Implication of gammadelta T cells in the human immune response to cytomegalovirus. (57/8017)

In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates. This in vitro expansion was inhibited by anti-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.  (+info)

The SF36 as an outcome measure of services for end stage renal failure. (58/8017)

OBJECTIVE: To evaluate the use of the short form 36 (SF36) as a measure of health related quality of life of patients with end stage renal failure, document the results, and investigate factors, including mode of treatment, which may influence it. DESIGN: Cross sectional survey of patients with end stage renal failure, with the standard United Kingdom version of the SF36 supplemented by specific questions for end stage renal failure. SETTING: A teaching hospital renal unit. SUBJECTS AND METHODS: 660 patients treated at the Sheffield Kidney Institute by haemodialysis, peritoneal dialysis, and transplantation. Internal consistency, percentage of maximal or minimal responses, SF36 scores, effect sizes, correlations between independent predictor variables and individual dimension scores of the SF36. Multiple regression analysis of the SF36 scores for the physical functioning, vitality, and mental health dimensions against treatment, age, risk (comorbidity) score, and other independent variables. RESULTS: A high response rate was achieved. Internal consistency was good. There were no floor or ceiling effects other than for the two "role" dimensions. Overall health related quality of life was poor compared with the general population. Having a functioning transplant was a significant predictor of higher score in the three dimensions (physical functioning, vitality, and mental health) for which multiple regression models were constructed. Age, sex, comorbidity, duration of treatment, level of social and emotional support, household numbers, and hospital dialysis were also (variably) significant predictors. CONCLUSIONS: The SF36 is a practical and consistent questionnaire in this context, and there is evidence to support its construct validity. Overall the health related quality of life of these patients is poor, although transplantation is associated with higher scores independently of the effect of age and comorbidity. Age, comorbidity, and sex are also predictive of the scores attained in the three dimensions studied. Further studies are required to ascertain whether altering those predictor variables which are under the influence of professional carers is associated with changes in health related quality of life, and thus confirm the value of this outcome as a measure of quality of care.  (+info)

Annual Report of the German Renal Registry 1998. QuaSi-Niere Task Group for Quality Assurance in Renal Replacement Therapy. (59/8017)

During the past 3 years, the basis of a German Renal Registry has been established. An agreement between end-stage renal disease (ESRD) therapy providers, insurance companies and the government has been reached to fund and support the registry office and its electronic data base. An overall acceptable compliance has been achieved to provide data voluntarily, although in the future the data submission will have to be mandatory to achieve complete data sampling within an acceptable time frame. In Germany, 713 patients per million population (p.m.p.) are on renal replacement therapy (RRT). The incidence of new patients commencing RRT is 156 p.m.p. These numbers are comparable with those reported from other European countries such as France, Italy and Spain, but significantly lower than those reported from the US or Japan. More than 92% of all dialysis patients are treated by haemodialysis and only a limited number with peritoneal dialysis. Approximately 25% of the patients have a functioning kidney graft. The transplantation rate of 25 p.m.p. is far from sufficient if compared with Spain, Austria or the US. Although an increasing number of diabetic patients commenced RRT, the percentage, i.e. approximately 30%, is less than in the US or Japan. The annual growth of the population on renal replacement cannot currently be given precisely because the database is still limited, but it seems to be approximately 3-4%.  (+info)

Polycystic kidney disease as a risk factor for post-transplant diabetes mellitus. (60/8017)

BACKGROUND: Insulin resistance with compensatory hyperinsulinaemia has been reported in adult polycystic kidney disease (APKD) patients. Diabetes mellitus is a common complication following transplantation and previous studies have demonstrated that inadequate insulin secretion was a prerequisite for the development of post-transplant diabetes mellitus (PTDM). We conducted a retrospective study to determine whether APKD is a risk factor for PTDM. METHODS: Twenty-six consecutive patients transplanted because of end-stage renal disease due to APKD were studied. A control patient matched for age, gender, immunosuppressive therapy and transplant year was selected for each APKD patient. PTDM was defined by fasting glycaemia exceeding 7.8 mmol/l and the need for insulin or oral antidiabetic therapy. RESULTS: Age, renal function, immunosuppressive regimen, number of acute rejection, cumulative dose of steroids and haemodialysis duration before transplantation were similar in both groups. PTDM occured in 10 APKD patients and four controls (34.6% vs 15.3%; P < 0.005). Among diabetic patients, six APKD patients and two controls required insulin therapy (60% vs 50%; P = n.s.). Diabetic patients were significantly older (55.8 +/- 7 years vs 50.2 +/- 11 years; P < 0.05). CONCLUSION: Although retrospective, this study suggests that APKD confers an increased risk of PTDM.  (+info)

