Plasma PZP level elevation: a potential correlate of diabetic kidney disease progression

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease in type 2 diabetes mellitus (T2DM) patients. Recent studies have demonstrated that pregnancy zone protein (PZP), a hepatic cytokine, plays a role in regulating glucose and lipid metabolism. This retrospective study aimed to investigate the connection between plasma PZP concentrations and DKD.

All participants were stratified by estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The discovery cohort included 130 participants, from whom plasma samples were collected for four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics. In contrast, plasma PZP concentrations were measured using the enzyme-linked immunosorbent assay (ELISA) in a validation cohort of 283 participants. Comparisons of clinical parameters, Spearman's rho correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed. Data were retrieved from public databases, and plasma PZP expression was simultaneously assessed in db/db mice and in primary hepatocytes treated with high glucose and palmitic acid (HGPA).

4D-DIA quantitative proteomics identified PZP as a differentially expressed protein in DKD patients. In the validation cohort, plasma PZP levels were significantly increased in DKD patients. Spearman's rho correlation analysis revealed positive correlations between plasma PZP concentrations and systolic blood pressure (SBP), HbA1c, low-density lipoprotein (LDL), Cr, blood urea nitrogen (BUN), and UACR, as well as negative correlations with high-density lipoprotein (HDL) and eGFR. A multiple logistic regression analysis demonstrated a significant correlation between PZP and DKD progression (mild DKD: OR = 1.007; severe DKD: OR = 1.011). The ROC curve area was 0.8143. Plasma PZP levels in db/db mice were notably elevated, and a positive correlation with the UACR was observed. Moreover, PZP mRNA expression in HGPA-treated primary hepatocytes was twice as high as that in untreated cells.

In summary, elevated plasma PZP levels are independently associated with DKD.