Albuminuria is Associated with Higher Turnover-Related Bone Histomorphometric Indices in Chronic Kidney Disease Stages 3–4
Ricardo Neto, Bernardo Fernandes, Juliana Magalhães, Inês Alencastre, João FrazãoAbstract
Background
Biological determinants of bone turnover in chronic kidney disease (CKD) remain incompletely understood. Although albuminuria is an established marker of kidney damage and predictor of renal and cardiovascular outcomes, its relationship with bone remodeling, as assessed by quantitative bone histomorphometry, has not previously been investigated.
Methods
We performed a cross-sectional study of 56 adults with CKD stages 3–4 who underwent transiliac bone biopsy with quantitative histomorphometry following double tetracycline labeling. Associations between 24-hour urinary albumin excretion and individual bone histomorphometric parameters were evaluated using multivariable linear regression. Models were adjusted for age, sex, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF23).
Results
In multivariable analyses, higher 24-hour urinary albumin excretion was associated with a histomorphometric pattern consistent with increased bone turnover, reflected by greater bone formation and cell surface indices. Specifically, log₁₀-transformed urinary albumin excretion was associated with higher bone formation rate (B = 0.295, 95% CI 0.088 to 0.501; P = 0.008), osteoblast surface (B = 0.588, 95% CI 0.187 to 0.988; P = 0.005) and osteoclast surface (B = 0.464, 95% CI 0.041 to 0.887; P = 0.033). Associations with mineralization-related parameters and bone volume were not statistically significant.
Conclusions
In patients with CKD stages 3–4, higher urinary albumin excretion was independently associated with quantitative histomorphometric indices of higher bone turnover. These findings suggest that albuminuria may mark a bone remodeling phenotype not fully captured by eGFR, iPTH and FGF23. Larger prospective studies are needed to define the biological basis and clinical implications of this association.