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. 2024 Mar 19;14(1):6643.
doi: 10.1038/s41598-024-56277-x.

Renal biopsies from donors with acute kidney injury show different molecular patterns according to the post-transplant function

Flavia Neri  1   2 , Maria Letizia Lo Faro  3 , Maria Kaisar  3 , Ka Ho Tam  4 , Martyna Borak  5 , Jan Lindeman  6 , Annalisa Angelini  7 , Marny Fedrigo  7 , Jesper Kers  8   9   10 , James Hunter  3 , Rutger Ploeg  3
Affiliations

Renal biopsies from donors with acute kidney injury show different molecular patterns according to the post-transplant function

Flavia Neri et al. Sci Rep. .

Abstract

The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. The aim of our study was to identify protein mediators implicated in either recovery or failure of these organs. Forty kidney biopsies from donors with (20) and without AKI (20) were selected and then subdivided according to the post-transplant outcome defined as a threshold of 45 ml/min for the eGFR at 1 year from transplantation. Tissue homogenates were analysed by western blot to assess how the levels of 17 pre-selected proteins varied across the four groups. Samples from AKI kidneys with a poor outcome showed a fourfold increase in the levels of PPARg and twofold reduction of STAT1 compared to the other groups (p < 0.05). On the contrary, antioxidant enzymes including TRX1 and PRX3 were increased in the AKI kidneys with a good outcome (p < 0.05). An opposite trend was observed for the detoxifying enzyme GSTp which was significantly increased in the AKI group with poor versus good outcome (p < 0.05). The importance of lipid metabolism (PPARg) and inflammatory signals (STAT1) in the function recovery of these kidneys hints to the therapeutical targeting of the involved pathways in the setting of organ reconditioning.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow diagram describing the process of sample selection.
Figure 2
Figure 2
Histograms reporting expression intensities of western blot analysis of the proteins differently expressed in the four donor groups (A). Representative imaging of the immuno-blots for PPARg and PRX, TRX, STAT1 and GSTp in the four groups, with beta actin as loading control (B).
Figure 3
Figure 3
On the top of the figure, histograms show the average Remuzzi–Karpinski score (A), ATI score (B), intensity of PPARg expression in renal glomeruli (C) and tubules (D) across the study groups. On the lower part, representative images of histology (on the left) and immunohistochemistry (on the right) are shown across the study groups.
See this image and copyright information in PMC

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