Kidney Function Decline in the Elderly: Impact of Lipoprotein-Associated Phospholipase A₂

Abstract

Background: Whether lipoprotein-associated phospholipase A₂ (Lp-PLA₂) levels are associated with kidney function decline has not been well studied. Methods: We investigated associations of Lp-PLA₂ antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≧3 ml/min/1.73 m² per year. We stratified by baseline preserved GFR (≧60 ml/min/1.73 m²). Results: Mean age was 72 ± 5 years. Average eGFRcys decline was –1.79 ml/min/1.73 m² (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA₂ antigen, eGFRcys decline was faster among persons in the second, β –0.31 (95% CI –0.52, –0.10), third –0.19 (–0.41, 0.02) and fourth quartiles –0.26 (–0.48, –0.04) after full adjustment. Persons in the highest quartile of Lp-PLA₂ antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA₂ activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m²) at baseline. Conclusion: Higher levels of Lp-PLA₂ antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population

“…This indicates substantial information can be gained by linking the two components and supports a role of the aforementioned conversion enzyme in kidney disease. The other significant ratio of phosphatidylcholine diacyl C42:5/phosphatidylcholine acylalkyl C36:0 may be related to the enzyme lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), which was described to be associated with important clinical outcomes such as CKD progression and cardiovascular events (Box 1) [22].…”

MMP-2 and 9 in Chronic Kidney Disease

“…Additionally, as SPLA2 is important in inflammation, which promotes the inflammatory response, thus the activation of this axis will increases the related inflammatory response. Yet, SPLA2 also plays an important role in the development of renal injury and CKD [ 53 , 54 ]; therefore, in people with congenital MMP-2 deficiency, the occurrence and development progression of CKD may also be closely associated with this axis.…”

Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

“…Plasma NT-proBNP was measured at baseline and then at visit 3 (3.2 years apart) by the Veterans Affairs San Diego Healthcare System, using an Elecsys 2010 analyzer (Roche Diagnostics); intra- and interassay coefficients of variation were 1.3 and 4.8%, respectively [11], and the reported day-to-day variations were 5.5 and 2.6% when mean concentrations were 6.4 pmol/L and 113.6 pmol/L, respectively [12]. IL-6 concentrations (pg/mL) were measured by ultrasensitive enzyme-linked immunosorbent assay (ELISA; Quantikine HS Human IL-6 Immunoassay; R&D Systems, Minneapolis, MN, USA) [13–15]. …”