This is the current release of the guideline.

Definitions for the strength of each guideline (A, B, or C [CPR]), based on the quality of the supporting evidence as well as additional considerations, are provided at the end of the "Major Recommendations" field.

Clinical Practice Guidelines (CPGs) for Diabetes and Chronic Kidney Disease (CKD)

Guideline 1: Screening and Diagnosis of Diabetic Kidney Disease (DKD)

CKD in patients with diabetes may or may not represent DKD. In the absence of an established diagnosis, the evaluation of patients with diabetes and kidney disease should include investigation into the underlying cause(s).

1.1 Patients with diabetes should be screened annually for DKD. Initial screening should commence:

• 5 years after the diagnosis of type 1 diabetes; (A) or
• From diagnosis of type 2 diabetes. (B)

  1.1.1. Screening should include:

  • Measurements of urinary albumin-creatinine ratio (ACR) in a spot urine sample; (B)
  • Measurement of serum creatinine and estimation of glomerular filtration rate (GFR). (B)

1.2 An elevated ACR should be confirmed in the absence of urinary tract infection with 2 additional first-void specimens collected during the next 3 to 6 months. (B)

• Microalbuminuria is defined as an ACR between 30-300 mg/g.
• Macroalbuminuria is defined as an ACR >300 mg/g.
• 2 of 3 samples should fall within the microalbuminuric or macroalbuminuric range to confirm classification.

1.3 In most patients with diabetes, CKD should be attributable to diabetes if:

• Macroalbuminuria is present; (B) or
• Microalbuminuria is present
  • In the presence of diabetic retinopathy (B)
  • In type 1 diabetes of at least 10 years' duration (A)

1.4 Other cause(s) of CKD should be considered in the presence of any of the following circumstances: (B)

• Absence of diabetic retinopathy
• Low or rapidly decreasing GFR
• Rapidly increasing proteinuria or nephrotic syndrome
• Refractory hypertension
• Presence of active urinary sediment
• Signs or symptoms of other systemic disease; or
• >30% reduction in GFR within 2-3 months after initiation of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB).

Guideline 2: Management of Hyperglycemia and General Diabetes Care in CKD

Hyperglycemia, the defining feature of diabetes, is a fundamental cause of vascular target-organ complications, including kidney disease. Intensive treatment of hyperglycemia prevents DKD and may slow progression of established kidney disease.

2.1 Target hemoglobin A_1c (HbA_1c) for people with diabetes should be <7.0%, irrespective of the presence or absence of CKD. (A)

Guideline 3: Management of Hypertension in Diabetes and CKD

Most people with diabetes and CKD have hypertension. Treatment of hypertension slows the progression of CKD.

3.1 Hypertensive people with diabetes and CKD stages 1-4 should be treated with an ACE inhibitor or an ARB, usually in combination with a diuretic. (A)

3.2 Target blood pressure in diabetes and CKD stages 1-4 should be <130/80 mmHg. (B)

Guideline 4: Management of Dyslipidemia in Diabetes and CKD

Dyslipidemia is common in people with diabetes and CKD. The risk of cardiovascular disease (CVD) is greatly increased in this population. People with diabetes and CKD should be treated according to current guidelines for high-risk groups.

4.1 Target low-density lipoprotein cholesterol (LDL-C) in people with diabetes and CKD stages 1-4 should be <100 mg/dL; <70 mg/dL is a therapeutic option. (B)

4.2 People with diabetes, CKD stages 1-4, and LDL-C >100 mg/dL should be treated with a statin. (B)

4.3 Treatment with a statin should not be initiated in patients with type 2 diabetes on maintenance hemodialysis therapy who do not have a specific cardiovascular indication for treatment. (A)

Guideline 5: Nutritional Management in Diabetes and CKD

Management of diabetes and CKD should include nutritional intervention. Dietary modifications may reduce the progression of CKD.

5.1 Target dietary protein intake for people with diabetes and CKD stages 1-4 should be the recommended daily allowance (RDA) of 0.8 g/kg body weight per day. (B)

Clinical Practice Recommendations (CPRs) for Diabetes and Chronic Kidney Disease

Clinical Practice Recommendation 1: Management of Albuminuria in Normotensive Patients With Diabetes and Albuminuria as a Surrogate Marker

Treatments that lower urinary albumin excretion may slow progression of DKD and improve clinical outcomes, even in the absence of hypertension. However, most people with diabetes and albuminuria have hypertension; management of hypertension in these patients is reviewed in Guideline 3.

