Renal Transplantation

The incidence of end-stage renal disease is rising, and renal transplantation is the most desirable treatment for many of these patients, as it permits homeostasis and a quality of life superior to that achievable by dialysis. More than half of the almost 30,000 organ transplants performed in the United States in 2014 were renal. The two sources of donor kidneys are cadavers and living donors. The shortage of deceased donor kidneys has increased the need for living donors.

The results of renal transplantation are quite good. Currently, 90% to 95% of transplant recipients survive the first year after surgery, and at least 80% of those transplanted kidneys are functioning at that time. Short-term and long-term survival rates of functioning transplanted kidneys correlate positively with meticulous immunosuppression, careful human leukocyte antigen (HLA) matching, the experience of the transplant team, and an ideal recipient age (5 to 50 years). However, even among elderly patients (>70 years), transplantation offers significantly lower mortality than dialysis. The duration of a successful transplant is limited. Despite careful selection and management of patients, only a minority of transplanted kidneys retain useful function longer than 10 years. Patients may receive subsequent grafts after a first one has failed, and the duration of function of the first graft is a useful predictor of the longevity of the next transplantation.

A variety of radiologic procedures are used in the selection of donors and recipients, as well as in the management and detection of posttransplant complications.

PRETRANSPLANT EVALUATION

Living Donor Evaluation

About 20% of transplanted kidneys are obtained from living donors, and most donors are related to the recipients. After appropriate HLA matching is performed, the donor undergoes radiologic evaluation to be sure that the kidney considered for donation does not have a morphologic or vascular abnormality that would contraindicate surgery. The remaining kidney must be sufficiently normal that the donor is not at risk for subsequent renal insufficiency.

Laparoscopic nephrectomy has become the preferred method of harvesting the donor kidney. Since the exposure is limited, it is important to provide an imaging evaluation to guide the procedure. Computed tomography (CT) is the preferred modality due to its high spatial resolution and sensitivity to vascular calcification and renal stones.

Both computed tomography angiography (CTA; Fig. 9.1) and magnetic resonance angiography (MRA; Fig. 9.2) have proven to be accurate in distinguishing whether each kidney has one or two
main renal arteries. CT is used more commonly than MR to evaluate prospective renal donors, and images are routinely reformatted to display the anatomy of the artery and to identify the point at which the first branch occurs (Fig. 9.3). These CT-reformatted images are also used to depict renal venous anatomy (Figs. 9.4, 9.5 and 9.6). MRA has the disadvantage of low sensitivity for small renal stones and is more likely than CTA to miss tiny polar accessory arteries, further supporting CT as the primary imaging modality for evaluating prospective renal donors.

FIGURE 9.1. CTA. Single renal arteries are seen on this volume-rendered image. Portions of the renal veins are also visible.

FIGURE 9.2. MRA. Single renal arteries are seen on this T1-weighted three-dimensional spoiled gradient-echo image.

Several techniques are available to reduce the radiation dose of the donor CT examination. Unenhanced views of the kidneys are necessary to find small stones and are helpful in detecting vascular calcification. Arterial phase images are obtained to assess the vascular supply, and delayed images are useful to evaluate the collecting system. The scout view from a CT urogram depicts the renal collecting systems, bladder, and ureter (Fig. 9.7). Axial images collimated to 1.5 mm as well as coronal, sagittal, and 3D-reconstructed images should be available for review at the workstation.

Evaluation of the kidneys should include an assessment of renal volume, as this parameter closely predicts renal function. Large kidneys are preferable; donors with large remaining kidneys achieve better renal function than those with small ones; large donated kidneys have fewer complications in recipients; and small transplanted kidneys may have insufficient function to serve a large recipient. Simple cysts and small nonobstructing stones may not absolutely disqualify a donor candidate, but tumors, postinflammatory fibrosis, hydronephrosis, and other conditions can jeopardize the health of the donor and/or recipient and usually prohibit transplantation.

