URINARY CYTOKINE PATTERNS IN RENAL ALLOGRAFT RECIPIENTS

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137 Cytokine expression in transplant biopsies has been found to correlate with acute rejection episodes. We postulated that urinary cytokine is a combination of filtered, secreted, and in situ production and that individual patients would have characteristic patterns reflective of the clinical state. Urine was collected from renal allograft patients attending clinic. We validated ELISA assays for IL-4, IL-6, MCP-1, RANTES, and TNF-α under conditions which permitted accurate determinations despite wide ranges of urinary pH, osmolarity, and protein content. For each patient, urinary cytokine concentrations (Ucyt) were measured on three or more occasions spanning a period of at least six weeks. The cytokine concentrations were converted into an estimate of cytokine excretion in ng per 24 hours (CytExc) using the formula: CytExc = (Ucyt x Wt)/(Ucreat × 70), where (Wt) is the patient weight in Kg. Recipients of a renal allograft were classified into 3 groups by an individual blinded to the cytokine results: Group 1- stable good function (Creat<2); Group 2- resolved acute azotemia(Creat<2); Group 3-chronic stable dysfunction (Creat>2). Results: 1) The distribution of urinary cytokine readily segregated into"high" and "low" excretors for each cytokine. 2) The pattern of cytokine excretion was stable with individual patients 3) Patients in Group 1 tended to have low IL-4 and IL-6 excretion and high TNF- α(figure). 4) Patients in Group 3, in contrast, had high IL-4 and IL-6 and low TNF- α excretion. 5) Patients in Group 2 had an intermediate profile closer to Group 3. 6) The mean TNF- α, IL-6, and IL-4 levels were significantly different in Group 1 vs Group 3 and Group 1 vs Group 2. This was not the case for either RANTES or MCP-1 (data not shown). Our findings indicate that urinary cytokine patterns are a promising tool for investigation of renal transplant pathophysiology.