Keywords
peripheral arterial disease - renal failure - transplant
Atherosclerosis is frequent in patients with end-stage renal disease awaiting kidney
transplantation (KT).[1] The increasing incidence of iliac occlusive disease (IOD) in KT patients is related
to the advanced age of recipients and the increased incidence of atherosclerosis in
chronic renal failure.[2] Furthermore, there is increased incidence of atherosclerotic comorbidities including
diabetes, hypertension, and hypercholesterolemia.[3] Cardiovascular events are a primary cause of mortality in these patients and often
preclude KT.[3]
[4]
[5]
[6] Despite preoperative preparations, IOD is commonly encountered at KT that requires
concomitant treatment of the vascular lesion to assure proper allograft vascular in-
and outflow.[4] Current literature demonstrates a range from 1.3 to 13% incidence of significant
IOD at the time of KT.[5]
[6] We sought to review our institutional experience for this significant risk factor
for renal allograft survival.
Methods
We identified all patients from our three transplant centers at our regional sites
(Florida, Arizona, and Minnesota) with IOD requiring iliac artery endarterectomy undergoing
KT between January 1, 2000 and November 30, 2018. Data collection included details of each patient's clinical presentation, comorbidities,
KT evaluation, surgical management, and follow-up through a retrospective chart review.
This study was approved by the Mayo Clinic Institutional Review Board (IRB#17–007736).
Informed consent was waived by the IRB as this study was deemed minimal risk to patients.
Our primary end-point was allograft survival. Our secondary end-points included mortality
and perioperative complications. Data are reported using means and standard deviations
for continuous variables or as frequencies for categorical variables. Differences
between categorical variables were tested using χ2 test and differences between continuous variables were tested using Student's t-test when deemed appropriate. Long-term outcomes were performed descriptively due
to the relatively few patients in our cohort. Analyses were performed using JMP 14
(SAS Institute, Cary, NC).
Kidney Transplantation Selection
Evaluation of KT candidates at the Mayo Clinic is based on a multidisciplinary patient
care approach standardized across all Mayo Clinic sites (Florida, Arizona, and Minnesota).
All patients considered for transplantation undergo a multipart evaluation with the
following objectives: (1) to confirm severely limited kidney function, (2) to assess
the patient's ability to tolerate operative intervention, (3) to ensure that there
is good long-term allograft and patient survival, and (4) to ensure that there is
a good social and financial support to successfully sustain the transplanted organ.
A transplant committee comprised of a transplant nurse coordinator, nephrologist,
surgeon, pharmacist, psychiatrist, social worker, and nutritionist is involved in
the evaluation process for potential KT recipients based on the following criteria:
-
The transplant recipient should meet the medical indications of the United Network
of Organ Sharing
-
The transplant recipient must be younger than 80 years of age. Should he/she be older
than 80 years, the recipient is evaluated on a case-by-case basis.
-
The transplant recipient must have kidneys with severely diminished function. The
glomerular filtration rate should be less than or equal to 20 mL/min/m2.
-
The transplant recipient should have a body mass index (BMI) of less than or equal
to 40 kg/m2. Those individuals with BMIs between 40 and 45 kg/m2 will be considered on a case-by-case basis.
-
The transplant recipient should be able to comply with transplant-related management
and medical follow-up.
-
The transplant recipient should have a good social support system. There should be
no psychiatric/psychological barriers for transplantation.
-
The transplant recipient should have adequate financial resources including health
care insurance with medication coverage.
Once the recipient starts the evaluation process, a myriad of tests and consultations
is prompted, which is included in [Table 1]. Based on these evaluations, the decision to proceed with transplantation is reached.
Absolute contraindications for transplantation include active infection, active malignancy,
active substance use/abuse, reversible renal failure, uncontrolled psychiatric disorders,
documented treatment nonadherence, and/or short life expectancy. A relative contraindication
for KT has included severe calcifications of the iliac arteries observed on noncontrast
computed tomography.
