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M J Mallat

Publications and source records attributed to M J Mallat.

7 recordsLinked to original sources
PubMed2001

Risk factors of cyclosporine nephrotoxicity after conversion from Sandimmune to Neoral.

BACKGROUND: In 1995 - 1996, we switched from a once-daily Sandimmune dose to a twice-daily dose regimen of Neoral. Concurrent with the switch we changed our target trough level from 100 microg/l at 24 hours to the generally accepted 12-hour level of 150 microg/l. We performed a retrospective cohort study to assess cyclosporine toxicity following this switch and to identify risk factors for nephrotoxicity. PATIENTS AND METHODS: Of 212 patients with a stable graft function pre-conversion clinical parameters at 1 and 12 months post-conversion were compared with those at time of conversion. Cyclosporine nephrotoxicity was defined as a significant decline of the reciprocal of the serum creatinine concentration over time post-conversion in the absence of other obvious causes for declining graft function. Risk factors of cyclosporine nephrotoxicity were assessed using logistic regression analysis. RESULTS: The mean cyclosporine trough level rose from 87 microg/l at the time of conversion to 139 microg/l at 12 months post-conversion whereas the daily drug dose increased over the same period from 233 mg to 252 mg. Mean serum creatinine increased by 10% from 135 to 148 micromol/l (p < 0.001). Cyclosporine nephrotoxicity was present in 42 patients (20%). Cyclosporine dose and trough level did not predict nephrotoxicity but beta-blockers (OR 0.35, 95% CI 0.17-0.72) and calcium channel blockers (OR 0.35, 95% CI 0.19-0.82) reduced the risk of nephrotoxicity, independent from an effect on blood pressure. CONCLUSION: 20% of stable renal transplant patients experienced chronic cyclosporine nephrotoxicity after conversion from a once-daily Sandimmune regimen to a twice-daily Neoral regimen with dose adjustments to a trough level of 150 microg/l. beta-blockers and calcium channel blockers reduced the risk of nephrotoxicity.

Adrenergic beta-Antagonists↗
PubMed2000

Delayed graft function influences renal function, but not survival.

BACKGROUND: In renal transplantation, the impact of delayed graft function (DGF) on prognosis is controversial. We analyzed the risk factors of DGF and its impact on graft function and prognosis. METHODS: Seven hundred thirty-four cadaveric renal transplants performed between 1983 and 1997 were analyzed. DGF was diagnosed when serum creatinine levels increased, remained unchanged, or decreased less than 10% per day in three consecutive days in the first week after transplantation. Creatinine clearances of more or less than 50 or 30 mL/min at one year were used as cut-off points for optimal and suboptimal graft function, respectively. The logistic regression model was used to identify independent risk factor related to DGF and renal function one year after transplantation. The Cox regression model was used to examine the influence of DGF on long-term graft survival. RESULTS: Multivariate analysis revealed the following risk factors for DGF: recipient pretransplantation mean arterial blood pressure of less than 100 mm Hg (OR = 2.08, 95% CI, 1.43 to 3.03), female donor to male recipient combination (OR = 1.55, 95% CI, 1.02 to 2.35), donor age of more than 50 years (OR = 2.21, 95% CI, 1.49 to 3.26), cold ischemia time of more than 28 hours (OR = 1.78, 95% CI, 1.19 to 2.63), and peak panel reactive antibodies of more than 50% (OR = 1.7, 95% CI, 1.15 to 2.55). The incidence of DGF was one of the independent risk factors for suboptimal graft function at one year (OR = 1.68, 95% CI, 1.14 to 2.48), together with donor age of more than 50 years (OR = 2.39, 95% CI, 1.61 to 3.57), female donor gender (OR = 1.99, 95% CI, 1.42 to 2.78), the occurrence of acute rejection episodes (OR = 2.66, 95% CI, 1.87 to 3.78), peak panel-reactive antibodies of more than 50% (OR = 1.67, 95% CI, 1.15 to 2.47), and sharing of 1 to 3 versus 4 to 8 cross-reactive antigens groups (OR = 1.65, 95% CI, 1.09 to 2. 49). Moreover, DGF was one of the two independent risk factors for acute rejection episodes, but it had no independent effect on graft survival. CONCLUSION: Several risk factors for DGF were identified, of which a low recipient pretransplant mean arterial blood pressure, the transplantation of kidneys from female donors to male recipients, and a prolonged cold ischemia time are potentially avoidable. Although DGF is one of the several risk factors of acute rejection and suboptimal function at one year, it is not independently associated with an increased rate of graft loss.

