Apolipoprotein A-IV Predicts Progression of Chronic Kidney Disease

Abstract

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n ‫؍‬ 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m 2 ; P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P ‫؍‬ 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype ⑀2/⑀4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Progression of Chronic Kidney Disease

“…For example, independent studies correlated male gender to a significantly faster progression to ESRD (14), whereas this association was debated by other authors because it seemed to be strongly confounded by other factors (15). Higher serum phosphate and calcium-phosphate product, unlike serum calcium, were associated with an increased independent risk of progressive CKD (16), as well as several circulating factors such as fibroblast growth factor 23, apolipoprotein-A4, asymmetric dimethylarginine, and B-type natriuretic peptide (17)(18)(19)(20).…”

Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease

“…Furthermore, high plasma apoA-IV concentrations predicted, independent of baseline GFR, the progression of primary nondiabetic kidney disease, defined as doubling of serum creatinine or necessity of renal replacement therapy, during a prospective 7-yr follow-up study (48). These findings were unexpected, given the physiologic functions in reverse cholesterol transport and the antioxidative properties of apoA-IV.…”

Fibroblast Growth Factor 23 (FGF23) Predicts Progression of Chronic Kidney Disease

“…These patients were recruited from eight nephrology departments in Germany, Austria, and South Tyrol as described previously. 32 The study was approved by the institu- The inserted tables present sensitivity and specificity of the four cutoffs derived from the quintile thresholds for c-terminal and intact FGF23, respectively. For c-terminal FGF23, the threshold between the third and fourth quintiles was equal to the ROC-derived optimal cutoff.…”