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Biomedical subjects

F Vincenti

Publications and source records attributed to F Vincenti.

At least 55 records · Page 3Linked to original sources

Long-term outcome in kidney transplant patients with hepatitis C (HCV) infection.

To assess the prevalence and long-term impact of HCV on kidney transplant recipients, we assayed 716 pre-transplant sera using a first-generation ELISA. The anti-HCV positive sera were confirmed by a 6-antigen radioimmunoassay (RIA). Patients were followed up for 5 years. Graft survival, function, evidence of chemical hepatitis (AST > 2x normal), patient mortality and cause of death were evaluated. The prevalence of anti-HCV antibody was 10.3%. In the 638 patients who were followed up for 5 years, there were no differences in graft function, graft survival, overall mortality, or death from sepsis or liver disease. Peak AST levels were significantly higher in anti-HCV positive patients compared to anti-HCV negative patients. At 5 years, the AST levels remained significantly higher in the anti-HCV positive group, however, this was only 6 U/1 > normal. Liver biopsies performed 3 to 7 years post-transplant in 80% of anti-HCV positive patients with chemical hepatitis showed 12% CAH, 50% mild hepatitis and 38% normal histology. Six (9.7%) patients seroconverted from anti-HCV positive to anti-HCV negative 2 to 5 years post-transplant. The presence of anti-HCV does not appear to alter long-term patient or graft survival, and histologic evidence of severe chronic liver disease was rare in anti-HCV positive patients with chemical hepatitis. From these results, the presence of anti-HCV antibody should not preclude kidney transplantation.

Adolescent↗

Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis.

To test the hypothesis that a circulating mediator is associated with recurrent idiopathic focal glomerulosclerosis (FGS), we studied the effect of plasmapheresis on reducing proteinuria in patients with the disease. An in vitro assay measured the capacity of sera before and after plasmapheresis to cause increased albumin permeability (P(albumin)++) in isolated rat glomeruli. Nine patients (five males aged 2 to 66 years) who underwent plasmapheresis for recurrent FGS were identified. Study variables included age, sex, time from diagnosis of recurrence to first pheresis, glomerular hyalinosis, complications, outcome, and proteinuria before and after plasmapheresis. Rat glomeruli were isolated in medium containing 4 g/dL bovine serum albumin, and P(albumin) was determined from the change in glomerular volume in response to an albumin gradient after incubation of the glomeruli in a 1:50 dilution of patient serum. Plasmapheresis reduced proteinuria from a mean of 12 +/- 7.46 g/24 hr to 5.1 +/- 7.39 g/24 hr (P = 0.03). Six patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had lasting remissions. Preplasmapheresis biopsies in the patients who did not achieve remissions showed both epithelial foot process effacement and glomerular sclerosis. Serum samples were available from four patients for albumin testing in vitro. P(albumin)++ was reduced from a mean of 0.76 +/- 0.17 before pheresis to 0.18 +/- 0.31 after (P = 0.07). Therefore, the mechanism by which plasmapheresis reduces proteinuria in patients with recurrent FGS involves the decreased capacity of sera from these patients to injure the glomerular permeability barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hepatitis C--its prevalence in end-stage renal failure patients and clinical course after kidney transplantation.

There is a high incidence of chronic liver disease in end-stage renal failure patients on dialysis. Hepatitis C virus appears responsible for 80% of posttransfusion hepatitis, and up to 80% of sporadic hepatitis and cryptogenic cirrhosis. Anti-HCV antibodies correlate highly with the presence of active infection. The clinical implications of HCV infection in patients undergoing renal transplantation is unknown. Part I: We undertook a descriptive cross-sectional study of all renal failure patients admitted for kidney transplant between 1/84 and 12/88. Pretransplant sera were assayed for anti-HCV using an ELISA. Patients were divided into anti-HCV-positive (study group) and anti-HCV-negative (controls). Part II: A cohort study was performed with both groups followed from the time of transplantation to the present. Comparisons were made by t tests, chi-square analysis with Yates correction, Mann Whitney test for nonparametric results and multiple regression analysis. Part I: Anti-HCV was present in 76 of 716 sera assayed. There were no differences in sex, age, number of previous transplants, and underlying renal disease. Four variables predicted the presence of anti-HCV: number of blood transfusions; duration on dialysis; i.v. drug abuse, and nonwhite race. Part II: A group of 596 patients was further analyzed. The mean duration of follow-up was not different between the two groups. There were no differences in graft survival, overall mortality, or mortality secondary to liver disease or sepsis. Based on these results, the presence of anti-HCV should not be a contraindication for kidney transplantation.

