Evidence in chronic kidney disease–mineral and bone disorder guidelines: is it time to treat or time to wait?

Abstract

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many important complications associated with CKD and may at least partially explain the extremely high morbidity and mortality among CKD patients. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline document was based on the best information available at that time and was designed not only to provide information but also to assist in decision-making. In addition to the international KDIGO Work Group, which included worldwide experts, an independent Evidence Review Team was assembled to ensure rigorous review and grading of the existing evidence. Based on the evidence from new clinical trials, an updated Clinical Practice Guideline was published in 2017. In this review, we focus on the conceptual and practical evolution of clinical guidelines (from eMinence-based medicine to eVidence-based medicine and ‘living’ guidelines), highlight some of the current important CKD–MBD-related changes, and underline the poor or extremely poor level of evidence present in those guidelines (as well as in other areas of nephrology). Finally, we emphasize the importance of individualization of treatments and shared decision-making (based on important ethical considerations and the ‘best available evidence’), which may prove useful in the face of the uncertainty over the decision whether ‘to treat’ or ‘to wait’.

Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease

“…CKD‐MBD is characterized by one or more abnormalities in circulating minerals or their regulating hormones (eg calcium, phosphorus, PTH and vitamin D), bone abnormalities and vascular calcification. 11 …”

Hyperphosphatemia with elevated serum PTH and FGF23, reduced 1,25(OH)2D and normal FGF7 concentrations characterize patients with CKD

“…Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by deranged metabolism of calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25(OH) 2 D). [1][2][3] In addition to changes in calciotropic and phosphotropic factors, CKD-MBD is frequently associated with bone abnormalities and vascular calcifications, which contribute to the substantial burden of cardiovascular disease in patients with CKD. [4] The complex pathophysiology of CKD and associated bone and mineral disorders involve a number of feedback loops between the kidneys, parathyroid glands, bones, intestine, and vasculature.…”

Phosphate, Microbiota and CKD

“…High dose calcium (in early clinical trials up to 17 g/day of calcium carbonate were prescribed) may also cause precipitation of bile and fatty acids in the form of soap and decrease the absorption of fat-soluble vitamins such as vitamin D and the microbiota metabolite vitamin K, which inhibits vascular calcification [ 31 , 32 ]. However, current guidelines recommend against high-dose calcium-based binders [ 13 , 33 ]. Magnesium carbonate results in a lower calcium load and improved gastrointestinal tolerability [ 25 ].…”