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OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY
INTERNATIONAL SOCIETY OF NEPHROLOGY
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1960
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KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
VOLUME 3 | ISSUE 1 | JANUARY 2013
http://www.kidney-international.org

KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease

FOUNDING SPONSOR

National Kidney Foundation®
KDIGO gratefully acknowledges the following consortium of sponsors that make our initiatives possible: Abbott, Amgen, Bayer Schering Pharma, Belo Foundation, Bristol-Myers Squibb, Chugai Pharmaceutical, Coca-Cola Company, Dole Food Company, Fresenius Medical Care, Genzyme, Hoffmann-LaRoche, JC Penney, Kyowa Hakko Kirin, NATCO—The Organization for Transplant Professionals, NKF-Board of Directors, Novartis, Pharmacosmos, PUMC Pharmaceutical, Robert and Jane Cizik Foundation, Shire, Takeda Pharmaceutical, Transwestern Commercial Services, Vifor Pharma, and Wyeth.
Sponsorship Statement: KDIGO is supported by a consortium of sponsors and no funding is accepted for the development of specific guidelines.

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© 2013 KDIGO
VOL 3 | ISSUE 1 | JANUARY (1) 2013
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KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
v Tables and Figures
vii KDIGO Board Members
viii Reference Keys
x CKD Nomenclature
xi Conversion Factors & HbA \( _{1c} \) Conversion
xii Abbreviations and Acronyms
1 Notice
2 Foreword
3 Work Group Membership
4 Abstract
5 Summary of Recommendation Statements
15 Introduction: The case for updating and context
19 Chapter 1: Definition, and classification of CKD
63 Chapter 2: Definition, identification, and prediction of CKD progression
73 Chapter 3: Management of progression and complications of CKD
91 Chapter 4: Other complications of CKD: CVD, medication dosage, patient safety, infections, hospitalizations, and caveats for investigating complications of CKD
112 Chapter 5: Referral to specialists and models of care
120 Methods for Guideline Development
128 Biographic and Disclosure Information
134 Acknowledgments
136 References
| c | o | p | E | This journal is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE) www.publicationethics.org

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TABLES
<table><tr><td>18</td><td>Table 1.</td><td>KDIGO nomenclature and description for grading recommendations</td></tr><tr><td>20</td><td>Table 2.</td><td>Criteria for CKD</td></tr><tr><td>20</td><td>Table 3.</td><td>Criteria for definition of CKD</td></tr><tr><td>27</td><td>Table 4.</td><td>Classification of CKD based on presence or absence of systemic disease and location within the kidney of pathologic-anatomic findings</td></tr><tr><td>27</td><td>Table 5.</td><td>GFR categories in CKD</td></tr><tr><td>28</td><td>Table 6.</td><td>Albuminuria categories in CKD</td></tr><tr><td>31</td><td>Table 7.</td><td>Relationship among categories for albuminuria and proteinuria</td></tr><tr><td>32</td><td>Table 8.</td><td>CGA staging of CKD: examples of nomenclature and comments</td></tr><tr><td>33</td><td>Table 9.</td><td>Prognosis of CKD: Relationship of outcomes and strength of relationship to Cause (C), GFR (G), Albuminuria (A) and other measures</td></tr><tr><td>35</td><td>Table 10.</td><td>Annual percentage change in GFR across diagnosis categories</td></tr><tr><td>39</td><td>Table 11.</td><td>Sources of error in GFR estimating using creatinine</td></tr><tr><td>41</td><td>Table 12.</td><td>Equations based on serum creatinine assays in adults that are traceable to the standard reference material</td></tr><tr><td>44</td><td>Table 13.</td><td>Performance comparison of creatinine-based GFR estimating equations in North America, Europe, and Australia</td></tr><tr><td>48</td><td>Table 14.</td><td>Performance comparison of creatinine-based GFR estimating equations outside of North America, Europe, and Australia</td></tr><tr><td>50</td><td>Table 15.</td><td>Sources of error in GFR estimating using cystatin C</td></tr><tr><td>52</td><td>Table 16.</td><td>Equations based on IDMS traceable creatinine and IFCC traceable cystatin C assays</td></tr><tr><td>54</td><td>Table 17.</td><td>Performance comparison of cystatin C-based estimating equations in North American and European populations</td></tr><tr><td>55</td><td>Table 18.</td><td>Strengths and limitations of GFR measurement methods and markers</td></tr><tr><td>59</td><td>Table 19.</td><td>Factors affecting urinary ACR</td></tr><tr><td>64</td><td>Table 20.</td><td>Decline in kidney function in various populations (longitudinal studies only)</td></tr><tr><td>65</td><td>Table 21.</td><td>Decline in kidney function in CKD populations</td></tr><tr><td>67</td><td>Table 22.</td><td>Studies evaluating rapid progression (general population studies only)</td></tr><tr><td>68</td><td>Table 23.</td><td>CKD progression and risk of all-cause mortality and ESRD using baseline (first) eGFR</td></tr><tr><td>68</td><td>Table 24.</td><td>Association between absolute and percentage change in kidney function and risk of ESRD, based on adjustment for eGFR at the first and last measurement</td></tr><tr><td>77</td><td>Table 25.</td><td>Intensive versus normal glycemic control and albuminuria outcome</td></tr><tr><td>78</td><td>Table 26.</td><td>Recommended Daily Intake of sodium for healthy children</td></tr><tr><td>81</td><td>Table 27.</td><td>Prevalence of CKD complications by GFR category derived from CKD cohorts</td></tr><tr><td>81</td><td>Table 28.</td><td>Hemoglobin cutoffs for people living at sea level</td></tr><tr><td>87</td><td>Table 29.</td><td>Phosphate binding agents in routine clinical practice and their ranked cost</td></tr><tr><td>89</td><td>Table 30.</td><td>Summary data for bisphosphonates and CKD</td></tr><tr><td>100</td><td>Table 31.</td><td>Peripheral arterial disease and CKD</td></tr><tr><td>103</td><td>Table 32.</td><td>Cautionary notes for prescribing in people with CKD</td></tr><tr><td>107</td><td>Table 33.</td><td>Risk factors for infection in people with CKD</td></tr><tr><td>110</td><td>Table 34.</td><td>Components of community CKD management programs</td></tr><tr><td>114</td><td>Table 35.</td><td>Early versus late referral: consequences and benefits</td></tr><tr><td>114</td><td>Table 36.</td><td>Outcomes of early versus late referral</td></tr><tr><td>122</td><td>Table 37.</td><td>Topics of interest for the management of CKD guideline</td></tr><tr><td>123</td><td>Table 38.</td><td>Literature yield of primary articles for all topics</td></tr><tr><td>123</td><td>Table 39.</td><td>Classification of study quality</td></tr><tr><td>124</td><td>Table 40.</td><td>GRADE system for grading quality of evidence</td></tr><tr><td>124</td><td>Table 41.</td><td>Final grade for overall quality of evidence</td></tr><tr><td>124</td><td>Table 42.</td><td>Balance of benefits and harm</td></tr><tr><td>125</td><td>Table 43.</td><td>KDIGO nomenclature and description for grading recommendations</td></tr><tr><td>125</td><td>Table 44.</td><td>Determinants of strength of recommendation</td></tr><tr><td>125</td><td>Table 45.</td><td>The Conference on Guideline Standardization checklist for reporting clinical practice guidelines</td></tr></table>
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FIGURES