Renal vascular assessment is crucial. Arterial conditions such as atherosclerosis or fibromuscular disease (Fig. 9.8) are contraindications to donor nephrectomy. Accessory renal arteries are important to demonstrate (Fig. 9.9). Duplicated renal arteries are not an absolute contraindication, but arterial luminal diameters should be measured because arteries smaller than 3 mm are difficult to anastomose to recipient vessels. Triplicated renal arteries usually preclude donor nephrectomy. Very small polar arteries can often be sacrificed, but since small lower pole arteries may give branches to the renal pelvis and proximal ureter, postoperative ureteral complications are more likely if these vessels are occluded. The distances between the origin from the aorta and first bifurcation of all major renal arteries should be measured; if these segments are short, surgery becomes more difficult.

FIGURE 9.3. CTA. A single right renal artery is reformatted to clearly display the first branching vessel.

FIGURE 9.4. CTA. A single right renal vein is clearly demonstrated.

FIGURE 9.5. CTA. A single left renal vein is clearly demonstrated.

FIGURE 9.6. CT angiogram reveals a single artery and vein supplying each kidney.

FIGURE 9.7. CT urography. A scout view demonstrates a single ureter bilaterally. The prostate is enlarged, there is a TURP defect, and the bladder is trabeculated.

FIGURE 9.8. Fibromuscular dysplasia is seen bilaterally.

FIGURE 9.9. Accessory renal artery. Volume-rendered image from CTA demonstrates two left renal arteries (arrows).

Renal venous anatomy must also be analyzed. Retroaortic or circumaortic left renal veins are found in approximately 5% of potential donors and are important to recognize, as are duplicated right renal veins, found in almost 15% of donor evaluations. The distance between the junction of the vein with the inferior vena cava and the first bifurcation should be measured. Finally, renal venous tributaries, such as adrenal, lumbar, and gonadal veins, should be described.

The left kidney is preferred for donation, as the left renal vein is longer and surgical resection is often easier (Fig. 9.5). Single renal arteries are preferred, though small accessory arteries may sometimes be ignored. Potential donors with accessory arteries at the lower pole may have branches supplying the renal pelvis or ureter and are usually avoided.

Perirenal fat is removed from the donor kidney before transplantation. Thus, an assessment of the amount of fat in the perirenal space is useful. Simple renal cysts are seldom a problem as they are easily excised. Indeterminant lesions should be carefully evaluated before surgery. Ureteral duplication, found in 1% of the population, presents a technical challenge, but is not an absolute contraindication for transplantation.

Chu et al. found renal or extrarenal abnormalities in more than 40% of potential renal donors, though most were incidental findings that did not prevent organ donation. Renal abnormalities, which are absolute contraindications to transplantation including solitary kidney, horseshoe kidney, or polycystic kidney disease, were found in <1% of potential donors.

Recipient Evaluation

Due to the success of heterotopic renal transplantation, orthotopic transplantation is rarely performed. With heterotopic transplantation, the donor kidney is placed in an extraperitoneal location in the iliac fossa. CT is helpful in confirming that there is space within the fossa for the transplanted kidney. The renal artery and vein are anastomosed to the external iliac vessels. There are many techniques for reconstructing the urinary tract, but an antirefluxing ureteroneocystostomy is commonly created.

Virtually all recipients have their kidneys imaged in the course of treatment for renal failure, often a combination of ultrasound, CT, MRI, and radionuclide studies. Sometimes, specific imaging of the recipient’s native kidneys will be necessary during the pretransplant workup. Evaluation for acquired renal cystic disease and the neoplasms that such kidneys develop is best performed by CT. Patients with autosomal dominant polycystic kidney disease may also benefit from a CT examination prior to transplantation if extreme enlargement or persistent bleeding makes them candidates for nephrectomy. Patients with severe vesicoureteral reflux may require surgical therapy, so voiding cystourethrography may be necessary in patients with recurrent urinary tract infections. Voiding cystourethrography may also be indicated in patients who have been anuric so long that their ability to void normally after transplantation is questioned. Bladders in such patients may have only a small capacity and, when studied by cystography, may demonstrate benign extravasation. This finding does not indicate gross perforation of the bladder and is not a contraindication to transplantation.

