SEQUENTIAL DETERMINATIONS OF URINARY CYTOLOGY AND PLASMA AND URINARY LYMPHOKINES IN THE MANAGEMENT OF RENAL ALLOGRAFT RECIPIENTS

Publisher Website
Google Scholar
Abstract
Urine cytology, plasma (P), and urinary (U) interleukin-2 (IL-2) and IL-2 receptor (IL-2R) levels were evaluated as immunological monitoring techniques in 65 renal allograft recipients. Normal individuals showed normal urine cytology, IL-2(U) = 0, IL-2(P) = 0.4 .+-. 0.1 ng/ml (mean .+-. SEM) and IL-2R(P) = 318 .+-. 26 U/ml. Stable transplants also showed normal urine cytology, no IL-2(U), IL-2(P) = 0.8 .+-. 0.2 ng/ml, and IL-2R(P) = 326 .+-. 29 U/ml. Rejection episodes (n = 21) were accompanied by cytologic changes, including lymphocyturia, exfoliation of immature tubular cells, platelet aggregates, and fibrin deposits. The corresponding lymphokine changes wer IL-2(U) = 39.6 .+-. 1.4 ng/ml, IL-2(P) = 79 .+-. 21 ng/ml, and IL-2R = 1884 .+-. 202 U/ml, all markedly increased. Successful treatment was associated with return of all parameters to normal; treatment failure was associated with continued abnormalities. Fourteen rejections unresponsive to Solumedrol (500 mg .times. 5 days) required OKT3 rescue (5 mg .times. 14 days). In the 11 that were reversed, onset of OKT3 therapy was characterized by markedly increased exfoliation of necrotic cellular debris, lymphocytes, and collecting duet cells. Interestingly, serum creatinine increases of 57.2 .+-. 18.9% (range 25-90%) over pre-OKT3 levels were noted. Maximal changes occurred 48-72 hr after the first dose, followed by gradual return to normal. Rejections unresponsive to OKT3 (n = 3) showed no cytologic changes from the pretreatment mean creatinine increase of 13.2 .+-. 2.7% (range 9-15%), and maximum change occurred 24 hr after the first dose. Rejections responsive to Solumedrol only (n = 4) showed gradual improvement of all parameters. Rejections treated with Solumedrol following failed OKT3 prophylaxis (n = 3) did not reverse and continued to show rejection associated cytologic changes and abnormal creatinines. Patients experiencing CsA toxicity (n = 12) showed mild creatinine elevations, normal or negative IL-2(P) and IL-2R(P) levels, and no IL-2(U). They showed distinctive cytologic changes consisting of swollen convoluted tubular cells with nuclear pyknosis and cytoplasmic vacuoles. Pretransplant IL-2(P) levels of patients who subsequently rejected were elevated, with 19/21 patients with preoperative IL-2 levels >15 ng/ml having subsequent rejections. In contrast, pretransplant creatinine, urine cytology, and IL-2(U) levels showed no correlation to subsequent clinical course. These results suggest that (1) renal allograft rejection is strongly associated with the appearance of IL-2, lymphocytes, and collecting duct cells in urine, (2) successful outcome of OKT3 treatment can be predicted by a sharp initial increase in creatinine and exfoliated cells in the urine, (3) CsA toxicity and rejection have distinct cytologic and lymphokine profiles, and (4) high plasma IL-2 levels prior to transplant are associated with subsequent rejections.