Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04625140 |
| Other study ID # |
2020_161 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2021 |
| Est. completion date |
August 30, 2025 |
Study information
| Verified date |
February 2023 |
| Source |
University Hospital, Akershus |
| Contact |
Christian Aalborg, M.D. |
| Phone |
+4793043516 |
| Email |
christian.aalborg[@]ahus.no |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This study will investigate the ability of renal MRI to detect fibrosis, how this correlates
to renal function and how well renal MRI biomarkers can predict decline in kidney function
over time. We will also assess the correlation of renal MRI and kidney function to markers of
renal ageing in blood, urine and tissue samples.
Description:
Chronic kidney disease (CKD) is an increasing health concern worldwide, with an estimated
prevalence of 11% in the Norwegian population. Progression of CKD and development of
end-stage kidney disease is closely related to the extent and progression of renal fibrosis.
Traditionally the assessment of renal fibrosis is made by renal biopsy, which in addition to
diagnostics also evaluates the degree of renal fibrosis.
However, the evaluation of fibrosis from a renal biopsy is limited by the risk of
complications. Due to its invasive nature, clinicians often reserve a biopsy for situations
where the anticipated yield will have therapeutic value. This means the fibrotic burden is
often not assessed, and information on scar burden and kidney-prognosis is lost. Furthermore,
we know that fibrosis may be unequally distributed throughout the kidney. Since a biopsy only
samples a small portion of kidney tissue, it is inherently susceptible to sampling bias.
In contrast, Magnetic Resonance Imaging (MRI) techniques can assess whole organ fibrotic
burden. Since it is a non-invasive procedure, MRI can evaluate renal fibrosis in patients not
eligible for renal biopsy. Moreover, it can be performed at several time-points for temporal
renal fibrosis assessments. Recent developments in MRI techniques have made it possible to
assess renal fibrosis with MRI. These techniques rely on the different biological properties
of fibrotic and non-fibrotic tissues, including reduced microcirculation, restriction of
water motion and reduced oxygenation. From several MRI biomarkers currently available, five
show particular promise in quantifying degree of renal fibrosis: Diffusion weighted MRI,
T1-mapping and T2-mapping, T1-rho and arterial-spin labelling. A recently developed MRI-patch
which combines these five techniques, makes it possible to perform a MRI-scan with
simultaneous measurements whilst not prolonging examination time for the patient. We
hypothesize that combining these MRI-techniques will give additional information, and thus
provide a better correlation to histological-assessed fibrosis than any technique alone.
Markers of renal ageing may also predict development of renal fibrosis as accelerated renal
ageing trough p16INK4a pathway activation, leading to cellular senescence, is involved in the
development of renal fibrosis in CKD. Senescent cells are characterized by irreversible
growth arrest and express a pro-inflammatory and pro-fibrotic senescent-associated secretory
phenotype (SASP). This biochemical foot print can be detected by immunohistochemistry. We aim
to assess the correlation between degree of renal fibrosis and markers of renal ageing, as
well as to what extent decline in kidney function can be predicted by change in markers of
renal ageing.
This study will be one of the first to evaluate correlation between multiparametric MRI and
morphometric estimates of renal fibrosis. We will study whether activation of pathways
involved in renal ageing are associated with progressive renal fibrosis and deterioration of
renal function. Finally, we will evaluate the utility of temporal measurements of renal
fibrosis for prediction of renal function deterioration with a non-invasive method.
