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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 15  |  Issue : 3  |  Page : 251-256

Transplant renal artery stenosis: urgent and judicious to avoid disaster; A narrative review


1 Department of Vascular Surgery and Transplantation, National Institute of Nephrology, Colombo, Sri Lanka; Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool, United Kingdom
2 Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool, United Kingdom
3 Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool; Royal Liverpool University Hospital, Liverpool, United Kingdom
4 Faculty of Health and Science, Institute of Learning and Teaching, University of Liverpool, Liverpool; Sheffield Teaching Hospitals, Sheffield, United Kingdom

Date of Submission25-Aug-2020
Date of Decision04-Oct-2020
Date of Acceptance08-Jan-2021
Date of Web Publication30-Sep-2021

Correspondence Address:
Dr. Nalaka Gunawansa
Department of Vascular Surgery and Transplantation, National Institute of Nephrology, Jayantha Weerasekera Mawatha, Colombo 01000, Sri Lanka

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_108_20

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  Abstract 

Transplant renal artery stenosis (TRAS) remains a dreaded complication of renal transplant surgery with potentially devastating sequelae. TRAS occurring early in the posttransplant period is mainly due to technical faults related to the graft implantation process. Late TRAS, in contrast, is more the result of either progressive atherosclerotic disease in the recipient vasculature or immunological, infective, and drug toxicity-related intimal injury. The clinical presentation may range from asymptomatic incidentally detected lesions to frank stenosis causing refractory hypertension or graft dysfunction. Accurate diagnosis with prompt intervention in the clinically significant lesions is the hallmark of successful management in TRAS, thereby averting the possible risk of renal artery thrombosis and graft loss.

Keywords: Graft dysfunction, posttransplant hypertension, renal artery stenosis, renal artery thrombosis, renal transplant


How to cite this article:
Gunawansa N, Aziz D, Sharma A, Halawa A. Transplant renal artery stenosis: urgent and judicious to avoid disaster; A narrative review. Indian J Transplant 2021;15:251-6

How to cite this URL:
Gunawansa N, Aziz D, Sharma A, Halawa A. Transplant renal artery stenosis: urgent and judicious to avoid disaster; A narrative review. Indian J Transplant [serial online] 2021 [cited 2021 Nov 29];15:251-6. Available from: https://www.ijtonline.in/text.asp?2021/15/3/251/327382


  Introduction Top


Transplant renal artery stenosis (TRAS) is the most common vascular complication following renal transplantation (RT). While minor degrees of TRAS may remain asymptomatic, progressive disease can result in significant morbidity culminating in renal artery thrombosis and eventual graft loss. The reported incidence of TRAS varies between 1% and 23% among different publications, with the most common presentation being at 3–24 months post-RT.[1] Early TRAS, usually categorized as those that manifest before 30 days post-RT, often results from technical issues related to the transplant surgery [Table 1]. Unlike late TRAS that develops progressively over time due to factors such as chronic rejection, infections, or atherosclerotic disease, early TRAS results in acute presentations with graft dysfunction. The resulting clinical findings are more significant, with rapid deterioration and potential graft loss, if not detected or corrected early.
Table 1: Etiology of early transplant renal artery stenosis[1],[2]

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  Pathogenesis and Etiology Top


Anatomically, TRAS may be classified according to the location of the stenosis in relation to the donor renal artery–recipient artery anastomosis. Accordingly, TRAS may be described as either preanastomotic, anastomotic, or postanastomotic. Preanastomotic TRAS results from native iliac artery disease that causes stenosis just at or proximal to the site of the anastomosis. This can result from native iliac artery atherosclerotic disease or mechanical injury caused by the clamps applied at the time of surgery. Anastomotic TRAS is primarily a stenosis that occurs due to technical faults at the anastomosis itself. These include the use of improper size of suture material, damage to the arterial intima caused by poor handling and suturing technique, or angulation. Postanastomotic TRAS occurs beyond the site of the actual anastomosis and may be caused by intimal flaps in the donor renal artery caused by cannulation or instrumentation. Postanastomotic stenosis may also occur due to kinking of the graft renal artery, especially in case of transplanting a right deceased donor kidney. Rarely, TRAS may be multiple and diffuse, occurring at different sites across the allograft arterial tree. This results more from diffuse intimal damage caused by immunological injury or preservation injury, especially in deceased donor transplants (DDTs) with a prolonged cold storage preservation.