Evaluation of the vessels to which the transplanted kidney’s artery and vein will be anastomosed is important. An unenhanced CT permits assessment of the degree of recipient vascular calcification; the severity of calcification is directly proportional to the degree of difficulty in performing the anastomosis. Some centers perform CTA of the common and external iliac arteries as well to evaluate them for stenosis or occlusion.

Patients with end-stage renal disease often have undergone one or more biopsies. These may lead to an arteriovenous fistula or pseudoaneurysm. While most of these are asymptomatic, some may lead to hematuria or hypertension and should be treated prior to transplantation.

COMPLICATIONS OF RENAL TRANSPLANTATION

Since it requires no intravascular contrast administration and has no ionizing radiation, ultrasound is usually the imaging modality chosen to evaluate patients after renal transplantation. Imaging of the recipient (Fig. 9.10) may show no abnormalities.

Complications of renal transplantation may be divided into those that affect the renal parenchyma and its small vessels, those that involve primarily the large vessels and their surgery, those that involve the transplanted ureter and its anastomosis, and those that appear as fluid collections in the surgical bed of the recipient. Long-term complications of renal transplantation consist primarily of neoplasms for which recipients are at increased risk due to immunosuppression.

Renal Complications

Table 9.1 reveals the times during or after transplantation that these complications are most likely to appear. These times, and some of the clinical and radiologic data that can be acquired, frequently permit a confident diagnosis of the specific complication. However, it is often difficult to establish a specific diagnosis without biopsy of the renal cortex for histologic examination.

Acute Tubular Necrosis

Acute tubular necrosis (ATN) usually occurs in the period immediately after transplantation and is related to ischemia of the transplanted kidney before vascular anastomosis. Such ischemia may occur in cadaveric donors during the agonal period of the donor and in any donor kidney during the delay between the harvesting of the kidney and the completion of vascular anastomoses in the recipient. The duration of the ischemia is directly related to the likelihood of ATN. Most episodes of ATN resolve spontaneously and appear to have little adverse effect on ultimate graft survival.

FIGURE 9.10. CT urography of two patients with kidneys transplanted into their right iliac fossae. Left: Volume-rendered image. Right: Coronal reformat.

TABLE 9.1 Temporal Sequence of Causes of Parenchymal Complications of Renal Transplants

ATN	During or immediately after surgery
Hyperacute rejection	During surgery to a few hours afterward
Accelerated acute rejection	First week after surgery
Acute rejection	1-4 wk after surgery
Chronic rejection	Months to years after surgery
Cyclosporine toxicity	1-3 mo after surgery

ATN may manifest as anuria, rising creatinine, and mild enlargement and tenderness of the graft. Graft tenderness and fever are less likely to be prominent signs of ATN than of cases of acute rejection, but the clinical picture seldom allows confident differentiation between the two conditions. ATN usually appears within 1 or 2 days after transplantation and usually resolves within a few days to a few weeks of initial onset; however, some cases may persist for several weeks before recovery. Patients who experience ATN after transplantation may require dialysis for a week until renal function returns. ATN is much more common in cadaveric transplants than living related donors.

Cyclosporine Nephrotoxicity

Cyclosporine, together with prednisone, has been the mainstay of immunosuppressive therapy. It is, however, both nephrotoxic and hepatotoxic. Newer drugs, including sirolimus, tacrolimus, and mycophenolate mofetil, permit reduction in doses of cyclosporine and diminished nephrotoxicity, albeit at the cost of increased risk of hyperlipidemia and diabetes. Cyclosporine nephrotoxicity may be acute, subacute, or chronic. Both acute and subacute
nephrotoxicity may be treated by lowering the dose of cyclosporine; chronic nephrotoxicity is seldom reversible. Acute toxicity appears to potentiate initial graft dysfunction related to ischemia and may also prolong it. Because measurement of blood cyclosporine levels does not always permit distinction of cyclosporine nephrotoxicity from other causes of transplant dysfunction, imaging data may be critical in the differential diagnosis of a failing transplant.

