Introduction: The case for updating and context

In 2003, the US-based KDOQI (Kidney Disease Outcomes Quality Initiative) group published Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease (CKD). In the absence of randomized controlled trials (RCTs), ATP III Guidelines (Adult Treatment Panel III) were considered to be generally applicable to patients with estimated glomerular filtration rate (eGFR) Z15 ml/min/ 1.73 m (GFR categories G1-G4, formerly CKD stages 1–4) with the exception that: (1) CKD was classified as a coronary heart disease (CHD) risk equivalent, (2) complications of lipid-lowering therapies may result from reduced kidney function, (3) indications for the treatment of dyslipidemias other than preventing acute cardiovascular disease (CVD) may be applicable, and (4) treatment of proteinuria might also be an effective treatment for dyslipidemias. At that time the Work Group included children and adolescents with CKD (defined by the onset of puberty) in these guidelines, and recommended that they be managed in the same way as adults. The 2003 publication anticipated that an update should be performed in about 3 years from the time of publication of major important trials in the general population and in patients with CKD, and recommended to review ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial), SEARCH (Study Evaluating Additional Reductions in Cholesterol and Homocysteine), TNT (Treating to New Targets), IDEAL (Incremental Decrease in Endpoints Through Aggressive Lipid Lowering), ALLIANCE (Aggressive Lipid Lowering Initiation Abates New Cardiac Events), PROVE IT (Pravastatin or Atorvastatin in Evaluation and Infection Therapy), PROSPER (Prospective Study of Pravastatin in the Elderly at Risk), FIELD (Fenofibrate Intervention and Event Lowering in Diabetes), CARDS (Collaborative Atorvastatin Diabetes Study), ASPEN (Atorvastatin as Prevention of Coronary Heart Disease Endpoints in Patients with Non-Insulin-Dependent Diabetes Mellitus), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and ACCORD (Action to Control Cardiovascular Risk in Diabetes). Several trials in patients with CKD that were ongoing included ALERT (Assessment of Lescol in Renal Transplantation), 4D (Die Deutsche Diabetes Dialyse Studie), PREVEND IT (Prevention of REnal and Vascular ENdstage Disease Intervention Trial), AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events), and SHARP (Study of Heart and Renal Protection). Since that time, all these studies have been published and most have been synthesized in two recent meta-analyses in order to bring all information into context. In 2007 KDOQI issued Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease and included a set of guidelines on Management of Dyslipidemia in Diabetes and Chronic Kidney Disease. The guidelines adopted trends in treating people with very high risk and recommended treatment to target low-density lipoprotein cholesterol (LDL-C) of o2.6 mmol/l (o100 mg/dl) for people with diabetes and eGFR categories G1-G4. The target of o1.8 mmol/l (o70 mg/dl) was considered a therapeutic option. The guidelines included the results of the 4D study, which to the surprise of many, demonstrated that lowering LDL-C with atorvastatin in hemodialysis (HD) patients with type 2 diabetes did not produce statistically significant reductions in the primary outcome measure. The study had strong impact on a recommendation for HD patients which stated that ‘‘treatment with a statin should not be initiated in patients with type 2 diabetes on maintenance HD therapy who do not have a specific cardiovascular indication for treatment.’’ Four years later, AURORA was hoped to provide clarification of whether LDL-C lowering with rosuvastatin would offer any benefit to HD patients. Like 4D, the main results of AURORA were negative. Since then, multiple hypotheses have been raised to explain these unexpected findings. A different cardiovascular pathology with vascular stiffness, calcification, structural heart disease, and sympathetic overactivity contributing to an increasing risk for cardiac arrhythmia and heart failure was deemed responsible. The results of SHARP, a very large international RCT, is highly relevant to this discussion. SHARP showed a significant decrease in major atherosclerotic events with simvastatin and ezetimibe compared with placebo in dialysis-dependent and non-dialysis-dependent patients. The overall objective for the guideline is to advise about the management of dyslipidemia and use of cholesterollowering medications in adults and children with known CKD. Questions addressed by the guideline include how and when to assess lipid status, and how and when to prescribe lipid-lowering treatment in the target population. The target audience of the guideline includes nephrologists, primary care physicians, non-nephrology specialists (e.g., cardiologists, diabetologists, etc), clinical chemists and other practitioners caring for adults and children with CKD worldwide. The guideline is also expected to be suitable for use in public policy and other healthcare arenas. As a global guideline it is sensitive to issues related to ethnicity and geographical considerations and is written for use in different health care settings. The Work Group included an international group of kidney specialists, diabetologists, cardiologists, epidemiologists, lipidologists and a professional evidence review team i n t r o d u c t i o n http://www.kidney-international.org