16 Figure 1. Conceptual model of CKD
22 Figure 2. Normal values for GFR by age
23 Figure 3. Relationship of eGFR with mortality
23 Figure 4. Relationship of albuminuria with mortality
28 Figure 5. Age-standardized rates of death from any cause, cardiovascular events, and hospitalization, according to the eGFR among 1,120,295 ambulatory adults
29 Figure 6. Summary of continuous meta-analysis for general population cohorts with ACR
30 Figure 7. Summary of categorical meta-analysis for general population cohorts with ACR
31 Figure 8. Prevalence of CKD in the USA by GFR and albuminuria
34 Figure 9. Prognosis of CKD by GFR and albuminuria category
39 Figure 10. Determinants of the serum level of endogenous filtration markers
43 Figure 11. Performance of the CKD-EPI and MDRD Study equations in estimating measured GFR in the external validation data set
46 Figure 12. Comparison of distribution of GFR and CKD prevalence by age (NHANES 1999-2004)
47 Figure 13. Meta-analysis of NRI for all-cause mortality, CVD mortality, and ESRD
50 Figure 14. Association of CKD definitions with all-cause mortality and ESRD
53 Figure 15. Performance of three equations for estimating GFR
57 Figure 16. Suggested protocol for the further investigation of an individual demonstrating a positive reagent strip test for albuminuria/proteinuria or quantitative albuminuria/proteinuria test
63 Figure 17. GFR and albuminuria grid to reflect the risk of progression
69 Figure 18. Distribution of the probability of nonlinearity with three example trajectories demonstrating different probabilities of nonlinearity
86 Figure 19. Summary estimates for risks of all-cause mortality and cardiovascular mortality associated with levels of serum phosphorus, PTH, and calcium
88 Figure 20. Prevalence of deficiency of \(1,25(\mathrm{OH})_{2}\mathrm{D}_{3}\), \(25(\mathrm{OH})\mathrm{D}_{3}\), and secondary hyperparathyroidism by GFR intervals
113 Figure 21. Referral decision making by GFR and albuminuria
116 Figure 22. The CKD chronic care model
Additional information in the form of supplementary materials can be found online at http://www.kdi GO. org/clinical_practice_guidelines/ckd.php
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KDIGO Board Members
Garabed Eknoyan, MD
Norbert Lameire, MD, PhD
Founding KDIGO Co-Chairs
Kai-Uwe Eckardt, MD
Immediate Past Co-Chair
Bertram L Kasiske, MD
KDIGO Co-Chair
Omar I Abboud, MD, FRCP
Sharon Adler, MD, FASN
Rajiv Agarwal, MD
Sharon P Andreoli, MD
Gavin J Becker, MD, FRACP
Fred Brown, MBA, FACHE
Daniel C Cattran, MD, FRCPC
Allan J Collins, MD, FACP
Rosanna Coppo, MD
Josef Coresh, MD, PhD
Ricardo Correa-Rotter, MD
Adrian Covic, MD, PhD
Jonathan C Craig, MBChB, MM (C
Angel LM de Francisco, MD
Paul E de Jong, MD, PhD
Ana Figueiredo, RN, MSc, Ph
Mohammed Benghanem Gharbi, MD
Gordon Guyatt, MD, MSc, BSc, FRCPC
David Harris, MD
Lai Seong Hooi, MD
Enyu Imai, MD, PhD
Lesley A Inker, MD, MS, FRCP
David C Wheeler, MD, FRCP
KDIGO Co-Chair
Michel Jadoul, MD
Simon Jenkins, MBE, FRCGP
Suhnggwon Kim, MD, PhD
Martin K Kuhlmann, MD
Nathan W Levin, MD, FACP
Philip K-T Li, MD, FRCP, FACP
Zhi-Hong Liu, MD
Pablo Massari, MD
Peter A McCullough, MD, MPH, FACC, FACP
Rafique Moosa, MD
Miguel C Riella, MD
Adibul Hasan Rizvi, MBBS, FRCP
Bernardo Rodriguez-Iturbe, MD
Robert Schrier, MD
Justin Silver, MD, PhD
Marcello Tonelli, MD, SM, FRCPC
Yusuke Tsukamoto, MD
Theodor Vogels, MSW
Angela Yee-Moon Wang, MD, PhD, FRCP
Christoph Wanner, MD
Elena Zakharova, MD, PhD
NKF-KDIGO GUIDELINE DEVELOPMENT STAFF
Kerry Willis, PhD, Senior Vice-President for Scientific Activities
Michael Cheung, MA, Guideline Development Director
Sean Slifer, BA, Guideline Development Manager
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Reference Keys
NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE RECOMMENDATIONS
Within each recommendation, the strength of recommendation is indicated as Level 1, Level 2, or Not Graded, and the quality of the supporting evidence is shown as A, B, C, or D.
<table><tr><td rowspan="2">Grade*</td><td rowspan="2">Patients</td><td colspan="2">Implications</td></tr><tr><td>Clinicians</td><td>Policy</td></tr><tr><td>Level 1‘We recommend’</td><td>Most people in your situation would want the recommended course of action and only a small proportion would not.</td><td>Most patients should receive the recommended course of action.</td><td>The recommendation can be evaluated as a candidate for developing a policy or a performance measure.</td></tr><tr><td>Level 2‘We suggest’</td><td>The majority of people in your situation would want the recommended course of action, but many would not.</td><td>Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences.</td><td>The recommendation is likely to require substantial debate and involvement of stakeholders before policy can be determined.</td></tr></table>
*The additional category ‘Not Graded’ was used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence. The most common examples include recommendations regarding monitoring intervals, counseling, and referral to other clinical specialists. The ungraded recommendations are generally written as simple declarative statements, but are not meant to be interpreted as being stronger recommendations than Level 1 or 2 recommendations.
<table><tr><td>Grade</td><td>Quality of evidence</td><td>Meaning</td></tr><tr><td>A</td><td>High</td><td>We are confident that the true effect lies close to that of the estimate of the effect.</td></tr><tr><td>B</td><td>Moderate</td><td>The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.</td></tr><tr><td>C</td><td>Low</td><td>The true effect may be substantially different from the estimate of the effect.</td></tr><tr><td>D</td><td>Very low</td><td>The estimate of effect is very uncertain, and often will be far from the truth.</td></tr></table>
ADULT GFR ESTIMATING EQUATIONS
2009 CKD-EPI creatinine equation: \( 141 \times \min(\text{SCr}/\kappa, 1)^{\alpha} \times \max(\text{SCr}/\kappa, 1)^{-1.209} \times 0.993^{\text{Age}} [\times 1.018 \text{ if female}] [\times 1.159 \text{ if black}] \) , where SCr is serum creatinine (in mg/dl), \( \kappa \) is 0.7 for females and 0.9 for males, \( \alpha \) is -0.329 for females and -0.411 for males, min is the minimum of SCr/ \( \kappa \) or 1, and max is the maximum of SCr/ \( \kappa \) or 1.
Equations expressed for specified sex and serum creatinine level
<table><tr><td>Gender</td><td>Serum creatinine</td><td>Equation for estimating GFR</td></tr><tr><td>Female</td><td>\( \leqslant 0.7 \) mg/dl (\( \leqslant 62 \) μmol/l)</td><td>\( 144 \times (Scr/0.7)^{-0.329} \times 0.993^{Age} \) [× 1.159 if black]</td></tr><tr><td>Female</td><td>\( &gt;0.7 \) mg/dl (\( &gt;62 \) μmol/l)</td><td>\( 144 \times (Scr/0.7)^{-1.209} \times 0.993^{Age} \) [× 1.159 if black]</td></tr><tr><td>Male</td><td>\( \leqslant 0.9 \) mg/dl (\( \leqslant 80 \) μmol/l)</td><td>\( 141 \times (Scr/0.9)^{-0.411} \times 0.993^{Age} \) [× 1.159 if black]</td></tr><tr><td>Male</td><td>\( &gt;0.9 \) mg/dl (\( &gt;80 \) μmol/l)</td><td>\( 141 \times (Scr/0.9)^{-1.209} \times 0.993^{Age} \) [× 1.159 if black]</td></tr></table>
2012 CKD-EPI cystatin C equation: \( 133 \times \min(\text{SCysC}/0.8, 1)^{-0.499} \times \max(\text{SCysC}/0.8, 1)^{-1.328} \times 0.996^{Age} \) [× 0.932 if female], where SCysC is serum cystatin C (in mg/l), min indicates the minimum of SCysC/0.8 or 1, and max indicates the maximum of SCysC/0.8 or 1.
