Canadian Society of Nephrology Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

Abstract

Professional societies throughout the world, including the Canadian Society of Nephrology (CSN), agree there is a need for developing clinical practice guidelines for patients with chronic kidney disease (CKD). However, as illustrated by the case of the plethora of anemia guidelines for CKD that have been completed (and updated) by many national professional societies since 2000,1Manns B.J. White C.T. Madore F. et al.Introduction to the Canadian Society of Nephrology clinical practice guidelines for the management of anemia associated with chronic kidney disease.Kidney Int Suppl. 2008; 110: S1-S3Crossref PubMed Scopus (9) Google Scholar, 2National Kidney FoundationIV. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: update 2000.Am J Kidney Dis. 2001; 37: S182-S238PubMed Google Scholar, 3National Kidney FoundationKDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease.Am J Kidney Dis. 2006; 47: S1-S146PubMed Google Scholar, 4McMahon L. The CARI guidelines Biochemical and haematological targets. Haemoglobin.Nephrology (Carlton). 2008; 13: S44-S56Crossref PubMed Scopus (4) Google Scholar, 5Locatelli F. Aljama P. Barany P. et al.Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure.Nephrol Dial Transplant. 2004; 19: ii1-ii47Crossref PubMed Scopus (99) Google Scholar creation of guidelines by individual professional societies results in significant duplication of effort. In this context, KDIGO (Kidney Disease: Improving Global Outcomes) was established in 2003 with its stated mission to “improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines.”6Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar The KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) represents a 2-year comprehensive effort to review the relevant evidence in CKD-MBD.6Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar The CSN congratulates KDIGO on an excellent review of the available evidence. Although the CSN welcomes the KDIGO evidence synthesis and global clinical practice guidelines initiative, the CSN1Manns B.J. White C.T. Madore F. et al.Introduction to the Canadian Society of Nephrology clinical practice guidelines for the management of anemia associated with chronic kidney disease.Kidney Int Suppl. 2008; 110: S1-S3Crossref PubMed Scopus (9) Google Scholar and other professional societies, including Kidney Disease Outcomes Quality Initiative (KDOQI),7Rocco M.V. Berns J.S. KDOQI in the era of global guidelines.Am J Kidney Dis. 2009; 54: 781-787Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar believe that local factors require consideration when making recommendations to guide care. As such, the CSN guidelines committee formed a work group to evaluate the KDIGO CKD-MBD guidelines and determine the extent to which they were relevant within a Canadian context. This CSN work group believes that any limitations of these guidelines relate not to the effort of the KDIGO work group, but to the lack of information for the significance of mineral metabolism abnormalities in early-stage CKD, and more specifically, to the lack of conclusive information about how to guide management throughout CKD stages 3-5. The KDIGO CKD-MBD guidelines focus on the management of children and adults with nondialysis and dialysis CKD and patients with kidney transplants. Given that the focus of the CSN is adults with CKD and the Canadian Society of Transplantation is preparing a commentary on the transplant-specific CKD-MBD guidelines, this commentary focuses on KDIGO guidelines relevant to adults with nondialysis and dialysis CKD. While preparing this commentary, the CSN work group carefully considered 2 recent Canadian sets of guidelines that have addressed mineral metabolism in CKD. These include: (1) the 2006 CSN hemodialysis guidelines,8Jindal K. Chan C.T. Deziel C. et al.Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology.J Am Soc Nephrol. 