Clinical relevance of low levels of preformed alloantibodies detected by flow cytometry in the first year post-kidney transplantation.

OBJECTIVE: To determine the prevalence of transplants performed with a false-negative cytotoxicity cross-match and to analyze the clinical relevance of alloantibodies (Ab) detected only by flow cytometry (flow). METHODS: We studied 66 patients undergoing kidney transplantation from a cadaveric donor. All patients had a simultaneous negative T+AHG+DTT and B+DTT. Pretransplant sera were retrospectively analyzed by flow cytometry according to an Emory University protocol: (1) T+ and B-: Ab anti-class I; (2) T- and B+: anti-class II; (3) T+B+: anti-class I + II. Chi-square, Fisher exact, Student t test, and Kaplan Meier analyses were employed with significance assigned at P < or = .05. RESULTS: The overall incidence of false-negative cytotoxicity was 33.3% (22/66), namely, 6.1% (n = 4) anti-class I; 9.1% (n = 6) anti-class II; and 18.2% (n = 12) anti-class I + II. Primary nonfunctioning grafts occurred in 6.8% (3/44) and 13.6% (3/22) negative and positive flow patients (two anti-class I + II and one class II; P = .39). The incidence of graft loss in the first year was respectively, 13.6% (6/44) and 18.2% (4/22; two anti-class II and two anti-class I + II; P = .72). Compared to flow-negative grafts, creatinine levels were significantly higher among flow-positive patients at 8 and 12 weeks. One-year graft survivals were 86.4% among negative versus 81.8% for the positive group (P = .67). CONCLUSIONS: We observed that 33% of kidney transplant recipients had low levels of alloantibodies detected only by flow. This single factor was associated with the worst graft function in the first trimester with a suggestion of a higher risk for non-functioning graft.

Antigenemia for cytomegalovirus in renal transplantation: choosing a cutoff for the diagnosis criteria in cytomegalovirus disease.

Cytomegalovirus (CMV) infection is a frequent complication in transplant recipients, causing a high level of morbidity and mortality. We studied 203 consecutive renal transplant recipients performed between January 2000 and December 2001. Patients underwent weekly measurements of CMV pp65 antigen to assess CMV activity from the 4th to the 12th week posttransplantation. The results were reported as number of cells positive for the pp65 antigen among 10(5) granulocytes. In order to define a best cutoff to diagnose CMV disease with desirable sensitivity and specificity, we used a receiver operator characteristics (ROC) curve. The cutoff of four positive cells corresponded to a sensitivity of 93% and specificity of 60% (AUC = 0.87) for the diagnosis of CMV disease. The chosen cutoff for starting antiviral treatment was 10 cells, since this was associated with a sensitivity of 92% and specificity of 70% (AUC = 0.90). In conclusion, the highly sensitive cutoff points for the diagnosis of antigenemia was four cells and 10 cells for initiation of antiviral therapy.

Immunoglobulin G-positive in B-cell cross-match decreases kidney allograft survival.

We retrospectively studied all 1149 transplants performed at our center between 1993 and 2003 to determine the incidence and clinical effect of pretransplant B-positive cross-match on kidney graft survival. The patients were divided in two groups: B-negative (n = 1102) and B-positive in current sera (n = 47; 4.1%). AB-positive test was more frequent among regrafted patients (14% vs 3%; P = .00). Demographic data were not different between the groups. The overall rate of graft loss was similar (26% vs 24%, respectively; P = .86). However, early nonsurgical graft losses were more frequent among B-positive patients (46% vs 20%, respectively; P = .04). IgM was the most frequent immunoglobulin in the B-positive group (76% IgM and 24% IgG). There was no significant difference between B-negative and B-positive groups in the 1-, 5-, and 10-year graft survival rates (87% vs 83%, 73% vs 78%, 64% vs 66%, respectively; P = .87). The graft survival was significantly reduced comparing an IgG anti-B cell to the B-negative group (P = .03) as well as IgG compared to IgM (P = .004). In conclusion, only B-positive cross-match due to IgG decreased graft survival. Even though it is an uncommon situation (0.9%), this study stressed the clinical value of the B-cell cross-match as a tool to identify patients with a higher immunological risk.

Comparison between RFLP-PCR and antigenemia for pp65 antigen for diagnosis of cytomegalovirus disease after kidney transplantation.

Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The purpose of this study was to analyze the diagnostic efficacy of PCR-RFLP compared to antigenemia for CMV disease (CMVD) in kidney transplant recipients. From November 2001 to February 2002, 19 renal adult transplant recipients were followed with weekly measurements of CMV pp65 antigen to monitor the activity of CMV from the week 4 to 12 posttransplantation. Only 4 (21.1%) patients did not develop viremia during the first 12 posttransplantation weeks. Active infection was observed in 15 patients (78.9%): asymptomatic viremia in 6 (31.6%) and CMVD in 9 (47%). All patients who developed CMVD showed positivity in both methods during the observation period. The number of positive cells ranged from 11 to 292 cells in patients with CMVD and one to eight cells among those with asymptomatic viremia. Both methods revealed 100% sensitivity for CMVD diagnosis. The specificity was 60% for antigenemia and 70% for PCR, with positive predictive values of 60% and 75%, respectively.

Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation.

Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The aim of this study was to determine the incidence of latent and active infections with CMV during the first 3 months after kidney transplantation. From January 2000 to December 2001, 203 consecutive adult renal transplant recipients underwent weekly measurements of pp65 CMV antigen from the 4th to the 12th posttransplantation week. Latent infection (seropositivity) was found in 92% of the population. Primary infection occurred in 4.9% (10 of 203), among whom 66% were previously seronegative patients. Among the primary infection patients, 70% (7 of 10) developed severe disease. The overall incidence of viremia was 69.5%, being more frequent among cadaver recipients (79% vs 59%; P =.02). The overall incidence of CMV disease was 38.4% (78 of 203) with 24.6% classified as severe disease requiring antiviral therapy. In conclusion, our population showed a high prevalence of latent infection with viremia. Not all patients developed clinical disease. Most subjects experienced a mild spectrum of symptoms, probably due to the prospective search for active infection during the major risk period after kidney transplantation.