Serum WNT4 protein as an indicator of chronic glomerulonephritis but not a marker of inflammatory cell infiltration and fibrosis: A preliminary study

Adv Clin Exp Med. 2022 Mar;31(3):249-259. doi: 10.17219/acem/143543.

Abstract

Background: The WNT signaling pathway contributes to renal fibrosis, which is a hallmark of chronic kidney disease (CKD). Serum concentration of WNT4 could be used to monitor the kidney disease; however, no data have yet been published on the subject.

Objectives: This study measures WNT4 protein in serum of CKD patients depending on the stage, type of nephropathy, the non-nephrotic (NNP) or nephrotic proteinuria (NP), inflammatory cell infiltration in kidney parenchyma (IIKP), interstitial fibrosis in biopsy and serum creatinine. We also evaluated the usefulness of the serum WNT4 as a marker of fibrosis and IIKP.

Material and methods: The WNT4 protein level in serum of CKD patients and healthy individuals was measured using enzyme-linked immunoassay (ELISA). Patients' blood biochemical profiles and kidney biopsies were evaluated with common laboratory methods.

Results: The serum level of WNT4 protein was higher in CKD patients (i) regardless of the underlying etiology and at early stages of disease; (ii) with lupus nephritis and Immunoglobulin A (IgA) nephropathy; (iii) without or with a small area of IIKP; and (iv) with a small area covered with fibrosis. No difference was observed between NNP and NP patients. The utility of serum WNT4 as a marker of IIKP and fibrosis was not confirmed. Negative correlations with total and low-density lipoprotein (LDL)-cholesterol were found in CKD and IIKP patients. In patients with serum WNT4 above the median value, serum creatinine was higher. However, no correlation between serum WNT4 and creatinine level was found.

Conclusions: The observed increase in serum WNT4 protein in the early stages of CKD and in patients diagnosed with immune-mediated glomerular disease may suggest that WNT4 may act as a mediator of inflammation. A certain association with the dysregulation of serum lipid metabolism can also be suspected. Serum WNT4 protein may be considered as the indicator of chronic glomerulonephritis, but not a diagnostic marker of IIKP and fibrosis.

Keywords: WNT4; chronic kidney disease; inflammatory cells infiltration; kidney fibrosis; serum.

MeSH terms

  • Fibrosis
  • Glomerulonephritis* / complications
  • Glomerulonephritis* / pathology
  • Glomerulonephritis, IGA* / complications
  • Glomerulonephritis, IGA* / pathology
  • Humans
  • Kidney / pathology
  • Wnt4 Protein

Substances

  • WNT4 protein, human
  • Wnt4 Protein