Objectives: Transplant renal artery stenosis is a fre­quently recognized complication of kidney transplant procedures. A single-center retrospective study was conducted to examine the use of 3-dimensional computed tomography reconstruction in diagnosing transplant artery stenosis.

Materials and Methods: During 2013 at our center, 86 patients underwent kidney transplant. All patients underwent ultrasonographic analyses. Patients with clinically suspected transplant renal artery stenosis were examined by 3-dimensional computed tomog­raphy reconstruction and were treated with endo­vascular approaches or medically managed.

Results: Ten patients were diagnosed with transplant renal artery stenosis by 3-dimensional computed tomography reconstruction. No evidence of contrast-induced nephrotoxicity was observed. Nine of the 10 patients underwent percutaneous transluminal angio­plasty, whereas the remaining patient was treated conservatively. Procedural success rate was 100%. Patients were followed for a mean period of 20 ± 3 months. Blood pressure improved from a mean of 163/90 to 132/73 mm Hg at the end of the follow-up period. In the 9 patients who underwent angioplasty, serum creatinine improved from 198 ± 24 to 134 ± 16 µmol/L at the end of the follow-up period. The cystatin C level in some patients declined after interventional therapy.

Conclusions: Three-dimensional computed tomography reconstruction is a safe choice for patients who present with increased serum creatinine levels and refractory hypertension. Percutaneous transluminal angioplasty is the preferred therapeutic technique for transplant renal artery stenosis.

Key words : Kidney transplantation, Percutaneous transluminal angioplasty, Stenting

Introduction

Transplant renal artery stenosis (TRAS) is a frequently recognized complication of kidney transplant procedures. It has an incidence of 1% to 23%.^1,2 It is a common reason for acute transplant renal dysfunction and refractory hypertension. Several causes can lead to TRAS, including trauma of the donor vessels during surgery, malpositioning of the kidney or local endothelial injury from the perfusion catheter tip, atherosclerosis, and/or immunologic factors; the usual site is anastomotic or perianastomotic.^3-6 Transcatheter therapy of TRAS with angioplasty or stenting has been shown to improve blood pressure control and renal function.⁷ However, accurate identification of patients with cor­rectable renovascular hypertension can be difficult.

The diagnosis of TRAS has been derived using a range of imaging modalities, including magnetic resonance angiography, digital subtraction angio­graphy, color Doppler flow imaging, and multislice spiral computed tomography (CT) angiography. Multislice spiral CT provides a tool for examination of the transplanted renal artery.^8,9 The multislice spiral CT scanning technique and postprocessing procedures help to improve the accuracy and sensitivity of the detection of renal artery lesions.¹⁰ However, CT angiography may require large amounts of iodinated contrast agent,¹¹ and the safety and diagnostic performance of this method should be further evaluated.

Percutaneous transluminal angioplasty (PTA) has been demonstrated to be successful in the treatment of TRAS in terms of short-term improvements of renal function.¹² However, data on the long-term effects of PTA on graft survival are scarce. The recurrence rate of TRAS after PTA is very high, and the subsequent management in this setting remains elusive, with some authors advocating intervention with PTA with endovascular stenting and others recommending a more conservative approach.¹³

In our center, 3-dimensional computed tomo­graphy (3DCT) reconstruction has been used for patients at high risk of TRAS. To examine the application value of 3DCT reconstruction in kidney transplant recipients, we retrospectively reviewed all cases suspicious of TRAS. Here, we report our experiences regarding treatment of TRAS and follow-up information on treated patients.

Materials and Methods

This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Shandong University 2nd Hospital. Written informed consent was obtained from all participants.

This is a single-center retrospective study that examined the use of 3DCT reconstruction in the diagnoses of TRAS in eligible kidney transplant recipients who were transplanted during 2013 and who had follow-up until March 2015. During the study period, 86 kidney transplants were performed at our center. Of these, 56 (65%) were from deceased donors and 30 (35%) were from living donors.

Ultrasonographic examination was routinely done for all patients. The ultrasonographic criterion used to diagnose TRAS was a peak systolic velocity of > 2 m/s at the stenotic site. Renal transplant recipients who presented with refractory hyper­tension and/or allograft dysfunction received 3DCT scans, including patients who were diagnosed as TRAS according to ultrasonographic criteria. Iodixanol was used in angiography. Computed tomography scans were performed after intravenous administration of iodixanol contrast medium at 1.3 mL/kg patient weight, with maximum of 100 mL.

