines in the field of kidney disease

Guideline Coordination  Canadian Society of Nephrology (CSN) Guidelines  Caring for Australians with Renal Impairment (CARI) Guidelines - ANZSN  United Kingdom Renal Association Guidelines  European Best Practice (EBPG) Guidelines – ERA/EDTA  Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines - NKF  KDIGO

Guideline Coordination  Globalize (Share) the Evidence – Localize the Decision Making  New CPGs: Global KDIGO Guidelines – Local Implementation  Existing CPGs: Coordinated, cooperative process of updating

Guideline Coordination What we can do together  Uniformity in grading the evidence and strength of recommendations (“Grading the evidence and recommendations for clinical practice guidelines-A position statement from KDIGO”).  Reconciliation of currently recommended targets (KDIGO Website-Compare Guidelines).  Hepatitis C guidelines as first global guidelines in nephrology for subsequent adoption by participating organizations, which could then devote their resources to implementation. Extend to CKD-MBD and Transplant CPGs, with opportunity to provide input and participate early in the review process.

Coordination with WHO  Liaison member on Guideline Development Groups (where applicable).  Participation in Controversies Conferences.  Incorporation of KDIGO CKD Staging into ICD  Adopt the WHO Guidelines for Guidelines methodology.

Website Guideline Database Comparison of guidelines as a tool for the harmonization of recommended interventions: The KDIGO website Kidney International, 2007

Website Resources  International Clinical Practice Guidelines in Nephrology  Guideline Development Summaries  Target Ranges Comparisons  Position Statements  CKD-Mineral and Bone Disorder  Classification of CKD

Website Resources  Global Nephrology Guideline Database:  Guideline Overviews  Guideline Summaries by Topic  Guideline Target Comparisons

 WHAT DO WE KNOW (Available Evidence)  WHAT CAN WE DO WITH WHAT WE KNOW (Recommendations vs. Guidelines)  WHAT DO WE NEED TO KNOW (Gaps in knowledge, Research questions) KDIGO Controversies Conferences

Third KDIGO Controversies Conference Care of the Kidney Transplant Recipient Co-chairs: F. Delmonico, USA M. Zeier, Germany Lisbon, Portugal February 2-4, 2006

Fourth KDIGO Controversies Conference CKD as a Global Public Health Problem: Approaches and Initiatives Co-Chairs: Andrew Levey, Kai-Uwe Eckardt, Adeera Levin, Allan Collins, Meguid El-Nahas Amsterdam, Netherlands October 12-14, 2006

NKF-KDOQI Definition of CKD KDIGO Modifications (Amsterdam 2004) Structural or functional abnormalities of the kidneys for >3 months, as manifested by either: 1. Kidney damage, with or without decreased GFR, as defined by  pathologic abnormalities  markers of kidney damage  urinary abnormalities (proteinuria)  blood abnormalities (renal tubular syndromes)  imaging abnormalities  kidney transplantation 2. GFR <60 ml/min/1.73 m 2, with or without kidney damage

Conceptual Model for CKD CKD death ComplicationsComplications Screening for CKD risk factors: diabetes hypertension age >60 family history US ethnic minorities CKD risk reduction; Screening for CKD Diagnosis & treatment; Treat comorbid conditions; Slow progression Estimate progression; Treat complications; Prepare for replacement Replacement by dialysis & transplant NormalNormal Increased risk Kidney failure DamageDamage  GFR

Sixth KDIGO Controversies Conference Coordination of Global Practice Guidelines for Anemia in CKD Co-Chairs: Francesco Locatelli & Allen Nissenson New York October 15-16, 2007

Fifth KDIGO Controversies Conference Clinical Practice Guidelines: Methodology and Transparency Co-Chairs: Robert Alpern, Charles van Ypersele, Katrin Uhlig, & Alison MacLeod New York October 12-13, 2007

KDIGO Position Statements  Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO) Levey AS, at al: Kidney Int 2005;67:  Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO) Moe S, et al: Kidney Int 2006;69:  A report of the Lisbon Conference on the care of the kidney transplant recipient. Abbud-Filho M, et al: Transplantation 83:S1-22, 2007  Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. (KDIGO) Levey AS, et al: Kidney Int 72: , 2007

Mineral and Bone Initiative  Educational Resources: Clinical Guide to Bone and Mineral Metabolism in CKD  Position Statements: Chronic Kidney Disease-Mineral and Bone Disorder  Bone Biopsy/Bone Biomarker Correlation Study

Clinical Guide to Bone and Mineral Metabolism in CKD

Definition, Evaluation, and Classification of Renal Osteodystrophy. A Position Statement from KDIGO Kidney Int 69: , 2006 Second KDIGO Controversies Conference

SUMMARY

Our primary goal is to improve patient care. We hope to accomplish this in the short term by helping clinicians know and better understand the evidence (or lack of evidence) that determines current practice. By making this guideline broadly applicable, our purpose is to also encourage and enable the establishment and development of transplant programs worldwide. Finally, by providing comprehensive evidence-based recommendations, this guideline will also help define areas where evidence is lacking and research is needed. Helping to define a research agenda is an often neglected, but very important function of clinical practice guideline development. Kai-Uwe Eckardt, MD KDIGO Co-Chair Bertram L. Kasiske, MD KDIGO Co-Chair

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