Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT05014022 |
Other study ID # |
21057 |
Secondary ID |
302569 |
Status |
Not yet recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
October 1, 2021 |
Est. completion date |
April 1, 2022 |
Study information
Verified date |
August 2021 |
Source |
University of Nottingham |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
One in five patients admitted to hospital suffer a sudden reduction in kidney function,
termed acute kidney injury (AKI). Rather than kidney 'injury' being caused by physical
trauma, the term describes reversible damage caused by conditions such as being dehydrated or
having an infection. Having AKI puts patients at an increased risk of long-term health
problems, especially chronic kidney disease (CKD). CKD can also lead to other important
health problems including a higher risk of heart disease and stroke. If we can reduce the
progression of AKI to CKD this will benefit patients.
Currently, there is a gap in the follow-up of patients after AKI due to a lack of evidence
about which patients should be followed up and when. Treatments for AKI during the episode
and afterwards to prevent CKD are limited. This is mainly due to a lack of understanding
about how and when the kidney recovers after AKI. New tools are needed in order to better
identify patients at risk of CKD after AKI. This study aims to address these gaps in our
knowledge by studying a group of AKI patients in detail.
Ultimately, the aim of this study is to produce results that will allow better planning of
follow-up for patients as well the planning of future research to develop new treatments to
reduce the risk of CKD in people recovering from AKI.
Description:
Acute kidney injury (AKI) is a sudden loss of renal function occurring in up to 20% of
hospitalised patient. People who survive an episode of AKI are at increased risk of long-term
effects on their health, in particular the development or progression of chronic kidney
disease (CKD). At present, there are no interventions proven to reduce the development of CKD
after an episode of AKI.
A significant gap exists in the current provision of post-AKI follow-up care. Current methods
of assessing renal recovery are overly reliant on serum creatinine, an imperfect measure that
over-estimate the degree of renal recovery due to the effect of critical illness on muscle
mass. Based on expert opinion only, it is currently recommended that everyone who has
experienced AKI should have kidney function and albuminuria checked at 90 days. In reality,
current practice falls significantly below these standards. Less than half of patients with
the most severe AKI see a nephrologist after discharge. Even for patients who have required
dialysis for AKI, follow-up rates can be as low as 12%. Lack of evidence prevents a more
evolved approach. Improving post-AKI care and reducing the development or progression of CKD
could therefore directly benefit large numbers of patients. This is particularly pertinent
with the additional restrictions on hospital appointments due to COVID-19. More evidence is
urgently needed to inform which patients need follow-up and to integrate new techniques that
significantly improve assessments of renal recovery.
Important knowledge gaps make it difficult to move directly to testing new interventions in
randomised trials. AKI is not a single condition, rather a heterogeneous syndrome with a
variety of causes affecting a wide range of people. Outcomes differ between clinical settings
and are affected by factors related to AKI (e.g. its severity or duration), but also by an
individual's co-existing long-term conditions, and possibly by their frailty. As well as CKD
development, AKI is associated with higher long-term mortality rates, increased heart failure
events, hospital readmissions, recurrent AKI and poorer quality of life. Which groups are
most at risk of the different outcomes is not well established; similarly the groups that
would have the greatest benefit from interventions to reduce the development of CKD are not
currently known. It is therefore likely that subgroups of people who have sustained AKI will
benefit from different models of post- AKI care i.e. a one-size fits all approach is unlikely
to be beneficial or cost-effective. Finally, the timing of the renal recovery phase after an
episode of AKI is poorly understood outside of experimental models, which differ in a number
of ways from clinical AKI. Failure of recovery of creatinine by 90 days after AKI strongly
associates with subsequent long-term reductions in renal function, suggesting that
interventions may be needed prior to this time point, but descriptions of renal recovery
between AKI and 90 days are lacking.
MRI has emerged as an imaging modality with promise to improve the understanding and
characterisation of renal pathophysiology. It is a versatile technique in which structural
and functional MRI measurements can be performed in a single multiparametric scan session to
assess altered renal tissue microstructure, oxygenation, perfusion and blood flow. MRI is
non-invasive, safe and avoids sampling bias by characterising the entire kidney with high
spatial resolution. MRI does not involve ionising radiation, is repeatable (allowing serial
assessments over time) and the MRI measures do not require gadolinium contrast agents. A
series of recent systematic reviews covering the main functional renal MRI measures conclude
that evidence is now needed to accelerate the translation of multiparametric renal MRI for
clinical use. The reviews focussed on: arterial spin labelling (ASL, a measure of renal
perfusion); Blood Oxygen Level Dependent (BOLD, sensitive to changes in renal oxygenation);
longitudinal (T1) relaxation time (increases with scarring, correlates with fibrosis in the
heart and liver; diffusion weighted imaging (DWI, sensitive to changes in renal tissue
microstructure); and Phase Contrast (PC-MRI, a measure of renal artery blood flow).
Considering the high incidence of AKI, the long-term consequences of AKI present a major
unmet clinical need affecting large numbers of people, with no proven interventions nor data
to inform optimal care provision. If patients at risk of developing CKD could be better
identified, this would provide a basis upon which interventions to improve patient outcomes
could be planned.
The outputs of this study would directly inform planning of future research in the following
ways:
- Collection of data supporting a larger prospective cohort study of AKI patients, using
data from this study to directly inform study design and MRI protocols
- Identification of those at greatest risk of developing CKD after AKI will make clinical
trials more efficient and more likely to succeed
- Increasing understanding of the time course of renal recovery will allow planning of the
optimal time points for interventions and patient follow-up
- Demonstrate the potential application of renal MRI in NHS scanners leading to improved
clinical evaluation of patients