Investigators have identified biomarkers of chronic kidney disease-mineral bone disorder (CKD-MBD) in the diabetic foot that may identify patients at increased risk for amputation.

“Earlier identification of low serum markers and radiographic foot impairments in patients with CKD-MBD syndrome may help identify those at greater risk of vessel calcification, foot fracture, and amputation,” according to Michael A. Jones, MD, and colleagues from Atrium Health Wake Forest Baptist in Winston-Salem, North Carolina and colleagues.

The investigators performed a retrospective review of electronic health records from 152 patients with diabetes and stage 1 to 5 CKD. The presence of 1 or more of the following biomarkers on foot radiograph — peripheral neuropathy, pedal vessel calcification, and/or buckling ratio of the 2nd and 5th metatarsals of 3.5 or greater (indicating decreasing resistance to bending) — increased with CKD stage, Dr Jones and colleagues reported in Diabetes Research and Clinical Practice. The presence of all 3 biomarkers increased at CKD stage 3.

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The risk for partial foot amputation increased 2.6-, 5.2-, and 13.6-fold in CKD stage 3, 4, and 5, respectively, compared with CKD stage 1, although the increased risk was statistically significant only for patients with CKD stage 5, the investigators reported. Patients with all 3 biomarkers on foot radiograph had a significant 11.2-fold increased risk of partial foot amputation compared with patients who had no biomarkers.

“The presence of the CKD-MBD syndrome in the diabetic neuropathic foot should alert the patient and the health care team to provide immediate interventions to avert a minor amputation and a subsequent major lower extremity amputation with further disability,” Dr Jones’ team stated.

The investigators also noted that serum chemistry on the comprehensive metabolic panel significantly related with buckling ratio. Decreasing serum total calcium, total alkaline phosphatase, and albumin along with increasing blood urea nitrogen may signal other foot problems such as persistent inflammation, pedal osteolysis, neuropathic (Charcot) arthropathy or fracture, acquired foot deformities, plantar ulcerations with delayed wound healing, ischemia, or infection.


Jones MA, George TS, Bullock GS, Sikora RR, Vesely BD, Sinacore DR. Biomarkers of chronic kidney disease-mineral bone disorder (CKD-MBD) in the diabetic foot: A medical record review. Diabetes Res Clin Pract. 2022 Dec;194:110160. doi:10.1016/j.diabres.2022.110160