Equations expressed for serum cystatin C level
<table><tr><td></td><td>Serum cystatin C</td><td>Equation for estimating GFR</td></tr><tr><td>Female or male</td><td>≤0.8 mg/l</td><td>133 × (SCysC/0.8)-0.499 × 0.996Age[×0.932 if female]</td></tr><tr><td>Female or male</td><td>&gt;0.8 mg/l</td><td>133 × (SCysC/0.8)-1.328 × 0.996Age[×0.932 if female]</td></tr></table>
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2012 CKD-EPI creatinine-cystatin C equation: \( 135 \times \min(\text{SCr}/\kappa, 1)^{\alpha} \times \max(\text{SCr}/\kappa, 1)^{-0.60^{1}} \times \min(\text{SCysC}/0.8, 1)^{-0.375} \times \max(\text{SCysC}/0.8, 1)^{-0.711} \times 0.995^{\text{Age}} [ \times 0.969 \text{ if female} ] [ \times 1.08 \text{ if black}], \) where SCr is serum creatinine (in mg/dl), SCysC is serum cystatin C (in mg/l), \( \kappa \) is 0.7 for females and 0.9 for males, \( \alpha \) is -0.248 for females and -0.207 for males, \( \min(\text{SCr}/\kappa, 1) \) indicates the minimum of SCr/ \( \kappa \) or 1, and \( \max(\text{SCr}/\kappa, 1) \) indicates the maximum of SCr/ \( \kappa \) or 1; \( \min(\text{SCysC}/0.8, 1) \) indicates the minimum of SCysC/0.8 or 1 and \( \max(\text{SCysC}/0.8, 1) \) indicates the maximum of SCysC/0.8 or 1.
Equations expressed for specified sex, serum creatinine, and serum cystatin C level
<table><tr><td>Gender</td><td>Serum creatinine</td><td>Serum cystatin C</td><td>Equation for estimating GFR</td></tr><tr><td rowspan="2">Female</td><td rowspan="2">≤0.7 mg/dl (≤62 μmol/l)</td><td>≤0.8 mg/l</td><td>130 × (SCr/0.7)\( ^{-0.248} \) × (SCysC/0.8)\( ^{-0.375} \) × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td>&gt;0.8 mg/l</td><td>130 × (SCr/0.7)\( ^{-0.248} \) × (SCysC/0.8)-0.711 × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td rowspan="2">Female</td><td rowspan="2">&gt;0.7 mg/dl (&gt;62 μmol/l)</td><td>≤0.8 mg/l</td><td>130 × (SCr/0.7)\( ^{-0.601} \) × (SCysC/0.8)\( ^{-0.375} \) × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td>&gt;0.8 mg/l</td><td>130 × (SCr/0.7)\( ^{-0.601} \) × (SCysC/0.8)-0.711 × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td rowspan="2">Male</td><td rowspan="2">≤0.9 mg/dl (≤80 μmol/l)</td><td>≤0.8 mg/l</td><td>135 × (SCr/0.9)\( ^{-0.207} \) × (SCysC/0.8)\( ^{-0.375} \) × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td>&gt;0.8 mg/l</td><td>135 × (SCr/0.9)\( ^{-0.207} \) × (SCysC/0.8)-0.711 × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td rowspan="2">Male</td><td rowspan="2">&gt;0.9 mg/dl (&gt;80 μmol/l)</td><td>≤0.8 mg/l</td><td>135 × (SCr/0.9)\( ^{-0.601} \) × (SCysC/0.8)\( ^{-0.375} \) × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr><tr><td>&gt;0.8 mg/l</td><td>135 × (SCr/0.9)\( ^{-0.601} \) × (SCysC/0.8)-0.711 × 0.995\( ^{Age} \) [× 1.08 if black]</td></tr></table>
PEDIATRIC GFR ESTIMATING EQUATIONS
Creatinine-based equations
<table><tr><td>41.3 × (height/SCr)</td></tr><tr><td>40.7 × (height/SCr)\( ^{0.64} \) × (30/BUN)\( ^{0.202} \)</td></tr></table>
BUN, blood urea nitrogen in mg/dl; height in meters; SCr, serum creatinine in mg/dl
Cystatin C-based equations
<table><tr><td>70.69 × (SCysC)\( ^{-0.931} \)</td></tr><tr><td>SCysC, serum cystatin C in mg/l.</td></tr></table>
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CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE
USED BY KDIGO
CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health and CKD is classified based on cause, GFR category, and albuminuria category (CGA).
Prognosis of CKD by GFR and albuminuria category
<table><tr><td rowspan="4" colspan="5">Prognosis of CKD by GFR and Albuminuria Categories: KDIGO 2012</td><td colspan="3">Persistent albuminuria categories Description and range</td></tr><tr><td>A1</td><td>A2</td><td>A3</td></tr><tr><td>Normal to mildly increased</td><td>Moderately increased</td><td>Severely increased</td></tr><tr><td>&lt;30 mg/g &lt;3 mg/mmol</td><td>30-300 mg/g 3-30 mg/mmol</td><td>&gt;300 mg/g &gt;30 mg/mmol</td></tr><tr><td rowspan="6">GFR categories (ml/min/1.73 m2) Description and range</td><td>G1</td><td>Normal or high</td><td>≥90</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>G2</td><td>Mildly decreased</td><td>60-89</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>G3a</td><td>Mildly to moderately decreased</td><td>45-59</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>G3b</td><td>Moderately to severely decreased</td><td>30-44</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>G4</td><td>Severely decreased</td><td>15-29</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>G5</td><td>Kidney failure</td><td>&lt;15</td><td></td><td></td><td></td><td></td><td></td></tr></table>
Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red, very high risk.
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CONVERSION FACTORS OF METRIC UNITS TO SI UNITS
<table><tr><td>Parameter</td><td>Metric units</td><td>Conversion factor</td><td>SI units</td></tr><tr><td>Albumin (serum)</td><td>g/dl</td><td>10</td><td>g/l</td></tr><tr><td>Blood urea nitrogen (BUN)</td><td>mg/dl</td><td>0.357</td><td>mmol/l</td></tr><tr><td>Creatinine (serum)</td><td>mg/dl</td><td>88.4</td><td>μmol/l</td></tr><tr><td>Creatinine clearance</td><td>ml/min</td><td>0.01667</td><td>ml/s</td></tr><tr><td>Hemoglobin</td><td>g/dl</td><td>10</td><td>g/l</td></tr><tr><td>Phosphate (serum)</td><td>mg/dl</td><td>0.323</td><td>mmol/l</td></tr><tr><td>PTH (parathyroid hormone, serum)</td><td>pg/ml</td><td>0.106</td><td>pmol/l</td></tr><tr><td>Urea (plasma)</td><td>mg/dl</td><td>0.167</td><td>mmol/l</td></tr><tr><td>Uric acid</td><td>mg/dl</td><td>59.485</td><td>μmol/l</td></tr><tr><td>Vitamin D, 25-hydroxyvitamin D</td><td>ng/ml</td><td>2.496</td><td>nmol/l</td></tr></table>
Note: Metric unit × conversion factor = SI unit.