Immunologic parameters as predictive factors of cytomegalovirus disease in renal allograft recipients. (61/8017)

Cytomegalovirus (CMV) disease is a major problem in renal transplant recipients, but few predictive markers of the disease are known. Several immunologic parameters of potential relevance for the defense against CMV were measured after renal transplantation in 25 patients before any manifestations of CMV infection occurred. In 10 patients who later developed CMV disease, plasma levels of interleukin-8 were significantly higher, whereas the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) were significantly lower than in 15 patients who did not develop CMV disease. Also, lower numbers of CD4+ and CD8+ lymphocytes were observed in patients who later had CMV disease. These findings were independent of previous rejection therapy and were particularly pronounced in patients with primary CMV infection. Interleukin-8 and MIP-1alpha may be predictive markers of CMV disease and could be of potential use in selecting patients for prophylactic treatment.  (+info)

Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process? (62/8017)

Allograft rejection can be caused by numerous factors such as damage to the donor kidney during surgical removal or implantation, injury sustained during the transport process between the donor and recipient, and suboptimal allograft perfusion during the intra- and post-operative period. In cadaveric allografts, damage can occur during cold storage, during the transit stage between donor and recipient, and hemodynamic instability due to the initial damage that caused its removal from the donor (such as brain death or trauma). We hypothesize that rejection requires recognition of this injury in addition to recognition of alloantigens. If indeed injury proves to be one factor in acute rejection episodes, then therapeutic efforts can be made to reduce injury during the transplantation process.  (+info)

Correlation of histology to clinical rejection reversal: a thymoglobulin multicenter trial report. (63/8017)

Correlation of histology to rejection reversal: A Thymoglobulin Multicenter Trial report BACKGROUND: Histology may provide a link between clinical response to antirejection therapy and graft function. In a subset of centers, renal biopsy was a secondary end point for the Thymoglobulin Multicenter Trial. METHODS: Thirty-eight patients had a protocol biopsy one to two weeks following the end of therapy. Inclusion and post-treatment biopsies were graded and scored according to Banff criteria by a central pathologist who was blinded to the type and outcome of therapy and the timing of the biopsy. RESULTS: The majority of patients (31 of 38) had moderate rejection on their inclusion biopsy. An improvement of at least one Banff grade occurred in 58% of the patients. The treatment was clinically successful in 33 patients, but two thirds of the patients (25 out of 38) demonstrated residual inflammation in the graft. The degree of improvement of inflammation was proportionate to rejection severity (P = 0.006). Banff scoring indicated that residual inflammation was less in Thymoglobulin-treated patients than in those receiving Atgam (P < 0.05) and correlated with the incidence of recurrent rejection (P = 0.015). CONCLUSIONS: These data demonstrate a discrepancy between clinical and histological resolution of acute renal allograft rejection. Residual infiltrates in the graft following rejection therapy are common and, despite clinical improvement, may indicate an increased risk for recurrent rejection.  (+info)

Cyclosporine-associated thrombotic microangiopathy in renal allografts. (64/8017)

BACKGROUND: The association between cyclosporine (CsA) and thrombotic microangiopathy (TMA) in renal allografts is well documented. However, predisposing factors and therapy guidelines are not adequately characterized. METHODS: We reviewed 188 patients with kidney or kidney-pancreas transplants who were treated between January 1994 and December 1996 with prednisone, CsA, or tacrolimus, and azathioprine or mycophenolate. We analyzed 50 patients who had graft biopsies: 26 with TMA and 24 with no TMA, as well as 19 patients with well-functioning grafts who never required biopsy. RESULTS: TMA was observed in 26 of 188 renal graft recipients (14%). TMA was confined to the allograft kidney without any systemic evidence in 24 of the 26 patients. At the time of the diagnosis of TMA, 24 of the patients were on CsA, with 19 on the microemulsion form. Conversely, 5 of 18 control patients with no graft dysfunction were on the microemulsion form of CsA (P = 0.0026). Graft loss was seen in 8 of 26 patients with TMA. Conversion from CsA to tacrolimus resulted in a one-year salvage of graft function in 13 of 16 (81%) patients. CONCLUSIONS: TMA was the cause of renal graft dysfunction in 14% of renal graft recipients and was associated with the use of the microemulsion form of CsA. Systemic signs of TMA were rare, underscoring the importance of the graft biopsy in making the diagnosis. The most successful strategy was switching from CsA to tacrolimus, with good graft function in 81% of the recipients one year after the TMA episode.  (+info)