Refractory hypertension was defined as arterial pressure > 140/90 mm Hg despite 2 or more antihypertensive drugs or hypertension requiring multiple drugs not controlled by pretransplant antihypertensive drug requirements.¹⁴ Allograft dysfunction was defined as a 25% rise of serum creatinine from baseline. A narrowing of > 50% of the luminal diameter of the artery was considered hemodynamically significant.¹⁵

Age, sex, serum creatinine level, and blood pressure were recorded for each patient; cystatin C levels were recorded for some patients. Maintenance immunosuppressant regimen included cyclosporine or tacrolimus, mycophenolate sodium, and cortico­steroids in all patients.

Data are presented as means ± standard deviation. Statistical analyses were performed with SPSS software (version 16; IBM Corp, Armonk, NY), using t test whenever appropriate. A P value < .05 was considered statistically significant.

Results

Ten kidney transplant recipients (6 male and 4 female patients) with features of renal artery stenosis were confirmed to have TRAS by 3DCT reconstruction. On the basis of the 86 kidney transplant procedures during 2013 at our center, the incidence of TRAS was estimated as 11.6% (10/86). However, stenosis was not detected by ultrasonographic examination in 4/10 patients. Creatinine levels after CT angiography were not significantly different from those shown before angiography. No evidence of contrast-induced nephrotoxicity related to 3DCT was observed.

Nine patients with TRAS underwent PTA, whereas the remaining patient was treated conser­vatively. The success rate of PTA was 100%, as shown by angiographic evidence of complete resolution of stenosis after PTA with or without stent deployment. In total, 11 PTA surgeries were performed. Nine patients underwent transluminal balloon dilation; 2 patients received stent placement during the first interventional surgery, and another 2 patients underwent endovascular intervention with stent placement during a second PTA procedure due to relapse of artery stenosis (Figure 1). A female patient (patient 8) had normal blood pressure and serum creatinine levels; therefore, no interventional procedures were performed to correct the stenosis.

All 9 patients showed improvements in symptoms after renal artery PTA (Table 1). At the time of TRAS diagnosis, systemic blood pressure was significantly increased from baseline, with mean systolic blood pressure increasing from 139 ± 13 to 163 ± 23 mm Hg (P < .05) and mean diastolic blood pressure increasing from 72 ± 9 to 90 ± 11 mmHg. At the most recent follow-up, systolic blood pressure decreased to 132 ± 12 and diastolic blood pressure to 73 ± 8 mm Hg (P < .05 vs peak value).

Creatinine levels postprocedure were drama­tically decreased versus that shown before the procedure. In the 9 patients, serum creatinine levels improved from 198 ± 24 to 134 ± 16 μmol/L at the end of the follow-up period (P < .05 vs peak value). Cystatin C was not routinely measured in our hospital; therefore, we only have results for 6 patients with TRAS. The cystatin C level was lower after the interventional therapy than before (P > .05). Mean follow-up duration was 20 ± 3 months after transplant (range, 15-25 mo). Data of patients with TRAS are shown in Table 2.

Discussion

Transplant renal artery stenosis is a common cause of renal insufficiency after kidney transplant. Among the patients who underwent kidney transplant at our center during 2013, nearly one-tenth of recipients were found to have TRAS, which is consistent with the previous literature.^1,2 With 3DCT reconstruction, an accurate diagnosis was immediately established, and graft function was saved from deterioration after PTA surgery. There was no loss of graft function in the recipients who underwent transplant surgery at our center during the study year (2013), which is better than results shown in our previous investigation. There should be more focus on this vascular complication after kidney transplant.

We found 3DCT reconstruction to be efficient and safe in diagnosing TRAS. Usually, TRAS patients present with refractory hypertension and increased serum creatinine levels. Ultrasonographic exami­nation is routinely used to investigate the cause. However, this type of examination depends too much on the examiner’s skills and experiences. Angiography is the criterion standard for diagnosis of artery stenosis, but it is not a first-choice screening tool because of its invasiveness. Magnetic resonance and CT angiography tests are noninvasive and are accurate diagnostic methods when TRAS is suspected, and they have unique advantages.9 Magnetic resonance angiography does not require the use of an iodinated contrast agent; however, it tends to overestimate the severity of stenosis. Computed tomography angiography is generally preferred because of high spatial resolution, visualization of calcium, and better urographic images. At our center, we perform CT angiography for these patients.