Table 1
Laboratory, cardiovascular, pulmonary, imaging studies, and consultations required
for kidney transplantation (KT) evaluation
|
Laboratory testing
|
|
Metabolic panel
|
Serologies
|
|
Total and direct bilirubin
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Alkaline phosphatase
Albumin and total protein
Total cholesterol
High-density lipoprotein (HDL) cholesterol
Triglycerides, low-density lipoprotein (LDL) cholesterol
Albumin
Blood urea nitrogen
Calcium
Chloride
Potassium
Sodium
Phosphorus
Creatinine
Glucose
Bicarbonate
Rheumatologic workup as indicated
If patient has good pastures, order anti-glomerular basement membrane (GBM) antibody
ABO blood group testing drawn on two separate occasions
Human leukocyte antigen (HLA) typing
Single antigen bead
Troponin T
Hemoglobin A1C
C peptide (if diabetic)
Thyroid-stimulating hormone (TSH)
Parathyroid hormone (PTH)
Pregnancy testing in females under 60 (unless they have had a hysterectomy)
Serum protein electrophoresis (SPEP) with reflex for age > 50, history of Monoclonal
gammopathy of undetermined significance (MGUS), myeloma, amyloid considered in patients
with history of proteinuric kidney disease of unknown etiology
|
For all patients
Cytomegalovirus (immunoglobulin G [IgG] only)
Herpes simplex virus ½ (IgG only)
Varicella zoster virus (IgG only)
Measles and rubella (IgG only)
Ebstein–Barr virus (antibody profile—Epstein–Barr virus viral capsid antigen IgG/IgM
and Epstein–Barr nuclear antigen)
HIV ½ antibody
Syphilis IgG
HBsAb, HBs antigen, HBcAb
Hepatitis C virus (HCV) antibody (Ab)
HCV RNA if suspected to have recent HCV infection
Hepatitis A virus (HAV)—total antibody
For selected candidates (any candidate at risk for infection by virtue of residency
or travel):
Coccidioides immitis serology (EIA—enzyme immunoassay, ID—immunodiffusion, and CF—complement fixation)
Strongyloides serology
Schistosoma serology
Trypanosoma cruzi serology
Hematology
Prothrombin time (PT)/international normalized ratio (INR)
Complete blood count (CBC) with differential
Urine tests
Urinalysis
Random urine protein and creatinine
Gram stain (reflex urine culture)
|
|
Cardiovascular and pulmonary testing
|
|
Electrocardiogram (EKG)
Echocardiogram to evaluate valves and pulmonary pressures
Stress test for patients with diabetes, age >59, prior coronary artery disease (CAD),
or tobacco use
Carotid duplex ultrasound for all patients with a history of CAD, stroke, transient
ischemic attack (TIA), diabetes, or severe peripheral arterial disease (PAD)
Thrombophilia workup: for history of lupus, clotting of access, miscarriages or prior
clotting, consider thrombophilia clinic or order the following tests/thrombophilia
profile
|
|
Antithrombin activity plasma
Cardiolipin (phospholipid) antibody
Coagulation survey, lupus like anticoagulants
Protein C activity
Protein A free plasma
Prothrombin G20210A nucleotide
Beta 2 glycoprotein 1 antibodies (IgG, IgM, and IgA)
|
|
Radiology imaging studies
|
|
Chest X-ray posterior–anterior and lateral views
Duplex scan of kidneys to evaluate for kidney size and presence of cysts
Computed tomography (CT) of the abdomen/pelvis without contrast in patients who are
older than 65 years of age or with diabetes mellitus (DM), PAD, and if they have been
on hemodialysis or peritoneal dialysis for more than 3 years. If complex renal cysts
are present, then abdominal CT with contrast should be done annually with urology
evaluation
Magnetic resonance angiography (MRA) of the brain without contrast should be obtained
for all autosomal dominant polycystic kidney disease (ADPKD) patients, who have not
had one completed
|
|
Cancer screening
|
|
Usual screening according to the American Cancer Society guidelines
|
|
Consultations
|
|
Transplant nephrology
Transplant surgery
Transplant nurse coordinator
Transplant pharmacist
Transplant nutrition
Transplant financial coordinator
Infectious diseases (if indicated)
Psychology and psychiatry consultation (if indicated)
Cardiology, if patient has history of cardiac problems or abnormal echocardiogram/stress
test
Other consultations and tests, as indicated
|
Results
There was a total of 6,757 KT at our three sites (Florida, Arizona, and Minnesota).
