Two kidney-transplant women with therapy-resistant hypertension: diagnostic error of a renal artery stenosis

Gaëtan Clerbaux1,, Pierre Goffette2, Yves Pirson1 and Eric Goffin1

1 Department of Nephrology and 2 Department of Radiology, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium

Keywords: angiography; colour Doppler ultrasound; gadolinium; magnetic resonance angiography; transplant renal artery stenosis

Cases

Patient 1
This was a 57-year-old woman with end-stage renal disease (ESRD) due to chronic pyelonephritis who had received a cadaver kidney graft in July 1980 after 42 months of haemodialysis. Maintenance immunosuppression included azathioprine and prednisolone. Hypertension appeared a few months after kidney transplantation (KT) and was treated by methyldopa 250 mg three times a day. A systolo-diastolic murmur was noticed 6 months after KT. A first graft arteriography was performed in 1982. It revealed parietal irregularities with a <20% stenosis involving the first 2 cm of the transplant renal artery stenosis (RAS). In 2000, hypertension became resistant to a treatment combining isradipine and atenolol. Cockroft creatinine clearance and 24 h proteinuria were 72 ml/min and 150 mg, respectively.

A colour Doppler ultrasound (CDU) using a HDI 3000 machine with a 3.5 or 5 MHz sectorial transducer was performed. Peak systolic velocity (PSV) was measured at 3.36 m/s in the ostial part of the transplant renal artery, raising the suspicion of the existence of transplant RAS, since truncal angle-corrected PSV above 2 m/s is a generally accepted criterion for this diagnosis [13]. A magnetic resonance angiography (MRA) was also performed, using a breath-hold gadolinium (GD)-enhanced fast 3D gradient echo sequence with multiplanar and maximum intensity projection reconstructions (3D-GD-MRA) (1.5 Tesla Philips Gyroscan magnet). An 80% post-ostial stenosis of the transplant renal artery was demonstrated (Figure 1AGo).



View larger version (89K):
[in this window]
[in a new window]
 
Fig. 1.  (A) 3D-GD-MRA showing short, circular juxta-ostial stricture (arrow) superior to 80% in diameter. (B) IADSA failing to show significant renal artery stenosis. A slight irregularity (arrow) is observed on the upper edge of the proximal part of the allograft artery. The surgical metallic clips located very distally to the suspected stenotic area cannot be responsible for the false-positive on MRA.

 
Intra-arterial digital subtraction angiography (IADSA) was then repeated. Surprisingly, the image was unchanged as compared to the examination performed 18 years earlier, showing a <20% narrowing on the upper edge of the transplant renal artery. Moreover, pressure measurement between iliac artery and transplant renal artery revealed no gradient. Notably, metal clips were present at some distance from the transplant artery (Figure 1BGo).

Patient 2
A 49-year-old woman with ESRD due to haemolytic uraemic syndrome had received a cadaver kidney in September 1991 after 14 months of haemodialysis. Immunosuppression included cyclosporin, azathioprine and prednisolone. Hypertension appeared immediately after KT. In 2000, hypertension became resistant to a combination of bisoprolol, amlodipine, moxonidine, frusemide and quinapril. At that time, Cockroft creatinine clearance was 68 ml/min. A transplant RAS was suspected despite the absence of murmur. CDU was normal. MRA then was performed. Two graft arteries were shown on the 3D GD-enhanced MRA: the superior artery, rapidly dividing into segmentary branches appeared normal, whereas in the inferior artery a >50% stenosis was demonstrated at the intersection between the vertical and the horizontal parts (Figure 2AGo). However, conventional arteriography failed to show RAS. Three metal clips were noted in the soft tissues adjacent to the inferior artery (Figure 2BGo).



View larger version (67K):
[in this window]
[in a new window]
 
Fig. 2.  (A) 3D-GD-MRA, showing a tight concentric 8 mm-length stenosis on the truncal inferior transplant artery (arrow). The stricture is located at the intersection between the vertical and horizontal segments of the artery. (B) IADSA in right posterior oblique projection showing no stenosis of the truncal inferior transplant artery. Metallic clips located near the arterial curvature (arrow) are probably responsible for the false-positive MRA result (see text).