2006; 17: S1-S27PubMed Google Scholar which had a target audience of Canadian nephrologists and addressed the management of mineral metabolism in dialysis patients with CKD; and (2) the 2008 CSN guidelines focusing on the overall management of patients with nondialysis CKD targeting general practitioners.9Levin A. Hemmelgarn B. Culleton B. et al.Guidelines for the management of chronic kidney disease.CMAJ. 2008; 179: 1154-1162Crossref PubMed Scopus (267) Google Scholar Although the present commentary focuses on the KDIGO guidelines, important differences between the KDIGO CKD-MBD recommendations and the relevant CSN guidelines, as well as the reasons for these discrepancies, are noted when applicable. Although this commentary is most relevant to Canadian nephrologists and specialists who care for patients with dialysis and nondialysis CKD, some of the commentary may be relevant for general practitioners who care for patients with CKD. In general, the CSN work group is of the opinion that CKD-MBD care should not be undertaken by general practitioners; rather, their focus should continue to be on therapies that have proven efficacy in patients with CKD, including cardiovascular risk reduction. Across the Canadian health care jurisdictions, there is variable but highly restricted access to public funding for expensive medications (including non–calcium-based phosphate binders and calcimimetics), reflecting their high cost and limited outcome data beyond putative surrogate end points.10Manns B.J. Mendelssohn D.C. Taub K.J. The economics of end-stage renal disease care in Canada: incentives and impact on delivery of care.Int J Health Care Finance Econ. 2007; 7: 149-169Crossref PubMed Scopus (79) Google Scholar Acknowledging this reality and to maintain consistency with previous CSN guidelines, the resource implications of guidelines were considered when preparing this commentary.1Manns B.J. White C.T. Madore F. et al.Introduction to the Canadian Society of Nephrology clinical practice guidelines for the management of anemia associated with chronic kidney disease.Kidney Int Suppl. 2008; 110: S1-S3Crossref PubMed Scopus (9) Google Scholar The rationale for this is as follows. Given that the budget for health care is finite, directing excessive resources toward expensive marginally effective therapies limits the resources available to be used for other effective therapies.11Klarenbach S.W. Economic evaluation in renal disease.J Nephrol. 2007; 20: 251-259PubMed Google Scholar, 12Klarenbach S. Manns B. Economic evaluation of dialysis therapies.Semin Nephrol. 2009; 29: 524-532Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar In many Canadian jurisdictions, renal programs are responsible for caring for a defined group of dialysis and selected nondialysis patients with CKD with a finite pool of resources.10Manns B.J. Mendelssohn D.C. Taub K.J. The economics of end-stage renal disease care in Canada: incentives and impact on delivery of care.Int J Health Care Finance Econ. 2007; 7: 149-169Crossref PubMed Scopus (79) Google Scholar Careful consideration of both an intervention's effectiveness (and the magnitude of effect) and cost is needed to deploy resources to maximize health outcomes for our patients. Because physicians often are in a position to compare the benefits and risks of specific therapies, they should take an active role in deciding which therapies should be made available, by reimbursement, to Canadian patients. Having said that, an alternate point of view expressed within the CSN is that as nephrologists, we are advocates for our patients, and failure to champion promising therapeutic interventions will lead to inadequate access to novel strategies.13Mendelssohn D.C. The evolution of nephrology guidelines: calling for a mid-course adjustment.Nephrol News Issues. 2009; 23: 41-44PubMed Google Scholar, 14Phillips N. Barrett B. Mendelssohn D.C. The role of physicians in political advocacy Results of a Canadian Society of Nephrology survey.Nephrol News Issues. 2008; 22 (32-33): 6-7Google Scholar This viewpoint may be influenced by the poor outcomes for dialysis patients and the belief that strict adherence to principles of evidence-based medicine is limited by the paucity of well-performed randomized controlled trials.15Strippoli G.F. Craig J.C. Schena F.P. The number, quality, and coverage of randomized controlled trials in nephrology.J Am Soc Nephrol. 2004; 15: 411-419Crossref PubMed Scopus (270) Google Scholar In the opinion of this CSN workforce, the KDIGO guidelines in general considered these issues and crafted recommendations that generally were acceptable, avoiding overly prescriptive recommendations when evidence was not definitive. Although this approach may be criticized, the reality is that nephrology has the fewest randomized trials of any medical subspeciality,15Strippoli G.F. Craig J.C. Schena F.P. The number, quality, and coverage of randomized controlled trials in nephrology.J Am Soc Nephrol. 