Acute Disease↗
PubMed1999

Sharing cross-reactive groups of MHC class I improves long-term graft survival.

BACKGROUND: Renal transplant loss from chronic rejection remains substantial. To increase our understanding of this syndrome, we identified risk factors predicting late graft loss, with a special emphasis on the impact of human lymphocyte antigen (HLA) matching. METHODS: We studied all 654 cadaveric kidney transplants performed in our center between 1983 and 1996 that had survived for more than six months. Eighty-two transplants, lost because of chronic rejection, were used as the outcome variable. The influence of HLA mismatches and shares on long-term graft survival was evaluated at the level of private antigens and cross-reactive groups (CREG) of multiple histocompatibility complex (MHC) class I. HLA and other recipient, donors and transplant parameters were studied using univariate and multivariate Cox regression analysis. RESULTS: The cohort had a mean number of 1.9 HLA mismatches. Because of the homozygosity of HLA antigens, HLA mismatches were not reciprocal to shares. CREG and HLA-A-B mismatches had a relative risk for graft loss of 1.19 (95% CI, 0.97 to 1.45) and 1.05 (0.84 to 1.32) per mismatch. In contrast, the relative risk per shared CREG and broad HLA-A-B antigen was 0.76 (0.63 to 0.92) and 0.79 (0.61 to 1.03). Multivariate analysis revealed that individuals sharing less than four CREGs had a relative risk of 2.13 (1.29 to 3.75) for late graft loss. Other independent predictors were a recipient age of less than 50 years, relative risk 1.95 (1.02 to 3.71); a donor age of more than 50 years, relative risk 1.68 (1.01 to 2.80); acute rejection (vascular vs. no rejection), relative risk 3.52 (1.72 to 7.18); proteinuria (dipstick > 1+ vs. negative), relative risk 2.86 (1.29 to 6.35); and a serum creatinine concentration of more than 150 micromol/liter at six months, relative risk 3.41 (1.96 to 5.94). CONCLUSION: We identified several coexisting recipient-, donor-, and transplant-related risk factors for graft loss from chronic rejection. In this well-matched group of renal transplants, HLA mismatches and shares had a nonreciprocal relationship. Sharing of HLA antigens, especially CREG of MHC class I, was associated with improved long-term survival.

Adult↗
PubMed1997

Patient survival after renal transplantation; more than 25 years follow-up.