1.1 Normotensive people with diabetes and macroalbuminuria should be treated with an ACE inhibitor or an ARB. (C)

1.2 Treatment with an ACE inhibitor or an ARB may be considered in normotensive people with diabetes and microalbuminuria. (C)

1.3 Albuminuria reduction may be considered a treatment target in DKD. (C)

Clinical Practice Recommendation 2: Multifaceted Approach to Intervention in Diabetes and CKD

Multiple risk factors are managed concurrently in patients with diabetes and CKD, and the incremental effects of treating each of these risk factors appear to add up to substantial clinical benefits.

2.1 The care of people with diabetes and CKD should incorporate a multifaceted approach to intervention that includes instruction in healthy behaviors and treatments to reduce risk factors. (C)

2.2 Target body mass index (BMI) for people with diabetes and CKD should be within the normal range (18.5-24.9 kg/m²). (C)

Clinical Practice Recommendation 3: Diabetes and CKD in Special Populations

The increasing incidence of diabetes in children, young adults, the elderly, and members of disadvantaged and transitional populations is responsible for an increasing incidence of DKD in these groups. Racial/ethnic differences in susceptibility to DKD also may play a role. In pregnant women, the presence of diabetes and CKD may adversely affect the health of both the mother and her offspring.

3.1 Screening and interventions for diabetes and CKD should focus on populations at greatest risk. (C)

3.2 Although management of diabetes and CKD in special populations should follow the same principles as management in the majority population, there are special considerations in the treatment of children, adolescents, and the elderly. (C)

3.3 Population-based interventions may be the most cost-effective means for addressing the burden of CKD in special populations. Implementation and evaluation of population-based interventions should take into account the heterogeneity of the populations at risk. (C)

3.4 Specialists in high-risk pregnancy and kidney disease should co-manage pregnancy in women with diabetes and CKD. (C)

3.5 Treatment of DKD with renin-angiotensin system (RAS) inhibitors before pregnancy may improve fetal and maternal outcomes, but these medicines should be discontinued as soon as a menstrual period is missed or after a positive pregnancy test. (C)

3.6 Insulin should be used to control hyperglycemia if pharmacological therapy is necessary in pregnant women with diabetes and CKD. (C)

Clinical Practice Recommendation 4: Behavioral Self-Management in Diabetes and CKD

Behavioral self-management in patients with diabetes and CKD is particularly challenging because of the intensive nature of the diabetes regimen. Education alone is not sufficient to promote and sustain healthy behavior change, particularly with such a complex regimen.

4.1 Self-management strategies should be key components of a multifaceted treatment plan with attention to multiple behaviors: (C)

• Monitoring and treatment of glycemia
• Blood pressure
• Nutrition
• Smoking cessation
• Exercise
• Adherence to medicines

Definitions:

Rating the Strength of Guideline and Clinical Practice Recommendation (CPR) Statements

A It is strongly recommended that clinicians routinely follow the guideline for eligible patients. There is strong evidence that the practice improves health outcomes.

B It is recommended that clinicians routinely follow the guideline for eligible patients. There is moderately strong evidence that the practice improves health outcomes.

C (CPR) It is recommended that clinicians consider following the CPR for eligible patients. This recommendation is based on either weak evidence or on the opinions of the Work Group and reviewers that the practice might improve health outcomes.

Health outcomes are health-related events, conditions, or symptoms that can be perceived by individuals to have an important effect on their lives. Improving health outcomes implies that benefits outweigh any adverse effects.

Rating the Quality of Evidence

The strength of evidence was graded using a rating system that primarily takes into account: (1) the methodological quality of the studies; (2) whether the studies were carried out in the target population (i.e., patients with chronic kidney disease and diabetes, or in other populations) and (3) whether the studies examined health outcomes directly, or examined surrogate measures for those outcomes (e.g., reducing death or improving albuminuria). These 3 separate study characteristics were combined to provide a preliminary strength of evidence provided by pertinent studies. In addition, aspects of the GRADE recommendations for grading the quality of evidence and the strength of recommendations were incorporated to determine a final strength of evidence.

Strong: ^aEvidence includes results from well-designed, well-conducted study/studies in the target population that directly assess effects on health outcomes.

Moderately Strong: ^bEvidence is sufficient to determine effects on health outcomes in the target population, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; OR ^cevidence is from a population other than the target population, but from well-designed, well-conducted studies; OR ^devidence is from studies with some problems in design and/or analysis; ^eOR evidence is from well-designed, well-conducted studies or surrogate endpoints for efficacy and/or safety in the target population.