2004; 15: 411-419Crossref PubMed Scopus (270) Google Scholar leading to a slim evidence base available to guide therapy. There is a lack of definitive evidence for potentially promising therapies, and this has led to variation in perspectives of Canadian nephrologists, as well as variation in access to therapies in Canada. The workforce strongly believes that nephrology as a community needs to focus its academic pursuits on improving the nephrology evidence base, and this should be done in partnership with industry and nonindustry funding agencies. The development and review of this commentary were consistent with CSN policies set out for the conduct of clinical practice guidelines. The CSN guideline committee determined that this commentary was of priority, and a Chair was selected to guide the commentary process. Individual members were selected based on their interest and expertise, taking into consideration relevant conflicts of interest. Commentary development took place during fall 2009 using the original KDIGO CKD-MBD guidelines,6Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar as well as the primary documents referenced within this report; additional literature searching was left to the discretion of individual members. After repeated teleconferences, all authors approved the final text of the commentary. Because this was a commentary rather than a guideline, consensus was sought, and when it could not be achieved, both perspectives are raised. The final document was sent out for peer review by the CSN guidelines committee. The reviews were considered and responded to, with incorporation of further revisions before ratification by the CSN guidelines committee and CSN executive. This commentary does not seek to discuss all KDIGO recommendations; rather, it was our intent to focus commentary on recommendations that are based on better quality evidence (ie, level 1 in the guideline6Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar) or are more controversial. The KDIGO recommendations are provided in boxes, with CSN concurrence indicated. Implications and commentary relevant for Canadian health care are offered in the text when appropriate. For some recommendations (typically those that are opinion based), specific comments are not provided in italics. In chapter 3.1, there are 3 level 1 recommendations (Box 1). Our work group believed that one recommendation deserved further discussion; namely, the statement “We recommend monitoring serum levels of calcium, phosphorus, PTH [parathyroid hormone], and alkaline phosphatase activity beginning in CKD stage 3 (1C)” and the suggested monitoring intervals of every 6-12 months in stage 3 CKD. Given that the frequency of abnormalities in serum calcium and phosphorus levels is rare at a glomerular filtration rate (GFR) >40 mL/min (almost no patients with GFR >40 mL/min in a cross-sectional analysis of more than 1,800 patients with CKD stages 3-5 patients had abnormal calcium or phosphorus levels16Levin A. Bakris G.L. Molitch M. et al.Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease.Kidney Int. 2007; 71: 31-38Crossref PubMed Scopus (1161) Google Scholar), it is difficult to present a substantive argument in favor of routine measurement of calcium and phosphorus in patients with stage 3 CKD. This is particularly true given that the impact of managing abnormalities in mineral metabolism in patients with stage 3 CKD is unknown, and most patients will not go on to require dialysis, but instead will die of other causes.17Hemmelgarn B.R. Manns B.J. Zhang J. et al.Association between multidisciplinary care and survival for elderly patients with chronic kidney disease.J Am Soc Nephrol. 2007; 18: 993-999Crossref PubMed Scopus (141) Google Scholar Moreover, when one considers that >95% of Canadian patients with stages 3-5 nondialysis CKD have stage 3 CKD,18Hemmelgarn B. Manns B. Lloyd A. et al.Relation between kidney function, proteinuria, and adverse outcomes.JAMA. 2010; 303: 423-429Crossref PubMed Scopus (818) Google Scholar this recommendation may inadvertently direct attention to a cohort of patients without identifiable laboratory abnormalities.Box 1KDIGO Recommendations Concerning Diagnosis of CKD-MBD: Biochemical Abnormalities3.1.1. We recommend monitoring serum levels of calcium, phosphorus, PTH, and alkaline phosphatase activity beginning in CKD stage 3 (1C). [see comments] In children, we suggest such monitoring beginning in CKD stage 2 (2D).3.1.2. In patients with CKD stages 3-5D, it is reasonable to base the frequency of monitoring serum calcium, phosphorus, and PTH on the presence and magnitude of abnormalities and the rate of progression of CKD (not graded). Reasonable monitoring intervals would be: in CKD stage 3: for serum calcium and phosphorus, every 6-12 months; and for PTH, based on baseline level and CKD progression. In CKD stage 4: for serum calcium and phosphorus, every 3-6 months; and for PTH, every 6-12 months. In CKD stage 5, including 5D: for serum calcium and phosphorus, every 1-3 