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Renal Transplant Evaluation Radionuclide Evaluation of Renal Transplants Eva V. Dubovsky, Charles D. Russell, and Belkis Erbas Chronic renal failure caused by hypertension or by have taken place in this field in recent years. These parenchymal kidney disease is a very common global changes comprise new criteria for the selection of health problem. Patients with chronic renal failure transplant candidates, newer techniques for the diag- have two therapeutic options, dialysis and transplanta- nosis of medical and surgical complications after trans- tion, of which transplantation has become a preferred plantation, the use of new tracers (Tc-99m MAG3), and modality. This review article is an update of a more new antirejection regimens. comprehensive previous review (Semin Nucl Med, Copyright 1995 by W.B. Saunders Company 181-198, 1988) and concentrates on the changes that ENAL TRANSPLANTATION has be- is not responsive to currently available therapy. R come the preferred treatment for end- Hypertension and complicating infections such stage renal disease because survival is longer as cytomegalovirus also limit graft survival. than with dialysis? Recently reported patient survival rates for cadaver grafts were 94% for COMPLICATIONS OF RENAL recipients of a first or second graft and 92% for TRANSPLANTATION patients with multiple grafts. 2 The 1-year sur- Acute tubular necrosis (ATN), acute rejec- vival rate for a transplanted cadaver kidney was tion (AR), and CR are the complications most 80%, 74%, and 66% for first, second, and commonly seen in referrals to Nuclear Medi- multiple transplants, respectively. Results were cine. ATN is seen in the immediate posttrans- even better for living-related donor grafts, with plant period in a high percentage of cadaver graft survival rates of 95% for human lympho- grafts, but only infrequently in transplants from cyte antigen (HLA): identical grafts and about living related donors. Acute rejection typically 90% for 1-haplotype-matched grafts. The pro- occurs at least 4 or 5 days after transplantation. jected graft half-lives were 26 years for HLA- It is most common in the first year, but can identical grafts and 12 to 14 years for single occur at any time, particularly with lapses in haplotype-mismatched grafts. immunotherapy. CR typically occurs after a Transplantation technology has progressed period of 1 year, but episodes of AR can lead to residual impairment of function that is indistin- greatly since the first successful kidney graft guishable from CR on radionuclide studies. A performed 40 years ago between monozygotic number of less common complications can also twins) Advances have occurred in methodology be identified on radionuclide studies. These for identifying tissue antigens and antibodies. 4,5 complications tend to occur at characteristic New drugs are available for immunosuppres- time intervals after transplantation, as indicated sion. Newer immunosuppressive agents cur- in Table 1.8,9 rently in clinical trials include FK-506, Rapa- The immunologic complications are related mYcin, RS-61443, and 15-deoxysperqualin. 6 to the quality of HLA matching between donor Monoclonal antibodies are also used to modify and recipient. 4,5 Best results are obtained in the immune response. OK-T3 is available for HLA-identical siblings and in cadaver grafts routine use and other monoclonal antibodies with HLA A, B, DR matches. When such close are undergoing trials. These agents can be used matching is not obtained, AR is common. It is in rescue protocols to treat otherwise unrespon- graded histologically from grade 1 (interstitial sive rejection, and may ultimately lead to the development of steroid-free maintenance immu- notherapy. From the Division of Nuclear Medicine, University of Many factors effect the long term results, Alabama Hospital, and the Nuclear Medicine Service, V..A. including the quality of the transplanted kidney Medical Center--Birmingham, Birmingham, AL. and the socioeconomic status, age, race, and Address reprint requests to E.V. Dubovsky, MD, PhD, general health of the recipient. 7 Chronic allo- Division of Nuclear Medicine, University of Alubama Hospital, 619-19th St S, Birmingham, AL 35233-6835. graft nephropathy (chronic rejection [CR]) lim- Copyright 1995 by W.B. Saunders Company its graft survival, but it is poorly understood and 0001-2998/94/2501-000555. 00/0 Seminars in Nuclear Medicine, Vol XXV, No 1 (January), 1995: pp 49-59 49 50 DUBOVSKY, RUSSELL, AND ERBAS Table 1. Complications After Transplantation Pertinent CR is a slow, irreversible process leading to a to Nuclear Medicine gradual loss of graft function. 