Clinical Practice Guidelines

KDIGO Guideline for Anemia

The Work Group developing the KDIGO Clinical Practice Guideline on Anemia in CKD is chaired by Drs. John McMurray and Patrick Parfrey. It is anticipated that this guideline will publish in early 2012.

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Guideline Workgroup Roster

NAME/AFFILIATION	CONTACT INFORMATION
Co–Chair: John J V McMurray, MD, FRCP, FESC Professor	BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA UNITED KINGDOM
Co Chair: Patrick S Parfrey, MD, FRCPC University Research Professor Associate Dean for Clinical Research	Memorial University Medical School Division of Nephrology Patient Research Centre, Rm. 1407, 300 Prince Phillip Drive, St John's, Newfoundland A1B 3V6, CANADA
John W Adamson, MD Clinical Professor of Medicine	Division of Hematology/Oncology University of California at San Diego VA Medical Center MC 111E 3350 La Jolla Village Drive San Diego, CA 92161 USA
Pedro Aljama, MD, PhD Professor	Unidad de Investigación, Servicio de Nefrología Hospital Universitario Reina Sofía, 14004 Córdoba, SPAIN
Jeffrey S Berns, MD Associate Dean–Graduate Medical Education–UPHS Associate Chief & Renal Fellowship Program Director Renal–Electrolyte and Hypertension Division	Hospital of the University of Pennsylvania 3400 Spruce St., 1 Founders Pavilion Philadelphia, PA 19104 USA
Julia Bohlius, MD, MScPH	University of Bern Institute of Social and Preventive Medicine Division of International & Environmental Health Finkenhubelweg 11 – CH–3012 Bern SWITZERLAND
Tilman B Drüeke, MD FRCP Inserm Research Director Emeritus	Inserm Unit ERI–12 CHU de Médecine et de Pharmacie Université de Picardie Jules Verne 1 rue des Louvels 80037 Amiens, FRANCE
Fredric O Finkelstein, MD Renal Research Institute Chief of Nephrology, Hospital of St. Raphael	Yale University 136 Sherman Avenue New Haven, CT 06511 USA
Steven Fishbane, MD Chief, Division of Nephrology and Hypertension Winthrop–University Hospital	200 Old Country Road, Suite 135 Mineola, NY 11501 USA
Tomas Ganz, PhD, MD Professor of Medicine and Pathology	CHS 37-055, Department of Medicine David Geffen School of Medicine Los Angeles, CA 90095-1690 USA
Iain C Macdougall, BSc, MD, FRCP Consultant Nephrologist Honorary Senior Lecturer	Renal Unit, King's College Hospital London, SE5 9RS, UNITED KINGDOM
Ruth A McDonald, MD Professor, Pediatrics University of Washington	Seattle Children’s Hospital Division of Nephrology, A-7931 4800 Sand Point Way NE Seattle, WA 98105 USA
Lawrence P McMahon, MBBS, MD Professor of Nephrology and Director, Department of Renal Medicine	Department of Renal Medicine Eastern Health Integrated Renal Service (EHIRS) Monash University c/- Box Hill Hospital Arnold Street Box Hill, 3128 AUSTRALIA
Gregorio T Obrador, MD, MPH Professor of Medicine and Dean Universidad Panamericana School of Medicine	Donatello 59 Col. Insurgentes Mixcoac Mexico, D.F. 03920 MEXICO
Giovanni FM Strippoli, MD	Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro (Ch), ITALY
Günter Weiss, MD Professor for Internal Medicine	Medical University of Innsbruck Dept. for Internal Medicine I Clinical Immunology and Infectious Diseases Anichstr. 35 A–6020 Innsbruck AUSTRIA
Andrzej Wiecek, MD, PhD, FRCP Professor of Internal Medicine and Chief of Department	Department of Nephrology, Endocrinology and Metabolic Diseases Silesian University School of Medicine PL–40–027 Katowice, Francuska 20–24, POLAND

Guideline Scope

Focus

We anticipate a comprehensive updating of the existing KDOQI guidelines for anemia. [1, 2]
Our guideline will address patients with anemia and CKD on dialysis and those who do not require dialysis. Specific subpopulations of interest include pediatric patients and transplant recipients with CKD. A review of existing guidelines from other organizations will also be conducted.

