1. Doppler in transplant renal artery stenosis
Dr. Muhammad Bin Zulfiqar
PGR FCPS SHL

2. Christian Doppler (1803 – 1853) Famous for what is called now “Doppler effect”
1841: Professor of mathematics & physics Prague polytechnic 1842: Published his famous book “ On the colored light of the binary stars & some other stars of the heavens ” 1850: Head of institute of experimental physics Vienna University

3. First reported case of transplant renal artery stenosis
Case records of the Massachusetts General Hospital
Case 43 – N Engl J Med 1966;275:721–729.

4. Transplant renal artery stenosis
Potentially curable cause of refractory HTN
75% of all post-transplant vascular complications
Incidence varies upon definition & diagnostic techniques
12% Routine Doppler in asymptomatic recipients
2% Doppler to confirm clinical suspicion
Timing Can present at any time
Usually 3 mo – 2 yr after transplantation
Bruno S et al. J Am Soc Nephrol 2004 ; 15 : 134 – 141.

5. Clinical presentation of TRAS
Severe HTN Difficult to treat
Vascular murmur Not specific
Graft dysfunction Specially after ACEi
Erythrocytosis Found by some authors
Asymptomatic Doppler done as routine screening
Some patients may even have paradoxically normal or low BP, rapid deterioration of renal function, or even acute renal failure because of overzealous diuretic therapy or addition of either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ATA II) to the antihypertensive treatment.
Reference:
Curtis JJ, Luke RG, Whelchel JD, Diethelm AG, Jones P, Dustan HP: Inhibition of angiotensin-converting enzyme in renal-transplant
recipients with hypertension. N Engl J Med 308: 377–381,1983.
Bruit:
The presence of a bruit is not specific because it may be caused by physiologic vascular turbulence in the iliac or femoral arteries possibly sustained by increased blood perfusion close to the anastomosis. Bruits from proximal iliac vessel stenoses or biopsy-induced parenchymal arteriovenous fistulas can also confound the clinical picture. However, significant stenosis can occur in the absence of an audible bruit.
ACEI: Angiotensin-Converting Enzyme Inhibitors
Buturovic´-Ponikvar J. Nephrol Dial Transplant 2003 ; 18 : v74 – v77.

6. Causes of post-transplant HTN 65 - 90% of patients
Calcineurin inhibitors Cyclosporine - Tacrolimus
Corticosteroids Largely depends on dosage
Transplant RAS 2 – 10 %
Post-biopsy AVF Rare cause
Chronic graft rejection
Native kidneys & pre-transplant HTN
Potential mechanisms responsible for renal vasoconstriction caused by cyclosporine
Increased production of endothelin-1
Activation of renin–angiotensin system
Reduced production of nitric oxide
Increased production of TGFβ1
Prostaglandin imbalance
Increased sympathetic activity
Ponticelli C. Medical complications of kidney transplantation.
Informa Healthcare, London, UK, 2007.

7. Locations for graft artery stenosis Three 3 main locations
At the site of anastomosis
Probably a consequence of surgical technique
Distal from the site of anastomosis
Cause is still ill-defined
At the distal arterial branches
Multiple stenoses – Expression of chronic rejection

8. Diagnostic procedures of TRAS
Performance
Plasma renin activity
Less informative than unilateral RAS of native kidneys
Serum potassium
Normal or  in patients on Cyc, tacrolimus or RI
Renal scintigraphy
Good sensitivity 75% – Poor specificity 67%
CDUS
Good sensitivity (87-94%) – Good specificity (86-100%)
Spiral or MSCT
Contrast medium – High cost – Limited accessibility
Angiography:
Need for relatively large amounts of radio-contrast medium that may precipitate acute renal failure particularly in patients with renal dysfunction. Thromboembolism is an even more severe complication that can cause irreversible graft function loss, and is reported in up to 9% of cases. Groin hematomas, pseudoaneurysms, and traumatic arteriovenous fistulas are other possible complications that, all together, occur in less than 10% of cases.
Because of the substantial risks and the relatively high costs, renal angiography cannot be considered a screening procedure, but it is
electively indicated when a stenosis is suspected on the basis of non-invasive tests. An additional, practical feature of the procedure
is that, as soon as the diagnosis is established, the stenosis can be immediately corrected by transluminal angioplasty
followed by the deployment of a stent. The effectiveness of the intervention can then be immediately verified by a
second angiographic evaluation.
MRI
Gadolinium – High cost – More limited accessibility
Arteriography
Gold standard test – Invasive – Contrast medium
Bruno S et al. J Am Soc Nephrol 2004 ;15 : 134 – 141.