BACKGROUND: The determinators of patient survival after renal transplantation are incompletely known, and conflicting results have been reported. This may have been influenced by time-related changes in patient selection, post-transplantation management and immunosuppressive regimens. This study was performed to evaluate in recipients of a first renal transplant the effect of patient characteristics, transplantation era, and the immunosuppressive regimen on patient survival. METHODS: We used data from the Leiden Renal Transplant Database of all first renal transplantations performed between 1966 and 1994 in Leiden, the Netherlands. The effect of the following parameters on mortality was investigated: era of transplantation, sex, age at transplantation, cause of renal failure, immunosuppressive regimen, type and duration of pretransplantation dialysis, hypertension, diabetes mellitus, and smoking. In addition we analysed the causes of death. Results were expressed as crude mortality rates, relative risks of mortality, and standardized mortality ratios as compared with death rates in the Dutch population. RESULTS: The analysis comprised 86 living donor transplant recipients and 916 cadaver transplant recipients. After adjustment for age and sex, the relative risk of mortality for living donor transplant recipients compared with cadaver transplant recipients was 0.5 (95% CI 0.2 to 1.03, P = 0.06). In first cadaver kidney transplant recipients the risk of first-year mortality improved significantly with time, which coincided with the introduction of cyclosporin. The risk of mortality after the first year was higher in patients aged over 40 years at transplantation, men, smokers, and in the presence of hypertension or diabetes, but the effect of individual factors on mortality was small. We found no effect of the type of pretransplantation dialysis or the duration of pretransplantation haemodialysis on post-transplantation mortality. The standardized mortality ratio for recipients of first renal transplants was 14 times the population average in the first year after transplantation and was still four times in the remaining years. CONCLUSION: In the present study, time-related changes in patient management were responsible for improved patient survival in the first year after transplantation during the study period. Many individual factors contributed moderately to the risk of mortality after the first year. Compared to the general population the mortality rate of renal transplant recipients was significantly higher during the whole follow-up period.

Adult↗
PubMed1996

[Results of kidney transplantation in Leiden, 1966-1994, and prognostic factors].

OBJECTIVE: Evaluating prognostic determinants and results of renal transplantation. DESIGN: Descriptive study. SETTING: Leiden University Hospital, The Netherlands. METHODS: Follow-up of all 1289 patients who had a kidney transplantation in Leiden University Hospital between March 1966 and December 1994. The following determinants were investigated: age and sex of donors and recipients. HLA matching, type of immunosuppression, presensitization, presence of diabetes mellitus, and living or post-mortem donor. RESULTS: Renal transplantation was very successful during the first few years, one-year graft survival dropped to 50% during the second decade and gradually increased to almost 90% during the last years. 5-year and 10-year graft survival were 65% and 50% respectively. The mean age of recipients increased from 32.8 years to 45.7 years, that of donors from 24.9 to 37.9 years. Duration of dialysis before transplantation increased from 19.7 months to 35.7 months. The introduction of cyclosporine and matching on the HLA-DR locus were responsible for better transplantation results. Other favourable prognostic factors were absence of diabetes mellitus, absence of panel reactive antibodies, kidney from a living donor, male donor and donor age between 20 and 50 years. CONCLUSION: Both short term and long term results of renal transplantation improved in spite of a strong increase of mean donor age and mean recipient age and an increase of co-morbidity of the recipients. Introduction of HLA-DR matching and cyclosporine immunosuppression contributed to better graft survival.

Adult↗
PubMed1995

Tissue antigens in tubulointerstitial and vascular rejection.

We propose that tissue-specific alloantigens are of importance in interstitial and vascular rejection. To study this hypothesis we took the following approaches: multivariate analysis on our database (N = 482) was performed, the specificity of T cells cultured from kidneys with rejection was analyzed, and non-anti-HLA antibodies reactive with endothelium were studied. First we observed that in a cohort study of 482 patients receiving a cadaveric renal allograft 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. The incidence of vascular rejection was increased in patients with delayed graft function, HLA-DR mismatches, a prolonged cold ischemia period, and previous transplantations. Next we examined 40 graft infiltrating cell (GIC) lines cultured from renal biopsies taken during rejection episodes. Thirteen GIC lines reacted in a donor-specific fashion to proximal tubular cells (PTEC) but not to donor splenocytes. These GIC recognize polymorphic tissue-specific peptides in the context of allo-MHC Class I. Finally, we studied if non-conventional allo-antigen systems on endothelial cells could be the target of the humoral immune response during vascular rejection. We found the endothelial monocyte (EM) system, and another system that is present on endothelial cells and platelets, which can be tested in an antibody-dependent cellular cytotoxicity assay (ADCC).

Graft Rejection↗