HbA \( _{1c} \) CONVERSION CHART
<table><tr><td>DCCT (%)</td><td>IFCC (mmol/mol)</td><td>DCCT (%)</td><td>IFCC (mmol/mol)</td><td>DCCT (%)</td><td>IFCC (mmol/mol)</td><td>DCCT (%)</td><td>IFCC (%)</td><td>DCCT (mmol/mol)</td></tr><tr><td>5.0</td><td>31</td><td>6.0</td><td>42</td><td>7.0</td><td>53</td><td>8.0</td><td>64</td><td>9.0</td></tr><tr><td>5.1</td><td>32</td><td>6.1</td><td>43</td><td>7.1</td><td>54</td><td>8.1</td><td>65</td><td>9.1</td></tr><tr><td>5.2</td><td>33</td><td>6.2</td><td>44</td><td>7.2</td><td>55</td><td>8.2</td><td>66</td><td>9.2</td></tr><tr><td>5.3</td><td>34</td><td>6.3</td><td>45</td><td>7.3</td><td>56</td><td>8.3</td><td>67</td><td>9.3</td></tr><tr><td>5.4</td><td>36</td><td>6.4</td><td>46</td><td>7.4</td><td>57</td><td>8.4</td><td>68</td><td>9.4</td></tr><tr><td>5.5</td><td>37</td><td>6.5</td><td>48</td><td>7.5</td><td>58</td><td>8.5</td><td>69</td><td>9.5</td></tr><tr><td>5.6</td><td>38</td><td>6.6</td><td>49</td><td>7.6</td><td>60</td><td>8.6</td><td>70</td><td>9.6</td></tr><tr><td>5.7</td><td>39</td><td>6.7</td><td>50</td><td>7.7</td><td>61</td><td>8.7</td><td>72</td><td>9.7</td></tr><tr><td>5.8</td><td>40</td><td>6.8</td><td>51</td><td>7.8</td><td>62</td><td>8.8</td><td>73</td><td>9.8</td></tr><tr><td>5.9</td><td>41</td><td>6.9</td><td>52</td><td>7.9</td><td>63</td><td>8.9</td><td>74</td><td>9.9</td></tr><tr><td>DCCT(%)</td><td>IFCC(mmol/mol)</td><td>DCCT(%)</td><td>IFCC(mmol/mol)</td><td>DCCT(%)</td><td>IFCC(mmol/mol)</td><td>DCCT(%)</td><td>IFCC(mmol/mol)</td><td>DCCT(%)</td><td>IFCC(mmol/mol)</td></tr><tr><td>10.0</td><td>86</td><td>11.0</td><td>97</td><td>12.0</td><td>108</td><td>13.0</td><td>119</td><td>14.0</td><td>130</td></tr><tr><td>10.1</td><td>87</td><td>11.1</td><td>98</td><td>12.1</td><td>109</td><td>13.1</td><td>120</td><td>14.1</td><td>131</td></tr><tr><td>10.2</td><td>88</td><td>11.2</td><td>99</td><td>12.2</td><td>110</td><td>13.2</td><td>121</td><td>14.2</td><td>132</td></tr><tr><td>10.3</td><td>89</td><td>11.3</td><td>100</td><td>12.3</td><td>111</td><td>13.3</td><td>122</td><td>14.3</td><td>133</td></tr><tr><td>10.4</td><td>90</td><td>11.4</td><td>101</td><td>12.4</td><td>112</td><td>13.4</td><td>123</td><td>14.4</td><td>134</td></tr><tr><td>10.5</td><td>91</td><td>11.5</td><td>102</td><td>12.5</td><td>113</td><td>13.5</td><td>124</td><td>14.5</td><td>135</td></tr><tr><td>10.6</td><td>92</td><td>11.6</td><td>103</td><td>12.6</td><td>114</td><td>13.6</td><td>125</td><td>14.6</td><td>136</td></tr><tr><td>10.7</td><td>93</td><td>11.7</td><td>104</td><td>12.7</td><td>115</td><td>13.7</td><td>126</td><td>14.7</td><td>137</td></tr><tr><td>10.8</td><td>95</td><td>11.8</td><td>105</td><td>12.8</td><td>116</td><td>13.8</td><td>127</td><td>14.8</td><td>138</td></tr><tr><td>10.9</td><td>96</td><td>11.9</td><td>107</td><td>12.9</td><td>117</td><td>13.9</td><td>128</td><td>14.9</td><td>139</td></tr></table>
IFCC-HbA \( _{1c} \) (mmol/mol) = [DCCT-HbA \( _{1c} \) (%) - 2.15] × 10.929
Abbreviations: DCCT, Diabetes Control and Complications Trial; IFCC, International Federation of Clinical Chemistry and Laboratory Medicine.
Source: Diabetes UK, www.diabetes.org.uk.
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Abbreviations and Acronyms
<table><tr><td>4C</td><td>Cardiovascular Comorbidity in Children with CKD</td><td>cTnI</td></tr><tr><td>AASK</td><td>African American Study of Kidney Disease and Hypertension</td><td>cTnT</td></tr><tr><td>ABPM</td><td>Ambulatory blood pressure monitoring</td><td>CVD</td></tr><tr><td>ACCORD</td><td>Action to Control Cardiovascular Risk in Diabetes</td><td>DCCT/EDIC</td></tr><tr><td>ACE-I</td><td>Angiotensin-converting enzyme inhibitor</td><td></td></tr><tr><td>ACR</td><td>Albumin-to-creatinine ratio</td><td>DIG</td></tr><tr><td>ACS</td><td>Acute coronary syndrome</td><td>DPI</td></tr><tr><td>ADVANCE</td><td>Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation</td><td>DXA</td></tr><tr><td>AER</td><td>Albumin excretion rate</td><td>eGFR</td></tr><tr><td>AGREE</td><td>Appraisal of Guidelines for Research and Evaluation</td><td>EMU</td></tr><tr><td>AKD</td><td>Acute kidney disease</td><td>ERT</td></tr><tr><td>AKDN</td><td>Alberta Kidney Disease Network</td><td>ESA</td></tr><tr><td>AKI</td><td>Acute kidney injury</td><td>ESCAPE</td></tr><tr><td>ANP</td><td>Atrial natriuretic peptide</td><td></td></tr><tr><td>APPROACH</td><td>Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease</td><td>ESRD</td></tr><tr><td>AusDiab</td><td>Australian Diabetes, Obesity and Lifestyle study</td><td>ESUR</td></tr><tr><td>ARB</td><td>Angiotensin-receptor blocker</td><td>FGF-23</td></tr><tr><td>BMD</td><td>Bone mineral density</td><td>GBCA</td></tr><tr><td>BMI</td><td>Body mass index</td><td>GFR</td></tr><tr><td>BNP</td><td>B-type natriuretic peptide</td><td></td></tr><tr><td>BP</td><td>Blood pressure</td><td>Hb</td></tr><tr><td>BSA</td><td>Body surface area</td><td>\( HbA_{1c} \)</td></tr><tr><td>BUN</td><td>Blood urea nitrogen</td><td>HBV</td></tr><tr><td>CAD</td><td>Coronary artery disease</td><td>HDL-C</td></tr><tr><td>CAPRICORN</td><td>Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction</td><td>HOPE</td></tr><tr><td>CGA</td><td>Cause, GFR and Albuminuria categories</td><td>HOT</td></tr><tr><td>CHARM</td><td>Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity</td><td>HR</td></tr><tr><td>CHF</td><td>Congestive heart failure</td><td>HUN T 2</td></tr><tr><td>CHS</td><td>Cardiovascular Health Study</td><td>ICD</td></tr><tr><td>CI</td><td>Confidence interval</td><td>ICU</td></tr><tr><td>CIBIS II</td><td>Cardiac Insufficiency Bisoprolol Study II</td><td>IDF</td></tr><tr><td>CKD</td><td>Chronic kidney disease</td><td>IDMS</td></tr><tr><td>CKD-EPI</td><td>CKD Epidemiology Collaboration</td><td>IQR</td></tr><tr><td>CKD-MBD</td><td>Chronic Kidney Disease-Mineral and Bone Disorder</td><td>IRMM</td></tr><tr><td>CKiD</td><td>Chronic Kidney Disease in Children</td><td>ItalKid</td></tr><tr><td>COGS</td><td>Conference on Guideline Standardization</td><td>JCTLM</td></tr><tr><td>COPERNICUS</td><td>Carvedilol Prospective Randomized Cumulative Survival</td><td>KDIGO</td></tr><tr><td>COX-2</td><td>Cyclooxygenase-2</td><td>KDOQI</td></tr><tr><td>Cr-EDTA</td><td>Chromium-ethylenediamine tetraacetic acid</td><td>LDL-C</td></tr><tr><td>CREATE</td><td>Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta Trial</td><td>LIFE</td></tr><tr><td>CREDO</td><td>Clopidogrel for Reduction of Events During Observation</td><td>LPD</td></tr><tr><td>CrCl</td><td>Creatinine clearance</td><td>LVH</td></tr><tr><td>CRIC</td><td>Chronic Renal Insufficiency Cohort</td><td>MAP</td></tr><tr><td>CRP</td><td>C-reactive protein</td><td>MDRD MESA</td></tr></table>
