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Summary of KDIGO 2012 CKD Guideline: behind the scenes, need for guidance, and a framework for moving forward

2013; Elsevier BV; Volume: 85; Issue: 1 Linguagem: Inglês

10.1038/ki.2013.444

1523-1755

Adeera Levin, Paul E. Stevens,

Health Systems, Economic Evaluations, Quality of Life

The 2012 KDIGO Guideline for CKD evaluation, classification, and management has updated the original 2002 KDOQI Guidelines, using newer data and addressing issues raised over the last decade concerning definitions and assessment. This review highlights the key aspects of the CKD guideline, and describes the rationale for specific wording and the scope of the document. A précis of key concepts in each of the five sections of the guideline is presented. The guideline document is intended for general practitioners and nephrologists, and covers CKD evaluation, classification, and management for both adults and children. Throughout the guideline, we have attempted to overtly address areas of controversy or non-consensus, international relevance, and impact on practice and public policy. The 2012 KDIGO Guideline for CKD evaluation, classification, and management has updated the original 2002 KDOQI Guidelines, using newer data and addressing issues raised over the last decade concerning definitions and assessment. This review highlights the key aspects of the CKD guideline, and describes the rationale for specific wording and the scope of the document. A précis of key concepts in each of the five sections of the guideline is presented. The guideline document is intended for general practitioners and nephrologists, and covers CKD evaluation, classification, and management for both adults and children. Throughout the guideline, we have attempted to overtly address areas of controversy or non-consensus, international relevance, and impact on practice and public policy. After a decade of focused research and clinical practice in chronic kidney disease (CKD), the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of CKD1.KDIGO CKD Work Group KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Int Suppl. 2013; 3: 1-150Abstract Full Text Full Text PDF Scopus (1579) Google Scholar serves to update the original 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for CKD: Evaluation, Classification, and Stratification.2.National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am J Kidney Dis. 2002; 39: S1-S266Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar That decade has brought controversy, validation, and new ideas but has also highlighted CKD as global public health issue.3.Levey A.S. Atkins R. Coresh J. et al.Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from kidney disease improving global outcomes.Kidney Int. 2007; 72: 247-259Abstract Full Text Full Text PDF PubMed Scopus (1037) Google Scholar Through use of a common language and classification system, the original guidance stimulated new knowledge, resulting in the need for this new guideline. It is beyond the scope of this document to review each statement and all the nuances and issues related to the guideline development, so the reader is encouraged to read the original document. This overview is intended to highlight the important concepts in the guideline, some old and some new. Moreover, we wish to ensure an understanding of the rationale for specific wording, and how and why specific topics were or were not addressed, and the depth to which they were addressed. Throughout the guideline, we have attempted to overtly address areas of controversy or non-consensus, international relevance, and impact on practice and public policy. The reader is encouraged to review those specific areas within each of the sections in addition to the scientific and evidence base for rationale, so as to gain further insights into the specific recommendation statement. The guideline document1.KDIGO CKD Work Group KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Int Suppl. 2013; 3: 1-150Abstract Full Text Full Text PDF Scopus (1579) Google Scholar aims to provide state-of-the-art guidance on the evaluation, management, and treatment for both adult and pediatric populations with CKD. The intended audience is diverse and includes nephrologists, primary-care practitioners, and other specialists, as well as allied health-care professionals. We appreciate that different health-care systems exist around the world, and so attempt to provide best practice recommendations. It is recognized that there will be variation in the ability to implement some of the recommendations in different jurisdictions, but by identifying best practices and describing the evidence base, we hope to encourage advocacy for those best practices to improve the care of patients with CKD around the world. Individual country commentaries and implementation efforts are encouraged and should highlight major areas of controversy or relevance. The development of this 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. Important statements that serve as educational or practical comments are ungraded and included for the readership. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.4.Atkins D. Best D. Briss P.A. et al.Grading quality of evidence and strength of recommendations.BMJ. 2004; 328: 1490Crossref PubMed Google Scholar We used the GRADE system to rate the strength 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 clinical 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. 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. 