EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Prospective renal donors are a select population of healthy individuals who have been thoroughly screened for significant comorbidities before they undergo multidetector computed tomography. Our aim was to determine the prevalence of incidental findings on preoperative multidetector computed tomography in a healthy cohort of potential living donors for kidney transplant.

Materials and Methods: A prospective study was performed of prospective living kidney transplant donors at a national kidney transplant center. Study inclusion criteria were all potential kidney donors who underwent multidetector computed tomography during the living-donor assessment process over a 5-year period (January 2012 to 2017).

Results: Our cohort included 375 potential living donors who had multidetector computed tomography; mean age was 44.33 years (range, 21-71.5 y). In total, there were 228 incidental findings identified in 158 individuals. Of the 375 potential donors, 193 (51%) proceeded to living donor nephrectomy. On multidetector computed tomography, 97 incidental findings were identified in the donor cohort versus 131 in the cohort that did not proceed to donation. Bosniak 1 renal cysts were the most common incidental finding (n = 46) followed by liver cysts < 1.5 cm (n = 42) and urinary tract calculi (n = 21). There was 1 incidentally detected pathologically proven malignancy.

Conclusions: A variety of incidentally detected lesions of moderate to high importance were detected in this healthy donor cohort. Individuals undergoing assessment with multidetector computed tomography for living donor nephrectomy should be counseled on medical, financial, and psychological implications of incidentally detected lesions during the kidney transplant evaluation process.

Key words : End-stage renal disease, Renal transplant

Renal transplantation is the best definitive treatment option for patients with end-stage renal disease.¹ Only a minority of patients with end-stage renal disease receive kidney transplants due to limited availability of deceased donor organs.² Globally, transplant units are attempting to establish and increase their living donor programs to increase the availability of kidneys for patients requiring transplant.^3,4 Living-donor renal transplant offers the opportunity to overcome organ shortages and is associated with excellent long-term graft survival among recipients. Moreover, living donor grafts have improved long-term survival compared with deceased donor grafts as the duration of ischemia is minimal, the procedure is elective, donors are in optimal health, and transplant procedures can be performed in patients who are preemptive for dialysis.^2,5

A thorough and accurate evaluation of prospective renal donors is important for planning elective transplant surgery and for minimizing perioperative complications. In prospective living donors for renal transplant, multidetector computed tomography (MDCT), including angiography and urography, is the standard imaging modality for accurately characterizing their renal vasculature and anatomy.^6,7Prospective renal donors are a select population of healthy individuals who have been thoroughly screened for significant comorbidities before undergoing MDCT. Therefore, this unique patient cohort is an ideal group for investigating the prevalence and significance of incidental findings on MDCT in an asymptomatic healthy population. Incidental lesions are frequently encountered in patient populations.⁸ They are associated with financial cost, patient anxiety, and the need for further testing (both noninvasive and invasive). With the now ubiquitous use of multiphase CT assessments of potential renal donors, we are seeing this healthy and prescreened population also being exposed to the hazards of the “incidentaloma.”

Materials and Methods

Overview of study design
The study was performed on all potential prospective living kidney transplant donors in a national kidney transplant center (Beaumont Hospital, Dublin, Ireland). Study inclusion criteria were all potential kidney donors who underwent MDCT during the living-donor assessment process over a 5-year period (January 2012 to January 2017). Exclusion criteria were potential living donors who did not proceed to MDCT.

Our study aimed to quantify the nature and incidence of incidental findings on MDCT for renal donor assessment and assess its impact on a national renal transplant service. This information can potentially be used to counsel donors regarding this potential source of harm in advance of renal donor assessment.

The primary endpoint was to determine the prevalence of incidental findings on preoperative MDCT in a healthy cohort of potential living donors for kidney transplant. An incidental finding was defined as “an incidentally discovered mass or lesion, detected by CT, magnetic resonance imaging (MRI), or other imaging modality performed for an unrelated reason.”⁸

Living-donor assessment process
In the Republic of Ireland and in the United Kingdom, assessment of living donors is subdivided into 3 stages.³
Stage 1
The first stage comprises an initial telephone assessment by a transplant coordinator to rule out an absolute contraindication to donor nephrectomy. Absolute contraindications to living donor nephrectomy are provided in Table 1. If no absolute contraindications are identified, donors then undergo an immunologic assessment of donor-specific antibodies and virtual cross-match against the potential recipient.
Stage 2
Potential living donors are assessed by a multidisciplinary team that includes nephrologists, transplant surgeons, immunologists, radiologists, social workers, and psychiatrists (if indicated). All donors are evaluated with blood, urine, and radiologic investigations. Imaging modalities include chest radiography, abdominal ultrasonography (US), and radioisotope renography to estimate glomerular filtration rate. If the tests deem that the individual is a reasonable candidate for donation, the candidate will then undergo abdominal MDCT to accurately characterize the renal anatomy and vasculature before elective donation.
Stage 3
Once the potential living donor and recipient have satisfactorily completed stage 2, a decision is made to proceed to transplant. The final stage of the assessment consists of a final immunologic and medical assessment 1 week before the prospective living donor transplant.