<table><tr><td>Cardiac troponin I</td></tr><tr><td>Cardiac troponin T</td></tr><tr><td>Cardiovascular disease</td></tr><tr><td>Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications</td></tr><tr><td>Digitalis Intervention Group</td></tr><tr><td>Dietary protein intake</td></tr><tr><td>Dietary pre- x-ray absorptiometry</td></tr><tr><td>Electrocardiography</td></tr><tr><td>Estimated GFR</td></tr><tr><td>Early morning urine</td></tr><tr><td>Evidence review team</td></tr><tr><td>Erythropoiesis-stimulating agent</td></tr><tr><td>Effect of Strict Blood Pressure Control and ACE-Inhibition on Progression of Chronic Renal Failure in Pediatric Patients</td></tr><tr><td>End-Stage Renal Disease</td></tr><tr><td>European Society of Urogenital Radiology</td></tr><tr><td>Fibroblast growth factor-23</td></tr><tr><td>Gadolinium-based contrast agent</td></tr><tr><td>Glomerular filtration rate</td></tr><tr><td>Glomerulonephritis</td></tr><tr><td>Grading of Recommendations Assessment, Development and Evaluation</td></tr><tr><td>Hemoglobin</td></tr><tr><td>Hemoglobin A1c</td></tr><tr><td>Hepatitis B virus</td></tr><tr><td>High-density lipoprotein cholesterol</td></tr><tr><td>Heart Outcomes Prevention Evaluation</td></tr><tr><td>Hypertension Optimal Treatment</td></tr><tr><td>Hazard ratio</td></tr><tr><td>High-resolution peripheral quantitative computed tomography</td></tr><tr><td>Nord-Trøndelag Health Study (1995-1997)</td></tr><tr><td>International Classification of Diseases</td></tr><tr><td>Intensive-care unit</td></tr><tr><td>International Diabetes Federation</td></tr><tr><td>Isotope-dilution mass spectrometry</td></tr><tr><td>Interquartile range</td></tr><tr><td>Institute for Reference Materials and Measurements</td></tr><tr><td>Italian Pediatric Registry of Chronic Renal Failure</td></tr><tr><td>Joint Committee for Traceability in Laboratory Medicine</td></tr><tr><td>Kidney Disease: Improving Global Outcomes</td></tr><tr><td>Kidney Disease Outcomes Quality Initiative</td></tr><tr><td>Low-density lipoprotein cholesterol</td></tr><tr><td>Losartan Intervention For Endpoint Reduction in Hypertension</td></tr><tr><td>Low-protein diet</td></tr><tr><td>Left ventricular hypertrophy</td></tr><tr><td>Mean arterial pressure</td></tr><tr><td>Modification of Diet in Renal Disease</td></tr><tr><td>Multi-Ethnic Study of Atherosclerosis</td></tr></table>
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<table><tr><td>MI</td><td>Myocardial infarction</td><td>PTH</td></tr><tr><td>MRI</td><td>Magnetic resonance imaging</td><td>QOL</td></tr><tr><td>NAPRTCS</td><td>North American Pediatric Renal Trials and Collaborative Studies</td><td>RAASRBC</td></tr><tr><td>NCEP III</td><td>Third Report of the National Cholesterol Education Program</td><td>RCTRENAAL</td></tr><tr><td>NECOSAD</td><td>Netherlands Cooperative Study on the Adequacy of Dialysis Study Group</td><td>RR</td></tr><tr><td>NHANES</td><td>National Health and Nutrition Examination Survey</td><td>RRT</td></tr><tr><td>NICE</td><td>National Institute for Health and Clinical Excellence</td><td>SCORE</td></tr><tr><td>NIH</td><td>National Institutes of Health</td><td>SCysC</td></tr><tr><td>NKDEP</td><td>National Kidney Disease Education Program</td><td>SD</td></tr><tr><td>NKF</td><td>National Kidney Foundation</td><td>SEEK</td></tr><tr><td>NSAID</td><td>Nonsteroidal anti-inflammatory drug</td><td>SHARP</td></tr><tr><td>NSF</td><td>Nephrogenic systemic fibrosis</td><td>SPECT</td></tr><tr><td>NT-proBNP</td><td>N-terminal pro-BNP</td><td>SUA</td></tr><tr><td>ONTARGET</td><td>Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint trial</td><td>TREAT</td></tr><tr><td>OR</td><td>Odds ratio</td><td>UKPDS</td></tr><tr><td>PAD</td><td>Peripheral arterial disease</td><td>USA-PRC</td></tr><tr><td>PCR</td><td>Protein-to-creatinine ratio</td><td></td></tr><tr><td>PER</td><td>Protein excretion rate</td><td></td></tr><tr><td>PICARD</td><td>Program to Improve Care in Acute Renal Disease</td><td>USRDS</td></tr><tr><td>PICODD</td><td>Population, Intervention or Predictor, Comparator, Outcome, study Design, and Duration of follow-up</td><td>VADTVal-HeFTVLPD</td></tr><tr><td>PREVEND</td><td>Prevention of Renal and Vascular Endstage Disease</td><td>WBCWHO</td></tr></table>
<table><tr><td>PTH</td><td>Parathyroid hormone</td></tr><tr><td>QOL</td><td>Quality of life</td></tr><tr><td>RAAS</td><td>Renin-angiotensin-aldosterone system</td></tr><tr><td>RBC</td><td>Red blood cell</td></tr><tr><td>RCT</td><td>Randomized controlled trial</td></tr><tr><td>RENAAL</td><td>Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan</td></tr><tr><td>RR</td><td>Relative risk</td></tr><tr><td>RRT</td><td>Renal replacement therapy</td></tr><tr><td>SCORE</td><td>Systematic COronary Risk Evaluation</td></tr><tr><td>SCr</td><td>Serum creatinine</td></tr><tr><td>SCysC</td><td>Serum cystatin C</td></tr><tr><td>SD</td><td>Standard deviation</td></tr><tr><td>SEEK</td><td>Study for the Evaluation of Early Kidney disease</td></tr><tr><td>SHARP</td><td>Study of Heart and Renal Protection</td></tr><tr><td>SPECT</td><td>Single photon emission computed tomography</td></tr><tr><td>SUA</td><td>Serum uric acid</td></tr><tr><td>TREAT</td><td>Trial to Reduce Cardiovascular Events with Aranesp Therapy</td></tr><tr><td>UKPDS</td><td>United Kingdom Prospective Diabetes Study</td></tr><tr><td>USA-PRC</td><td>USA-People&#x27;s Republic of China Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology</td></tr><tr><td>USRDS</td><td>US Renal Data System</td></tr><tr><td>VADT</td><td>Veterans Affairs Diabetes Trial</td></tr><tr><td>Val-HeFT</td><td>Valsartan Heart Failure Trial</td></tr><tr><td>VLPD</td><td>Very low-protein diet</td></tr><tr><td>WBC</td><td>White blood cell</td></tr><tr><td>WHO</td><td>World Health Organization</td></tr></table>
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Notice
Kidney International Supplements (2013) 3, 1; doi:10.1038/kisup.2012.73
SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINE
This Clinical Practice Guideline document is based upon systematic literature searches last conducted in June 2011, supplemented with additional evidence through November 2012. It is designed to provide information and assist decision making. It is not intended to define a standard of care, and should not be construed as one, nor should it be interpreted as prescribing an exclusive course of management. Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Every health-care professional making use of these recommendations is responsible for evaluating the appropriateness of applying them in any particular clinical situation. The recommendations for research contained within this document are general and do not imply a specific protocol.