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. The balance of few grade A evidence-based recommendations (17%; 12 statements) and many ungraded recommendations can help define areas where research is needed. Although many would state that this guideline should be much shorter given the paucity of evidence, we and the Work Group, as well as the public groups consulted, were committed to constructing a comprehensive guidance document that was transparent and useful. We would submit that defining the research agenda is an often neglected, but very important, function of clinical practice guideline development. We would suggest that the implementation of the more granular cause, glomerular filtration rate (GFR), and albuminuria (CGA) system, with refined subcategories within GFR level 3 into 3a and 3b, and albuminuria categories will help practitioners with risk assessment as well as management plans. Perhaps most importantly, it will also lead to improvements in clinical trial design and execution by ensuring recruitment of the specific patient populations. We retained the original definition of CKD, and added a short qualifier phrase (with implications for health) to emphasize that some abnormalities of structure or function may not have any clinical significance (e.g., small simple cysts). We present an enhanced classification framework for CKD, which includes additional dimensions to previous simple GFRs categories, and have avoided the word ‘stages’ throughout the document. As it is now clear that GFR is only one important dimension in the assessment of those with kidney disease, we have added a statement that emphasizes the need to include cause and albuminuria categories in addition to the GFR categories. A classification based on these three dimensions (CGA) is recommended. The rationale for this includes the need to remind practitioners that CKD is not a diagnosis but rather a condition or abnormal state, and that causes of CKD should be sought, within reason, so that appropriate treatment of underlying cause can be initiated. Other changes include the further refinement of GFR category 3, into 3a and 3b, based on substantial data that there are differences in outcomes and risk for those who have GFR values between 45 and 60 versus 30 and 45ml/min per 1.73m2. In this section, the reader is also educated about the importance of albuminuria as a key dimension in risk assessment. A practical table describing the relationships between protein-to-creatinine ratio to dipsticks and urine albumin-to-creatinine ratio (ACR) is provided here. Issues related to assays and measurements serve to enlighten clinicians as to the current potential problems with these measures. It is recognized that in many parts of the world, urine ACR is not available in general use, but again we offer the table for equivalences as a rough guide. For practical purposes, we give direct instructions for the laboratories as to how best to report both estimated GFR (eGFR) values and albuminuria. In particular and in accordance with contemporary international laboratory initiatives, the use of the term ‘microalbuminuria’ is discouraged and more quantitative description of albuminuria by category or by specific value is encouraged. This is predicated on the data suggesting increased risk at all levels of urine albumin excretion. Of note, the laboratory physicians support this change in terminology. Some have argued that there will be problems in removing ‘microalbuminuria’ from general usage, but by advocating an alternative in this guideline, and the rationale for it, we hope to change that practice. This does not negate the previous body of literature using the term, as it maps to levels of A2 (30–300mg/g (3–30mg/mmol)) in the new system. We would envision the use of this CGA system, including cause, and levels of GFR and albuminuria, to help with individual patient descriptions in clinical practice, and also for enrollment into clinical trials. Patients could be identified as having diabetic nephrosclerosis, with eGFR of 21ml/min per 1.73m2, and ACRs of 40mg/mmol (to be very specific) or could be abbreviated using the terminology ‘diabetes, G4, A3’. Also in section 1, statements detailing the use of specific equations are developed in detail. The fundamental message is to obtain the best estimate of GFR through use of the best equation validated in the population of interest. The utility and caveats of creatinine- and cystatin-C-based estimating equations are also discussed. We provide guidance into when to directly measure GFR, when there is an overwhelming importance to be precise with respect to clinical decisions (e.g., nephrectomy or use of highly toxic drugs). We do not advocate regular direct measurement in usual clinical practice, but do remind the readers that all equations provide only estimates of true GFR. Overall, we advocate the use of the ‘heat map’ (see graphical representation at the end of this review, Chapter 1, section 1.3.3) as generated by the dimensions of GFR and albuminuria to guide clinicians in risk assessment, and use that grid throughout the guideline to highlight risks and actions. We envision that implementation tools based on the heat map will be developed. This section elaborates on the prognosis of CKD and the identification of its progression, and offers suggestions as to how to define rapid progression. In addition, we highlight for practitioners that some minor variations in kidney function may occur over time, without necessarily heralding irreversible progression. The definition of rapid progression, defined as a change in GFR over a set