11 It is graded Most FrequentTime histologically from grade 1 (interstitial fibrosis Complication of Occurrence Comments and tubular atrophy), through grade 2 (similar Surgical but more extensive change), to grade 3 (severe Wound infec- Within first few Surgical and tion weeks medical treat- fibrosis with loss of tubules).10 The mechanism ment is not well understood, and the presently avail- Abscess Few days/weeks Drainage able antirejection drugs are not very effective. Hematoma Within hours to Drainage Hyperacute rejection is seldom seen. Graft days failure occurs immediately on transplantation. Lymphocele Second to fourth Drainage, scle- month rosing agents Within 1 hour, polymorph accumulation is seen Urine leak Within hours to Surgical repair in glomerular and peritubular capillaries.I~ Cap- days illary thrombosis then occurs. It is presumably Obstruction caused by preexisting antibodies that escape Intrinsic pres- Days, months, Clots, scars, cal- detection in pretransplantation screening. sure years culi surgical repair A variety of surgical complications can occur. Extrinsic Days, months, Lymphocele, Vascular complications such as arterial or ve- pressure years hematoma, nous thrombosis, stenosis, arterial-venous fistu- drainage lae. and pseudoaneurysms can occur either in Renal artery ste- Anytime Medical therapy, nosis PTA or surgery the immediate postoperative period or later, and are all detectable by radionuclide studies. 12 Medical Obstruction may be either intrinsic (clots, stones. Ischemic Present at time of Cadaveric ureteral stenosis) or extrinsic (lymphoceles, he- damage kidney trans- mx-common matoma, abscesses) and are similarly detect- (ATN) plantation Resolves without therapy able. 13 Urine leaks typically occur soon after Immunologic Within minutes to Preformed anti- transplantation and are also seen on radionu- hyperacute hours bodies, irrevers- clide studies. ible-rare Impaired graft function often is caused by Acute Rapid develop- Predominantly multiple contributing causes. AR frequently ment after sev- cell mediated, eral days, most reversible with occurs before ATN has fully resolved. Cyclospo- common during therapy rin toxicity may be a contributing factor, and it is first three difficult to identify. The original disease that months necessitated transplantation may recur. Func- Chronic Usually after a few Humoral, irrevers- tion may also be affected by drugs such as months or ible years, slowly antibiotics, angiotensin converting enzyme in- developing hibitors,14 or radiographic-contrast agents. 15 Other Although this chapter deals with radionu- Cyclosporin While on medica- Improvement after clide methods, alternative diagnostic proce- tion (high withdrawal plasma levels) dures should be kept in mind. Sonography is Recurrent dis- Any time Biopsy excellent for detection of perigraft fluid collec- ease tions and urinary tract obstruction, but to date has not proven reliable for identifying rejec- tion. 16 For identification of stones and stenoses, mononuclear infiltration), through grade 2 (fo- intravenous urography may be performed with cal severe tubulitis, mild to moderate intimal nonionic contrast agents. 15 For vascular compl i- arteritis), to grade 3 (severe intimal arteritis cations, arteriograms may be performed with with fibrinoid change, necrosis of medial smooth dilute contrast and digital subtraction. 12 CT and muscle cells, focal infarction, interstitial hemor- magnetic resonance imaging (MRI) can give rhage)J ~ Swelling, pain, and fever are observed very useful results in the differential diagnosis clinically. AR develops rapidly and is usually of surgical complications, but they currently treated successfully. play a limited role because of their cost. RADIONUCLIDE EVALUATION OF RENAL TRANSPLANTS 51 GENERAL CONSIDERATIONS tubular function). Thus, we propose reverting in Radionuclide diagnostic tests are valuable in part to Taplin's original terminology. renal transplantation because they provide a VASCULAR PHASE: EVALUATION noninvasive means to evaluate transplant func- OF BLOOD FLOW tion quickly and quantitatively, while simulta- neously screening for a variety of surgical com- Data Acquisition plications. The differential diagnosis frequently A large field of view camera with low-energy requires correlation with the patient's clinical all-purpose collimator is placed over the ante- course, current therapy, prior scintigraphic find- rior abdomen in such a way that the abdominal ings, and the results of other diagnostic tests. aorta, the graft, and both iliac arteries are For example, the scintigraphic findings are quite included in the field of view. After bolus intrave- similar for ATN and AR, so that these two nous injection of Tc-99m pentetate (DTPA) (5 entities are best differentiated by progressive to 15 mCi or 185 to 555 MBq) or Tc-99m MAG3 changes on serial studies. A baseline study 1 or (3 to 10 mCi or 111 to 370 MBq), the
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