KDIGO Releases CKD-MBD Guidelines, Targets PCPs, Nephrologists

Pam Harrison

February 22, 2018

Updated recommendations for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) place a greater emphasis on basing treatment decisions on trends in laboratory values rather than a single abnormal result. The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Work Group published the updated clinical practice guidelines online February 19 in the Annals of Internal Medicine.

"The process of updating the 2009 CKD–MBD guideline to accommodate data from new studies found that many of the original recommendations remain current," Markus Ketteler, MD, Klinikum Coburg GmbH, Germany, and colleagues write. However, evidence published since 2009 supported the revision of 15 recommendations made in the previous guidelines and should be of interest not only to nephrologists but also to primary care physicians (PCPs), who care for most patients with CKD, senior author Mary Leonard, MD, professor and chair, Department of Pediatrics, Stanford University, Palo Alto, California, told Medscape Medical News. The first revision concerns the use of bone mineral density (BMD) testing to assess fracture risk.

"[T]he 2009 guideline recommended that BMD testing not be routinely performed in patients with CKD stage G3a to G5D and CKD–MBD," the authors observe. On review of more recent evidence, the work group felt that the use of dual-energy X-ray absorptiometry testing is "reasonable," provided findings of a low or diminishing BMD lead to the initiation of new interventions to either prevent falls or treat osteoporosis. Because dual-energy X-ray absorptiometry is unable to differentiate between different types of renal osteodystrophy, the authors also feel it is reasonable to carry out a bone biopsy in the same group of patients, provided results again will prompt a change in treatment.

The work group also suggests that physicians use trends in serum parathyroid hormone (PTH) to guide treatment rather than rely on a one-time value. "When PTH trends are inconsistent, it is reasonable to perform bone biopsy if the results could lead to changes in therapy," they add. In contrast, the authors no longer recommend physicians obtain a bone biopsy before introducing antiresorptive therapy in patients with CKD stage G4 to G5D, as the earlier guidelines recommended; Evidence now supports the effectiveness of antiresorptive therapies in patients with CKD stage 3a to G4.

Physicians should also base treatment decisions on serial assessments of phosphate, calcium, and PTH levels and consider all values together, not as stand-alone single values. "It is apparent that therapeutic maneuvers aimed at improving one variable often have unintended effects on others," the authors caution. "Thus, treatment approaches for CKD–MBD should be made based on serial assessments of these variables taken together," they reaffirm. Earlier guidelines also indicated that physicians should aim to maintain normal serum phosphate levels for those with CKD stage G3a to G4.

Now, the work group recommends that only patients with hyperphosphatemia be treated and that hypercalcemia be avoided in patients with CKD G3a to G5D. The authors also suggest that prevention, as opposed to treatment of hyperphosphatemia, may be beneficial in patients with CKD stage G3a to G5D, although more research is needed to confirm this. Another new recommendation is to use a dialysate calcium concentration of between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L) for patients with CKD stage G5D. Previous guidelines also indicated that physicians should aim to maintain normal serum calcium levels and to aggressively correct hypocalcemia with calcium in the setting of calcimimetic treatment.

"Given the unproven benefits of calcimimetic treatment and the potential for harm, an individualized approach should be used to treat hypocalcemia rather than recommending correction of hypocalcemia in all patients," the authors emphasize. They add, however, that correction of significant hypocalcemia may still be beneficial. Recommendations surrounding the use of phosphate-lowering treatment have also been modified. In the new guidelines, the work group indicates that any decision to initiate treatment with a phosphate-lowering agent in patients with CKD with stage G3a to G5D should be based on either "progressively" or "persistently" elevated serum phosphate levels.

When treatment is initiated, "we suggest restricting the dose of calcium-based phosphate binders," the authors add. The current recommendation in favor of calcium-free phosphate binders is based on evidence suggesting that too much calcium may be detrimental across all grades of CKD. Guideline authors also recommend that patients with CKD stage G3a to G5D limit their dietary intake of phosphate as part of their treatment regimen to reduce phosphate levels.

Patients also need to be educated about "hidden" sources of dietary phosphate to meet dietary restrictions.

Secondary Hyperparathyroidism

"The 2009 recommendations for treatment of [secondary hyperparathyroidism] were expanded to reflect that modest increases in PTH may represent an appropriate adaptive response to decreasing kidney function," the authors state. Thus, the new recommendation is to treat only those patients not receiving dialysis with CKD stage G3a to G5 whose PTH values are either progressively increasing or persistently above the upper limit of normal, and again, not to treat on the basis of a single elevated value. Factors that can contribute to high PTH levels, including high serum phosphate levels, low serum calcium levels, too much dietary phosphate, and vitamin D deficiency, should be modified where possible.

The work group also caution against routine use of both calcitriol and vitamin D analogues in patients with CKD stage G3a to G5 not receiving dialysis, but to reserve their use for patients with CKD stage G4 to G5 with severe and progressive hyperparathyroidism. If dialysis patients do need to have PT levels lowered, "we suggest calcimimetics, calcitriol, or vitamin D analogues, or a combination of calcimimetics with calcitriol or vitamin D analogues," the work group writes.

The authors also note that whatever physicians use to lower PTH should take into account what else a patient is receiving, as well as calcium and phosphate levels. Last, in patients with CKD stage G3a to G5D who have either low BMD levels or have experienced a fragility fracture, physicians need to consider both the magnitude and the reversibility of the patient's biochemical profile as well has the likelihood that their CKD will progress.

A bone biopsy may again be considered to assess the risk of treating the patient with an antiresorptive agent. "CKD is usually asymptomatic and its prevalence is increasing, [which] may be explained by the increasing prevalence of diabetes and hypertension," Leonard observed. "So it's important for PCPs to recognize CKD, as they bear much of the responsibility for optimizing early management."

"And it's important to measure CKD-MBD laboratory parameters [as] outlined in these KDIGO guidelines," Leonard concluded.

The guidelines were supported by KDIGO. Ketteler reports receiving grants from Amgen and personal fees from Amgen, Fresenius Medical Care, Medice, Sanofi, and Vifor Fresenius Medical Care Renal Pharma outside the submitted work. Several coauthors have disclosed a variety of financial relationships including personal fees, nonfinancial support, grants, and other support from companies including Amgen, Kirin Corporation, OPKO, Daiichi Sankyo, ONO Pharmaceutical, Keryx, Ardelyx, Sanofi, Vifor Fresenius Medical Care, Kyowa Hakko Kirin, Bayer Japan, Torii Pharmaceutical, Zoll, AbbVie, FibroGen, Relypsa, Sanifit, ZS Pharma, Chugai, Sanofi Genzyme, Shire, and Otsuka. The remaining work group members and Leonard have disclosed no relevant financial relationships.

Ann Intern Med. Published online February 19, 2018. Full text

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