SECTION II: DISCLOSURE
Kidney Disease: Improving Global Outcomes (KDIGO) makes every effort to avoid any actual or reasonably perceived 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. All members of the Work Group are required to complete, sign, and submit a disclosure and attestation form showing all such relationships that might be perceived as or are actual conflicts of interest. This document is updated annually and information is adjusted accordingly. All reported information is published in its entirety at the end of this document in the Work Group members' Biographic and Disclosure Information section, and is kept on file at the National Kidney Foundation (NKF), former Managing Agent for KDIGO.
Copyright © 2012 by KDIGO. All rights reserved.
Single photocopies may be made for personal use as allowed by national copyright laws. Special rates are available for educational institutions that wish to make photocopies for non-profit educational use. No part of this publication may be reproduced, amended, or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without explicit permission in writing from KDIGO. Details on how to seek permission for reproduction or translation, and further information about KDIGO's permissions policies can be obtained by contacting Danielle Green, Managing Director, at danielle.green@kdigo.org
To the fullest extent of the law, neither KDIGO, Kidney International Supplements, National Kidney Foundation (KDIGO's former Managing Agent) nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
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Foreword
Kidney International Supplements (2013) 3, 2; doi:10.1038/kisup.2012.74
It is our hope that this document will serve several useful purposes. 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 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.
We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and the strength of recommendations. In all, there were 12 (17.1%) recommendations in this guideline for which the overall quality of evidence was graded 'A,' whereas 36 (51.4%) were graded 'B,' 17 (24.3%) were graded 'C,' and 5 (7.1%) were graded 'D.' Although there are reasons other than quality of evidence to make a grade 1 or 2 recommendation, in general, there is a correlation between the quality of overall evidence and the strength of the recommendation. Thus, there were 43 (62.3%) recommendations graded '1' and 26 (37.7%) graded '2.' There were 9 (13.0%) recommendations graded '1A,' 23 (33.3%) were '1B,' 10 (14.5%) were '1C,' and 1 (1.4%) was '1D.' There were 2 (2.9%) recommendations graded '2A,' 13 (18.8%) were '2B,' 7 (10.1%) were '2C,' and 4 (5.8%)
were ‘2D.’ There were 41 (37.3%) statements that were not graded.
Some argue that recommendations should not be made when evidence is weak. However, clinicians still need to make decisions in their daily practice, and they often ask, “What do the experts do in this setting?” We opted to give guidance, rather than remain silent. These recommendations are often rated with a low strength of recommendation and a low quality of evidence, or were not graded. It is important for the users of this guideline to be cognizant of this (see Notice). In every case these recommendations are meant to be a place for clinicians to start, not stop, their inquiries into specific management questions pertinent to the patients they see in daily practice.
We wish to thank the Work Group Co-Chairs, Drs. Adeera Levin and Paul Stevens, along with all of the Work Group members who volunteered countless hours of their time developing this guideline. We also thank the Evidence Review Team members and staff of the National Kidney Foundation who made this project possible. Finally, we owe a special debt of gratitude to the many KDIGO Board members and individuals who volunteered time reviewing the guideline, and making very helpful suggestions.
Bertram L Kasiske, MD David C Wheeler, MD, FRCP KDIGO Co-Chair KDIGO Co-Chair
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Work Group Membership
Kidney International Supplements (2013) 3, 3; doi:10.1038/kisup.2012.75
WORK GROUP CO-CHAIRS
Adeera Levin, MD, FRCPC
University of British Columbia
Vancouver, Canada
Paul E Stevens, MB, FRCP
East Kent Hospitals University
NHS Foundation Trust
Canterbury, United Kingdom
WORK GROUP
Rudy W Bilous, MD
Newcastle University and James Cook University Hospital
Middlesbrough, United Kingdom
Josef Coresh, MD, PhD, MHS
Johns Hopkins University
Baltimore, USA
Angel LM de Francisco, MD, PhD
Hospital Universitario Valdecilla
Santander, Spain
Paul E de Jong, MD, PhD
University Medical Center Groningen
Groningen, The Netherlands
Kathryn E Griffith, BM, BS, MSc, MRCP, MRCGP
University Health Centre, York University
York, United Kingdom
Brenda R Hemmelgarn, MD, PhD, FRCP(C)
University of Calgary
Alberta, Canada
Kunitoshi Iseki, MD
University Hospital of the Ryukyus
Nishihara, Okinawa, Japan
Edmund J Lamb, PhD, FRCPath
East Kent Hospitals University
NHS Foundation Trust
Canterbury, United Kingdom
Andrew S Levey, MD
Tufts Medical Center
Boston, USA
Miguel C Riella, MD, PhD, FACP
Evangelic University Hospital
Curitiba, Brazil
Michael G Shlipak, MD, MPH
VA Medical Center, UCSF
San Francisco, USA
Haiyan Wang, MD
Peking University First Hospital
Beijing, China
Colin T White, MD, FRCPC
University of British Columbia
Vancouver, Canada
Christopher G Winearls, MB, DPhil, FRCP
Oxford Radcliffe Hospitals NHS Trust
Oxford, United Kingdom
EVIDENCE REVIEW TEAM
Tufts Center for Kidney Disease Guideline Development and Implementation
Tufts Medical Center, Boston, MA, USA:
Katrin Uhlig, MD, MS, Project Director; Director, Guideline Development
Dana Miskulin, MD, MS, Staff Nephrologist
Amy Earley, BS, Project Coordinator
Shana Haynes, MS, DHSc, Research Assistant
Jenny Lamont, MS, Project Manager
In addition, support and supervision were provided by:
Ethan M Balk, MD, MPH; Program Director, Evidence Based Medicine
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Abstract
Kidney International Supplements (2013) 3, 4; doi:10.1038/kisup.2012.76
The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) serves to update the 2002 KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification following a decade of focused research and clinical practice in CKD. The document aims to provide state-of-the-art guidance on the evaluation, management and treatment for all patients with CKD. Specifically, the guideline retains the definition of CKD but presents an enhanced classification framework for CKD; elaborates on the identification and prognosis of CKD; discusses the management of progression and complications of CKD; and expands on the continuum of CKD care: timing of specialist referral, ongoing management of people with progressive CKD, timing of the initiation of dialysis, and finally the implementation of a treatment program which includes comprehensive conservative management. The development of the guideline followed an explicit process of evidence review and appraisal. Treatment approaches are addressed in each chapter and guideline recommendations are based on systematic reviews of relevant trials. Practical comments or statements which serve as educational purposes are ungraded, but included as important information for the readership. Appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. Ongoing areas of controversies, limitations of the evidence, and international relevance are discussed and additional suggestions are provided for future research.