 

Discussion

In these two patients with a clinical suspicion of transplant RAS, GD-enhanced MRA led to an erroneous diagnosis of transplant RAS. This diagnosis was also strongly suggested by CDU in the first case but not in the second one. These cases illustrate the pitfalls in the interpretation of transplant artery MRA images and provide the opportunity to discuss the accuracy and place of CDU and GD-enhanced MRA in the diagnosis of transplant RAS.

RAS is a potentially curable cause of arterial hypertension or allograft dysfunction after KT. The reported incidence varies from 1 to 12% [4,5]. The diagnosis of transplant RAS should be suspected whenever arterial hypertension develops or worsens rapidly after KT, especially when a bruit is audible over the graft or when administration of an ACE inhibitor induces a decline in graft function. Conventional arteriography remains the gold standard for the diagnosis of transplant RAS. Therefore, there has been a search for a suitable, non-invasive alternative technique.

CDU is largely used as a first-step diagnostic tool in the diagnosis of transplant RAS. The measurement of PSV is regarded as the best discriminating parameter for the detection of transplant RAS [2]. PSV measures the maximum velocity recorded during the systolic phase of arterial flow.

With a transplant renal artery, PSV has to be corrected according to the angle between the probe and graft arterial axis; this is generally made by inbuilt software. There are some controversies on the diagnostic cut-off value of PSV. Using a value of >1 m/s as positive, Erley et al. [1] reported a sensitivity of 100% and specificity of 75%, while Baxter et al. [2] obtained a sensitivity of 100% and a specificity of 95% with a higher cut-off >2.5 m/s. Tortuosity, arteriovenous fistula, and/or angulation between renal artery and recipient iliac artery may account for high PSV in the absence of stenosis, and hence a false-positive test [3]. Thus, MRA has appeared as a complementary test to CDU and an interesting alternative to angiography.

More recently, MRA has emerged as another valuable non-invasive alternative including a three-dimensional representation of the vascular anatomy without the disadvantages of arteriography. The limitations of MRA include the difficulties of exploring accessory arteries, distal artery segments, and stented arteries [6], arteries adjacent to metallic structures and en-block renal grafts [68]. The 3D phase-contrast MRA technique was the first technique used to study renal graft arteries [9]. Its limitations were essentially associated with blood-flow artefacts that mimic stenosis [3]. The use of gadolinium injection, breath-hold sections, and ultra-rapid image acquisition techniques, as well as the development of new image reconstruction processes were all advances allowing improvement of the imaging quality while diminishing artefacts associated with breathing movements or blood flow [8,10]. Very few studies have been conducted on the reliability of 3D-GD-MRA in comparison to IADSA for the diagnosis of transplant RAS [7,8,1114]. By pooling the cases of the four available prospective series comparing 3D-GD-MRA and IADSA for clinically suspected transplant RAS (studies comprising 7, 6, 17 and 41 patients, respectively), we calculated that 3D-GD-MRA has a 96% sensitivity, a 96% specificity and a 98% negative predictive value [8,1214].

How to explain these two false-positive results of MRA?

In the first patient, a stenosis <20% is seen on the upper edge of the transplant renal artery after the ostium. There is, however, no pressure gradient between the iliac artery and the transplant renal artery, which confirms that there is no haemodynamically significant stenosis. Metal clips are too distant to explain an artefactual image of stenosis. The most likely explanation for the false-positive result with both CDU and MRA is an accelerated blood stream in the ostial area, accounting for high PSV (even when corrected for angulation) at CDU, and a loss of the magnetic signal at MRA mimicking high-grade stenosis (Figure 1Go).

This is not true for the second patient in whom CDU did not detect any flow acceleration whereas MRA was falsely positive. The metal clips in the close vicinity of the renal artery are probably responsible for the pseudostenosis image. As reported by others [15], metal clips can scatter the magnetic signal and thus mimic stenosis (Figure 2Go).

These two cases illustrate the pitfalls of GD-enhanced MRA in the diagnosis of transplant RAS. Based on the high sensitivity and availability of CDU, this technique remains the best screening tool. If CDU is doubtful or positive, is it useful to perform MRA?

Available studies report that specificity for MRA is only marginally better than that for CDU in the detection of transplant RAS. Furthermore, there is no study directly comparing CDU and GD-enhanced MRA in this setting.

Only a prospective study showing a significant gain in specificity provided by GD-enhanced MRA on CDU for transplant RAS would establish this technique as a valuable second step test in this indication.