months; and for PTH, every 3-6 months. In CKD stages 4-5D: for alkaline phosphatase activity, every 12 months or more frequently in the presence of increased PTH levels (see Chapter 3.2). In patients with CKD receiving treatments for CKD-MBD or in whom biochemical abnormalities are identified, it is reasonable to increase the frequency of measurements to monitor for trends and treatment efficacy and side effects (not graded). [see comments]3.1.3. In patients with CKD stages 3-5D, we suggest that 25(OH)D (calcidiol) might be measured, and repeated testing determined by baseline values and therapeutic interventions (2C). We suggest that vitamin D deficiency and insufficiency be corrected using treatment strategies recommended for the general population (2C). [see comments]3.1.4. In patients with CKD stages 3-5D, we recommend that therapeutic decisions be based on trends rather than on a single laboratory value, taking into account all available CKD-MBD assessments (1C) [CSN work group concurs]3.1.5. In patients with CKD stages 3-5D, we suggest that individual values of serum calcium and phosphorus evaluated together be used to guide clinical practice, rather than the mathematical construct of calcium-phosphorus product (2D).3.1.6. In reports of laboratory tests for patients with CKD stages 3-5D, we recommend that clinical laboratories inform clinicians of the actual assay method in use and report any change in methods, sample source (plasma or serum), and handling specifications to facilitate the appropriate interpretation of biochemistry data (1B) [CSN work group concurs]Abbreviations: CKD, chronic kidney disease; CKD-MBD, chronic kidney disease–mineral and bone disorder; CSN, Canadian Society of Nephrology; KDIGO, Kidney Disease: Improving Global Outcomes; PTH, parathyroid hormone. 3.1.1. We recommend monitoring serum levels of calcium, phosphorus, PTH, and alkaline phosphatase activity beginning in CKD stage 3 (1C). [see comments] In children, we suggest such monitoring beginning in CKD stage 2 (2D). 3.1.2. In patients with CKD stages 3-5D, it is reasonable to base the frequency of monitoring serum calcium, phosphorus, and PTH on the presence and magnitude of abnormalities and the rate of progression of CKD (not graded). Reasonable monitoring intervals would be: in CKD stage 3: for serum calcium and phosphorus, every 6-12 months; and for PTH, based on baseline level and CKD progression. In CKD stage 4: for serum calcium and phosphorus, every 3-6 months; and for PTH, every 6-12 months. In CKD stage 5, including 5D: for serum calcium and phosphorus, every 1-3 months; and for PTH, every 3-6 months. In CKD stages 4-5D: for alkaline phosphatase activity, every 12 months or more frequently in the presence of increased PTH levels (see Chapter 3.2). In patients with CKD receiving treatments for CKD-MBD or in whom biochemical abnormalities are identified, it is reasonable to increase the frequency of measurements to monitor for trends and treatment efficacy and side effects (not graded). [see comments] 3.1.3. In patients with CKD stages 3-5D, we suggest that 25(OH)D (calcidiol) might be measured, and repeated testing determined by baseline values and therapeutic interventions (2C). We suggest that vitamin D deficiency and insufficiency be corrected using treatment strategies recommended for the general population (2C). [see comments] 3.1.4. In patients with CKD stages 3-5D, we recommend that therapeutic decisions be based on trends rather than on a single laboratory value, taking into account all available CKD-MBD assessments (1C) [CSN work group concurs] 3.1.5. In patients with CKD stages 3-5D, we suggest that individual values of serum calcium and phosphorus evaluated together be used to guide clinical practice, rather than the mathematical construct of calcium-phosphorus product (2D). 3.1.6. In reports of laboratory tests for patients with CKD stages 3-5D, we recommend that clinical laboratories inform clinicians of the actual assay method in use and report any change in methods, sample source (plasma or serum), and handling specifications to facilitate the appropriate interpretation of biochemistry data (1B) [CSN work group concurs] Abbreviations: CKD, chronic kidney disease; CKD-MBD, chronic kidney disease–mineral and bone disorder; CSN, Canadian Society of Nephrology; KDIGO, Kidney Disease: Improving Global Outcomes; PTH, parathyroid hormone. Of note, one other recommendation (level 2C) suggested that “25(OH)D (calcidiol) levels might be measured, and repeated testing determined by baseline values and therapeutic interventions.” It was noted that the cost of laboratory tests, particularly measurement