An US Mathematical Model in Predicting Renal Transplant Rejection

Kidney Transplantation Clinical Trial

Official title:

An US Mathematical Model in Predicting Renal Transplant Rejection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03045731
• Other study ID #: FDU-ZS-US-001
• Status: Recruiting
• Start date: January 2016
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2021
• Source: Shanghai Zhongshan Hospital
• Contact: Wanyuan He, MD, PhD
• Phone: 0086-0-13916237059
• Email: he.wanyuan[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to establish an ultrasound mathematical model using acoustic radiation force impulse (ARFI) and contrast-enhanced ultrasonography (CEUS) for diagnosing the status of renal allografts.

Description:

• There are various reasons for renal failure after kidney transplantation, such as delayed graft function (DGF) and acute rejection, acute renal tubular necrosis, chronic rejection and toxicity of immunosuppressive drugs. The diagnosis of renal allografts dysfunction can determine the direction of therapy. Currently, the gold standard of diagnosing renal allografts status is biopsies. However, biopsy has several drawbacks. It is invasive and can cause serious complications. These drawbacks urge investigators to find an accurate and non-invasive method to detect renal function. Elastography is a new way to detect tissue elasticity and can evaluate the tissue elasticity quantitatively. This method is proved to be of great value in diagnosing hepatic fibrosis (≥stage 2). Even though the investigation about this method is relatively less in allograft, the recent research shows that tissue elasticity does have relationship with pathological changes of transplanted kidney. Another new method, contrast-enhanced ultrasonography (CEUS), can indicate the blood perfusion of organ microcirculation. The accuracy rate of diagnosis of acute rejection(AR) can be 80% by using this method. It also has advantage in diagnosing acute tubular necrosis(ATN) and CAN. In addition, it produces no radioactive contamination as well as renal toxicity. This method has no serious side effect so it will not influence the normal function of patients' bodies and it can be performed for many times easily.

• The research information about Elastography and CEUS is still at the primary stage. The value of one single parameter in diagnosing renal failure is restricted. So the establishment of an integrated mathematical model got by combining traditional methods (such as ultrasonography and color Doppler flow imaging) with these two new methods (Elastography and CEUS) is required to provide a systematical, multi-parameter diagnosis of allograft rejection.

• What investigators have investigated before shows that different pathological changes of renal allograft can lead to regular changes in shear wave speed (SWS) and hemodynamics. By in-depth study of these changes, investigators aim to develop a mathematical model to diagnose the status of renal allograft.

• To achieve this goal, the following things will be done:

1. Investigators plan to enroll 100 renal transplant recipients .

2. Before biopsy, these things will be done : a. Normal ultrasonography will be performed on transplanted kidney to measure their size, cortical thickness and vertebral body. b. Color Doppler flow imaging will be performed to see blood supply of transplanted kidney and resistive index (RI) of renal seg-mental will be measured. c. Contrast enhanced ultrasonography examination will be performed using Philips iU-22 ultrasonic apparatus with a C5-1 probe (Philips,Amsterdam, theNetherlands)with an intravenous bolus injection of 0.6-1.0mL SonoVue (Bracco, Milan, Italy). Area under curve (AUC), peak intensity (PI), time-to-peak (TTP), rise time (RT) and mean transit time (MTT) will be measured on central cortex of transplanted kidney. d. Elastography will be performed with a Siemens Acuson S2000 ultrasound machine using a 1- to 4-MHzcurved array multifrequency transducer (4 C1) (Siemens,Munich, Germany).

Shear wave velocity (SWV) will be measured.

3. Statistical analysis will be performed on the 10 quantitative parameters we got before (AUC, PI.etc ). The correlation between these parameters and condition of transplanted kidney (got by renal biopsy) will be evaluated. Then screening indexes will be optimized. On this basis, a mathematical model in diagnosing transplanted kidney is supposed to be built up.