Rejection

Graft rejection continues to represent a significant source of morbidity in the transplant patient. Rejection is classified into four categories: (1) hyperacute rejection, (2) accelerated acute rejection, (3) acute rejection, and (4) chronic rejection. Virtually every patient experiences some form of rejection after transplantation. Differentiation of graft rejection from other causes of intrinsic renal dysfunction is crucial because rejection may require increasing the dose of immunosuppressive therapy, whereas cyclosporine nephrotoxicity should be treated in the opposite way.

Hyperacute rejection is mediated by hormonal antibodies and is often manifested during surgery; the antigen-antibody reaction causes complement activation, which in turn damages the vascular endothelium, particularly in small vessels. These vessels become filled with fibrin thrombi, thereby making extensive cortical necrosis inevitable. A graft exhibiting hyperacute rejection is seldom salvageable, and transplant nephrectomy is performed immediately.

Some authors believe that accelerated acute rejection is an antibody-mediated form of rejection identical to hyperacute rejection, but with an onset delayed until 2 or 3 days after surgery. Others believe it is a manifestation of cell-mediated immunity. Diagnosis of an accelerated acute rejection usually occurs when a rejection episode occurs in the first week of transplantation. It is frequently, but not always, successfully treated with immunosuppression.

Acute rejection constitutes functional and pathologic changes characterized by a relatively rapid increase in serum creatinine (a rise of 25% or more above the baseline level occurring within 24 to 48 hours), graft swelling and tenderness, and fever. There is usually oliguria. Acute rejection is thought to occur because of a proliferation of C-lymphocytes and to represent a cell-mediated form of immunity. Histologically, acute rejection is characterized by a proliferation of mononuclear cells, eosinophils, and plasma cells that infiltrate the interstitium of the kidney. A vascular component may also be present. Biopsy specimens in acute rejection sometimes are classified as showing primarily interstitial rejection or both interstitial and vascular abnormalities. A vascular component connotes a poorer prognosis. Acute rejection may occur at any time after transplantation, but is most often encountered during the first 10 weeks after surgery.

Chronic rejection may appear months to years after surgery and usually has a more insidious onset than acute rejection. Graft swelling and tenderness and fever are less prominent features of chronic rejection than acute rejection. Pathologic examination may reveal endothelial swelling, smooth muscle proliferation in small vessels, and glomerular changes, as well as tubular atrophy, segmental fibrosis, and diffuse infiltration with inflammatory cells. In general, the changes of chronic rejection are irreversible and lead to progressive azotemia and hypertension. Chronic allograft nephropathy is often due to a combination of chronic rejection, antirejection drug nephrotoxicity, and a vasculopathy due to more protean risk factors such as hypertension, hyperlipidemia, diabetes, and smoking. Decline in renal function may be slowed by careful management of drugs, but is rarely, if ever, halted completely.

Imaging

Imaging of patients with functional abnormalities of transplanted kidneys is a critical step in the differential diagnosis of the cause of the transplant dysfunction, but imaging findings, considered alone, do not always allow an accurate and specific diagnosis. Sometimes, the abnormality is clear, but frequently, the clinical or laboratory data must be considered along with the radiologic findings to reach a firm diagnosis. Although nuclear medicine and Doppler ultrasound findings have been the subjects of considerable investigation, findings that permit accurate distinction among rejection, cyclosporine nephrotoxicity, and ATN in the absence of clinical information have been elusive, and biopsy is frequently necessary. Scintigraphy provides quantifiable assessment of the transplant’s handling of specific compounds, but the ability of gray-scale, Doppler, and color Doppler ultrasound to evaluate vessels, flow dynamics, anatomy, and peritransplant structures has led to its usual choice as the first imaging technique.

