DRWF awarded a one-year Open Funding grant to Professor Sally Marshall from Newcastle University back in 2008. The £29,559 awarded covered all of the MRI costs for the research. Here is an update on her findings…
The title of the research project was 'Development of high field magnetic resonance techniques for the non-invasive investigation of diabetic kidney disease'.
Professor Marshall says, 'The study was designed to develop magnetic resonance imaging (MRI) techniques for investigation of chronic kidney disease, particularly in diabetes. We wanted to find out why kidney disease develops and how we can make earlier diagnosis. We were interested particularly in kidney size, blood flow and oxygen levels.'
Ten people without diabetes or kidney disease, nine with longstanding type 1 diabetes and no kidney disease and eight individuals with type 1 diabetes and very early kidney disease participated. Six individuals with early kidney disease had two sets of scans, one on their usual blood pressure medication and the second after four weeks off specific blood pressure medication which affects kidney blood flow. The researchers kept blood glucose levels at 4-6 mmol/l throughout the scans in those with diabetes, using intravenous insulin as necessary. Participants had to drink a large amount of water to give the kidneys the “work” of excreting the extra fluid.
Intravenous injection of a dye allowed the researchers to identify the two layers of the kidney, the outer cortex and the inner medulla. The volumes of the cortex and the medulla were similar in the people without diabetes, with diabetes and with diabetes and early kidney disease.
The researchers measured the flow of blood into the kidney through the renal artery. The pattern of flow through the renal artery was similar in all participants, with no evidence of narrowing of the blood vessel in those with diabetes. The average flow rate was lower in participants with diabetes compared to those without diabetes. However, flow through the renal artery was similar in the diabetic participants with and without early kidney disease. After drinking the water, blood flow through the renal artery increased in all participants, but remained lower in those with diabetes compared to those without. The researchers had expected to find a normal or even higher blood flow in diabetic participants.
To try to understand why this was reduced, the researchers calculated “renal vascular resistance” from the blood pressure and flow rate through the renal artery. This reflects the stiffness in the blood vessels inside the kidney and thus the resistance to blood flow. The resistance was lowest in those without diabetes, intermediate in those with diabetes but no kidney disease and highest in those with diabetes and early kidney disease.
Professor Marshall continues, 'We know that the longer someone has diabetes, the stiffer their arteries in the general circulation. Our results suggest that the blood vessels inside the kidney also stiffen with increasing duration of diabetes.'
'Our measurements of the oxygen level in the kidney showed great variability. After drinking water, some areas of the inner part of the kidney had increased oxygen and some decreased oxygen. Because we used very precise methods of analysing the data, we were able to show that previous beliefs about measuring oxygen levels were not correct and potentially give the wrong answer.'
Professor Marshall says that the study has shown three important results: the normal volumes of outer cortex and inner medullary layers of the kidney; the decreased flow in the renal artery due to increased stiffness inside the kidney in individuals with longstanding diabetes; and the fact that current methods for measuring kidney tissue oxygen levels are not sensitive enough to provide robust consistent measurements.
The research has been published in Diabetologia 2011; 54:2421-2429.
Professor Marshall is now completing a pilot study to develop better MRI methods of looking at blood flow within the kidney, without the need to give dye injections. She says that it may be that drugs which reduce stiffness in the arteries in the general circulation, such as statins and ACE inhibitors, may also reduce stiffness within the kidneys.