It should be noted that the contrast medium is usually harmful to the kidney. The intravascular injection of iodinated radiographic contrast medium causes an immediate hemodynamic renal biphasic response, leading to a decrease in the glomerular filtration rate and renal ischemia, particularly in the renal medulla.^16,17 Among the iodinated radiographic contrast media available, iodixanol seems to be the least nephrotoxic, in that nonionic isosmolar contrast media have the same osmolality as plasma.¹⁸ With application of iodixanol in imaging investigations, contrast medium-induced kidney injury has been greatly reduced.^19,20 In our center, none of the 10 patients exhibited increased creatinine levels after CT angiography using iodixanol. However, we still suggest that an iodixanol level as low as possible be used.^21,22

Percutaneous transluminal angioplasty is a useful way to treat artery stenosis. Some small studies and case series have shown benefits from percutaneous intervention for TRAS^23,24; however, several case series have reported no significant differences in blood pressure control or renal function improve­ment between interventional and medical treatment groups.^25,26 In our 10 study patients, renal function returned to a normal state after PTA surgery.

Cystatin C has been identified as a promising marker of kidney function and is less influenced by extrarenal factors than serum creatinine.²⁷ Therefore, we compared the preangioplasty cystatin C level with postangioplasty data. We found that the cystatin C level was reduced after interventional surgery, although these results are limited due to the small number of patients, and no statistically significant differences were found. More patients should be included in the future to address this issue.

Stenting was performed when balloon dilation treatment failed. In 1 patient, the angiography showed that the stenosis sites were distal to the anastomotic site, located immediately after the renal artery bifurcation. During the procedure for this patient, the 2 renal artery branches both returned to the stenosis state directly after dilation balloons were withdrawn, with stents subsequently placed into the 2 branches. The stenosis may have been due to outside forces, with fibrous cord or other connective tissue around the 2 renal artery branches perhaps causing the stenosis. Balloon dilation is usually recommended first because there is no proper way to treat restenosis after stenting.²⁸

In summary, increased serum creatinine levels and refractory hypertension are 2 main clinical characteristics of TRAS. Three-dimensional CT reconstruction is a safe choice for patients with clinically suspected TRAS. Percutaneous translu­minal angioplasty is the preferred therapeutic technique for TRAS. Stents could be used when balloon dilation is insufficient to correct stenosis. Because this study reports a single center experience involving a relatively small number of patients, further prospective studies with larger samples are recommended to validate our observations.

References:

1. Ridgway D, White SA, Nixon M, Carr S, Blanchard K, Nicholson ML. Primary endoluminal stenting of transplant renal artery stenosis from cadaver and non-heart-beating donor kidneys. Clin Transplant. 2006;20(3):394-400.
   CrossRef - PubMed
   
2. Pappas P, Zavos G, Kaza S, et al. Angioplasty and stenting of arterial stenosis affecting renal transplant function. Transplant Proc. 2008;40(5):1391-1396.
   CrossRef - PubMed
   
3. Fervenza FC, Lafayette RA, Alfrey EJ, Petersen J. Renal artery stenosis in kidney transplants. Am J Kidney Dis. 1998;31(1):142-148.
   CrossRef - PubMed
   
4. Wong W, Fynn SP, Higgins RM, et al. Transplant renal artery stenosis in 77 patients--does it have an immunological cause? Transplantation. 1996;61(2):215-219.
   CrossRef - PubMed
   
5. Pouria S, State OI, Wong W, Hendry BM. CMV infection is associated with transplant renal artery stenosis. QJM. 1998;91(3):185-189.
   CrossRef - PubMed
   
6. Patel NH, Jindal RM, Wilkin T, et al. Renal arterial stenosis in renal allografts: retrospective study of predisposing factors and outcome after percutaneous transluminal angioplasty. Radiology. 2001;219(3):663-667.
   CrossRef - PubMed
   
7. Campbell JE, Bates MC. Transcatheter therapy for the treatment of atherosclerotic renal artery stenosis. J Cardiovasc Surg (Torino). 2008;49(5):609-618.
   PubMed
   
8. Sun IO, Hong YA, Kim HG, et al. Clinical usefulness of 3-dimensional computerized tomographic renal angiography to detect transplant renal artery stenosis. Transplant Proc. 2012;44(3):691-693.
   CrossRef - PubMed
   
9. Chen W, Kayler LK, Zand MS, Muttana R, Chernyak V, DeGoccardo GO. Transplant renal artery stenosis: clinical manifestations, diagnosis and therapy. Clin Kidney J. 2015;8(1):71-78.
   CrossRef - PubMed
   