The donor renal artery-to-recipient native artery anastomotic technique and preference may have a bearing on the occurrence of early TRAS. End-to-side anastomosis of the donor renal artery to the recipient external iliac artery carries a much lower risk of TRAS compared to end-to-end anastomosis performed to the recipient internal iliac artery.[3] The choice between end-to-side or end-to-end technique, however, is primarily dependent on individual surgeon preference. While the end-to-side anastomosis appears to be more popular due to its technical ease, end-to-end anastomosis to the internal iliac artery may be required in situations where the native external iliac artery is affected by atherosclerotic disease.[4]

Differences in the kidney harvesting and perfusion practices prior to implantation may also impact the possibility of TRAS. In live donor transplants (LDTs), the harvested kidney is perfused by direct cannulation of the renal artery at the back table. This direct cannulation may occasionally lead to intimal damage of the renal artery compared to DDTs where cold perfusion is performed at the aorta, distal to the renal artery itself. This, however, may be offset by the shorter preservation and cold ischemia time in LDT as opposed to DDT. Accordingly, the overall reported incidence of TRAS is higher with DDT (13.2%–17.7%) than LDT (1.3%–5.8%).[5],[6] DDT where the kidney is implanted with an aortic cuff (Carrel patch) carries a significantly lower risk of TRAS. The use of an aortic cuff avoids direct damages to the donor renal artery ostium as the anastomosis and the suture line travel away from the ostium. This also facilitates the use of donor kidneys with multiple renal arteries with the native aortic cuff instead of back-table reconstruction which can cause potential luminal narrowing. Nevertheless, the use of aortic cuff may result in a disproportionately long artery, especially in the right-sided kidney, causing postanastomotic kinking. Hence, the positioning of the kidney and the avoidance of such kinking need to be borne in mind with the use of an aortic cuff.

Older donor and recipient age (>65 years) as well as expanded criteria donors are also recognized risk factors for TRAS.[4] This may be explained by age and morbidity-related atherosclerotic disease in both the donor and recipient arteries.


  Clinical Presentation Top


The clinical presentation of TRAS can vary from asymptomatic disease which is detected on routine or screening imaging to frank disease, causing graft dysfunction. While the great majority of patients remain asymptomatic, the exact incidence of different clinical presentations remains undocumented due to regional and institutional variations in screening and diagnosis. Minor degrees of TRAS may be detected incidentally on duplex ultrasound (DUS) scan during routine imaging. Clinical examination findings may include a bruit auscultated over the graft due to turbulence of flow across the stenosis. In the absence of definitive clinical or biochemical graft dysfunction, these patients need close surveillance to monitor the possible progression of TRAS. Any evidence of graft dysfunction with image findings of TRAS needs close evaluation. Graft dysfunction that is not caused by ongoing immunological or infective pathology should always arouse the suspicion of possible TRAS. Conversely, TRAS may result in de novo or worsening of existing hypertension, accounting for 3%–12% of all patients with posttransplant hypertension.[2] In approximately 5% of cases with clinically significant TRAS, transplant recipients may present with acute-onset “flash” pulmonary edema, respiratory distress, and congestive cardiac failure. This is brought about by TRAS-associated sodium and water retention due to activation of the renin–angiotensin–aldosterone system.[7]


