Urinary Osteopontin Predicts Incident Chronic Kidney Disease, while Plasma Osteopontin Predicts Cardiovascular Death in Elderly Men

Abstract

Background and Objectives: The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied. Design, Setting, Participants, and Measurements: A community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up. Results: There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman ρ = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002). Conclusions: Higher urinary osteopontin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

“…With renal damage, osteopontin expression is significantly upregulated in all tubule segments and the glomeruli [41]. We confirm that high urinary osteopontin levels are predictors of renal structural damage and proteinuria without [42] and with LN [43]. Notably, osteo- pontin levels were often lower in patients with substantial damage as compared to that in no/minimal LN damage, even after adjustment for concurrent LN activity (NIH-AI).…”

Combining Neprilysin Inhibitor With AT2R Agonist Is Superior to Combination With AT1R Blocker in Providing Reno-Protection in Obese Rats

“…Studies using rat models of accelerated antiglomerular basement membrane glomerulonephritis (Lan et al, 1998), subtotal (5/6) renal mass ablation (Yu et al, 2000), and streptozotocin-induced diabetes (Fischer et al, 1998) have similarly concluded that with injury renal osteopontin expression is upregulated. The upregulated osteopontin in said models is correlated with proteinuria, and macrophage and monocyte accumulation within the kidney (Fischer et al, 1998;Lan et al, 1998;Yu et al, 2000) making its urinary excretion a biomarker of kidney injury (Phillips et al, 2016;Feldreich et al, 2017). Urinary osteopontin concentrations were increased by HSD-feeding, and among the HSD-fed groups were lowest in SAC/C21 treated OZR.…”

Strong Associations between Plasma Osteopontin and Several Inflammatory Chemokines, Cytokines, and Growth Factors

“…We have previously found several of these proteins to be inflammatory chemokines, cytokines, and growth factors, which are associated with atherosclerosis and incident CVD [ 19 , 20 , 21 ]. We have also found plasma osteopontin to be associated with incident CVD [ 12 ]. Given the tight coupling between osteopontin and several inflammatory chemokines, cytokines, and growth factors demonstrated both by traditional statistics as well as protein–protein interaction network analysis, it is hard to separate the role of osteopontin in CVD from the other proteins.…”

“…Plasma and urine osteopontin were measured using a commercial sandwich enzyme-linked immunosorbent assay (ELISA) kit (DY1433, R&D Systems, Minneapolis, MN, USA), as previously reported [ 12 ]. The limit of quantification (LOQ) of the Osteopontin ELISA was 62 pg/mL.…”