Guideline Statements27 guideline statementsMajor content areas:

ImmunosuppressionGraft monitoring and infectionsCardiovascular disease riskMalignanciesOther complications

Immunosuppression

1) Induction2) Maintenance: initial3) Maintenance: long-term4) Strategies to reduce cost5) Monitoring medications6) Treatment of acute rejection7) Chronic allograft nephropathy

Graft Monitoring and Infections8) Monitoring kidney function9) Kidney biopsy10) Recurrent disease11) Non-adnherence12) Vaccination13) Viral diseases14) Other infections

Cardiovascular Disease Risk

15)Diabetes mellitus16) Hypertension, dyslipidemia, tobacco

use and obesity17) Cardiovascular disease management

Malignancies

18)18)Cancer of the skin and lipCancer of the skin and lip19)19) Non-skin malignanciesNon-skin malignancies20)20) Immunosuppressive medication Immunosuppressive medication

reductionreduction

Other Complications

21)21)Bone diseaseBone disease22)22) Hematologic complicationsHematologic complications23)23) Hyperuricemia and goutHyperuricemia and gout24)24) Growth and developmentGrowth and development25)25) Sexual function and fertilitySexual function and fertility26)26) Life styleLife style27)27) Mental healthMental 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 MaintenanceImmunosuppressive 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 TeamGrading Evidence and Recommendations for Clinical Practice Guidelines.A Position Statement from KDIGO

Kidney Int 70:2058-2065, 2006

KDIGO Clinical Practice Guidelines

Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in Chronic Kidney DiseaseWorkgroup 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 RecipientWorkgroup 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 10-11.

Adopt the WHO Guidelines for Guidelines methodology.

Website Guideline DatabaseComparison 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

www.KDIGO.org

Website Resources Global Nephrology Guideline

Database: Guideline Overviews Guideline Summaries by Topic Guideline Target Comparisons

WWW.KDIGO.ORG

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 KDIGOControversies Conference

Care of the Kidney Transplant Recipient

Co-chairs: F. Delmonico, USA M. Zeier, Germany

Lisbon, PortugalFebruary 2-4, 2006

Fourth KDIGOControversies 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, NetherlandsOctober 12-14, 2006

NKF-KDOQI Definition of CKDKDIGO 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 transplantation2. GFR <60 ml/min/1.73 m2, with or without kidney

damage

Conceptual Model for CKD

CKDCKDdeathdeathCKDCKDdeathdeath

ComplicationsComplicationsComplicationsComplications

Screening Screening for CKDfor CKD

risk factors:risk factors:diabetesdiabetes

hypertensionhypertensionage >60age >60

family historyfamily historyUS ethnic US ethnic minoritiesminorities

CKD riskCKD riskreduction;reduction;

Screening forScreening forCKDCKD

DiagnosisDiagnosis& treatment;& treatment;

Treat Treat comorbidcomorbid

conditions;conditions;Slow Slow

progressionprogression

EstimateEstimateprogression;progression;

TreatTreatcomplications;complications;

Prepare forPrepare forreplacementreplacement

ReplacementReplacementby dialysisby dialysis

& transplant& transplant

NormalNormalNormalNormal IncreasedIncreasedriskrisk

IncreasedIncreasedriskrisk

KidneyKidneyfailurefailureKidneyKidneyfailurefailureDamageDamageDamageDamage GFRGFR GFRGFR

Sixth KDIGOControversies Conference

Coordination of Global Practice Guidelines for Anemia in CKD

Co-Chairs: Francesco Locatelli & Allen Nissenson

New YorkOctober 15-16, 2007

Fifth KDIGOControversies Conference Clinical Practice Guidelines: Methodology and Transparency

Co-Chairs: Robert Alpern, Charles van Ypersele, Katrin Uhlig, & Alison MacLeod

New YorkOctober 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;67:2089-2100.

Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO) Moe S, et al: Kidney Int 2006;69:1945-1953.

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 72:247-259, 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 69:1945-1953, 2006

Second KDIGOControversies 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, MDKDIGO Co-Chair

THANK YOU