Morbidity and mortality related to disturbances in mineral metabolism in CKD

Geoffrey A. Block, Jorge B. Cannata-Andia and David Goldsmith

in The Spectrum of Mineral and Bone Disorders in Chronic Kidney Disease

Second edition

Published on behalf of Oxford University Press

Published in print June 2010 | ISBN: 9780199559176
Published online November 2012 | e-ISBN: 9780191753350 | DOI:

Series: Oxford Clinical Nephrology Series

Morbidity and mortality related to disturbances in mineral metabolism in CKD

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It is reasonably clear that observational data support a significant relationship between biochemical markers of CKD-MBD (calcium, phosphorus, and PTH) and adverse clinical outcomes, and yet many fundamental questions remain unanswered. Do these observational data suggest or support a causal relationship between laboratory values and outcome? Should we establish clinical treatment target value guidelines based on observational data? What are the optimal values for these parameters? Does intervention to reduce elevated levels have an impact on clinical outcome? The answers to these questions are likely to be far more complex than can be answered by even well done observational studies.

While it is common to isolate single laboratory values when conducting such analyses in order to identify an independent relationship between the laboratory variable and a clinical outcome, the reality of clinical medicine is such that clinicians are faced with interpreting laboratory variables in aggregrate. Several reports have now attempted to replicate such complexity and consistently report that the RR is greatest among patients with simultaneously high calcium and phosphorus, often in association with overtly low (< 130pg/dL) or high (>600pg/dL) PTH. Supporting the complex nature of these relationships and the importance of treating multiple abnormal laboratory values concurrently, Danese et al. have shown that patients who achieve combinations of K/DOQI targets for Ca, P, and PTH have a survival advantage compared with those who achieve only a single parameter in target. These investigators further demonstrated the importance of consistent control of mineral metabolism as shown in Fig. 32.3.

It is almost certain that there is no single threshold value for calcium, phosphorus or PTH that independent of the other variables is ‘optimal’. Indeed, it appears that the ‘target’ value is a moving target that is likely to be modified by each patients unique underlying risk profile that changes over time. Data from Stevens et al. suggests that the optimal combination of calcium, phosphorus, and PTH varies with dialysis vintage, while data from the 4D study suggests that it varies by concurrent illness. Thus, we urge providers to use restraint and caution when trying to establish universal and widely applied target values.

In general, it appears that elevations in phosphorus above the upperlimit of normal can be demonstrably associated with adverse outcomes in patients with CKD on dialysis and that this threshold may be lower for patients with CKD not on dialysis or without CKD. Whether intervention to reduce the phosphate burden or reduce serum levels can modify this risk remains uncertain.

We agree with the recommendations of KDIGO that encourage the urgent conduct of randomized clinical trials to establish definitive evidence of the role of abnormal mineral metabolism in the exaggerated CV risk in patients with CKD and we caution against the rising tide of reliance upon observational data to define ‘optimal’ care. Nephrology is currently mired in the unenviable situation where observational data are used to generate clinical treatment ‘guidelines’, rather than being used to generate hypotheses to be tested with randomized controlled clinical trials. Unfortunately, such an approach has often proven to be erroneous when ultimately tested in properly conducted clinical trials. Remarkably, there are some in the community who go so far as to suggest that, on the basis of observational data alone, such randomized controlled trials are precluded from being conducted on ethical grounds. This intellectual nihilism must be resisted at all costs.

Chapter.  7505 words.  Illustrated.

Subjects: Rheumatology ; Nephrology

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