Attempting to Build Solid Recommendations on a Shaky Evidence Base

The Kidney Disease Improving Global Outcomes (KDIGO) organization recently published its ‘‘Clinical Practice Guidelines for the Diagnosis, Evaluation, Prevention and Treatment of Chronic Kidney DiseaseMineral and Bone Disorder (CKD-MBD)’’ (1). Although a number of clinical practice guidelines already exist in this topic area (2,3), the KDIGO CKDMBD Guidelines Work Group attempted to develop a high quality, unifying guideline that not only provided strong recommendations based on high-quality evidence but also attempted to provide guidance where evidence was poor quality, conflicting or nonexistent. The strengths of these guidelines include: • Extensive use of systematic search methods to ascertain high-level clinical evidence; • Adoption of the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (4) to harmonize guideline grading across different specialty areas and allow the provision of guidance even where the evidence was weak; • Attention to intervention-associated harms as well as benefits; • Broad professional representation on the Work Group; • Transparent declaration of authors’ potential conflicts of interests; • Explicit descriptions of situations where Work Group consensus was not obtained; and • Useful summaries of the generally poor evidence base in the field of CKD-MBD. These strengths are counterbalanced by a number of significant weaknesses, the most important of which is a lack of high-quality evidence for the diagnosis, evaluation, and treatment of CKD-MBD. Of the 61 guideline recommendations, only two (3%) were graded 1A (strong recommendations based on high-quality evidence). On the other hand, 12 (20%) recommendations were not graded at all, and 31 (51%) were graded 2C or 2D (weak recommendations based on low or very low quality evidence). The other limitations of the guidelines are • Heavy reliance on unvalidated surrogate outcome measures rather than patient-level outcomes for guideline recommendations; • Lack of consideration of health economics studies; • Lack of a summary of the highest research priorities in the Executive Summary; • Limited involvement of patients or consumers in the guideline writing except for the public consultation process; • Scant discussion of tools for assisting in the clinical implementation of the guidelines (including discussion of the structural barriers and costs associated with recommendations); • Scant consideration of previous systematic reviews of randomized controlled trials (RCTs) (5–8); and • Undue restriction of evidence reviews to published RCTs of at least 6 months duration and with a sample size of at least 50 patients, thereby leading to the possibility of reporting bias (9). Perhaps, the most contentious aspects of the KDIGO CKD-MBD Guidelines are its recommendations in relation to phosphate binders. Guideline 4.1. 5 suggests restricting the dose of calcium-based phosphate binders in patients with CKD stages 3-5D and hyperphosphatemia in the presence of arterial calcification. However, it is not clear how restricted the doses of calciumbased binders should be under these circumstances. Address correspondence to: David W. Johnson, Professor, Department of Nephrology, Level 2, ARTS Building, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Qld 4102, Australia, Tel. : +61-7-3176-5080, Fax: +61-7-3176-5480, or e-mail: david_johnson@health.qld. gov.au. Seminars in Dialysis—Vol 24, No 1 (January–February) 2011 pp. 22–24 DOI: 10.1111/j.1525-139X.2010. 00820.x a 2011 Wiley Periodicals, Inc.