Elevated osteoprotegerin predicts declining renal function in elderly women: a 10-year prospective cohort study.
BACKGROUND
Elevated osteoprotegerin (OPG) levels are inversely correlated with creatinine clearance and end-stage renal disease in patients with diabetes, however its role in predicting decline in renal function and progression to a more advanced stage disease in the elderly general population is unknown.


METHODS
This was a prospective cohort study of 1,157 elderly women with serum OPG measured in 1998 and renal function estimated using serum creatinine and cystatin C-based estimated glomerular filtration rate (eGFR) at 5-yearly intervals. The primary objective of the study was to determine the relationship of circulating OPG levels with 5- and 10-year renal decline.


RESULTS
At baseline, participants with elevated OPG above the median (≥2.2 ng/ml) had a 5.0% lower CKD-EPI-creatinine and cystatin C eGFR compared to participants with lower OPG levels. In multivariable-adjusted linear regression models, elevated OPG levels at baseline were associated with greater 5- and 10-year decline in CKD-EPI-creatinine and cystatin C eGFR (-0.105, p = 0.002 and -0.104, p = 0.010, respectively). Elevated OPG at baseline was associated with increased 5- and 10-year risk of rapid renal decline (OR 2.13, 95% CI 1.33-3.43, p = 0.002 and OR 4.10, 95% CI 1.49-11.27, p = 0.006, respectively) and renal disease hospitalizations or deaths (HR 1.99, 95% CI 1.31-3.03, p = 0.001) after adjusting for known risk factors.


CONCLUSIONS
Elevated OPG levels are associated with long-term renal dysfunction and may be provide a useful biomarker to predict the trajectory of renal decline in older women.
University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, W.A, Australia.
Joshua R
JR
Lewis
Wai H
WH
Lim
Kun
K
Zhu
Germaine
G
Wong
Satvinder S
SS
Dhaliwal
Ee M
EM
Lim
Thor
T
Ueland
Jens
J
Bollerslev
Richard L
RL
Prince
D000368:Aged; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008137:Longitudinal Studies; D015999:Multivariate Analysis; D053244:Osteoprotegerin / Q000097:blood*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood* / Q000175:diagnosis*; D012307:Risk Factors
D015415:Biomarkers; D055316:Cystatin C; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D003404:Creatinine