Multidetector computed tomography protocol
In our institution, a low-dose noncontrast CT followed by a combined arterial and urographic phase study is performed. Computed tomography scans are performed using a 16-slice MDCT scanner (Sensation 16, Siemens Healthcare, Deerfield, IL, USA) or a 128-slice MDCT scanner (Phillips 128, Phillips Healthcare, Bothwell, WA, USA). For the procedure, a low-dose noncontrast CT at 100 mA from the xiphisternum to the pubic symphysis is first performed to primarily evaluate for stone disease. Next, 50 mL of iopamidol (Niopam 300) are manually injected into a peripheral intravenous catheter to provide contrast opacification of the urinary tracts when excreted, which is followed by 100 mL of iopamidol (Niopam 370) pump-injected at 5 mL/s after a further 10 minutes. This is bolus tracked when triggered images are acquired from the xiphisternum to the pubic symphysis. This results in a combined study of the arterial system from the pump injection of contrast and of the urinary system from the hand contrast injection 10 minutes previously. All image data are reconstructed with a body soft-tissue algorithm in 1-mm-thick and 3-mm-thick sections. All CT angiograms are interpreted in axial, sagittal, and coronal reformations.

Living donor activity
Of the 375 potential living donors who proceeded to MDCT, 186 (50%) were female. The mean age of the prospective living-donor cohort was 44.33 years (range, 21-71.5 y). In total, there were 228 incidental findings on MDCT assessment in 158 subjects. Of the 375 potential donors undergoing MDCT, 193 (51%) proceeded to living donor nephrectomy. The remaining 182 individuals (49%) comprised the nondonor cohort.

Incidental findings
Table 2 stratifies incidental findings per the American College of Radiology white paper on managing incidental findings on abdominal CT.8 On MDCT, 97 incidental findings were identified in the donor cohort versus 131 in the nondonor cohort. Overall, 158 potential candidates (42%) had an incidental finding. Bosniak 1 renal cysts were the most common incidental finding (n = 46) followed by liver cysts < 1.5 cm (n = 42) and urinary tract calculi (n = 21) (Table 3). On MDCT, gallstones were identified in 7 individuals. Four adrenal adenomas were also identified, 3 of which were characterized on CT and 1 which was lipid-poor and required MRI for assessment. In 186 potential female donors, fibroids were the most common gynecologic finding identified (n = 12), followed by complex adnexal cysts (n = 4) and adnexal dermoids (n = 2). Table 3 lists all incidental findings (including those not detailed as per the American College of Radiology white paper8).

Incidental neoplasms
There was 1 incidentally detected pathologically proven malignancy in a potential donor (3-cm mass at the base of the urinary bladder). This candidate underwent transurethral resection of the mass and was subsequently diagnosed with a superficial urothelial carcinoma (pTaG1). The overall prevalence of malignancy was 0.3% (1/375). Postoperative surveillance with cystoscopy has so far been negative for tumor recurrence.

Further investigations
In our prospective donor population, 28 individuals (7.5%) had incidental findings requiring follow-up investigation (Table 4). Eleven individuals underwent further US scans, with the most common being assessment of the female pelvis in 9 individuals. Four individuals have remained under US follow-up for complex adnexal cysts.

Six candidates required MRIs, with 5 for visceral abnormalities that were subsequently characterized as benign entities. These included focal nodular hyperplasia in the liver, a retroperitoneal cyst, focal pancreatic fat, pancreatic cysts and an adrenal adenoma, and a lumbar spine finding that was characterized as an atypical hemangioma.

Imaging of the lung bases identified 5 individuals with pulmonary nodules who required CT follow-up; however, no lung malignancies were identified. One individual showed a pulmonary arteriovenous malformation and required a CT pulmonary angiogram, a subsequent formal angiography, and treatment of the malformation.

Colonoscopy was performed in 3 individuals who showed possible bowel abnormalities on MDCT; one person required further CT follow-up.

Living donor nephrectomy is becoming increasingly prevalent due to the global shortage of deceased donor organs. The accurate evaluation of the renal anatomy and vasculature of prospective donors is important for planning surgery, anticipating intraoperative difficulties, and preventing postoperative complications.^9,10 Multidetector computed tomography is the criterion standard imaging modality for accurately evaluating prospective kidney donors due to its ability to define renal collecting system, vasculature, and anatomic variations.¹¹Furthermore, CT arteriography and urography are less invasive than formal arteriography and urography. Herein, we investigated the prevalence of incidental findings on preoperative CT in healthy prospective renal donors. Our main finding is that a variety of incidentally detected lesions of moderate to high importance were detected in the liver, kidney, pancreas, lung, reproductive organs, and gastrointestinal systems in this healthy subject cohort.