Adolescent↗

Recurrent focal glomerulosclerosis: natural history and response to therapy.

PURPOSE: Recurrent focal glomerulosclerosis (FGS) has been well documented since it was first reported in 1972. However, the course of the disease after transplantation and the optimal treatment regimen have not been well defined since the introduction of newer treatment modalities. PATIENTS AND METHODS: We reviewed all the charts of patients with biospy-proven FGS who received renal transplants at our institution from January 1980 through December 1990. Case histories consistent with diagnoses other than primary FGS (such as reflux nephropathy or intravenous drug use) were eliminated from the study. During this time period, 78 allografts were received by 71 patients with FGS. Independent variables that were analyzed included sex, race, time in months between the diagnosis of FGS and end-stage disease (dialysis or transplantation), age at time of transplantation, type of dialysis, source of allograft (cadaveric or living related), haplotype matching, donor-specific transfusions, age and sex of the donor, post-transplantation acute tubular necrosis, rejection episodes, immunosuppression regimen, use of plasmapheresis and angiotensin converting enzyme (ACE) inhibitors, and outcome. RESULTS: FGS recurred in 25 allografts (32%) of 21 patients. Biopsy-proven diagnosis of recurrence was made a mean of 7.5 months (range: 0.5 to 44 months) after transplantation. Patients who had rapid progression to end-stage disease tended to experience more frequent recurrences. Of seven patients who received a second transplant, five patients lost the first graft to recurrent FGS, and four of those patients (80%) had a recurrence in the second allograft. Recurrent disease developed in 34% of patients concurrently treated with cyclosporine and in 28% of those treated with prednisone and azathioprine alone (NS). Patients with recurrent FGS who were treated with ACE inhibitors benefited from a significant reduction of proteinuria. Six patients underwent plasmapheresis after diagnosis of the recurrence. Three of five patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had reversal of epithelial foot process effacement and remission of proteinuria. End-stage disease eventually developed in 14 allografts (56%) an average of 23.7 months (range: 1 to 65 months) after diagnosis of recurrent disease. The cause of failure was chronic rejection in four allografts and recurrent disease in the remaining 10 allografts. CONCLUSIONS: FGS recurs in approximately 30% of allografts and causes graft loss in half of these. Patients who have lost a first allograft to recurrent FGS are at high risk for developing recurrent disease in a second allograft. Prolonged allograft survival is possible in patients with recurrent FGS and may best be obtained with a combination of treatment modalities including cyclosporine (perhaps in higher dosages than are routinely used in clinical renal transplantation), ACE inhibitors, and early use of plasmapheresis. The efficacy of these modalities supports the notion that recurrent FGS is caused by a circulating humoral mediator.

Adolescent↗

Cytokine and T cell receptor gene expression at the site of allograft rejection.

Intragraft cytokine and T cell receptor gene expression was analyzed in rejecting renal allografts by polymerase chain reaction (PCR). Message for IL-1 beta, IL-6, and TNF-alpha was detected in nephrectomy tissue with pathological evidence of acute or chronic rejection. Similarly, mRNA for both IL-6 and TNF-alpha was present in renal biopsies from acute rejecting kidneys. IL-2R, IL-4, and IL-5 mRNA was present in both rejecting and rejected kidney allografts, indicating that these cytokines may play a role in ongoing renal allograft rejection. Conversely, IL-2, IL-7, and IFN-gamma message was detected infrequently. In order to address the diversity of T cells in rejecting kidneys, we have analyzed the clonality of the TcR present within the allograft tissue. Rearranged TcR genes were identified in all allografts examined (n = 16) indicating the presence of T cells bearing the alpha/beta TcR. We have determined that there is a heterogeneous infiltration of T cells in the rejected allograft with TcR representing x = 7.47 +/- 2.4 families rearranged in samples obtained from nephrectomies, whereas x = 5.33 +/- 0.58 families were detected in samples obtained from biopsy tissue. These data indicate that (1) cytokines are produced locally which may contribute to graft cell destruction, (2) the heterogeneity of intragraft T cells during kidney allograft rejection may exist because nonspecific lymphocytes have been recruited to the site by locally produced cytokines or because T cells are responding to multiple epitopes or multiple donor antigens. Detection of intragraft cytokines and TcR may prove useful in elucidating the mechanism of rejection and therefore lead to improved immunosuppression.