Teaching points

  1. GD-enhanced MRA may give a false diagnosis of transplant RAS when there are blood-flow turbulences, tortuous vessels or ferromagnetic clips in the close vicinity of the graft artery.
  2. CDU remains the best screening test for clinically suspected transplant RAS.

Acknowledgments

We thank C. Van Ruyssevelt, MD, for logistic help and for advice.

Notes

Correspondence and offprint requests to: G. Clerbaux, MD, Department of Nephrology, Université Catholique de Louvain, Av. Hippocrate 10, 1200 Brussels, Belgium. Email: gaso.clerbaux{at}belgacom.net Back

References

  1. Erley CM, Duda SH, Wakat J-P et al. Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients—a prospective analysis. Transplantation 1992; 54:863–867[ISI][Medline]
  2. Baxter GM, Ireland H, Moss JG et al. Colour Doppler ultrasound in renal transplant artery stenosis: which Doppler index? Clin Radiol 1995; 50:618–622[ISI][Medline]
  3. Loubeyre P, Cahen R, Grozel F et al. Transplant renal artery stenosis: evaluation of diagnosis with magnetic resonance angiography compared with color duplex sonography and arteriography. Transplantation 1996; 62:446–450[CrossRef][ISI][Medline]
  4. Margules RM, Belzer FO, Kountz SL. Surgical correction of renovascular hypertension following renal allotransplantation. Arch Surg 1973; 106:13–16[CrossRef][ISI][Medline]
  5. Fervenza FC, Lafayette RA, Alfrey EJ, Petersen J. Renal artery stenosis in kidney transplants. Am J Kidney Dis 1998; 31:142–148[ISI][Medline]
  6. Laissy JP, Grand C, Matos C, Struyven J, Berger J-F, Schouman-Claeys E. Magnetic resonance angiography of intravascular endoprotheses: investigation of three devices. Cardiovasc Intervent Radiol 1995; 18:360–366[CrossRef][ISI][Medline]
  7. Ferreiros J, Mendez R, Jorquera M et al. Using gadolinium-enhanced three-dimensional MR angiography to assess arterial inflow stenosis after kidney transplantation. AJR 1999; 172:751–757[Abstract]
  8. Thornton MJ, Thornton F, O'Callaghan J et al. Evaluation of dynamic gadolinium-enhanced breath-hold MR angiography in the diagnosis of renal artery stenosis. AJR 1999; 173:1279–1283[Abstract]
  9. Gedroyc WMW, Negus R, Al-Kutoubi A, Palmer A, Taube D, Hulme B. Magnetic resonance angiography of renal transplants. Lancet 1992; 339:789–791[CrossRef][ISI][Medline]
  10. Davis CP, Hany TF, Wildermuth S, Schmidt M, Debatin JF. Postprocessing techniques for gadolinium-enhanced three-dimensional MR angiography. Radiographics 1997; 17:1061–1077[Abstract]
  11. Johnson DB, Lerner CA, Prince MR et al. Gadolinium-enhanced magnetic resonance angiography of renal transplants. Magn Reson Imaging 1997; 15:13–20[CrossRef][ISI][Medline]
  12. Chan YL, Leung CB, Yu SC, Yeung DK, Li PK. Comparison of non-breath-hold high resolution gadolinium-enhanced MRA with digital subtraction angiography in the evaluation on allograft renal artery stenosis. Clin Radiol 2001; 56:127–132[CrossRef][ISI][Medline]
  13. Luk SH, Chan JHM, Kwan TH, Tsui WC, Cheung YK, Yuen MK. Breath-hold 3D gadolinium-enhanced subtraction MRA in the detection of transplant renal artery stenosis. Clin Radiol 1999; 54:651–654[CrossRef][ISI][Medline]
  14. Huber A, Heuck A, Schleider J et al. Contrast-enhanced MR angiography in patients after kidney transplantation. Eur Radiol 2001; 11:2488–2495[CrossRef][ISI][Medline]
  15. McCarty M, Gedroyc WMW. Surgical clip artefact mimicking arterial stenosis: a problem with magnetic resonance angiography. Clin Radiol 1993; 48:232–235[ISI][Medline]




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Clerbaux, G.
Articles by Goffin, E.
PubMed
PubMed Citation
Articles by Clerbaux, G.
Articles by Goffin, E.