of PTH and vitamin D, is significant, and given budget limitations within publicly funded Canadian health care, this could direct resources away from other treatments for which better evidence of benefit is available. For example, the cost of a serum 25-hydroxyvitamin D assay is Can $100 locally. Until the clinical benefit of correcting nutritional vitamin D “insufficiency” has been established within the dialysis population or for patients with stages 4 and 5 CKD, it would seem premature to suggest screening with vitamin D assays. For patients with stage 3 CKD without biochemical evidence of MBD, it is reasonable to expect that the overall benefits of vitamin D supplementation in the general population (800-2,000 U/d) would apply, and Osteoporosis Canada does not recommend screening 25-hydroxyvitamin D assays in the general population for individuals already using routine supplementation.19Brown J.P. Josse R.G. 2002 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada.CMAJ. 2002; 167: S1-S34PubMed Google Scholar 1Patients with stage 3 CKD usually are managed by primary care practitioners rather than nephrologists. Our work group believed that routine laboratory monitoring for calcium, phosphate, PTH, and alkaline phosphatase is not warranted in stage 3 CKD, particularly in patients being managed exclusively within a general practice. An initial evaluation of laboratory markers of mineral metabolism should occur as GFR approaches 30 mL/min and could occur upon referral to a nephrologist because referral is recommended at GFR of 30 mL/min. Abnormalities in mineral metabolism that are detected by general practitioners should prompt nephrology assessment.2Vascular risk reduction must remain the focus of all physicians, particularly primary care physicians, in patients with stage 3 CKD because cardiovascular risk reduction strategies have improved clinical outcomes in patients with stage 3 CKD. In contrast, assessment and management of mineral metabolism in this group of patients has not been shown to improve outcomes and might interfere with the primary focus on vascular risk reduction. Fractures are more prevalent in patients with CKD stage 5 contrasted with the nonuremic population.6Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar This is particularly true of hip fractures in elderly dialysis patients, particularly those with diabetes. The KDIGO working group found little evidence that future fracture risk might be linked specifically to identifiable risk factors or modified by specific therapy. The CSN work group agrees that it is not possible to generalize the extensive epidemiologic characteristics of fractures (and evidence-based therapy) in the general population to patients with CKD. The diverse spectrum of the metabolic bone disease associated with renal osteodystrophy ranges from extensive deposits of woven bone in hyperparathyroidism to excessive unmineralized osteoid associated with osteomalacia; “adynamic” bone is more normal in structure. Not surprisingly, both bone mass and bone quality within the skeleton can vary widely according to the underlying pathobiological process. For this reason, the KDIGO working group emphasized at several points that bone biopsy with histomorphometric evaluation is the only certain method of classifying the underlying bone disease. Bone mineral density (BMD) measurements assume a stable ratio of calcium hydroxyapatite to organic matrix within bone to assess “bone mass.” In the general population, this relationship is valid enough that a diagnosis of osteoporosis can be made using the World Health Organization T score of −2.5 standard deviations less than “peak adult bone mass.”20Kanis J.A. WHO Study GroupAssessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report.Osteoporosis Int. 1994; 4: 368-381Crossref PubMed Scopus (1605) Google Scholar Moreover, the combination of age, BMD, and specific additional risk factors (particularly prevalent osteoporotic fractures) allows some prediction of the probability of future fractures in the next 10 years, as recommended by Osteoporosis Canada.21Siminoski K.G. Leslie W.D. Frame H. Recommendations for bone mineral density reporting in Canada.Can Assoc Radiol J. 2007; 56: 178-188Google Scholar However, BMD generally is lower in the dialysis population, particularly at cortical measurement sites (distal radius and hip), and the ability of BMD to predict fractures or other clinical outcomes in dialysis patients is weak and inconsistent. Moreover, in patients with nondialysis CKD stages 3-5 associated with abnormalities in mineral metabolism and dialysis CKD, BMD measurements do not distinguish between