Diffusion-MRI detects an increase in interstitial fibrosis earlier than the decline of renal function
Lena Berchtold*1, Lindsey A Crowe*2, Iris Friedli2, Solange Moll4, Thomas de Perrot2, Pierre- Yves Martin1, Jean-Paul Vallée**2, Sophie de Seigneux**1
*Equal contribution
** Equal contribution
1Service and Laboratory of Nephrology, Department of Internal Medicine Specialties and of Physiology and Metabolism, University and University Hospital of Geneva, Geneva,
Switzerland
2Service of Radiology, Department of Radiology and Medical Informatics, University Hospital of Geneva and University of Geneva, Geneva, Switzerland
4Institute of Clinical Pathology, Department of Clinical Pathology, University Hospital of Geneva, Geneva, Switzerland
Corresponding author:
Sophie de Seigneux
email: sophie.deseigneux@hcuge.ch
link to the published version : Nephrol Dial Transplant. 2020 Jul 1;35(7):1274-1276.
doi: 10.1093/ndt/gfaa007.
https://www.ncbi.nlm.nih.gov/pubmed/32160279
Interstitial fibrosis (IF) is one of the major predicting factors in chronic kidney disease (CKD), even independently of eGFR [1-3]. IF can currently only be assessed by the examination of a kidney biopsy, an invasive examination which is difficult to perform repeatedly. Diffusion Weighted Magnetic resonance imaging (MRI) is emerging as an
important tool for non–invasive IF evaluation in the kidney [4-7]. We recently adapted renal diffusion MRI with the application of a readout-segmented echo planar (EPI) sequence (RESOLVE) [8], allowing for the discrimination between the cortical and medullary parts of the kidney and the calculation of the cortico-medullary ADC difference (ΔADC). ∆ADC was better correlated than absolute ADC to IF assessed by standard histology in both native kidney disease and transplant patients [9]. Although a single time value of IF is clinically important, the follow up of IF is sometimes even more relevant for clinical decisions and particularly important for evaluation of the evolution of a disease. We have shown that our sequence was reproducible in healthy volunteers and patients [8] but the use of diffusion MRI for the follow up of IF of a given patient with renal disease was not yet evaluated. We thus aimed at analyzing the use of diffusion MRI for the follow up of IF in patients having undergone repeated biopsies and its value in comparison to renal function follow up.
We included in this study patients having undergone repeated biopsies for clinical purpose and who agreed to undergo repeated MRI at the time of each biopsy as previously described [10]. Baseline characteristics were collected through patient records. Serum creatinine and standard laboratory values were performed in our local laboratory. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Renal fibrosis was assessed on the kidney biopsy specimen and scored from 0 to 100% using Masson trichrome staining by the expert pathologist (S.M) who was blinded to all other results.
Patients were scanned on a 3T MR (Siemens AG, Erlangen Germany) using a RESOLVE strategy as described previously [10]. The analysis of the MRI images was blinded to all other markers. For statistical analysis, Spearman tests, after controlling the linearity of associations with scatterplots, and paired T-test were used. The study was approved by the local ethical
From September 2013 to November 2017, 19 kidney allografts patients had repeated biopsies for clinical purposes and parallel MRI examinations. The majority were Caucasian (89.5%) and male (63.2%). Median age was 51 years (Interquartile range (IQR): 43-56), median blood pressure 130/84 mmHg (IQR:126-136/78-91mmHg) and 57.9% of patients were overweight (BMI >=25kg/m2). Mean time from the allograft was 12.4 months (IQR:12.0-49.1) for the first biopsy and 38.4 months for the second one (IQR:23.7-75.5). The average interval between the two biopsies was 1.7 year (IQR:0.77-2.47). There was no significant correlation between eGFR and IF at baseline (r=-0.39, p=0.10), whereas baseline ΔADC correlated negatively with IF (r=-0.76, p<0.001). Between the two visits, IF as estimated from the renal biopsy, increased significantly from a fibrosis score of 20% (IQR:10 to 35%) to 32.5%
(IQR:20 to 40%) (p=0.03) in individual patients, whereas estimated renal function remained stable (eGFR 54 (IQR:42-70) to 52 (IQR:36-65) ml/min/1.73m2; p=0.19). ΔADC decreased significantly from 30 to -23 x10-6mm2/S (baseline IQR: -5 to109; follow up IQR: -100 to 47;
p=0.005) (Figure 1A). Considering the difference between the basal and follow-up values, there was a good correlation between the evolution in IF and that for ΔADC (r=-0.51, p=0.03) (Figure 1B) but not between the evolution of IF and eGFR (r=0.24, p=0.34).
Figure 1: A) Box Plot comparison of fibrosis, eGFR and ΔADC at baseline and follow-up.
The horizontal bar inside each box is the media, the top and bottom of the box indicate the interquartile range, and the T bars indicate the 95th percentile. B) Scatter plot of the difference of ΔADC at follow-up and baseline and the difference of fibrosis at follow-up and baseline.
MRI outperformed the eGFR to assess the evolution of IF within a given patient. ΔADC may be more reliable than eGFR to allow earlier detection of an increase in interstitial fibrosis.
This could be explained by the intrinsic sensitivity of ADC to renal architecture whereas eGFR is maybe more dependent also from extra-renal factors. Although several studies have used diffusion MRI as a tool to evaluate fibrosis, our study represents, to the best of our knowledge, the first study with repeated MRI and biopsy in same patients.
In summary, diffusion MRI appears to be reliable for IF follow up in an individual patient.
This justifies the ongoing research to develop MRI for every day clinical use in order to replace some invasive biopsies in the near future.
Disclosure None
ACKNOWLEDGEMENTS
SdS and JPV are supported by grants from the Swiss National Foundation (JPV grant 320038_159714 and SDS grant PP00P3_127454). This work was supported in part by the Centre for Biomedical Imaging (CIBM) of EPFL, University of Geneva and the University Hospitals of Geneva and Lausanne and the Swiss National Foundation for its financial support for the PRISMA MRI (R’Equip grants: SNF No 326030_150816).
Conflict of interest statement
The results presented in this paper have not been published previously in whole or part, except in abstract format.
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