Eyesha Hashim1, Darren Yuen2,3, General Leung1,4, and Anish Kirpalani1,4
1Medical Imaging, St. Michael's Hospital, Toronto, ON, Canada, 2Nephrology, St. Michael's Hospital, Toronto, ON, Canada, 3Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada, 4Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
Synopsis
Delayed
graft function (DGF) complicates 21-36% of all deceased donor kidney transplants,
and leads to early inpatient post-transplant dialysis, higher risk of graft
failure and death. In this abstract, we show that IVIM-derived flow
(f)-fraction, is significantly different in kidney allografts exhibiting DGF
compared to those that do not develop DGF. Furthermore, f fraction shows a
significant negative correlation with time to recovery and a positive trend
with renal function at 3 months post-transplant as measured with eGFR.
Introduction
While
kidney transplantation has revolutionized the care of patients with end-stage
kidney disease, the use of kidneys from older donors and donors after cardiac
arrest has dramatically increased the frequency of dysfunction of transplanted
kidneys immediately after implantation. This “delayed graft function” (DGF),
defined as the need for dialysis within the first week post-transplantation1, is estimated to complicate
21-36% of all deceased donor kidney transplants 2, and its incidence
continues to rise. Importantly, DGF is not just a short term
problem, but is also associated with a higher risk of later graft failure 3. Moreover, even if graft
function persists, DGF is also associated with a higher rate of death 4.
Currently, no
clinical tools exist that accurately predict the time to, and degree of, kidney
function recovery following DGF. DGF thus leads to longer hospitalization
stays, patient anxiety, and more complex discharge planning and outpatient care.
In this abstract, we investigated: (1) whether intravoxel incoherent motion (IVIM)-derived
flow (f)-fraction is different in kidney allografts exhibiting DGF compared to
those that do not develop DGF, and (2)
whether f fraction correlates with time to recovery as measured by the time to
come off of dialysis post-transplantation and with resumption of normal kidney
function at 3 months post-transplant as measured with estimated glomerular filtration rate (eGFR)Methods
This
prospective study was approved by our institutional review board. Twenty (20) kidney transplant inpatients,
10 with DGF and 10 with initial graft function, at our hospital consented to be
part of this study. The clinical data included a record of dialysis, blood tests
during hospital stay and at 3-months post-transplant. IVIM-DWI was performed
within 10 days post-transplant, on a 3.0 T MRI (Siemens Skyra) scanner with the
following parameters: single shot EPI readout, TR / TE = 3500 / 68 ms, 5 x 5 mm
thick slices for each of seven b values: 0, 50, 100, 300, 600, 800 and 1000 s/mm2,
NEX=2 for images with b >100 s/mm2, acquisition matrix=126x106
reconstructed to 256x256. The images were post-processed using a bi-exponential
IVIM equation5 in Matlab6 to calculate f-fraction on a
pixel-by-pixel bases. The regions of interest (ROIs) were drawn to represent
cortex, medulla and the entire renal parenchyma on 3-5 slices. The average of
all pixels in the ROIs was calculated to obtain cortical, medullar and
parenchymal values for f-fraction. The person processing the images was blind
to the DGF status and clinical data of patients. eGFR was calculated from serum
creatinine values using the Modification of Diet in Renal Disease formula7 3-months post-transplant, a time
when most transplant kidneys will have reached their maximum recovered function.
Time to recovery was defined as the number of days post-transplant until the
last dialysis session was needed. Student’s t-test was used to compare the
parameters between the two groups. Spearman’s correlation analysis was
performed to assess if f-fraction correlated with time to recovery and resumption
of normal kidney function at 3 months post-transplant.Results
We found significantly lower f-fraction in the
DGF group compared to patients that do not develop DGF for f-fraction measured
in both the cortex and medulla (Figure 1). We also found a significant negative
correlation between f-fraction and time to recovery (Figure 2) in the cortex, the
medulla and entire renal parenchyma with Spearman’s correlation coefficients of
-0.69 (p=0.02), -0.69 (p=0.02) and -0.74 (p=0.01) respectively. Finally, we
found a positive trend between f-fraction and eGFR at 3 months post-Transplant
in the cortex, the medulla and entire renal parenchyma (Figure 3). Discussion and Conclusion
While
other reports, using multiple imaging modalities including DWI, have
demonstrated lower perfusion in transplant kidneys with DGF8,9, our results are the
first to also show that MRI-derived f-fraction correlates with time to recovery
post -DGF. In this small pilot study, we also demonstrate a positive trend
between f-fraction and kidney function (as measured by eGFR) at 3 months
post-transplant. Our findings suggest that IVIM-DWI could be used to predict
time to recovery and thus aid in planning of care post-transplant.Acknowledgements
The authors wish to thank the research MRI technicians at our hospital, Cindy Hamid and Anthony Sheen, for their help in performing the imaging.
References
1. Perico,
N., Cattaneo, D., Sayegh, M.H. & Remuzzi, G. Delayed graft function in
kidney transplantation. Lancet 364, 1814-1827 (2004).
2. Bronzatto, E.J., da Silva Quadros,
K.R., Santos, R.L., Alves-Filho, G. & Mazzali, M. Delayed graft function in
renal transplant recipients: risk factors and impact on 1-year graft function:
a single center analysis. Transplant Proc
41, 849-851 (2009).
3. Giral-Classe, M., et al. Delayed graft function of more than six days strongly
decreases long-term survival of transplanted kidneys. Kidney Int 54, 972-978
(1998).
4. Tapiawala, S.N., et al. Delayed graft function and the risk for death with a
functioning graft. Journal of the
American Society of Nephrology : JASN 21,
153-161 (2010).
5. Le Bihan, D., et al. Separation of diffusion and perfusion in intravoxel
incoherent motion MR imaging. Radiology
168, 497-505 (1988).
6. The MathWorks Inc. (2014): MATLAB. (Natick, Massachusetts.).
7. Levey, A.S., et al. A more accurate method to estimate glomerular filtration
rate from serum creatinine: a new prediction equation. Modification of Diet in
Renal Disease Study Group. Ann Intern Med
130, 461-470 (1999).
8. Ren, T., et al. Evaluation of renal allografts function early after
transplantation using intravoxel incoherent motion and arterial spin labeling
MRI. Magn Reson Imaging 34, 908-914 (2016).
9. Hueper, K., et al. Diffusion-Weighted imaging and diffusion tensor imaging
detect delayed graft function and correlate with allograft fibrosis in patients
early after kidney transplantation. J
Magn Reson Imaging 44, 112-121
(2016).