Although CT is an efficient, minimally invasive and highly accurate diagnostic modality, it may lead to a delay or increase in exclusion rates for living donor nephrectomy due to increased detection of pathologic findings that are not clinically significant.¹² The prevalence and impact of incidental clinical findings (incidentalomas) on CT in an asymptomatic, young, and healthy population have so far been poorly described. Overall, we identified at least 1 incidental finding in 61% of our population. Tan and associates investigated the prevalence of incidental findings on preoperative abdominal CT in 1597 prospective renal donors.⁷ Their findings were consistent with ours, with 75% of prospective donors having at least 1 incidental finding on CT arteriography and 1.1% requiring additional investigations and follow-up. The prevalence of malignancy in their cohort was 0.1% (3/1597), which is also consistent with the prevalence of 0.3% (1/375) noted in our study. Maizlin and associates also investigated incidental extrarenal findings in 175 prospective renal donors and noted a prevalence of 40.6% (71/175).¹³ Findings were categorized as “high clinical importance” in 18 potential donors (10.3%) with additional investigations required in 49 potential donors (28%).¹³ Furthermore, highly and moderately significant extrarenal findings required an additional overall cost of $6137 (mean $35.1 per each case of all screened subjects).¹³ In our study, additional radiologic investigations were performed in 25 individuals: 11 requiring US, 6 requiring MRI, and 8 requiring CT. One person required radiologic intervention for a pulmonary arteriovenous malformation. Our findings showed that there is approximately a 42% chance of an incidental finding being identified in an MDCT during renal donor assessment. Of these incidental findings, 7.5% will require further investigations. This information will be useful in counseling donors on this potential source of harm, in advance of renal donor assessment.

The ability of MDCT to detect and characterize unforeseen extrarenal findings of low, medium, and high importance during the donor assessment process inevitably increases clinician workload, increases anxiety in the potential donor, and increases imaging costs.¹² Lerman and associates showed significantly elevated anxiety in individuals who were negative for malignancy during a breast cancer screening program.¹⁴ Berlin and colleagues also emphasized legal and ethical implications that should be considered when exposing a healthy population to intravenous contrast and significant radiation during conventional CT surveillance programs.¹⁵ Therefore, the psychologic effects associated with potential follow-up and treatment of extrarenal findings should be considered and relayed to potential donors during the initial stages of the donor assessment process.¹⁶ Conversely, serendipitous findings on CT may also lead to early diagnosis and treatment of curable diseases in asymptomatic subjects, thereby improving long-term clinical outcomes.7 In the present study, 1 potential donor presented with an incidental asymptomatic bladder tumor that was emergently treated with a minimally invasive endourologic procedure.

Previously, stone disease among donors was an absolute contraindication to renal donation.¹⁷ Prospective donors with incidentally detected urinary tract calculi were excluded due to the potential risk of recurrent calculi in the remaining donor kidney and/or the recipient kidney. However, these recommendations have recently been revised across several centers worldwide due to the global shortage of donor organs.^18,19 British Transplant Society guidelines currently recommend that potential donors with a limited history of small (ie, < 5 mm) urinary tract calculi and a negative metabolic screen for calculi can be considered as potential donors.20 In the present study, the incidence of asymptomatic nephrolithiasis was 5.6% (21/375) among the donor cohort. One-third (7/21) of those with asymptomatic calculi were accepted to proceed to organ donation as this cohort met the British Transplant Society guidelines for asymptomatic calculi.20 Similarly, Olsburgh and colleagues also investigated the incidence of renal calculi in 377 prospective renal donors and showed a 5% prevalence of asymptomatic renal stones, of which 36% proceeded to organ donation.¹⁷ Platt and associates also reviewed their MDCT findings in 154 prospective renal donors. The prevalence of incidental stone disease and renal cysts in their cohort was 6% (n = 9) and 6.5% (n = 10), respectively.²¹ Herein, the prevalence of incidentally detected renal cysts was 12% (46/375). Indeterminate hypodense renal masses in prospective donors can cause clinical dilemmas. Although they are unlikely to be malignant, they are often too small to characterize definitively and often require a form of sonographic surveillance for a period, thereby delaying the donation process. Presently, there is no definitive consensus on the duration of follow-up for small indeterminate renal masses in prospective donors; however, at least 2 years of stability appears to be sufficient.²²

The present study has limitations. It is a single-center, retrospective analysis of a prospectively maintained database. However, comprehensive follow-up of all candidates who underwent MDCT during the donor assessment process over a prolonged period was undertaken, and none were lost to follow-up.

Multidetector computed tomography is the current criterion standard imaging modality for accurately evaluating the anatomy and vasculature of prospective kidney donors. During the donor assessment process, MDCT also frequently detects clinically relevant findings that may impact donation, increase anxiety in potential donors, and lead to higher donor exclusion rates. Potential donors undergoing assessment with MDCT for living donor nephrectomy should be counseled on the medical implications of incidentally detected lesions during the assessment process.

Volume: 17 Issue: 2 April 2019

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