Keywords: Albuminuria; Chronic kidney disease; Classification; Clinical practice guideline; Evidence-based recommendation; GFR; Glomerular filtration rate; KDIGO; Proteinuria; Systematic review
CITATION
In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150.
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Summary of Recommendation Statements
Kidney International Supplements (2013) 3, 5–14; doi:10.1038/kisup.2012.77
Chapter 1: Definition and classification of CKD
1.1: DEFINITION OF CKD
1.1.1: CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. (Not Graded)
Criteria for CKD (either of the following present for >3 months)
<table><tr><td>Markers of kidney damage (one or more)</td><td>Albuminuria (AER ≥30 mg/24 hours; ACR ≥30 mg/g [≥3 mg/mmol])Urine sediment abnormalitiesElectrolyte and other abnormalities due to tubular disordersAbnormalities detected by histologyStructural abnormalities detected by imagingHistory of kidney transplantation</td></tr><tr><td>Decreased GFR</td><td>GFR &lt;60 ml/min/1.73 m2(GFR categories G3a-G5)</td></tr></table>
Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate.
1.2: STAGING OF CKD
1.2.1: We recommend that CKD is classified based on cause, GFR category, and albuminuria category (CGA). (1B)
1.2.2: Assign cause of CKD based on presence or absence of systemic disease and the location within the kidney of observed or presumed pathologic-anatomic findings. (Not Graded)
1.2.3: Assign GFR categories as follows (Not Graded):
GFR categories in CKD
<table><tr><td>GFR category</td><td>GFR (ml/min/1.73 m2)</td><td>Terms</td></tr><tr><td>G1</td><td>≥90</td><td>Normal or high</td></tr><tr><td>G2</td><td>60-89</td><td>Mildly decreased*</td></tr><tr><td>G3a</td><td>45-59</td><td>Mildly to moderately decreased</td></tr><tr><td>G3b</td><td>30-44</td><td>Moderately to severely decreased</td></tr><tr><td>G4</td><td>15-29</td><td>Severely decreased</td></tr><tr><td>G5</td><td>&lt;15</td><td>Kidney failure</td></tr></table>
Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate.
*Relative to young adult level
In the absence of evidence of kidney damage, neither GFR category G1 nor G2 fulfill the criteria for CKD.
1.2.4: Assign albuminuria* categories as follows (Not Graded):
*note that where albuminuria measurement is not available, urine reagent strip results can be substituted (Table 7)
Albuminuria categories in CKD
<table><tr><td rowspan="2">Category</td><td rowspan="2">AER (mg/24 hours)</td><td colspan="2">ACR (approximate equivalent)</td><td rowspan="2">Terms</td></tr><tr><td>(mg/mmol)</td><td>(mg/g)</td></tr><tr><td>A1</td><td>&lt;30</td><td>&lt;3</td><td>&lt;30</td><td>Normal to mildly increased</td></tr><tr><td>A2</td><td>30-300</td><td>3-30</td><td>30-300</td><td>Moderately increased*</td></tr><tr><td>A3</td><td>&gt;300</td><td>&gt;30</td><td>&gt;300</td><td>Severely increased**</td></tr></table>
Abbreviations: AER, albumin excretion rate; ACR, albumin-to-creatinine ratio; CKD, chronic kidney disease.
*Relative to young adult level.
**Including nephrotic syndrome (albumin excretion usually >2200 mg/24 hours [ACR >2220 mg/g; >220 mg/mmol]).
1.3: PREDICTING PROGNOSIS OF CKD
1.3.1: In predicting risk for outcome of CKD, identify the following variables: 1) cause of CKD; 2) GFR category; 3) albuminuria category; 4) other risk factors and comorbid conditions. (Not Graded)
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1.3.2: In people with CKD, use estimated risk of concurrent complications and future outcomes to guide decisions for testing and treatment for CKD complications. (Not Graded)
1.3.3: In populations with CKD, group GFR and albuminuria categories with similar relative risk for CKD outcomes into risk categories. (Not Graded)
<table><tr><td rowspan="4" colspan="4">Prognosis of CKD by GFR and Albuminuria Categories: KDIGO 2012</td><td colspan="4">Persistent albuminuria categories Description and range</td></tr><tr><td>A1</td><td>A2</td><td>A3</td><td></td></tr><tr><td>Normal to mildly increased</td><td>Moderately increased</td><td>Severely increased</td><td></td></tr><tr><td>&lt;30 mg/g &lt;3 mg/mmol</td><td>30-300 mg/g 3-30 mg/mmol</td><td>&gt;300 mg/g &gt;30 mg/mmol</td><td></td></tr><tr><td rowspan="6">GFR categories (ml/min/1.73 m2) Description and range</td><td>G1</td><td>Normal or high</td><td>≥90</td><td></td><td></td><td></td><td></td></tr><tr><td>G2</td><td>Mildly decreased</td><td>60-89</td><td></td><td></td><td></td><td></td></tr><tr><td>G3a</td><td>Mildly to moderately decreased</td><td>45-59</td><td></td><td></td><td></td><td></td></tr><tr><td>G3b</td><td>Moderately to severely decreased</td><td>30-44</td><td></td><td></td><td></td><td></td></tr><tr><td>G4</td><td>Severely decreased</td><td>15-29</td><td></td><td></td><td></td><td></td></tr><tr><td>G5</td><td>Kidney failure</td><td>&lt;15</td><td></td><td></td><td></td><td></td></tr></table>
Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red, very high risk.
1.4: EVALUATION OF CKD
1.4.1: Evaluation of chronicity
1.4.1.1: In people with GFR <60 ml/min/1.73 m\( ^{2} \) (GFR categories G3a-G5) or markers of kidney damage, review past history and previous measurements to determine duration of kidney disease. (Not Graded)
- If duration is \(>3\) months, CKD is confirmed. Follow recommendations for CKD.
- If duration is not \(>3\) months or unclear, CKD is not confirmed. Patients may have CKD or acute kidney diseases (including AKI) or both and tests should be repeated accordingly.
1.4.2: Evaluation of cause
1.4.2.1: Evaluate the clinical context, including personal and family history, social and environmental factors, medications, physical examination, laboratory measures, imaging, and pathologic diagnosis to determine the causes of kidney disease. (Not Graded)
1.4.3: Evaluation of GFR
1.4.3.1: We recommend using serum creatinine and a GFR estimating equation for initial assessment. (1A)
1.4.3.2: We suggest using additional tests (such as cystatin C or a clearance measurement) for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate. (2B)
1.4.3.3: We recommend that clinicians (1B):
- use a GFR estimating equation to derive GFR from serum creatinine (eGFR \( _{creat} \) ) rather than relying on the serum creatinine concentration alone.
- understand clinical settings in which eGFR\(_{\text{creat}}\) is less accurate.
1.4.3.4: We recommend that clinical laboratories should (1B):
- measure serum creatinine using a specific assay with calibration traceable to the international standard reference materials and minimal bias compared to isotope-dilution mass spectrometry (IDMS) reference methodology.
- report eGFR\(_{\text{creat}}\) in addition to the serum creatinine concentration in adults and specify the equation used whenever reporting eGFR\(_{\text{creat}}\).
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- report eGFR\(_{creat}\) in adults using the 2009 CKD-EPI creatinine equation. An alternative creatinine-based GFR estimating equation is acceptable if it has been shown to improve accuracy of GFR estimates compared to the 2009 CKD-EPI creatinine equation.
When reporting serum creatinine:
- We recommend that serum creatinine concentration be reported and rounded to the nearest whole number when expressed as standard international units ( \( \mu \) mol/l) and rounded to the nearest \( 100^{th} \) of a whole number when expressed as conventional units (mg/dl).
When reporting eGFR \( _{creat} \) :
- We recommend that eGFR\(_{\text{creat}}\) should be reported and rounded to the nearest whole number and relative to a body surface area of 1.73 m\( ^{2} \) in adults using the units ml/min/1.73 m\( ^{2} \).
