Mineral and Bone Initiative

Background
KDIGO Controversies Conference on Definition, Evaluation, and Classification of Renal Osteodystrophy
Clinical Practice Guidelines for the Management of Mineral and Bone Disorder
Clinical Guide: Basics of Bone and Mineral Metabolism in CKD – Professional Education Text
PTH Assay Standards Project
Bone Biopsy Quality Initiative

Background

Over the last decade there have been significant advances in the field of bone and mineral metabolism in patients with chronic kidney disease. Our diagnostic capabilities have been enhanced through the development of innovative techniques in radiographic imaging and new assay methodologies for PTH and other bone markers. New vitamin D analogs and phosphate binders, as well as calcimimetics, have been added to our therapeutic regimens. In addition, advances in the basic sciences of bone and vascular biology have led to improved understanding of vascular pathology and calcification, as well as new diagnostic techniques and therapies for the management of osteoporosis in the general population. Most importantly, we have gained an increased understanding and appreciation of the extraskeletal manifestations of mineral metabolism.

Despite the recent advances, a lack of consensus continues among clinicians worldwide on how to integrate these findings and therapeutic approaches into clinical practice; therefore, the management of bone and mineral metabolism in CKD patients remains fragmented and controversial. To begin to address these issues, in March 2003, the National Kidney Foundation held a conference in Washington, DC on “Controversies in Mineral Metabolism and Bone Disease in CKD.” This conference brought together a distinguished group of international experts in bone and mineral metabolism. After reviewing the most recent developments and the current clinical guidelines, the group made a series of recommendations on diagnostics, outcomes research and education initiatives designed to improve outcomes in renal osteodystrophy.

• Cunningham J, Sprague SM, Cannata-Andia J, Coco M, Cohen-Solal M, Fitzpatrick L, Goltzmann D, Lafage-Proust MH, Leonard M, Ott S, Rodriguez M, Stehman-Breen C, Stern P, Weisinger J: Osteoporosis in chronic kidney disease. Am J Kidney Dis 43:566-571, 2004
• Goodman WG, London G, Amann K, Block GA, Giachelli C, Hruska KA, Ketteler M, Levin A, Massy Z, McCarron DA, Raggi P, Shanahan CM, Yorioka N: Vascular calcification in chronic kidney disease. Am J Kidney Dis 43:572-579, 2004
• Martin KJ, Olgaard K, Coburn JW, Coen GM, Fukagawa M, Langman C, Malluche HH, McCarthy JT, Massry SG, Mehls O, Salusky IB, Silver JM, Smogorzewski MT, Slatopolsky EM, McCann L: Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy. Am J Kidney Dis 43:558-565, 2004
• Moe SM, Drueke TB: A bridge to improving healthcare outcomes and quality of life. Am J Kidney Dis 43:552-557, 2004
• Druek TD, Moe SM:  Disturbances of bone and mineral metabolism in chronic kidney disease:  an international initiative to improve diagnosis and treatment. Nephrol Dial Transplant 2004 Mar; 19(3):534-6.

The KDIGO Bone and Mineral Initiative Workgroup evolved from the Controversies in Mineral Metabolism and Bone Disease in CKD conference. This globally integrated initiative was designed to facilitate the recommendations of the conference attendees. Over the last several years, the KDIGO-Bone and Mineral Workgroup has developed a number of international programs to advance knowledge in diagnosing and treating the mineral and bone disorders of CKD.

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CONTROVERSIES CONFERENCE

One of the initiatives adopted by the KDIGO Board of Directors is a series of international Controversies Conferences to examine what is known, what can be done with what is known and what needs to be known on controversial topics of clinical relevance. The first KDIGO Controversies Conference on “Definition and Classification of Chronic Kidney Disease” was held in 2004.

The second KDIGO Controversies Conference on Definition, Evaluation, and Classification of Renal Osteodystrophy was held in September, 2005 in Madrid, Spain. This conference was designed to: (1) develop a simple, clinically relevant, and internationally acceptable definition and classification system, (2) develop a consensus for bone biopsy evaluation and classification, and (3) evaluate laboratory and imaging markers for the clinical assessment of patients with CKD. The conference was attended by more than 70 physicians with expertise in bone and mineral metabolism, representing 6 continents and 21 countries. There were a number of important recommendations pertaining to the nomenclature and criteria used to classify mineral and bone disorders in CKD that evolved from the deliberations and will be presented in a published position statement manuscript in 2006.  A principal recommendation from the conference was that the current descriptive terminology for mineral and bone abnormalities in CKD be refined.  Specifically, the term renal osteodystrophy (ROD) should be used when the abnormality has been evaluated and classified with bone biopsy. The many clinical, biochemical, and imaging abnormalities that have heretofore been identified as correlates of renal osteodystrophy should be defined more broadly as a syndrome or systemic disorder to be called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

Each of the conference participants were invited to submit an abstract of their work and concerns to facilitate the meeting discussions. Those abstracts, along with the conference agenda can be viewed here.

