FAZA PETMRI Kidney Graft Fibrosis Study

Summary

Fibrosis is the final common pathway of solid organ diseases and accounts for \~45% of deaths in the developed world. Fibrosis is characterized by excessive deposition of extracellular matrix that replaces normal organ parenchyma, leading to loss of function. Chronic kidney disease is invariably characterized by fibrosis and affects \>3 million Canadians. Although fibrosis can affect all compartments in the kidney. Interstitial fibrosis/tubular atrophy (IFTA) is the most potent predictor of kidney disease progression, regardless of its underlying cause. In addition to affecting native kidneys, IFTA also occurs in kidney allografts in transplanted patients, resulting in progressive kidney allograft dysfunction and, finally allograft loss with significant implications for patients' care and also financial implications for the healthcare system. However, early, noninvasive markers of IFTA or ongoing hypoxia in the kidney grafts are lacking. This is particularly problematic, since diagnosis of IFTA is often made late in the course of disease, and once IFTA develops, it is generally considered irreversible. There is thus an unmet clinical need to identify early markers of IFTA that could guide the use of novel anti-fibrotic therapies.

In patients with clinically decreasing allograft function or protienuria, indication (or for cause) biopsies are the gold standard test used to identify the cause for the functional decrease. However, biopsies carry significant procedural risk (e.g. bleeding and death) and suffer from a sampling bias - not all areas of the kidneys are accessible for biopsy and there is currently no way to target the fibrotic / hypoxic areas. Urine protein measurements are obviously also not suitable to resolve this clinical dilemma. There would thus be great clinical interest in developing non-invasive tools that could provide more information compared to traditional tests for monitoring renal hypoxia and injury through imaging and urinary biomarkers.

Our aims would be to image patients with different states of allograft function impairment and ideally find an imaging-based way to monitor those patients after transplantation. This way, an early detection of evolving interstitial fibrosis/tubular atrophy (IFTA) might be possible in a non-invasive way.The goal of this trial is to validate FAZA-PET/MR as a biomarker of hypoxia by correlating its uptake in patients with kidney allograft fibrosis with mass spectrometry based quantitative assays for monitoring of fibrotic markers in the urine of those same patients.

There would thus be great clinical interest in developing non-invasive tools that could provide more information compared to traditional tests for monitoring renal hypoxia and injury through imaging and urinary biomarkers. Whereas currently only allograft biopsy can be performed to detect (rather late stage) interstitial fibrosis/ tubular atrophy.

The study subjects' clinical management will not be changed based on the PET-MR scan within the trial.

Conditions

• Kidney Graft Fibrosis

Interventions

DIAGNOSTIC_TEST

FAZA PET/MRI scan

FAZA PET/MRI scan before the standard of care biopsy for case group

Sponsors & Collaborators

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• Patrick Veit-Haibach, MD · University Health Network, Toronto

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-05-26

Primary Completion

2023-06-13

Completion

2023-06-13

Countries

• Canada

Study Locations