Kidney fibrosis is a common cause of declining renal function in patients with chronic kidney disease (CKD) but cannot currently be detected without a kidney biopsy. However, imaging techniques might provide a noninvasive alternative for the assessment of renal fibrosis, according to a new report by Peter Boor and colleagues.
“We focused on potential biomarkers that would allow for the monitoring of fibrosis and might serve as end points in clinical trials,” explains Boor. The researchers showed that, in rodents and humans, the extracellular matrix protein elastin is not extensively expressed in healthy kidneys but is strongly upregulated in areas of fibrosis. The next step was to test an elastin-specific MRI agent, ESMA, which significantly accumulated in mouse fibrotic kidneys but not in healthy tissue. After incubation with ESMA, human biopsy samples of fibrotic kidneys also had a higher ESMA signal than samples from healthy kidneys. Techniques such as western blot and immunofluorescence verified elastin expression and the presence of renal fibrosis; in vivo and ex vivo competition experiments validated the specificity of the ESMA signal.
The researchers then used imaging with ESMA to monitor the progression of fibrosis in the adenine-induced nephropathy mouse model and demonstrated a progressive increase in the ESMA signal over 3 weeks. An analysis of the contrast-to-noise ratio indicated that the ESMA signal peaked at 24 h but was mostly cleared from the kidney after 72 h. Moreover, in two mouse models of fibrosis, mice treated with drugs that reduce fibrosis had significantly less elastin deposition than untreated mice (verified by histology), and this therapeutic response could be quantified by noninvasive imaging with ESMA. Last, in a model of reversible adenine nephropathy in which mice were allowed to recover after an initial injury, the ESMA imaging approach detected persistent fibrotic damage despite apparent normal kidney function according to serum markers.
“Our study lays the foundations for the translation of this diagnostic technique to patients with CKD,” concludes Boor.
Sun, Q. et al. Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis. Sci. Transl Med. https://doi.org/10.1126/scitranslmed.aat4865 (2019)
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Wang, M. Measuring fibrosis without biopsies. Nat Rev Nephrol 15, 388 (2019). https://doi.org/10.1038/s41581-019-0153-4