QUANTIFYING COMPENSATORY KIDNEY HYPERTROPHY AND HYPERFILTRATION WITH MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING

Abstract

Compensatory kidney hypertrophy and hyperfiltration describe the volume expansion and increase in glomerular filtration rate in the residual kidney tissue in the event of functional nephron loss. This project used multiparametric MRI to quantify tissue hypertrophy and haemodynamic adaptations in the remaining kidney after unilateral nephrectomy in human living kidney donors and in an experimental mouse model. The Manchester 2019 Living Donor Study was a retrospective study of the baseline characteristics and early GFR recovery in 76 living kidney donors. Their pre-donation eGFR was 95.6 ml/min/1.73m2. Their single kidney eGFR of the remaining kidney increased significantly on Day 3 after donation and remained stable at 63 ml/min/1.73m2 4-8 weeks after donation, restoring 66% of their pre-donation kidney function. The Living Kidney Donor MRI Study was a prospective longitudinal observational study. Serial multiparametric MRI scans and GFR measurements were performed in 22 living kidney donors to study compensatory kidney hypertrophy after donation. Rapid increases were observed in the remaining kidney volume (17%), single kidney GFR (24%), and single kidney blood flow (25%) within the first month after donation. The increases in kidney volume and GFR were significant within 4-7 days, without further change at 4 weeks, while the increase in kidney blood flow derived from both phase contract MRI and ASL lagged and became significant at 4 weeks. In addition, DWI-derived apparent diffusion coefficient (ADC) and whole kidney T2* increased significantly between pre-donation and 4-7 days after donation, without further changes at 4 weeks. DTI-derived fractional anisotropy (FA), kidney T1 and ASL-derived kidney tissue perfusion did not change significantly after donation. The Mouse Unilateral Nephrectomy Preclinical MRI Study explored the use of dynamic contrast-enhanced MRI in a mouse model of unilateral nephrectomy to quantify haemodynamic parameters at baseline and after surgery. After 4 weeks, the mouse remaining kidney volume had increased by 35% compared to baseline and kidney plasma volume had expanded by 20%. Remaining kidney T1 value had also significantly increased. In conclusion, compensatory kidney hypertrophy in the remaining kidney after unilateral nephrectomy was accompanied by parallel increases in single kidney GFR and blood flow. We also quantified phase contrast kidney blood flow, ASL perfusion, ADC, FA, T1 and T2* in living kidney donors. Further optimisation and validation in functional MRI parameters offer the exiting prospect of identifying imaging biomarkers of nephron loss and adaptive changes.

Date of Award	20 Oct 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Rachel Lennon (Main Supervisor), Josephine Naish (Co Supervisor), Penny L Hubbard Cristinacce (Co Supervisor), Paul Brenchley (Co Supervisor), Sandip Mitra (Co Supervisor) & Alastair Hutchison (Co Supervisor)