Abstract
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. 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. 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. 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. 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.
Highlights
The WNT signaling pathway contributes to renal fibrosis, which is a hallmark of chronic kidney disease (CKD)
The study was performed in patients with clinical suspicion of glomerular disease who underwent kidney biopsy, which has been performed based on the standard clinical indications, i.e. nephrotic syndrome, subnephrotic proteinuria, isolated hematuria, unexplained fall in glomerular filtration rate (GFR), as well as when symptoms of renal injury have occurred in the course of already diagnosed ‘systemic’ disease
The preliminary data presented here suggest that elevated levels of serum WNT4 protein may be associated with the immune system response
Summary
The WNT signaling pathway contributes to renal fibrosis, which is a hallmark of chronic kidney disease (CKD). The progression of CKD is associated with the acquisition of a mesenchymal phenotype by the epithelial cells of the convoluted tubules in a process called epithelialmesenchymal transition (EMT). This process of dedifferentiation of highly specialized, polarized and basement membrane-embedded tubular epithelial cells into myofibroblast-like cells which can digest the tubular basement membrane, migrate into the interstitium and start producing matrix proteins, is a well-recognized mechanism of progression in several chronic nephropathies. The expansion of fibrosis is a consequence of chronic and not fully resolved inflammation Both processes develop upon the activation of cell signal transduction pathways.[4,5,6,7,8]
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