Specific Tasks

Identifying patients and initiating evaluation
- No updated literature search planned

Identifying why, when, and which patients to treat for anemia and iron deficiency
- Retrieve large prospective and retrospective observational studies for:
  - Cross-sectional, multivariable analyses of Hb / iron status and QoL or “major symptoms”
  - Longitudinal, multivariable analyses of baseline Hb / iron status and clinical outcomes
    - These will be searched for and reviewed after the first meeting
Retrieve all RCTs which address intervention treatments for anemia in CKD
- Analyze by baseline Hb / iron status values and eligibility criteria
Retrieve previous systematic reviews and guidelines that address questions relating to treatment of anemia or iron deficiency in any population

Evaluating anemia treatments

Transfusion: including benefits and risks (to patients, blood supply, HD units)
Iron: including benefits and risks (including risk of IV iron in non CKD-5D)
ESAs: including benefits and risks
- Address target Hb (see below)
Other adjuvants: including benefits and risks

PICOD search eligibility parameters:

Population
- CKD, any stage. Any comorbidity (including cancer, CVD, etc.)
- Adults and children (will use looser eligibility criteria for studies of children)
- Will analyze all studies per baseline Hb (<8, 8-10, =10)

Interventions
- RBC transfusion
- Iron (all forms, routes of administration, dosages); see next page for further description
- ESA (all forms, dosages, targets, protocols, etc.)
  - Analyze by target Hb
- Pharmacological and non-pharmacological adjuvants to ESA
  - L-carnitine, vitamin C, androgens, pentoxifylline (include studies prior to KDOQI searches also), others (as per Work Group)

Comparators
- Other interventions
- “No” intervention
- Different forms, routes of administration, dosages, targets, protocols, etc.

Outcomes*
- Death (all-cause, disease-specific)
- Cardiac events (e.g., MI, unstable angina, incident disease)
- Stroke (and transient ischemic attacks)
- CKD progression (categorical; e.g., new RRT, predefined change in kidney function (e.g., doubling of SCr); not change in SCr/GFR, GFR slope, etc.)
- Quality of life (aim to restrict to validated measures; restrict to QoL measures relevant to anemia (e.g., vitality, physical function, fatigue)
- Thromboembolic events
  - Pulmonary embolism, symptomatic deep vein thrombosis, loss of vascular access
- Transfusion requirements
- Cognitive function, sexual function, other similar
- Objective physical function tests (e.g., walking test)
- Infections
- Loss of transplant eligibility due to antibody sensitization
- Antibody sensitization
- New cancer or progression of existing cancer
- Seizure
- Other clinically important adverse events (including transfusion reactions, anaphylaxis)
- ESA dose: for comparisons of different ESA regimens; for iron and adjuvant interventions
- Achieved Hb / Hb variability: for comparisons of different ESA regimens; for iron and adjuvant interventions

*Outcomes not included: Hospitalization, hypertension, left ventricular hypertrophy, dialysis adequacy, change in blood pressure, change in Hb (except as above), change in CHr or reticulocyte index

Study Design
- RCTs only
- Sample size: N > 50 per group
- Minimum follow-up duration: 6 months
- Language: Any
- Will also search for all existing systematic reviews that address these questions, including those of observation studies or registries, particularly regarding adverse events.

Iron therapy:
- Will collect all existing systematic reviews on iron treatment in all populations (with or without CKD), with or without concurrent ESA use, in patients with or without iron-deficiency anemia. (Will re-evaluate need for de novo systematic reviews in non-CKD populations based on existing systematic reviews.)
- Will include “large” observational studies (possibly restricted to those with multivariable analyses) of
  - Association (or prevalence of) anemia with iron deficiency (CKD population only)
  - Association (or prevalence of) iron overload with iron cumulative dose (CKD only)

Re-evaluation of studies in KDOQI systematic review, as necessary.

Addressing treatment resistance
- Update from 2006 KDOQI of all RCTs that meet criteria in population of patients with treatment resistance

References

National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 47:S1-S146, 2006 (suppl 3)
National Kidney Foundation. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease: 2007 Update of Hemoglobin Target. Am J Kidney Dis 50: 471-530, 2007