9. Sonography of renal allograft Routine exams
1 – 2 days after transplantation
Important standard to be compared with later changes
1 – 2 weeks after transplantation
3 months after transplantation

10. CDUS in transplant RAS Best screening tool
Main advantages Non-invasive
High sensitivity & specificity
Performed at bedside (ICU)
Follow-up
Main disadvantages Operator dependency
Time-consuming
Operator should consult the surgery report
Multiple arteries – Anastomotic problems

11. End-to-end arterial anastomosis
Artery
End-to-end anastomosis
to internal iliac artery
Vein
End-to-side anastomosis
to external iliac vein
Classical kidney transplantation surgery was described using end-to-end anastomosis to the internal iliac artery & end-to-side anastomosis to the external iliac vein. This technique is performed in many transplant centers until today.
However, some authors described the possibility of the occurrence of ED and renal artery stenosis with this type of anastomosis.
Classical kidney transplantation surgery
Possibility of erectile dysfunction & TRAS

12. End-to-side arterial anastomosis
Artery
End-to-side anastomosis
to external iliac artery
Vein
to external iliac vein
Possibilty of early obstruction, late stenosis
& steal phenomenon

13. Normal renal transplant End-to-side arterial anastomosis
Gaoa J et al. Clinical Imaging 2009 ; 33 : 116 – 122.

14. CDUS – 1st approach Extrarenal Doppler
Scanning of RA from anastomosis to hilus
Pic Systolic Velocity around anastomosis
Diagnosis severity of stenosis
Diagnosis non-significant relative stenosis
Possibility of localization
High operator dependency

15. Normal Pic Systolic Velocity Near the anastomosis
PSV = 105 cm / sec

16. CDUS – 2nd approach Intrarenal Doppler
Interlobar arteries (upper, middle, & lower poles)
Resistance index & Acceleration Time
Can be amplified by use of captopril
Not so operator dependent
Only diagnose high grade stenosis (> 80 %)
No possibility to localize stenosis along TRA

17. Resistance index or Pourcelot index
RI: S – ED / S
Normal: 50 – 70%
Abnormal: > 80 %

18. Normal resistance index
RI: 62%

19. RI & renal allograft survival 601 patients – Follow-up  3 years
Hannover -Germany
RI > 0.8 measured 3 months posttransplantation
has poor subsequent graft function & death
Radermacher J et al. N Engl J Med 2003 ; 349 : 115 – 24.

20. Accleration time AT Length of time in seconds from
onset of systole to peak systole
Normal value: < 0.07 second

21. Normal accleration time
AT: 0.05 sec

22. CDUS Combined approach
Combine both extra- & intrarenal Doppler examination as is suggested for native renal artery stenosis

23. Doppler of transplant RAS
Extra-renal Doppler
PSV > 2 m/sec *
Velocity gradient > 2
Distal spectral broadening
* Generally accepted criteria
Values differs from 1.5–3m/sec
Intra-renal Doppler
RI < 0.50
AT > 0.07 sec
AI < 3m/sec2
Only in severe stenosis
(> 80 % diameter reduction)
Clerbaux G et al. Nephrol Dial Transplant 2003 ; 18 : 1401 – 1404.

24. Severe transplant renal artery stenosis End-to-end-anastomosis
Stenotic anastomosis
PSV: 6.54 m/s
Proximal IIA
PSV: 0.78 m/s
Velocity ratio: 8

25. Severe transplant renal artery stenosis End-to-side-anastomosis
PSV: 3.74 m/s
Stenotic anastomosis
PSV: Proximal 1.29 m/s
Anastomosis 1.77 m/s
Distal 1.35 m/s
EIA
Velocity ratio: 2.3

26. PSV threshold for action
2.5 m/sec used by many centers
One report use the value of 3 m/sec*
Diagnosis of sub-clinical arterial stenosis may be
of no significance
No evidence these lesions progress to clinical significance
* Patel U. Clinical Radiology 2003 ; 58 : 772 – 777.

