# Morphometry and Immunoexpression of Metalloproteinase 2 and Its Inhibitor in the Fibrotic and Non-Fibrotic Grafted Kidney—Digital Analysis

## TL;DR

This study uses digital analysis to compare kidney tissue in fibrotic and non-fibrotic grafted kidneys, finding changes in structure and increased MMP-2/TIMP-2 ratios linked to fibrosis.

## Contribution

The study introduces digital morphometric and immunoexpression analysis to evaluate fibrotic changes in grafted kidneys.

## Key findings

- Fibrotic grafted kidneys show enlarged urinary space and renal corpuscle diameters.
- Proximal and distal tubule epithelial height is reduced in fibrotic kidneys.
- MMP-2/TIMP-2 ratio is higher in fibrotic renal tissue compared to healthy tissue.

## Abstract

Background: Metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), regulate the extracellular matrix (ECM) in various tissues. MMP-2 and TIMP-2 maintain this process in renal tissue. An imbalance in the MMP-2/TIMP-2 ratio alters the abundance and proportions of specific extracellular matrix components, leading to kidney fibrosis. We aimed to assess differences in the morphometric parameters of the kidney and the immunohistochemical (IHC) expression of MMP-2 and TIMP-2 in kidney biopsies according to their fibrotic state. Methods: The histological slides were scanned using the 3DHISTECH Pannoramic MIDI II Scanner, and the resulting digital images of the sections were analyzed using Pattern Quant software; the morphometric analyses were performed with the Slide Viewer application. Results: In the current manuscript, we have investigated the significant enlargement of the diameter of the urinary space and renal corpuscle, as well as the reduced height of the epithelial lining of the proximal and distal convoluted tubules, of grafted kidneys with fibrosis when compared to the non-fibrotic kidneys. Moreover, we have noticed a rising MMP-2/TIMP-2 ratio in the immunohistochemical reaction in the renal tissue of fibrotic grafted kidneys in comparison to healthy kidneys. Conclusions: These results suggest that the MMP-2/TIMP-2 ratio, together with the lower inhibition of MMP-2, may promote an increased extracellular matrix remodeling, which accompanies the development of fibrosis.