time period, is intended to help practitioners to identify those at higher risk, and those in whom increased vigilance is warranted. Additional studies are needed to help further refine these concepts, and ideally information systems in laboratories will help to simplify the more difficult calculations required for some of the definitions. This is the first attempt in a guideline to address the difficult issue of ‘true progression’ and will need further validation in clinical practice and studies. This section was included because of requests from practitioners and those involved in clinical trial design to clarify the concept using rigorous data methodology. The question has generated a series of novel papers examining this issue in different populations (general, high risk, and CKD), some of which are due to be published after the guideline. In this section, we discuss the management of progression and complications of CKD, using the best evidence to date, and leveraging the statements from other recent KDIGO guidelines (blood pressure, acute kidney injury, glomerulonephritis, and anemia).5.KDIGO BP Work Group KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease.Kidney Int Suppl. 2012; 2: 337-414Abstract Full Text Full Text PDF Scopus (415) Google Scholar, 6.KDIGO AKI Work Group KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Abstract Full Text Full Text PDF Scopus (102) Google Scholar, 7.KDIGO Anemia Work Group KDIGO clinical practice guideline for anemia in chronic kidney disease.Kidney Int Suppl. 2012; 2: 279-335Abstract Full Text Full Text PDF Scopus (668) Google Scholar, 8.KDIGO GN Work Group KDIGO clinical practice guidelines for glomerulonephritis.Kidney Int Suppl. 2012; 2: 1-143Abstract Full Text Full Text PDF Scopus (1987) Google Scholar This section is comprehensive in itemizing the different treatments for progression and the specific complications of CKD, which may contribute to progression. However, we limited the discussion and statements to those relevant to clinical practice and with some evidence base. Where there remains little data, we clearly state this. Many would have liked this section to be more comprehensive and directive; however, given the scope of the guideline, and the existence of other more detailed documents describing the management issues, we sought to highlight the key issues so that practitioners would gain a sense of the breadth and depth of complications related to CKD. As extensive research remains to be conducted to optimize treatment of complications of CKD, and of progression, we would encourage well-designed trials to be conducted. After these data are available, we would anticipate the need for updated guidance on many of these issues. This section is included as a reminder that it is important to appreciate the complexity of evaluating and treating patients with CKD and other conditions. We identified issues of patient safety and areas of evaluation of CKD patients for common conditions (heart disease and diabetes), and used this section to remind the practitioner to identify important events like infection, acute kidney injury, and imaging studies as modifiers of risk (of progression and of death), and as related to patient safety. We wanted to provide the reader with comprehensive guidance for common clinical scenarios. Also we highlight potential misunderstandings regarding common tests. For example, prognosis and treatment algorithms for elevations of B-type natriuretic peptide and troponin have not been evaluated and validated in CKD populations. We emphasize that those with CKD and evidence of cardiac disease be treated in accordance with best practices for those without CKD (i.e., appropriate diagnostic studies or/and medications should be offered). The value of hemoglobin A1c in patients with diabetes with more advanced CKD remains problematic, a fact not necessarily appreciated by many. We have listed in a table the commonly used drugs in CKD, and those needing dose reduction or cessation. We hope that the tables and issues identified in this section will be useful tools for practitioners. This section highlights the complexity of care associated with CKD in terms of diagnosis, monitoring, and treatment options. In this section of the guideline, we expand on the continuum of CKD care: timing of specialist referral, ongoing management of people with progressive CKD, timing the initiation of dialysis, and finally the implementation of a treatment program that includes comprehensive conservative management, including end-of-life care. We have recognized the paucity of data for many of these recommendations, and so many remain ungraded. As practical tips or key points, they serve to remind practitioners at all levels about the multiple dimensions required in the care of patients with CKD. We highlight the importance of multidisciplinary care teams to enhance care and outcomes of this complex condition. We appreciate that referral to specialists may vary by country or region, but underscore that the rationale for that referral should be to access specialist knowledge or services so that care is optimized. We stress that the continuum of care for patients living with CKD evolves over time and incorporates both patient and care team decision making at multiple points (‘no decision about me without me’). Decisions about dialysis timing should reflect a composite of clinical symptoms and laboratory parameters. All patients with CKD should be offered conservative treatment options with supportive services. It is clear that many of these specific suggestions will be