4. A ROC curve will be used to analyze the accuracy, sensitivity and specificity of this mathematical model.

5. Then the US model will be verified in another 80 renal transplant recipients. Investigators will compare the diagnosis efficacy of transplanted kidney status got by the US model with the kidney biopsy result. Any parameter can be adjusted according to the verification results.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 31, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults (over 18) who have undergone renal transplant at Zhongshan Hospital

• Understanding the research situation

• Signing informed consent voluntarily

Exclusion Criteria:

• Urinary obstruction

• Perirenal hematioma

• Infection in operative sites

Related Conditions & MeSH terms

• Kidney Transplantation

Locations

Country	Name	City	State
China	Zhongshan Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Arndt R, Schmidt S, Loddenkemper C, Grünbaum M, Zidek W, van der Giet M, Westhoff TH. Noninvasive evaluation of renal allograft fibrosis by transient elastography--a pilot study. Transpl Int. 2010 Sep;23(9):871-7. doi: 10.1111/j.1432-2277.2010.01057.x. Epub 2010 Feb 15. — View Citation

Benozzi L, Cappelli G, Granito M, Davoli D, Favali D, Montecchi MG, Grossi A, Torricelli P, Albertazzi A. Contrast-enhanced sonography in early kidney graft dysfunction. Transplant Proc. 2009 May;41(4):1214-5. doi: 10.1016/j.transproceed.2009.03.029. — View Citation

Fierbinteanu-Braticevici C, Andronescu D, Usvat R, Cretoiu D, Baicus C, Marinoschi G. Acoustic radiation force imaging sonoelastography for noninvasive staging of liver fibrosis. World J Gastroenterol. 2009 Nov 28;15(44):5525-32. — View Citation

Fischer T, Filimonow S, Rudolph J, Morgera S, Budde K, Slowinski T, Ebeling V, Taymoorian K, Giessing M, Thomas A. Arrival time parametric imaging: a new ultrasound technique for quantifying perfusion of kidney grafts. Ultraschall Med. 2008 Aug;29(4):418-23. Epub 2007 Feb 21. — View Citation

Grzelak P, Szymczyk K, Strzelczyk J, Kurnatowska I, Sapieha M, Nowicki M, Stefanczyk L. Perfusion of kidney graft pyramids and cortex in contrast-enhanced ultrasonography in the determination of the cause of delayed graft function. Ann Transplant. 2011 Jan-Mar;16(1):48-53. — View Citation

Hanamura K, Tojo A, Kinugasa S, Asaba K, Fujita T. The resistive index is a marker of renal function, pathology, prognosis, and responsiveness to steroid therapy in chronic kidney disease patients. Int J Nephrol. 2012;2012:139565. doi: 10.1155/2012/139565. Epub 2012 Dec 16. — View Citation

Scholbach T, Girelli E, Scholbach J. Dynamic tissue perfusion measurement: a novel tool in follow-up of renal transplants. Transplantation. 2005 Jun 27;79(12):1711-6. — View Citation

Schwenger V, Keller T, Hofmann N, Hoffmann O, Sommerer C, Nahm AM, Morath C, Zeier M, Krumme B. Color Doppler indices of renal allografts depend on vascular stiffness of the transplant recipients. Am J Transplant. 2006 Nov;6(11):2721-4. — View Citation

Schwenger V, Korosoglou G, Hinkel UP, Morath C, Hansen A, Sommerer C, Dikow R, Hardt S, Schmidt J, Kücherer H, Katus HA, Zeier M. Real-time contrast-enhanced sonography of renal transplant recipients predicts chronic allograft nephropathy. Am J Transplant. 2006 Mar;6(3):609-15. — View Citation

Schwenger V, Zeier M. Contrast-enhanced sonography as early diagnostic tool of chronic allograft nephropathy. Nephrol Dial Transplant. 2006 Oct;21(10):2694-6. Epub 2006 Jul 28. — View Citation

Stock KF, Klein BS, Vo Cong MT, Sarkar O, Römisch M, Regenbogen C, Büttner M, Schuster T, Matevossian E, Amann K, Clevert DA, Heemann U, Küchle C. ARFI-based tissue elasticity quantification in comparison to histology for the diagnosis of renal transplant fibrosis. Clin Hemorheol Microcirc. 2010;46(2-3):139-48. doi: 10.3233/CH-2010-1340. — View Citation

Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB. Clinical role of the renal transplant biopsy. Nat Rev Nephrol. 2012 Jan 10;8(2):110-21. doi: 10.1038/nrneph.2011.213. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The diagnosis of the status of kidney allografts from biopsy results		3 years