  Diagnosis Top


DUS scan is the first-line imaging modality in suspected TRAS [Figure 1]. [Table 2] depicts the typical waveform characteristics detected on DUS and its associated probability of TRAS.[8] Once DUS shows findings suggestive of TRAS, further imaging with contrast studies is carried out for confirmation and therapeutic interventions. The different imaging modalities used in the diagnosis of TRAS have their own merits as well as demerits and need to be selected on an individualized basis [Table 3]. Conventional angiography as a diagnostic modality is reserved for instances where simultaneous minimally invasive therapeutic interventions are also considered [Figure 2] and [Figure 3]. Isotope scintigraphy, although used in the past, has become quite obsolete in the context of modern-day diagnosis and management of TRAS. Poor sensitivity and specificity, difficulty in anatomical characterization, and limited applicability in planning therapeutic interventions have allowed other imaging modalities to be preferred over scintigraphy in TRAS.
Figure 1: Duplex ultrasound image with intraparenchymal flow characteristics of blunted systolic upstroke

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Table 2: Duplex ultrasound characteristics and probability of transplant renal artery stenosis[8]

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Table 3: Comparison of diagnostic imaging modalities in transplant renal artery stenosis

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Figure 2: Conventional angiographic image of the patient with postanastomotic transplant renal artery stenosis

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Figure 3: Reconstructed images from computerized tomographic angiography

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DUS measurement of peak systolic velocity (PSV), flow turbulence, and the resistive index (RI) in the extrarenal segment as well as the spectral waveform and RI in the intraparenchymal segments show characteristic findings.

The region of stenosis will have highly elevated PSV, flow turbulence, and low RI while the poststenotic region will show low amplitude flow with hypoperfusion. An intraparenchymal RI of >0.8 may indicate irreversible structural damage with sustained TRAS.[9]


  Duplex Ultrasound Diagnostic Criteria for Transplant Renal Artery Stenosis Top
[8]

At the site of stenosis:

  • Absolute PSV >200 cm/s or
  • Relative PSV more than twice that of adjacent iliac artery.


Distal to stenosis:

  • Poor systolic upstroke, acceleration time >0.1s [Figure 1]
  • Low amplitude flow with spectral broadening (tardus parvus change).



  Treatment Top


Refractory hypertension or graft dysfunction remains the hallmarks of clinically significant TRAS, helping to add perspective to routine imaging findings. Persistently elevated serum creatinine, in the absence of immunological or infectious pathology with DUS findings suggestive of TRAS, remains the most important clinical scenario requiring further evaluation and prompt intervention.


  Conservative Treatment Top


Mild-to-moderate TRAS without graft dysfunction can be managed expectantly with pharmacological treatment of hypertension. Indications for conservative treatment of TRAS include:[10]

  • Stable graft function
  • Extrarenal PSV <180 cm/s
  • Intrarenal RI of >0.50.


Hypertension can be controlled with judicious use of angiotensin-converting enzyme inhibitors (ACEi) while monitoring clinical results. Low-dose, short-acting ACEi can be used while monitoring serum creatinine and potassium levels within 7 days of initiation.[1] They need close surveillance with monitoring of graft function and repeat periodic DUS. Any deterioration of graft function (serum creatinine rise >30% from baseline or serum potassium >6 mEq/L), is considered an indication to abandon the conservative approach and proceed to active intervention.[11] Conversely, those who tolerate the initial trial of short-acting low-dose ACEi can then be converted to long-acting drugs such as ramipril or enalapril with once-daily dosing. Continued surveillance with 3–6 monthly DUS is indicated to determine any deterioration of TRAS regardless of hypertension control.


  Percutaneous Transluminal Angioplasty and Stenting Top


Once a decision has been made to intervene in TRAS, percutaneous transluminal angioplasty (PTA) remains the preferred first-line option. The reported technical success rate is >80%, with a corresponding clinical success rate of controlling hypertension (63%–80%) and restoring graft function (85%–90%).[12] The risk of recurrence after PTA alone is about 30% and can be minimized by transplant renal artery stenting [Table 4]. Simultaneous stenting increases the 3-year patency rate to over 90%.[22],[26] Such patients are maintained on life-long antiplatelet agents following stenting, with either aspirin or clopidogrel to minimize stent thrombosis.[27] Nevertheless, despite simultaneous stenting of the stenosed segment, re-stenosis causing clinical deterioration and requiring re-intervention can be as high as 18%.[24] Besides early failure following potential stent migration, the most common reason for long-term failure after bare-metal stenting is in-stent stenosis caused by progressive atherosclerotic disease and intimal hyperplasia. This can be circumvented to some degree with the use of newer drug-eluting (rapamycin and enoxaparin) stents instead of the bare-metal stents. The incorporated drugs in the drug-eluting stents act by inhibiting the intimal hyperplasia and thereby further improving long-term patency.[23],[24]
Table 4: Outcome following percutaneous intervention for confirmed transplant renal artery stenosis