10. Zhao XY, Tian J, Ru YH, et al. Application value of multislice spiral computed tomography angiography in the evaluation of renal artery variation in living donor kidney transplantation. Genet Mol Res. 2015;14(1):314-322.
    CrossRef - PubMed
    
11. Althoff CE, Günther RW, Hamm B, Rief M. Intra-arterial ultra low iodine CT angiography of renal transplant arteries. Cardiovasc Intervent Radiol. 2014;37(4):1062-1067.
    CrossRef - PubMed
    
12. Glebova NO, Brooke BS, Desai NM, Lum YW. Endovascular interventions for managing vascular complication of renal transplantation. Semin Vasc Surg. 2013;26(4):205-212.
    CrossRef - PubMed
    
13. Ngo AT, Markar SR, De Lijster MS, Duncan N, Taube D, Hamady MS. A systematic review of outcomes following percutaneous transluminal angioplasty and stenting in the treatment of transplant renal artery stenosis. Cardiovasc Intervent Radiol. 2015;38(6):1573-1588.
    CrossRef - PubMed
    
14. Etemadi J, Rahbar K, Haghighi AN, et al. Renal artery stenosis in kidney transplants: assessment of the risk factors. Vasc Health Risk Manag. 2011;7:503-507.
    PubMed
    
15. Fernández-Nájera JE, Beltrán S, Aparicio M, et al. Transplant renal artery stenosis: association with acute vascular rejection. Transplant Proc. 2006;38(8):2404-2405.
    CrossRef - PubMed
    
16. Murphy SW, Barrett BJ, Parfrey PS. Contrast nephropathy. J Am Soc Nephrol. 2000;11(1):177-182.
    PubMed
    
17. Heyman SN, Rosen S, Rosenberger C. Renal parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy. Clin J Am Soc Nephrol. 2008;3(1):288-296.
    CrossRef - PubMed
    
18. Andreucci M, Faga T, Pisani A, et al. Pathogenesis of acute renal failure induced by iodinated radiographic contrast media. Austin J Nephrol Hypertens. 2014;1(1):1-6.
19. Bruce RJ, Djamali A, Shinki K, Michel SJ, Fine JP, Pozniak MA. Background fluctuation of kidney function versus contrast-induced nephrotoxicity. AJR Am J Roentgenol. 2009;192(3):711-718.
    CrossRef - PubMed
    
20. Semerci T, Cuhadar S, Akçay FA, et al. Comparing the renal safety of isoosmolar versus low-osmolar contrast medium by renal biomarkers N-acetyl-β-D-glucosaminidase and endothelin. Angiology. 2014;65(2):108-112.
    CrossRef - PubMed
    
21. Holder MC, Lewis DA, Winstead PS. Preventing the harm of a closer look: contrast-induced nephropathy in adults. Orthopedics. 2012;35(4):298-303.
    CrossRef - PubMed
    
22. Limbruno U, Picchi A, Micheli A, et al. Refining the assessment of contrast-induced acute kidney injury: the load-to-damage relationship. J Cardiovasc Med (Hagerstown). 2014;15(7):587-594.
    CrossRef - PubMed
    
23. Henning BF, Kuchlbauer S, Boger CA, et al. Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis. Clin Nephrol. 2008;71(5):543-549.
    PubMed
    
24. Krishnamoorthy S, Gopalakrishnan G, Kekre NS, Chacko N, Keshava S, John G. Detection and treatment of transplant renal artery stenosis. Indian J Urol. 2009;25(1):56-61.
    CrossRef - PubMed
    
25. Geddes CC, McManus SK, Koteeswaran S, Baxter GM. Long-term outcome of transplant renal artery stenosis managed conservatively or by radiological intervention. Clin Transplant. 2008;22(5):572-578.
    CrossRef - PubMed
    
26. Zupunski A, Buturovic-Ponikvar J. Duplex-Doppler long-term follow-up of renal transplant artery stenosis: case controlled study. Ther Apher Dial. 2005;9(3):265-269.
    CrossRef - PubMed
    
27. Laville M, Juillard L. Contrast-induced acute kidney injury: how should at-risk patients be identified and managed? J Nephrol. 2010;23(4):387-398.
    PubMed
    
28. Marcucci G, Accrocca F, Giordano A, Antonelli R, Gabrielli R, Siani A. Results of surgical repair of carotid in-stent restenosis. J Cardiovasc Surg (Torino). 2012;53(6):707-714.
    PubMed