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Protein composition discovery could lead to an early test for kidney disease

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New research from Rachel Lennon and her team at the Wellcome Trust Center for Cell-Matrix Research (UK) could shed light on why gender and race has an effect on susceptibility to kidney disease.

“It’s well known that impaired kidney function is more common in African Caribbean individuals compared to those from a Caucasian background, and in men compared to women,” Lennon explained. “However, the reasons for the difference in susceptibility are only just being discovered.”

The team’s research focused on the structure around kidney cells, with the aim of understanding the contributing factors in kidney disease.

Mass spectrometry was used to analyze samples from the kidney filters of mice of different genetic backgrounds and sexes. The team observed significant differences in the composition and types of proteins, with the greatest difference identified between mice from different genetic backgrounds.

The researchers then used an electron microscope to view the filters. The scaffold of proteins that normally connects two types of cells in the filter was abnormal in susceptible mice, with splits and bulges. They were able to conclude from these two tests that both the composition and structure of the kidney filter was altered in susceptible mice.

“The most surprising thing about our findings were that the mice weren’t actually exhibiting any symptoms of kidney disease and were all still in full health despite having this different structure in their filters. Their kidneys appeared to be functioning normally,” described Lennon. “The next question, and the one that we are starting to look at for our next research paper, is when this difference in structure occurs – is it from birth or at a later stage?”

The team plans to investigate the reasons behind the structural difference, and if it would be possible to use this information to prevent kidney damage or prevent symptomatic kidney disease. They also plan to observe human tissue to determine whether the differences are present.

Lennon and her team think it likely that they will find the same trend in human kidney tissue: “At the moment we do see these changes in structure when looking at biopsies from kidney patients in clinic but we haven’t known what they mean. What we’re hoping is that this research will help develop a test that picks up kidney disease, or even just a susceptibility to kidney disease, before any damage has been done. We’re also keen to look at whether we could manipulate the process which leads to the structural change to develop new, more effective treatments.”

Sources: Randles MJ, Woolf AS, Huang JL et al. Genetic background is a key determinant of glomerular extracellular matrix composition and organization. J. Am. Soc. Nephrol. (Epub ahead of print) (2015); New finding could help develop test for kidney failure.

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