Hyperacute rejection infrequently leads to an imaging evaluation because it usually occurs in the operating room. Because renal cortical perfusion is markedly diminished or completely absent, Doppler ultrasound will reveal little or no cortical blood flow, radionuclide examinations will show almost complete absence of perfusion or tubular accumulation (Fig. 9.11), and angiography will reveal total or near-total lack of filling of small vessels.

Accelerated acute rejection demonstrates imaging findings consistent with acute rejection, but occurs within the first week after transplantation. Rare cases of cortical nephrocalcinosis (Fig. 9.12) have been described in patients whose transplants underwent severe immediate rejection but were left in situ for several years.

Gray-scale images (Fig. 9.13) of patients with acute transplant rejection may show an increase in the volume of the kidney,
swelling, and altered echogenicity of the renal pyramids and the cortex. The high echogenicity of the sinus of a normal kidney may be diminished. These findings are thought to reflect edema of the parenchyma and of the renal sinus fat. Edema of the collecting system walls may make them appear thickened. The sensitivity of these findings to diagnose rejection, however, and the ability to distinguish rejection from cyclosporine nephrotoxicity and ATN when the findings are not clearly present are poor.

FIGURE 9.11. Hyperacute rejection. Scintigram obtained a day after transplantation shows nearly complete absence of activity in transplanted kidney. (Courtesy of Rashid Fawwaz, M.D.)

FIGURE 9.12. Cortical nephrocalcinosis from acute severe rejection. Small, calcified renal allograft is in right lower quadrant.

FIGURE 9.13. Duplex Doppler ultrasonograms. A: Normal duplex study with a PI of 1.17. B: Mild rejection; RI = 0.78, PI = 1.7. C: Severe rejection with virtually complete absence of diastolic flow (arrow).

There is diminution of renal blood flow in rejection, cyclosporine nephrotoxicity, and ATN. Although there are variations in the severity of oligemia among cases of each condition, attempts have been made to use Doppler flow studies to distinguish acute rejection from ATN and cyclosporine nephrotoxicity by analyzing signals from the main renal artery and from intrarenal branches. In patients with acute rejection—especially those in whom vascular changes predominate in biopsy specimens, as opposed to those in whom the histologic changes are primarily interstitial where the resistive index (RI) is often elevated (Fig. 9.13). When the RI is 0.90 or higher, acute rejection is likely, although occasionally elevated RIs may be caused by arterial stenosis, renal vein thrombosis, acute severe ureteral obstruction, severe ATN, acute cyclosporine nephrotoxicity, pyelonephritis, and compression of the kidney by a perirenal fluid collection. With lower RIs, primarily interstitial acute
rejection, cyclosporine nephrotoxicity, and ATN are possible etiologies. Because rejection and ATN may not affect the entire kidney uniformly and because RIs may vary from observer to observer, the accuracy of this method of differential diagnosis is far from ideal and many authors feel that RI measurements are not useful. In some centers, the pulsatility index (PI) ([peak systolic frequency shift-diastolic frequency shift]/the mean frequency shift) is used as an alternative to measurement of the RI. A PI of 1.5 or greater is generally considered indicative of rejection. In patients with ATN, higher RI and PI values are associated with longer periods of recovery of function. Power Doppler findings have not improved upon the differentiation between acute rejection and other causes of graft failure.

RI and PI values may have prognostic significance as well. If they remain elevated in the first transplant month, even in patients with stable renal function, the kidneys are at increased risk to develop chronic allograft nephropathy, and the risk is worse if there are progressive rises in these indices. An elevated RI in the graft vessels also indicates an increased risk for the subsequent development or worsening of general cardiovascular disease, possibly because this parameter not only reflects abnormal vessels in the graft but also indicates decreased compliance of the systemic arteries in the rest of the body.

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