Albuminuria and rapid loss of GFR and risk of new hip and pelvic fractures.

Abstract

BACKGROUND AND OBJECTIVES:

The microvascular circulation plays an important role in bone health. This study examines whether albuminuria, a marker of renal microvascular disease, is associated with incident hip and pelvic fractures.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

This study reanalyzed data from the Ongoing Telmisartan Alone and in combination with Ramipril Global End Point Trial/Telmisartan Randomized Assessment Study in Angiotensin-Converting Enzyme Intolerant Subjects with Cardiovascular Disease trials, which examined the impact of renin angiotensin system blockade on cardiovascular outcomes (n=28,601). Albuminuria was defined as an albumin-to-creatinine ratio≥30 mg/g (n=4597). Cox proportional hazards models were used to determine the association of albuminuria with fracture risk adjusted for known risk factors for fractures, estimated GFR, and rapid decline in estimated GFR (≥5%/yr).

RESULTS:

There were 276 hip and pelvic fractures during a mean of 4.6 years of follow-up. Participants with baseline albuminuria had a significantly increased risk of fracture compared with participants without albuminuria (unadjusted hazard ratio=1.62 [1.22, 2.15], P<0.001; adjusted hazard ratio=1.36 [1.01, 1.84], P=0.05). A dose-dependent relationship was observed, with macroalbuminuria having a large fracture risk (unadjusted hazard ratio=2.01 [1.21, 3.35], P=0.007; adjusted hazard ratio=1.71 [1.007, 2.91], P=0.05) and microalbuminuria associating with borderline or no statistical significance (unadjusted hazard ratio=1.52 [1.10, 2.09], P=0.01; adjusted hazard ratio=1.28 [0.92, 1.78], P=0.15). Estimated GFR was not a predictor of fracture in any model, but rapid loss of estimated GFR over the first 2 years of follow-up predicted subsequent fracture (adjusted hazard ratio=1.47 [1.05, 2.04], P=0.02).

CONCLUSIONS:

Albuminuria, especially macroalbuminuria, and rapid decline of estimated GFR predict hip and pelvic fractures. These findings support a theoretical model of a relationship between underlying causes of microalbuminuria and bone disease.

• Authors: Joshua I Barzilay, Peggy Gao, Catherine M Clase, Andrew Mente, Johannes F E Mann, Peter Sleight, Salim Yusuf, Koon K Teo, OnTARGET/TRANSCEND Investigators
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 8 Issue 2 Pg. 233-40 (Feb 2013) ISSN: 1555-905X [Electronic] United States
• PMID: 23184565 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Benzimidazoles
• Benzoates
• Ramipril
• Telmisartan

Topics

• Albuminuria (complications, physiopathology)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Benzimidazoles (therapeutic use)
• Benzoates (therapeutic use)
• Cardiovascular Diseases (complications, drug therapy)
• Fractures, Bone (epidemiology, etiology)
• Glomerular Filtration Rate
• Hip Fractures (epidemiology, etiology)
• Humans
• Pelvic Bones (injuries)
• Prospective Studies
• Ramipril (therapeutic use)
• Risk Factors
• Telmisartan
• Time Factors