From these, 22 (0.32%) patients had concomitant IOD requiring iliac artery endarterectomy
at the time of transplantation. The demographic data, comorbidities, and the etiology
of kidney failure are presented in [Table 2]. Thirteen (59.1%) patients were male and the mean age at KT was 61.5 ± 7 years.
The most common etiology of kidney failure was diabetic nephropathy in 10 patients
(45.5%) followed by a combination of hypertensive/diabetic nephropathy in five patients
(22.7%) and hypertensive nephrosclerosis in three patients (13.6%). The mean time
from dialysis to transplantation was 2.9 ± 2.9 years. Sixteen patients (72.7%) received
renal allografts from deceased donors and six (27.3%) were recipients from living
donors.
Table 2
Patient characteristics of our kidney transplant (KT) cohort
|
Age at the time of transplant (years)
|
61.5 ± 7 years
|
|
Male sex
|
13 (59.1%)
|
|
Race/ethnicity
|
n (%)
|
|
Caucasian
|
11 (50)
|
|
African American
|
9 (40.1)
|
|
Latino
|
2 (9.1)
|
|
Body mass index (BMI, in kg/m2)
|
29.5 ± 4.5
|
|
Comorbidities
|
n (%)
|
|
Peripheral artery disease
|
22 (100)
|
|
Hypertension
|
21 (95.5)
|
|
Diabetes mellitus
|
14 (63.6)
|
|
Coronary artery disease
|
10 (45.5)
|
|
Hyperlipidemia
|
7 (31.8)
|
|
Chronic pulmonary obstructive Disease
|
2 (9.1)
|
|
Medication
|
n (%)
|
|
Acetylsalicylic acid
|
19 (86.4)
|
|
Beta blockers
|
15 (68.2)
|
|
Statins
|
10 (45.5)
|
|
Calcium channel blockers
|
10 (45.5)
|
|
Clopidogrel
|
6 (27.3)
|
|
Anticoagulation medications
|
4 (18.2)
|
|
Etiology of end-stage renal disease
|
n (%)
|
|
Diabetes mellitus
|
10 (45.5)
|
|
Diabetes/hypertension
|
5 (22.7)
|
|
Hypertension
|
3 (13.6)
|
|
Lupus nephritis
|
1 (4.5)
|
|
Interstitial nephritis
|
1 (4.5)
|
|
Proteinuric kidney disease
|
1 (4.5)
|
|
Focal segmental Glomerulosclerosis
|
1 (4.5)
|
|
Type of kidney donor
|
n (%)
|
|
Deceased donor
|
16 (72.7)
|
|
Living donor
|
6 (27.3)
|
|
Preoperative computed tomography
|
13 (59.1)
|
|
Preoperative serum creatinine (mg/dL)
|
7.4 ± 2.6
|
Preoperative cross-sectional imaging in the form of noncontrast CT was performed in
13 (59.1%) patients as part of their routine transplant evaluation, which includes
only patients over the age of 65 years, with complex renal cysts, history of peripheral
arterial disease, and diabetes mellitus and hemo- or peritoneal dialysis of over 3
years duration ([Fig. 1]). There was one (4.5%) patient with planned endarterectomy in our cohort. The rest
of our patients required intraoperative consultations with vascular surgery.
Fig. 1 Coronal view of a noncontrast computed tomography scan of the abdomen and pelvis
in a patient with significant Iliac occlusive disease (IOD) prior to kidney transplantation.
Immunosuppression is achieved by administration of induction medication followed by
maintenance therapy to prevent acute rejection and renal allograft loss. Long-term
follow-up after transplantation was managed by our transplant team in 19 (86.4%) patients
and in 3 (13.6%) patients by external providers. Follow-up is rigorous and requires
good patient adherence: visits every 2 weeks in the first 2 to 4 months; then, monthly
visits until the 6th month. Subsequently, visits every 2 months in the first year
and every 3 to 4 months until the third year and lastly one visit per semester thereafter.