Click here to see a full report of conference proceedings
Click here for a slide presentation on the meeting recommendations
Click here for conference description and agenda
Click here to see abstracts submitted by the conference participants

CLINICAL PRACTICE GUIDELINES

In an attempt to incorporate recent therapeutic advancements and to address ongoing controversies in patient management, several sets of clinical practice guidelines on the management of bone metabolism in CKD have been developed.

• Caring for Australians with Renal Impairment (CARI) Clinical Practice Guidelines
• European Best Practice Guidelines
• National Kidney Foundation-KDOQI Clinical Practice Guidelines
• UK Renal Association Clinical Practice Guidelines

The KDIGO Database Workgroup has developed comparative tables of recommended guideline targets for various physiological parameters in bone and mineral metabolism that can be viewed here. Guideline Summary

Most recently, the National Kidney Foundation, as part of its Kidney Disease Outcomes Quality Initiative (KDOQI), formed a work group that proposed a comprehensive set of 17 clinical practice guidelines specific to the management of bone metabolism and disease in children with CKD. KDOQI Guidelines for Children.

KDIGO International Clinical Practice Guidelines
In 2006, KDIGO will support the development of an international workgroup to propose new universal clinical practice guidelines for mineral and bone disorders in CKD. The KDIGO guidelines will be an update to the KDOQI guidelines and will integrate the newest scientific research and existing regional guidelines to improve outcomes on a global basis. News Release

CLINICAL GUIDE: BASICS OF BONE AND MINERAL METABOLISM IN CKD

The KDIGO-Mineral and Bone Workgroup facilitated the development of this comprehensive clinical education text that was published in January, 2006. This landmark educational tool was written for an international audience to provide critical knowledge on the pathophysiology and clinical management of the abnormalities of mineral and bone metabolism that are prevalent in CKD. Table of Contents

The content of the Clinical Guide includes:

• Basic bone and mineral physiology
• Diagnostic approaches, including bone biopsy, imaging techniques and bone biomarkers
• Pathophysiology and clinical manifestations of secondary hyperparathyroidism, renal osteodystrophy, and extraskeletal calcification
• Therapeutic options to manage bone and mineral disorders
• Unique aspects of bone and mineral metabolism in special populations - children, hypogonadism, and kidney transplantation
• Epidemiologic data linking abnormalities of bone and mineral metabolism to morbidity and mortality

The Clinical Guide is available through the NKF Kidney Learning System professional education catalogue.

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PTH ASSAY STANDARDS PROJECT

With the recent introduction of several new commercial assays for PTH (1-84) to go along with the variety of intact PTH assays used, the KDIGO Bone and Mineral Workgroup viewed this as an opportune time to develop a human Plasma PTH Survey Samples (PPSS) that can be used to compare assays across the various methodologies and clinical laboratories doing PTH measurements. The PPSS consists of 3 plasma samples, obtained by plasmapheresis, from Stage 5 CKD patients undergoing hemodialysis, with known elevations in PTH representing mild, moderate and severe secondary hyperparathyroidism. The plasma was lyophilized and packaged in vials for shipping. Laboratories can use any of the commercially available assay kits and simultaneously run these three samples. Any variation from the baseline reference can be reported in the laboratories’ literature to enhance interpretation of clinical results and to allow a more accurate comparison of research studies in bone and mineral metabolism.

The PPSS samples are now available. Further technical and ordering information can be obtained by contacting:

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BONE BIOPSY QUALITY INITIATIVE

KDIGO is facilitating the development and implementation of an international workgroup whose primary objectives will be to:

• Develop quality control protocol with ongoing inter lab exchange of bone biopsy samples to determine inter lab variability and promote quality/standardization in reporting histomorphometric results.
• Develop mechanism to collect all available normative data for bone biopsies. This could be both perspective and retrospective readings on normal population.

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