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Indications for simultaneous stenting include:[28]

  1. Residual stenosis >30% after balloon angioplasty alone
  2. Intimal damage/flow-limiting flap after angioplasty
  3. Flow pressure gradient >10 mmHg across the lesion after PTA.


Isolated postanastomotic short-segment (<2 cm) stenosis is considered an ideal lesion for successful treatment with PTA and stenting [Figure 4]. Anastomotic stenoses and those due to arterial kinking are less favorable with higher rates of technical failure. Early TRAS occurring soon after transplant is also less favorable for PTA due to potential disruption of the anastomosis by balloon dilatation.[29] Such lesions are better managed by open revision of the anastomosis and correction of any technical faults. The procedural morbidity in PTA is significantly less compared to open surgical revision. Nevertheless, the potential adverse outcomes include balloon-induced damage to the renal artery and thrombosis, rupture, perforation as well as distal embolization.[29] Furthermore, the local puncture site complications include hematoma and femoral artery pseudoaneurysm formation. Nevertheless, PTA and stenting offer an excellent minimally invasive treatment option in cases of established TRAS with very high technical and clinical success.[22]
Figure 4: Successful management of transplant renal artery stenosis with percutaneous angioplasty and stenting

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  Surgery Top


Indications for open surgical revision of TRAS include:[24],[27]

  • Very early anastomotic stenosis, where percutaneous intervention may disrupt the anastomosis
  • Renal arterial kinking where stenting is not feasible
  • Severe stenoses inaccessible to PTA
  • Failure of PTA or recurrence after PTA
  • Complications after PTA; arterial rupture, perforation, pseudoaneurysm, etc.


The techniques used in open surgical repair of TRAS are varied. These include simple resection and re-anastomosis of the stenosed segment, longitudinal arteriotomy, and vein patch repair or complete reconstruction of the transplant renal artery. Reconstruction of the renal artery can be performed using either isografts (patients' great saphenous vein or hypogastric artery) or allografts (cadaveric iliac artery). In the event of arterial kinking caused by a disproportionately long renal artery, revision of the anastomosis with arterial shortening can be done. The decision for open surgical repair needs to be taken with caution in order to achieve the best outcome in terms of graft and patient survival. While PTA remains the first-line therapeutic intervention, the definitive indications for open surgical repair need to be identified early in order to optimize the outcome and avert irreversible damage to the graft.

The need for re-operation, anesthesia, and further warm ischemia to the graft during surgical repair needs to be balanced against the benefit of definitive restoration of graft perfusion. The reported clinical success rates are >90%, with a late recurrence rate of 12%. However, surgical revascularization carries significant complications including risk of graft loss (15%–20%), ureteric injury (15%), and mortality (5%).[20],[30] Given the high procedural morbidity and mortality, surgical intervention should be a second-line option after PTA, wherever feasible.


  Conclusion Top


TRAS is one of the most common vascular complications following RT with potentially graft-threatening sequelae. Early TRAS is primarily due to technical issues associated with the transplant surgery. The presence of graft dysfunction in the absence of infective or immunological causes should be viewed with utmost vigilance. Immediate intervention and restoration of graft perfusion can avoid devastating complications of renal artery thrombosis and graft loss. PTA offers minimally invasive therapeutic options with excellent long-term results. The technical success rate of PTA can be further enhanced with the use of stenting. Selected patients where PTA is not feasible or is unsuccessful will require open surgical revascularization. Early diagnosis and judicious intervention to restore graft perfusion in the clinically significant TRAS remains the only definitive management option to salvage the graft at risk.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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29.
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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