The relationship between renal function and plasma concentration of the cachectic factor zinc-alpha2-glycoprotein (ZAG) in adult patients with chronic kidney disease

Abstract

Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the relationship between plasma ZAG concentration and renal function in patients with a large range of glomerular filtration rate (GFR). Plasma ZAG concentration and its relationship to GFR were investigated in 71 patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD and PD patients compared to non-CKD controls (P<0.01). The hemodialysis session further increased plasma ZAG concentration (+39%, P<0.01). An inverse relationship was found between ZAG levels and plasma protein (rs = -0.284; P<0.01), albumin (rs = -0.282, P<0.05), hemoglobin (rs = -0.267, P<0.05) and HDL-cholesterol (rs = -0.264, P<0.05) and a positive correlation were seen with plasma urea (rs = 0.283; P<0.01). In multiple regression analyses, plasma urea and HDL-cholesterol were the only variables associated with plasma ZAG (r2 = 0.406, P<0.001). In CKD-5 patients, plasma accumulation of ZAG was not correlated with protein energy wasting. Further prospective studies are however needed to better elucidate the potential role of ZAG in end-stage renal disease.

Figure 1. Plasma ZAG concentration is increased in end stage renal disease patients.

ZAG concentration was quantified in plasma from non-CKD subjects (N = 18), chronic kidney disease (CKD stage 1 to 5, N = 71), hemodialysis (HD, N = 17) and peritoneal dialysis (PD, N = 8) patients by enzyme immunoassay. eGFR was estimated using CKD EPI formula as described in methods. Data are presented as median (interquartile range). Different letters indicate a significant difference at the P<0.05 level.

Figure 2. Plasma ZAG concentration increases during hemodialysis session.

ZAG concentration was quantified by enzyme immunoassay before and after an hemodialysis session in ESRD patients (N = 8). ZAG concentrations were corrected for hemoconcentration as described in methods. Differences between pre and post dialysis concentrations were considered significant at the P<0.05 level (Wilcoxon test for paired samples). Abbreviation: HD, hemodialysis.

Figure 3. Plasma ZAG concentration in CKD-5 patients with a diagnostic of protein-energy wasting.

The boxes indicate the range (i.e. min to max) and the line indicate the median. Note that no difference was found to be significant at the P<0.05 level. Abbreviation: PEW, protein-energy wasting.

Figure 4. Plasma glycerol concentration in non-CKD and CKD patients.

Plasma glycerol was measured as an index of lipolysis in 17 non-CKD patients, 6 CKD-2, 4 CKD-4 and 12 CKD-5 patients. A) plasma glycerol concentration B) Plasma glycerol, concentration normalized to body fat mass as described in methods. No difference was found to be significant at the P<0.05 level using Kruskall & Wallis test.