histologic types of underlying renal osteodystrophy. For these reasons, we agree that BMD measurements should not be used as a diagnostic tool in CKD stages 3-5 (Box 2). However, it is reasonable to conclude that decreased BMD in patients with stage 3 CKD without biochemical evidence of MBD can still be used to diagnose underlying osteoporosis.Box 2KDIGO Recommendations Concerning Diagnosis of CKD-MBD: Bone3.2.1. In patients with CKD stages 3-5D, it is reasonable to perform a bone biopsy in various settings, including, but not limited to, unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and before treatment with bisphosphonates in patients with CKD-MBD (not graded). [see comments]3.2.2. In patients with CKD stages 3-5D with evidence of CKD-MBD, we suggest that BMD testing not be performed routinely because BMD does not predict fracture risk as it does in the general population and BMD does not predict type of renal osteodystrophy (2B). [see comments]3.2.3. In patients with CKD stages 3-5D, we suggest that measurements of serum PTH or bone-specific alkaline phosphatase can be used to evaluate bone disease because markedly high or low values predict underlying bone turnover (2B). [see comments]3.2.4. In patients with CKD stages 3-5D, we suggest not to routinely measure bone-derived turnover markers of collagen synthesis (such as procollagen type I C-terminal propeptide) and breakdown (such as type I collagen cross-linked telopeptide, cross-laps, pyridinoline, or deoxypyridinoline) (2C). [CSN work group concurs]Abbreviations: BMD, bone mineral density; CKD, chronic kidney disease; CKD-MBD, chronic kidney disease–mineral and bone disorder; CSN, Canadian Society of Nephrology; KDIGO, Kidney Disease: Improving Global Outcomes; PTH, parathyroid hormone. 3.2.1. In patients with CKD stages 3-5D, it is reasonable to perform a bone biopsy in various settings, including, but not limited to, unexplained fractures, persistent bone pain, unexplained hypercalcemia, unexplained hypophosphatemia, possible aluminum toxicity, and before treatment with bisphosphonates in patients with CKD-MBD (not graded). [see comments] 3.2.2. In patients with CKD stages 3-5D with evidence of CKD-MBD, we suggest that BMD testing not be performed routinely because BMD does not predict fracture risk as it does in the general population and BMD does not predict type of renal osteodystrophy (2B). [see comments] 3.2.3. In patients with CKD stages 3-5D, we suggest that measurements of serum PTH or bone-specific alkaline phosphatase can be used to evaluate bone disease because markedly high or low values predict underlying bone turnover (2B). [see comments] 3.2.4. In patients with CKD stages 3-5D, we suggest not to routinely measure bone-derived turnover markers of collagen synthesis (such as procollagen type I C-terminal propeptide) and breakdown (such as type I collagen cross-linked telopeptide, cross-laps, pyridinoline, or deoxypyridinoline) (2C). [CSN work group concurs] Abbreviations: BMD, bone mineral density; CKD, chronic kidney disease; CKD-MBD, chronic kidney disease–mineral and bone disorder; CSN, Canadian Society of Nephrology; KDIGO, Kidney Disease: Improving Global Outcomes; PTH, parathyroid hormone. 1In clinical practice, bone biopsy in dialysis patients rarely is performed in Canada. In part, this is due to the very limited laboratory services with the ability to process undecalcified bone specimens. With the exception of severe osteomalacia associated with aluminum intoxication, which might still occur in the minority of patients using aluminum-based binders, bone histologic evaluation may provide little additional relevant information that will change management in a way known to improve clinical outcomes.2Except in patients with stage 3 CKD without biochemical evidence of MBD, bone densitometry should not be used routinely in CKD stages 3-5D by Canadian nephrologists to form the basis of diagnostic and therapeutic decisions.3Although opinion based, it is routine practice in Canada to measure both intact PTH and serum total alkaline phosphatase in dialysis patients, and many nephrologists measure these in nondialysis patients with CKD as well. It is likely that markedly high or low values predict underlying bone turnover. The CSN work group noted that chapter 3.3 referred to patients with stages 3-5 nondialysis and dialysis CKD (Box 3).6Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009; 113: S1-S130PubMed Google Scholar However, it is important to emphasize that the level of evidence, prevalence, and therapeutic strategies are heterogeneous among the various CKD stages, and most evidence exists for dialysis CKD.Box 3KD