Detection of renal fibrosis and prediction of kidney function decline: The role of kidney MRI and markers of accelerated renal aging
Worldwide, chronic kidney disease (CKD) is an increasing health concern with an estimated prevalence of 11% in the Scandinavian 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 extent 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 in 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 the whole organ fibrotic burden. Being 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 assessment. 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 and restriction of water motion. From several MRI biomarkers currently available, four show particularly promising results in quantifying the degree of renal fibrosis: Diffusion weighted MRI, T1-mapping and T2*-mapping, T1-rho and arterial-spin labelling. We hypothesize that when combining these MRI techniques, they will complement each other and provide a better correlation to histologically assessed fibrosis than any technique alone.
Markers of renal ageing may predict development of renal fibrosis. Accelerated renal ageing through p16INK4a pathway activation, leading to cellular senescence, might be an underlying feature 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 footprint can be detected by immunohistochemistry.
The study cohort consists of patients scheduled for renal biopsy for diagnostic purposes. The aim of this study is to assess the utility of a multiparametric MRI protocol for detection of renal fibrosis compared with the gold-standard morphometric renal biopsy evaluation. Both procedures will be performed at baseline and after two years. In addition, this study will assess associations between degree of renal fibrosis and markers of renal ageing.
In a prospective cohort study design, adult patients scheduled for a kidney biopsy for diagnostic purposes at Department of Nephrology, Akershus University Hospital will be invited to participate in the study. The inclusion period is expected to last 20 months during which 70 participants will be recruited.
The research is performed in a collaboration between several Norwegian research groups and Aarhus University hospital.