During each follow-up visit, laboratory data are obtained for medication adjustments,
if needed. If acute rejection is noted, plasma exchange and/or corticosteroids and/or
immunosuppressant medication is initiated depending on the histologic grade of the
rejection.
Operative Procedure
In 19 (86.4%) of 22 patients, a right lower quadrant Gibson incision was made to obtain
access to the iliac vessels in the retroperitoneal space in the standard fashion.[7] The other three (13.6%) kidney allografts were placed in the left iliac fossa, two
of those secondary to advanced peripheral arterial disease in the right iliac vessels
([Fig. 2]). There were five patients who required iliac artery patching (two with bovine pericardium
and three with renal vein from the donor kidney). A single patient required a distal
external iliac artery stent. In all 22 patients, an end-to-side anastomosis was performed
from the renal artery and vein directly to the external iliac artery and vein, respectively.
The ureter was anastomosed directly into the bladder using a Lich-gregoir technique.
Mean operative time was variable at 225.1 ± 104.9 minutes (range: 137–560 minutes).
Fig. 2 Primary kidney transplantation are performed in the iliac fossa (Used with permission
of Mayo Foundation for Medical Education and Research. All rights reserved).
Postoperative and Long-Term Management
Mean length of hospital stay was 6.3 ± 4.3 days (range: 3–18 days). All patients were
placed on oral aspirin 81 mg. The significant discrepancy in hospitalization was predominantly
due to those patients who suffered from postoperative complications. Complications
were graded using the Clavien-Dindo system[8]
[9] (Clavien-Dindo Grade 2–4) and occurred in 13 (59.1%) patients, including 10 (45.5%)
with acute blood loss anemia requiring transfusion, 2 (9.1%) reoperations for hematoma
evacuation, 1 (4.5%) ischemic colitis requiring total abdominal colectomy, and 1 (4.5%)
renal vein thrombosis requiring nephrectomy ([Table 3]). Nine (40.9%) patients required hemodialysis in the first week following transplantation.
Table 3
Postoperative complications
|
Postoperative complications
|
n (%)
|
|
Acute blood loss anemia, requiring transfusion
|
10 (45.5)
|
|
Perinephric hematoma requiring reoperation
|
2 (9.1)
|
|
Ischemic colitis requiring colectomy
|
1 (4.5)
|
|
Graft thrombosis requiring nephrectomy
|
1 (4.5)
|
The perinephric hematoma evacuations were on patients with significantly large hematomas.
They measured 13 × 3.7 × 7.8 cm and 14 × 11 × 4 cm in size. The patient who developed
ischemic colitis was slow to recover following KT. She later developed a leukocytosis
of up to 40 × 109/L on postoperative day 9 along with significant abdominal pain. On postoperative
day 11, she underwent a flexible sigmoidoscopy that revealed colonic ischemia. She
then underwent total abdominal colectomy with end ileostomy.
There were two graft losses (9.1%) that occurred within 90 days of transplant. The
first one was described as a “difficult” vascular anastomosis during the transplantation.
This patient became oligoanuric within 24 hours and a duplex ultrasound on postoperative
day 1 revealed no blood flow to the new transplanted kidney. He underwent allograft
nephrectomy on this same day. The pathology report revealed extensive venous thrombosis
with cortical and medullary necrosis. The second patient with allograft loss had initially
delayed graft function of 7 days. His postoperative course was then unremarkable.
However, 30 days later, he was readmitted with acute renal injury. He was treated
for acute rejection with steroids, and underwent ultrasound and carbon dioxide angiogram
to no avail. The allograft function did not recover and his renal biopsy revealed
dense acute tubular necrosis of unknown etiology.
Mean follow-up was 3.5 ± 2.5 years. Overall allograft survival was 90.1% at 1-year
and 86.4% at 3-year follow-up. Overall mortality occurred in six (27.3%) patients.
Information regarding cause of death could only be found for one patient, who expired
from cardiac arrest; all others have unknown causes of death.
Discussion
Little is known about the surgical challenges and outcomes of KT in the face of IOD.