individualized to specific regional contexts, but the principles on which they are founded are universal. Kidney disease is defined as an abnormality of kidney structure or function with implications for the health of an individual, which can occur abruptly, and may either resolve or become chronic. CKD is a general term for heterogeneous disorders affecting kidney structure and function with variable clinical presentation, which is present for >3 months. The concept of CKD evolved after the recognition of the contribution of disordered kidney structure and function on the health of individuals across a wide range of severity. The utility of the concept is that recognition of CKD will have implications for individuals and their care. This guideline serves to remind us, as a nephrology and medical community, that we have learned much since 2002. A decade of systematic evaluation and research using common definitions, standardization of assays, and development of robust equations has allowed us to move forward. This KDIGO guideline addresses important areas of controversy, is applicable worldwide, and attempts to highlight areas of misconceptions so that we can move forward together as a medical community. The KDIGO 2012 CKD guideline re-emphasizes the value of the classification system, the need for robust definitions of progression of CKD, the treatment of complications of CKD, and the need for an integrated approach to care of this chronic condition. Most importantly, it highlights what remains as known and unknown areas of care, and serves to inform the research agenda for the next decade. We have progressed in our understanding and knowledge base, but we remain in need of robust large trials to inform clinical care. The goal of this guideline is to facilitate appropriate guidance as to the management and care of people with CKD. We present a framework for evaluation and assessment that should foster an extended collaborative research agenda over the next decade and inform guidelines in the future. The challenge for the renal community will be to ensure that important areas of controversy or confusion have been resolved with well-conducted clinical trials. In so doing, the next update of the KDIGO CKD 2012 guideline will be based on a growing foundation of evidence. 1.1.1: CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. (Not graded) 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): 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. 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) 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) (see grid below) 1.4.1: Evaluation of chronicity 1.4.1.1: In people with GFR 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 acute kidney injury (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 (eGFRcreat) rather than relying on the serum creatinine concentration alone.•Understand clinical settings in which eGFRcreat 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 with isotope-dilution mass spectrometry reference methodology.•Report eGFRcreat in addition to the serum creatinine concentration in adults and specify the equation used whenever reporting eGFRcreat.•Report eGFRcreat in adults using the 2009 CKD-Epidemiology Collaboration (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 (μmol/l) and rounded to the nearest 100th of a whole number when expressed as conventional units (mg/dl). When reporting eGFRcreat:•We recommend that eGFRcreat should be reported and rounded to the nearest whole number and relative to a body surface area of 1.73m2 in adults using the units ml/min per 1.73m2.•We recommend eGFRcreat levels <60ml/min per 1.73m2 should be reported as ‘decreased.’ 1.4.3.5: We suggest measuring cystatin C in adults with eGFRcreat 45–59ml/min per 1.73m2 who do not have markers of kidney damage if confirmation of CKD is required. (2C)•If eGFRcys/eGFRcreat-cys is also <60ml/min per 1.73m2, the diagnosis of CKD is confirmed.•If eGFRcys/eGFRcreat-cys is ≥60ml/min per 1.73m2, 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 eGFRcys and eGFRcreat-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 eGFRcys and eGFRcreat-cys.•Report eGFRcys and eGFRcreat-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 100th of a whole number when expressed as conventional units (mg/l). When reporting eGFRcys and eGFRcreat-cys:•We recommend that eGFRcys and eGFRcreat-cys be reported and rounded to the nearest whole number and relative to a body surface area of 1.73m2 in adults using the units ml/min per 1.73m2.•We recommend eGFRcys and eGFRcreat-cys levels <60ml/min per 1.73m2 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 preference, in all cases an early morning urine sample is preferred) (2B):(1)Urine ACR;(2)Urine protein-to-creatinine ratio;(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 protein-to-creatinine ratio 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) 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 ≥30mg/g (≥3mg/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., α1-microglobulin, monoclonal heavy or light chains, (known in some countries as ‘Bence Jones’ proteins)). (Not graded) 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 grid on next page). (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 or more of the following (not graded):•Decline in GFR category (≥90 (G1), 60–89 (G2), 45–59 (G3a), 30–44 (G3b), 15–29 (G4), 5ml/min per 1.73m2/year.•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) 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 blood pressure (BP), hyperglycemia, dyslipidemia, smoki