27. Spectral broadening Post-stenotic zone
Proportional to severity of stenosis
Cannot be precisely quantified: evaluated visually
Fill-in of spectral window > 50%  reduction
Severely disturbed flow > 70%  reduction
High amplitude
Low frequency Doppler signal
Flow reversal
Poor definition of spectral border

28. Spectral broadening
PSV = 5 m/sec

29. Pseudospectral broadening
High gain setting
Vessel wall motion
Site of branching
Abrupt change in vessel diameter
Increase velocity: Athletes - high cardiac output - AVF
Tortuous vessels
Aneurysm, dissection, & FMD

30. ‘Tardus-Parvus’ pattern Intrarenal Doppler
Decrease of PSV
Loss of early systolic peak
Prolongation of AT
Only severe stenosis (> 80%)

31. Doppler of transplant RAS
Extrarenal Doppler Intrarenal Doppler
PSV > 2.5 m/sec * RI < 0.50
Velocity gradient > 2 AT > 0.07 sec
Marked distal spectral broadening AI < 3m/sec2
* Generally accepted criterion for diagnosis
Cut-off value differs from series to series (1.5 – 3.0 m/sec)
Nephrol Dial Transplant 2003 ; 18 : 1401 – 1404.

32. Doppler parameters between EE & ES TRAS Retrospective – 38 patients – severe TRAS
End-to-End
(n = 19)
End-to-Side
P value
PSV at stenosis
PSV proximal to stenosis
PSV ratio
4.62 ± 0.64
0.66 ± 0.19
7.61 ± 2.52
3.65 ± 1.33
1.18 ± 0.41
3.25 ± 1.37
< 0.01
< 0.001
AT in intrarenal artery
0.11 ± 0.04
0.12 ± 0.05
> 0.05
Different criteria need to be established depending
on type of arterial anastomosis in severe TRAS
Gaoa J et al. Clinical Imaging 2009 ; 33 :116 – 122.

33. Special forms of TRAS Intimal dissection of TRA Kinking of TRA
Pseudo-TRAS

34. Intimal dissection of TRA Rarely documented in literature
Timing Within a week after transplantation
Causes Artery traction: harvesting, cannulation, clamp
Symptom Sudden onset of oligoanuria
CDUS Severe perfusion failure - Flap not visualized
Dx Angiography
DD Acute rejection: rare in first few days
ATN - Cyclosporine toxicity - RV thrombosis
Prognosis If not diagnosed: RA thrombosis - Graft loss
Takahashi M et al. AJR 2003;180:759 – 763.

35. Intimal dissection of TRA
Severe TRA stricture
Occlusion of IIA
Atherosclerosis of CIA
Angioplasty
1st stent placement Remaining intimal flap
2nd stent placement
No residual stenosis
Takahashi M et al. AJR 2003;180:759 – 763.

36. Kinking of transplant renal artery Artery longer than vein
Simulates hemodynamic & functional changes of TRAS
Occasionally occurs when right kidney transplanted
RRA longer than RRV
Kinking of artery when anastomosis completed
Subsequent surgical revision if not recognized at surgery
Gray DW. Transplant Rev1994 ; 8 : 15 – 21.

37. Kinking of renal artery False-positive result of CDUS
PSV 286 cm/s
Kink at anastomosis between TRA & IIA
Patel U et al. Clin Radiol 2003 ; 58 : 772 – 777.

38. Pseudo-TRAS Should always be taken into consideration
Iliac artery disease proximal to the anastomosis
Elderly patients or diabetic patients
Low flow to transplanted kidney
Signs & symptoms resembling those of TRAS
Claudication or other signs of limbs hypoperfusion
Treated by angioplasty or surgical revascularization
Aslam S et al. Transplantation 2001 ; 71 : 814 – 817.

39. Conclusion CDUS & TRAS
CDUS is best screening tool for diagnosis of TRAS
Need more precision in PSV for diagnosis of TRAS
Need different criteria for diagnosis in EE or ES
CDUS cannot diagnose intimal dissection
CDUS cannot diagnose kinking
Angiography remains the gold standard (MSCT?)

40. Thank You