Adolescent↗

Improved results with combined donor-specific transfusion (DST) and sequential therapy protocol.

A combined DST-sequential CyA therapy protocol has been described that results in optimum graft survival for 1- and 2-haplotype mismatched living related donor-recipient combinations. In addition to the excellent graft survival obtained through 4 years, lower prednisone and CyA dosage levels are achieved with significantly decreased infection rates during the posttransplant period.

Blood Transfusion↗

Inability of cyclosporine to completely prevent the recurrence of focal glomerulosclerosis after kidney transplantation.

From January 1984 through July 1986, 15 patients with biopsy-proven focal glomerulosclerosis (FGS) underwent kidney transplantation. Following transplantation, all patients were immunosuppressed with cyclosporine and prednisone. There were 8 men and 7 women with a mean age of 33 years (range, 16-47 years). Five patients (33%) had recurrence of FGS. Two patients had received kidneys from HLA identical siblings, and 3 patients were transplanted with cadaveric kidneys. In 4 out of 5 patients, the recurrence of FGS occurred within 3 months of transplantation. Of the 2 graft losses in this group, one was from recurrence of FGS. Ten patients followed for a mean of 25 months did not develop recurrence of FGS. No graft loss occurred in this group. Three patients with end-stage renal disease of unknown etiology were found to have FGS in the renal allograft and were presumed to have recurrence of FGS. All 3 patients developed the nephrotic syndrome following transplantation, and 1 patient has had progressive renal failure. Cyclosporine did not prevent the recurrence or the clinical manifestations of FGS following kidney transplantation. Additional studies are needed to determine if cyclosporine is effective in certain subgroups of patients with FGS.

Adolescent↗

The beneficial effect of pretransplant blood transfusions in cyclosporine-treated cadaver renal allograft recipients.

212 cyclosporine-treated recipients of mismatched first cadaveric renal allografts are evaluated with respect to the effect of pretransplant random blood transfusions. It is determined that transfusions do not effect patient survival or morbidity. Pretransplant random blood transfusions correlate with significantly improved allograft success. There is also a trend, although not statistically significant, for further improvement of allograft survival with increasing numbers of transfusions. The transfusion effect is not related to the time at which the transfusions are given up to 2 years prior to transplantation. Transfused patients have a higher percent reactive antibody (PRA) than untransfused patients, but this does not cause them to wait for a cadaveric allograft significantly longer than the untransfused patients. Rejections are less severe in transfused patients. It is concluded that cyclosporine-treated recipients of first cadaveric renal allografts benefit from pretransplant blood transfusions.

Blood Transfusion↗

Posttransplant renal rejection: comparison of quantitative scintigraphy, US, and MR imaging.

Accuracy of ultrasonography (US), quantitative scintigraphy, and magnetic resonance (MR) imaging in diagnosis of acute renal allograft rejection was studied in 46 patients who underwent renal biopsy. Thirty-three patients had acute rejection; six, cyclosporine nephrotoxicity, as shown by biopsy, clinical findings, and follow-up study; two, acute tubular necrosis; and five, normal biopsy findings and renal function. Accuracy in demonstrating rejection was 72% for US and 75% for scintigraphy, indicating no significant difference between the two. MR imaging was significantly more accurate, reaching a level of 98%. However, accuracy of MR in demonstrating acute tubular necrosis in a larger number of patients is not known, and its accuracy in indicating recurrent glomerulopathy or infectious disease has not been addressed. The definitive role of MR in evaluating posttransplant renal failure is currently not established, but because of its high sensitivity in detecting renal abnormality, MR can be used for cases when results of US or scintigraphy are equivocal or contradict clinical impressions or when biopsy cannot be performed for medical reasons.

Adult↗