As the population continues to age and as more patients present with diabetes, hypertension,
and longstanding smoking history, the incidence of kidney transplant recipients presenting
with significant IOD should be expected to increase.[10]
[11] In this study, we have identified 22 patients (0.32%) with extensive IOD at the
time of KT. While the safety of simultaneous reconstruction has been questioned previously,[8]
[9] Clavien et al[9] have demonstrated that concurrent interventions are both safe and feasible.
The primary end-point of our study was graft survival, which we demonstrated to be
90.1% at 1-year and 86.4% at 3-year follow-up, which is consistent with the national
means for any high-volume transplant center.[10] Comparatively, our three-site allograft survival is 96.0 and 90.3% at 1- and 3 years
post-KT, respectively. Two renal allografts were lost within 90 days secondary to
renal vein thrombosis on postoperative day 1 and acute tubular necrosis on postoperative
day 30. Despite this being a substantial loss, our early allograft loss is lower than
what has been previously reported.[4] This further reaffirms that endarterectomy at the time of KT is both safe, effective,
and may lead to long-term allograft survival. Of those patients requiring endarterectomy,
only one case was identified and planned in the preoperative setting. This may be
due to the infrequent use of cross-sectional imaging (59.1% of patients had preoperative
CT) to screen for IOD in our KT population. Since the conduction of the current study,
we have included a noncontrast CT as required preoperative assessment and a vascular
surgery consultation in those patients with significant IOD in our KT patient population.
We believe this highlights the importance of standardizing preoperative screening
protocols and the vital role of multidisciplinary approach to patient care in this
complex patient population.
Patients undergoing endarterectomy at the time of renal transplant are at increased
risk of complications. We recommend baseline surveillance of renal allografts on postoperative
day 0 utilizing Doppler ultrasound. Doppler ultrasound should be repeated for any
change in renal function, significant ultrasound abnormalities, or delayed allograft
function beyond expectations of the specific donor allograft. Doppler ultrasound represents
a noninvasive, low-cost screening tool in these complex patients. A low index of suspicion
should be maintained for the need to pursue CO2 contrast or traditional angiography versus early return to the operating room in
cases of atypical allograft function. It is worthwhile mentioning that in the current
endovascular era of managing many vascular diseases, this option has been mostly used
in the post-transplantation setting. Glebova et al[11] illustrate both a renal artery and an iliac artery stenosis managed with balloon
angioplasty. In a second review of 10-year data from the University of Michigan, 25
of their 34-patient cohort required endovascular balloon angioplasty due to renal
artery and iliac artery stenosis.[12]
Mortality on dialysis far exceeds our reported transplant mortality. The United States
Renal Data System reports 3-year survival on hemodialysis is only 57%; 3-year survival
on peritoneal dialysis is 70%.[13] In contrast, our patients requiring iliac intervention at the time of renal transplant
demonstrated 86.4% 3-year survival. This demonstrates significant survival benefit
in those patients eligible for combined vascular surgery and transplant over starting/remaining
on dialysis. Carefully selected patients have significant potential improvement in
both quality of life and overall survival by considering combined endarterectomy and
KT.
Limitations
Our review is a single-center retrospective review and as such, several limitations
need to be acknowledged. First, our limited number of KT patients with concomitant
IOD that required endarterectomy at the time of transplantation. Second, we believe
that although this cohort is limited, most likely many of the KT candidates were not
considered in the selection process due to the extensive IOD. In light of our current
findings, several practical changes have been introduced that include a noncontrast
CT as required preoperative assessment and a vascular surgery consultation in those
patients with significant IOD on imaging. Furthermore, we are unable to generalize
our outcomes to other transplant practices. Therefore, larger studies with multicenter
data are necessary.
Conclusion
IOD patients selected for KT are not common and although challenging, they do have
the same outcomes as our standard KT patients. The 1- and 3-year allograft survivals
were 90.1 and 86.4% versus 96.0 and 90.3% in the general KT patient population. With
these excellent outcomes, we recommend expanding the criteria for KT to include patients
with IOD with prior vascular surgery consultation to prevent progression of IOD or
prevention of wait list removal in select patients who are otherwise good candidates
for KT.
