Highlights
- •The diabetic foot is an overlooked target of CKD–MBD syndrome.
- •Progressive CKD-MBD in the diabetic foot leads to increased risk for minor foot amputation.
- •Foot radiography and serum markers may be effective screening tools for CKD-MBD in patients with diabetesmellitus.
- •Findings from this novel investigation may alert clinicians in helping to reduce nontraumatic lower extremity amputation.
Abstract
Aims
Determine the prevalence and relative risk of having single and combinations of biomarkers
of chronic kidney disease-mineral bone disorder (CKD-MBD) syndrome in the diabetic
foot from an electronic medical record (EMR) review.
Methods
Review of 152 patients with one foot radiograph and diagnoses of both diabetes mellitus
(DM) and chronic kidney disease (CKD) stages 1–5. Presence/absence of peripheral neuropathy
(PN), targeted serum markers, and both pedal vessel calcification (PVC) and buckling
ratio (BR) of 2nd and 5th metatarsals from radiographs were recorded. Prevalence of
single and combinations of foot biomarkers are reported as count and percentage. Risk
ratios (RR) with 95% confidence intervals (95% CI) were calculated to assess risk
of foot biomarkers in each stage of CKD-MBD.
Results
Prevalence and RR of PVC, PN, and BR ≥ 3.5 biomarkers, both single and in combination,
all increase with progression of CKD. The RR increases to 9.6 (95 % CI: 3, 26; p < 0.001)
when all 3 biomarkers present in stage 5.
Conclusions
PVC, PN, and BR ≥ 3.5 are prognostic biomarkers of CKD–MBD syndrome in the diabetic
foot. Recognition of these foot biomarkers may allow earlier interventions to help
reduce nontraumatic lower extremity amputation in individuals with diabetic CKD-MBD.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Diabetes Research and Clinical PracticeAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global Disability Burdens of Diabetes-Related Lower-Extremity Complications in 1990 and 2016.Diabetes Care. 2020; 43: 964-974
U.S. Department of Health and Human Services CDCaP. National Diabetes Statistics Report; 2020.
- Resurgence of Diabetes-Related Nontraumatic Lower-Extremity Amputation in the Young and Middle-Aged Adult U.S. Population.Diabetes Care. 2019; 42: 50-54
- Non-traumatic lower extremity amputations in the Medicare end-stage renal disease population.Kidney Int. 1999; 56 (10.1046/j.1523-1755.1999.00668.x): 1524-1533
- Association between renal failure and foot ulcer or lower extremity amputation in patients with diabetes.Diabetes Care. 2008; 31 (10.2337/dc07-2244): 1331-1336
- A Meta-analysis of Long-term Mortality and Associated Risk Factors following Lower Extremity Amputation.Ann Vasc Surg. 2017; 42: 322-327
- Definition, evaluation and classification of renal osteodystrophy: a position statement from the Kidney Disease: Improving Global Outcomes (KDIGO).Kidney Int. 2006; 69 (10.1038./sj.ki.5000414): 1945-1953
- Early chronic kidney disease-mineral bone disorder stimulates vascular calcification.Kidney Int. 2014; 85 (PMCID: PMC3836911): 142-150
- Accelerated cortical osteolysis of metatarsals in Charcot neuroarthropathy: a cross-sectional observational study.JBMR Plus. 2019; 3 (10.1002/jbm4.10243)
- A New Equation to Estimate Glomerular Filtration Rate.Ann Intern Med. 2009; 150 (10.7326/0003-4819-150-9-200905050-00006): 604-612
National Kidney Foundation. Kidney Disease: The Basics 2022. Available from: https://www.kidney.org/news/newsroom/fsindex#fast-facts.
- Structural adaptation to changing skeletal load in the progression toward hip fragility: the study of osteoporotic fractures.J Bone Mineral Res. 2001; 16: 1108-1119
- Impact of Charcot neuroarthropathy on metatarsal bone mineral density and geometric strength indices.Bone. 2013; 52 (10.1016/j.bome.2012.10.028): 407-413
- Pedal bone density, strength orientation and plantar loads preceding incipient metatarsal fracture after Charcot neuroarthropathy: 2 case reports.J Orthop Sports Phys Ther. 2013; 43 (10.2519/jospt.2013.4443): 744-751
- Dual-energy x-ray absorptiometry of human metatarsals: Precision, least significant change and association to ex vivo fracture force.Foot. 2013; 23: 63-69
R Core Team 2013. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org/.
- Reoperation and reamputation after transmetatarsal amputation: a systematic review and meta-analysis.J Foot Ankle Surgery. 2016; 55 (10.1053/j.jfas.2016.05.011): 1007-1012
- Transmetatarsal and minor amputation versus major leg amputation:30-day readmissions, reamputations, and complications.J Foot Ankle Surgery. 2020; 59 (10.1053/j.jfas.2019.09.019): 484-490
- Persistent inflammation with pedal osteolysis 1 year after Charcot neuropathic osteoarthropathy.J Diab Complicat. 2017; 31 (10.1016/j.diacomp.2017.02.005): 1014-1020
- Osteopenia and metatarsal fractures in diabetic neuropathy.Diabet Med. 1985; 2 (10.1111/j.1464-5491.tb00683.x): 461-464
- Acquired midfoot deformity and function in individuals with diabetes and peripheral neuropathy.Clin Biomech. 2016; 32 (10.1016/j.clinbiomech.2015.11.001): 261-267
- Total contact casting in treatment of diabetic plantar ulcers: Controlled clinical trial.Diabetes Care. 1989; 12 (10.2337/diacare.12.6.384)
- Pathways to diabetic limb amputation. Basis for Prevention.Diabetes Care. 1990; 13 (10.2337/diacare.13.5.513): 513-521
- Lower-extremity amputation risk after Charcot arthropathy and diabetic foot ulcer.Diabetes Care. 2010; 33 (10.2337/dc09-1497): 98-100
- Changes in classifications of chronic lower-limb wound codes in patients with diabetes: ICD-9-CM versus ICD-10-CM.Adv Skin Wound Care. 2015; 28 (10.1097/01.ASW.0000459576.85574.3f): 84-92
Article info
Publication history
Published online: November 17, 2022
Accepted:
November 13,
2022
Received in revised form:
October 30,
2022
Received:
October 4,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