Weak: ^fEvidence is insufficient to assess the effects on net health outcomes because it is from studies with some problems in design and/or analysis on surrogate endpoints for efficacy and/or safety in the target population; OR ^gthe evidence is only for surrogate measures in a population other than the target population; OR ^hthe evidence is from studies that are poorly designed and/or analyzed.

A clinical algorithm "Screening for Microalbuminuria" is provided in the original guideline document.

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

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

2007 Feb

National Kidney Foundation - Disease Specific Society

National Kidney Foundation (NKF)

NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) Diabetes and Chronic Kidney Disease Work Group

Work Group Members: Robert G. Nelson, MD, PhD (Co-Chair) National Institutes of Health, Phoenix, AZ; Katherine R. Tuttle, MD (Co-Chair) Providence Medical Research Center, University of Washington School of Medicine, Spokane, WA; Pablo Aschner, MD, Javeriana University School of Medicine, Bogota, Colombia; George L. Bakris, MD, University of Chicago-Pritzker School of Medicine, Chicago, IL; Rudy W. Bilous, MD, The James Cook University Hospital, Middlesbrough, UK; M. Luiza Caramori, MD, MSc, PhD, University of Minnesota Medical School, Minneapolis, MN; D. Jordi Goldstein-Fuchs, DSc, RD, University of Nevada School of Medicine, Reno, NV; S. Michael Mauer, MD, University of Minnesota Medical School, Minneapolis, MN; Mark E. Molitch, MD, Northwestern University Feinberg School of Medicine, Chicago, IL; Andrew Narva, MD, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; Michelle M. Richardson, PharmD, BCPS, Tufts–New England Medical Center, Boston, MA; Mary Ann Sevick, ScD, RN, University of Pittsburgh, Pittsburgh, PA; Michael Shlipak, MD, University of California San Francisco, San Francisco, CA; Christoph Wanner, MD, University Clinic Würzburg, Würzburg, Germany

Liaisons: Jeffrey A. Cutler, MD, MPH, National Heart, Lung and Blood Institute, Bethesda, MD; Thomas H. Hostetter, MD, Albert Einstein College of Medicine, Bronx, NY; Marc A. Pfeffer, MD, PhD, Harvard Medical School, Brigham Women's Hospital, Boston, MA

Evidence Review Team: Ethan Balk, MD, MPH, Evidence Review Team Project Director and Co-Director; Katrin Uhlig, MD, MS, Co-Director, Program Director, Nephrology; Gowri Raman, MD, Assistant Project Director; Priscilla Chew, MPH; Amy Earley, BS; Ashish Mahajan, MD, MPH; Rebecca Persson, BA; Christina Kwack Yuhan, MD

The National Kidney Foundation (NKF) makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the Work Group.

Specifically, all members of the Work Group are required to complete, sign, and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. All affiliations are published in their entirety at the end of this publication in the Work Group members' biographical sketch and are on file at the NKF.

Support for the development of the KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease was provided by: Amgen and Keryx.

The National Kidney Foundation gratefully acknowledges the following implementation sponsors: Merck, Novartis, Sanofi Aventis. Additional support for implementation was provided by Takeda Pharmaceuticals.

This is the current release of the guideline.

The following is available:

• Chronic kidney disease and diabetes: a new tool to break the cycle

These materials are available by contacting: National Kidney Foundation 30 East 33rd Street, New York, NY 10016 (phone: 212.889.2210 or 800.622.9010 or fax: 212.686.8916).

The following are available:

• Diabetes and chronic kidney disease (stages 1-4) (also available in Spanish)
• Diabetes and chronic kidney disease (stage 5) (also available in Spanish)
• Diabetes and chronic kidney disease: a guide for American Indians and Alaska natives
• Quality of life with diabetes and CKD
• Chronic kidney disease and diabetes: a new tool to break the cycle

These patient education materials are available by contacting: National Kidney Foundation 30 East 33rd Street, New York, NY 10016 (phone: 212.889.2210 or 800.622.9010 or fax: 212.686.8916).

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

This NGC summary was completed by ECRI Institute on June 19, 2007. The information was verified by the guideline developer on August 23, 2007.

K/DOQI is a trademark of the National Kidney Foundation, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage retrieval system, without permission in writing from the National Kidney Foundation.