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Moderate, Severe Albuminuria Identified as Fracture Risk Factors

Albuminuria increases the risk for fragility fractures in patients with chronic kidney disease (CKD), new study findings suggest.

In a study of 2.72 million community-dwelling adults in Alberta, Canada who had a least 1 creatinine and albuminuria measurement from April 1, 2008 to March 31, 2019, individuals with severe albuminuria had significant 37%, 31%, and 22% increased odds of hip fracture, vertebral fracture, and any fracture, respectively, compared with those who had no or mild albuminuria, Sandra M. Cooke-Hubley, MD, MPH, MSc, of Memorial University in St. Johns, Newfoundland, Canada, and colleagues reported in Kidney International Reports. Patients with moderate albuminuria had significant 25%, 20%, and 18% greater odds of hip, vertebral, and any fracture, respectively. 

“This study demonstrates the important role of albuminuria as a risk factor for fragility fracture in CKD and may help inform risk stratification and prevention strategies in this high-risk population category,” the investigators concluded.


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The investigators defined no or mild albuminuria as an albumin-creatinine ratio (ACR) less than 30 mg/g, protein-creatinine ratio (PCR) less than 150 mg/g, or trace or negative dipstick findings. They defined moderate albuminuria as ACR 30-300 mg/g, PCR 150-500 mg/g, or 1+ dipstick, and severe albuminuria as ACR above 300 mg/g, PCR greater than 500 mg/g, or 2+ dipstick or more. In all, 94% of patients had no or mild albuminuria, 4.7% had moderate albuminuria, and 1.3% had severe albuminuria.

Dr Cooke-Hubley and colleagues also examined the risk for fragility fracture by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and KDIGO risk categories. The relationship between eGFR and any type of fracture showed a U-shaped association. Compared with patients who had an eGFR of 60-89, those with an eGFR of 90 or higher had significant 21% greater odds of fracture. Patients with an eGFR of 45-49 had significant 6% lower odds, whereas those with an eGFR of 30-44 and 15-29 had significant 5% and 17% increased odds, respectively. Patients in the KDIGO moderate, high-, and very high-risk categories had significant 3%, 12%, and 25% increased odds of any type of fracture compared with those in the low-risk category. The investigators observed similar trends for spine, pelvic, and hip fracture.

“We propose that albuminuria may be a prognostic indicator for incident fracture risk in the population with CKD, and that the KDIGO risk categories which combine albuminuria and eGFR can also be used to prognosticate fracture risk,” the authors wrote. “These findings underscore the importance of using albuminuria in addition to eGFR when evaluating metabolic bone health and fracture risk.”

The authors discussed hypotheses to explain the link between albuminuria and fragility fracture. One hypothesis relates to endothelial dysfunction and vascular perfusion. “In the

glomerular basement membrane, endothelial dysfunction can modify glomerular barrier permeability, leading to increased albuminuria in the urine,” Cooke-Hubley and colleagues wrote. “Albuminuria, as marker of endothelial dysfunction, may impact bone perfusion and reduce the rate of remodeling, leading to a loss of [bone mineral density] and increase risk of fracture.”

In addition, they noted that albuminuria may be a marker of diminished bone quality because of its association with inflammation. Oxidative stress and inflammation are known to affect bone quality, such as in conditions as diabetes mellitus, rheumatoid arthritis, and multiple myeloma, they pointed out.

Reference

Cooke-Hubley SM, Senior P, Bello AK, Wiebe N, Klarenbach SW. Degree of albuminuria is associated with increased risk of fragility fractures independent of eGFR. Kidney Int Rep. Published online August 28, 2023. doi:10.1016/j.ekir.2023.08.016