KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Chapter 6: Summary and research recommendations

Kidney International (2009) 76 (Suppl 113), S111-S114;doi:10.1038/ki.2009.194

As detailed throughout this guideline, there is a paucityof high-quality studies evaluating the clinical benefit of various treatmentsgiven to patients with chronic kidney disease-mineral and bone disorder(CKD-MBD). Table 44 summarizes the number and quality of randomized controlledtrials by end points. More detailed summaries are provided in Table 45 and (Supplementary Tables 54 and 55). As CKD-MBD is unique to patients with CKDstages 3-5D and stages 1-5T, we unfortunately do not have treatment studies inthe general population that we can apply to the management of our patients. The Work Group a priori decided that we should focus only on randomized controlledtrials with at least 6 months' duration and sufficient sample size to guidetreatment decisions. Therefore, additional randomized controlled trials ofshorter duration are not included in this table. However, it is unlikely thatthese shorter studies provided high-quality evidence on clinical end points.Owing to the paucity of randomized controlled trials in this field, the WorkGroup made the attempt to also use observational studies with large sample sizeof treatment effects that were relevant to the guideline treatment questions,under the condition that they showed a relative risk of > 2.0 or < 0.5 forpatient-centered outcomes. No observational treatment studies meeting thesecriteria were identified.

This guideline contains mostly level 2 recommendations.These are formulated on the basis of the expert judgment of the Work Group andthe review of evidence that is either of low quality or that does not examinepatient-centered end points. As detailed in Chapter 2, there are importantdifferences in the implications for level 1 and level 2 recommendations(Chapter 2).

The grading of recommendations adopted for the guidelineis shown in Table 46 (also shown in Chapter 2).

It is important to reinforce that level 2 recommendationsare not meant to be used for quality performance measures by dialysis providersor payers. Level 2 recommendations should also not be considered mandatory fora specific therapeutic approach. Instead, level 2 recommendations are meant toguide clinicians in caring for patients, and these recommendations must bevalidated by future research. It is also important that the grade for thestrength of the recommendation and the quality of the evidence corresponding toeach statement (see Chapter 2) be included whenever a recommendation isreproduced or communicated. Only then will the true state of the evidence berecognized by all.

Given that the majority of the recommendations in thisdocument are level 2, it should be obvious that much additional high-qualityresearch is needed in the field of CKD-MBD to resolve uncertainties and allowthe formulation of more level 1 recommendations in the future. In each of theindividual chapters, there are several research recommendations. The Work Groupalso felt that it was important to prioritize research, and determined thatfuture studies such as those below are of critical importance to advance thefield and improve patient care.

• Develop a risk-stratification tool based on CKD-MBDcomponents and evaluate its predictive accuracy for clinical outcomes inpatients with CKD stages 3-5, 5D, and 3-5T.
• Determine whether, in patients with CKD-MBD, a singlemeasurement of bone mineral density (measured by dual energy X-rayabsorptiometry or quantitative computed tomography) and serial changes in bonemineral density can predict fractures.
• Determine whether the presence or absence ofvascular/valvular calcification in patients with CKD-MBD is an appropriatestratification and selection tool to identify individuals who may benefit fromspecific interventions.
• Determine whether the effect of an intensive CKD-MBDtreatment approach (for example, protocol-driven combination therapy to achievespecific serum phosphorus and parathyroid hormone targets) vs a less intensivetreatment approach (for example, protocol-driven combination therapy allowinghigher serum phosphorus and parathyroid hormone targets) vs standard careimproves clinical outcomes in patients with CKD stages 3-5D.
• Determine whether treating down to normal serumphosphorus levels (as compared with phosphorus levels of 5.5-6.5 mg/dl;1.78-2.10mmol/l) with the use of combinations of different phosphate bindersand other approaches improves clinical outcomes in patients with CKD stages4-5D and 4-5T.
• Determine whether treatment to a lower vs higher serumparathyroid hormone target improves or worsens clinical outcomes in patientswith CKD stages 3-5, CKD stage 5D, and CKD stages 3-5T.
• Determine whether treatment with vitamin D(ergocalciferol or cholecalciferol) or calcidiol [25(OH)D], compared withcalcitriol or vitamin D analogs, improves clinical outcomes in patients withCKD stages 3-5, CKD stage 5D, and CKD stages 1-5T.
• Determine which phosphate binders and other serumphosphorus-lowering treatments are able to improve survival in patients withCKD stages 3-5D and CKD stages 3-5T.
• Determine whether treatment with bisphosphonates,teriparatide, or raloxifene reduces fractures or vascular calcification inpatients with CKD stages 3-5D and CKD stages 1-5T.
• Determine whether strategies to reverse adynamic bonedisease by measures such as endogenous stimulation of parathyroid hormonesecretion (for example, using low-calcium dialysate) or exogenous teriparatideadministration, affect clinical outcomes in patients with CKD stages 4-5D orCKD stages 1-5T, compared with placebo.

SUPPLEMENTARY MATERIAL

Supplementary Table 54. Summary ofcumulative evidence matrix of adverse events.
Supplementary Table 55. Adverseevent reporting.
Supplementary material is linked to the online version of thepaper at http://www.nature.com/ki