- We recommend eGFR\(_{\text{creat}}\) levels less than 60 ml/min/1.73 m\( ^{2} \) should be reported as “decreased.”
1.4.3.5: We suggest measuring cystatin C in adults with eGFR \( _{creat} \) 45–59 ml/min/1.73 m \( ^{2} \) who do not have markers of kidney damage if confirmation of CKD is required. (2C)
- If eGFR\(_{\text{cys}}\)/eGFR\(_{\text{creat-cy}}\) is also <60 ml/min/1.73 m\(^2\), the diagnosis of CKD is confirmed.
- If eGFR\(_{\text{cys}}\)/eGFR\(_{\text{creat-cy}}\) is \(\geq\)60 ml/min/1.73 m\(^2\), the diagnosis of CKD is not confirmed.
1.4.3.6: If cystatin C is measured, we suggest that health professionals (2C):
- use a GFR estimating equation to derive GFR from serum cystatin C rather than relying on the serum cystatin C concentration alone.
- understand clinical settings in which eGFR\(_{\text{cys}}\) and eGFR\(_{\text{creat-cys}}\) are less accurate.
1.4.3.7: We recommend that clinical laboratories that measure cystatin C should (1B):
- measure serum cystatin C using an assay with calibration traceable to the international standard reference material.
- report eGFR from serum cystatin C in addition to the serum cystatin C concentration in adults and specify the equation used whenever reporting eGFR\(_{cys}\) and eGFR\(_{creat-cys}\).
- report eGFR\(_{cys}\) and eGFR\(_{creat-cys}\) in adults using the 2012 CKD-EPI cystatin C and 2012 CKD-EPI creatinine-cystatin C equations, respectively, or alternative cystatin C-based GFR estimating equations if they have been shown to improve accuracy of GFR estimates compared to the 2012 CKD-EPI cystatin C and 2012 CKD-EPI creatinine-cystatin C equations.
When reporting serum cystatin C:
- We recommend reporting serum cystatin C concentration rounded to the nearest \(100^{\text{th}}\) of a whole number when expressed as conventional units (mg/l).
When reporting eGFR \( _{cys} \) and eGFR \( _{creat-cys} \):
- We recommend that eGFR\(_{cys}\) and eGFR\(_{creat-cys}\) be reported and rounded to the nearest whole number and relative to a body surface area of 1.73 m\(^{2}\) in adults using the units ml/min/1.73 m\(^{2}\).
- We recommend eGFR\(_{cys}\) and eGFR\(_{creat-cys}\) levels less than 60 ml/min/1.73 m\(^{2}\) should be reported as “decreased.”
1.4.3.8: We suggest measuring GFR using an exogenous filtration marker under circumstances where more accurate ascertainment of GFR will impact on treatment decisions. (2B)
1.4.4: Evaluation of albuminuria
1.4.4.1: We suggest using the following measurements for initial testing of proteinuria (in descending order of preference, in all cases an early morning urine sample is preferred) (2B):
1) urine albumin-to-creatinine ratio (ACR);
2) urine protein-to-creatinine ratio (PCR);
3) reagent strip urinalysis for total protein with automated reading;
4) reagent strip urinalysis for total protein with manual reading.
1.4.4.2: We recommend that clinical laboratories report ACR and PCR in untimed urine samples in addition to albumin concentration or proteinuria concentrations rather than the concentrations alone. (1B)
1.4.4.2.1: The term microalbuminuria should no longer be used by laboratories. (Not Graded)
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1.4.4.3: Clinicians need to understand settings that may affect interpretation of measurements of albuminuria and order confirmatory tests as indicated (Not Graded):
- Confirm reagent strip positive albuminuria and proteinuria by quantitative laboratory measurement and express as a ratio to creatinine wherever possible.
- Confirm ACR≥30 mg/g (≥3 mg/mmol) on a random untimed urine with a subsequent early morning urine sample.
- If a more accurate estimate of albuminuria or total proteinuria is required, measure albumin excretion rate or total protein excretion rate in a timed urine sample.
1.4.4.4: If significant non-albumin proteinuria is suspected, use assays for specific urine proteins (e.g., \( \alpha_{1} \) -microglobulin, monoclonal heavy or light chains, [known in some countries as “Bence Jones” proteins]). (Not Graded)
Chapter 2: Definition, identification, and prediction of CKD progression
2.1: DEFINITION AND IDENTIFICATION OF CKD PROGRESSION
2.1.1: Assess GFR and albuminuria at least annually in people with CKD. Assess GFR and albuminuria more often for individuals at higher risk of progression, and/or where measurement will impact therapeutic decisions (see figure below). (Not Graded)
2.1.2: Recognize that small fluctuations in GFR are common and are not necessarily indicative of progression. (Not Graded)
2.1.3: Define CKD progression based on one of more of the following (Not Graded):
- Decline in GFR category ( \( \geq \) 90 [G1], 60–89 [G2], 45–59 [G3a], 30–44 [G3b], 15–29 [G4], <15 [G5] ml/min/1.73 m \( ^{2} \) ). A certain drop in eGFR is defined as a drop in GFR category accompanied by a 25% or greater drop in eGFR from baseline.
- Rapid progression is defined as a sustained decline in eGFR of more than 5 ml/min/1.73 m\( ^{2} \)/yr.
- The confidence in assessing progression is increased with increasing number of serum creatinine measurements and duration of follow-up.
2.1.4: In people with CKD progression, as defined in Recommendation 2.1.3, review current management, examine for reversible causes of progression, and consider referral to a specialist. (Not Graded)

GFR and albuminuria grid to reflect the risk of progression by intensity of coloring (green, yellow, orange, red, deep red). The numbers in the boxes are a guide to the frequency of monitoring (number of times per year).
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2.2: PREDICTORS OF PROGRESSION
2.2.1: Identify factors associated with CKD progression to inform prognosis. These include cause of CKD, level of GFR, level of albuminuria, age, sex, race/ethnicity, elevated BP, hyperglycemia, dyslipidemia, smoking, obesity, history of cardiovascular disease, ongoing exposure to nephrotoxic agents, and others. (Not Graded)
Chapter 3: Management of progression and complications of CKD
3.1: PREVENTION OF CKD PROGRESSION
BP and RAAS interruption
3.1.1: Individualize BP targets and agents according to age, coexistent cardiovascular disease and other comorbidities, risk of progression of CKD, presence or absence of retinopathy (in CKD patients with diabetes), and tolerance of treatment as described in the KDIGO 2012 Blood Pressure Guideline. (Not Graded)
3.1.2: Inquire about postural dizziness and check for postural hypotension regularly when treating CKD patients with BP-lowering drugs. (Not Graded)
3.1.3: Tailor BP treatment regimens in elderly patients with CKD by carefully considering age, comorbidities and other therapies, with gradual escalation of treatment and close attention to adverse events related to BP treatment, including electrolyte disorders, acute deterioration in kidney function, orthostatic hypotension and drug side effects. (Not Graded)
3.1.4: We recommend that in both diabetic and non-diabetic adults with CKD and urine albumin excretion <30 mg/24 hours (or equivalent*) whose office BP is consistently >140 mm Hg systolic or >90 mm Hg diastolic be treated with BP-lowering drugs to maintain a BP that is consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic. (1B)
3.1.5: We suggest that in both diabetic and non-diabetic adults with CKD and with urine albumin excretion of \( \geq \) 30 mg/24 hours (or equivalent*) whose office BP is consistently >130 mm Hg systolic or >80 mm Hg diastolic be treated with BP-lowering drugs to maintain a BP that is consistently \( \leq \) 130 mm Hg systolic and \( \leq \) 80 mm Hg diastolic. (2D)
3.1.6: We sugge

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