The Maastricht Transplant Center: clinical setting and epitope searches in HLA class II molecules: does the structural localization of a polymorphic site contribute to its immunogenicity?

Our understanding of the immunological processes influencing the clinical outcome after kidney transplantation has advanced majorly over the last few decades. However, many factors still restrict graft and patient survival. Within the Maastricht transplant center we have successfully implemented an alternative immunosuppressive regimen involving Tacrolimus monotherapy in order to minimize the adverse effects associated with long-term use of immunosuppressive drugs. This clinical development has an impact on pre-transplant risk stratification which requires that patients are closely monitored immunologically. In this review we will elaborate on our strategy regarding the analysis of epitopes in HLA-DQ and HLA-DP molecules. In this respect we have also looked at the immunodominance of certain epitopes by assessing their structural localization, conformation and physiochemical properties.

Do blood pressure and arterial wall properties change after conversion from cyclosporine to tacrolimus?

Cardiovascular disease is the leading cause of death in renal transplant recipients. Arterial wall properties are surrogate markers for arteriosclerosis. Previous investigations have shown that the cardiovascular risk profile is better with tacrolimus compared to cyclosporine. Renal function, blood pressure, and lipid levels improve. The hypothesis is that arterial wall properties will improve after conversion from cyclosporine to tacrolimus. Thirty-four stable renal recipients were converted from cyclosporine microemulsion to tacrolimus without changing concomitant medication. Before and after conversion we performed wall track ultrasounds of the carotid and the brachial arteries; pulse wave velocity (PWV); laboratory investigations; 24-hour ABPM; estimates of renal function; and Framingham risk scores. After conversion the 24-hour ambulatory blood pressure monitoring (ABPM) did not change. Total cholesterol, LDL cholesterol, and triglycerides improved significantly. Renal function (Cockroft) improved. There were no significant changes in arterial wall properties, or in PWV. Framingham comparative risk scores improved only significantly in patients not receiving statins. In conclusion, 3 months after conversion from cyclosporine to tacrolimus total cholesterol, LDL cholesterol, and triglycerides were significantly decreased and renal function significantly improved. Contrary to expectation, ABPM did not change, probably due to prolonged use (>10 years) of cyclosporine. There was also no difference in arterial wall properties.

Efficacy and tolerance of three different calcium acetate formulations in hemodialysis patients.

BACKGROUND: Calcium acetate (CaAc) is an effective phosphate binder in patients with chronic renal failure. However, an important side effect is gastro-intestinal discomfort. Phos-ex (Cablon, The Netherlands) is the only commercially available non-coated CaAc formulation in our country. We developed two new CaAc formulations: neutral-coated CaAc (NCCaAc) and enteric-coated CaAc (ECCaAc). METHODS: In a randomised double-blinded cross-over trial we compared efficacy and tolerance of the three formulations in 19 stable hemodialysis patients, with a mean age of 63 years (range, 36-85), who had been on hemodialysis for 19 months (range, 6-47). Patients were randomised to receive NCCaAc or ECCaAc, with meals, for a period of 10 weeks and after cross-over for another 10 weeks. During a third non-blinded period, patients received Phos-ex for 10 weeks. RESULTS: Serum phosphate was significantly higher with ECCaAc compared to NCCaAc (1.89 +/- 0.07 vs. 1.70 +/- 0.08 mmol/l, P < 0.05). Serum Ca was significantly lower with ECCaAc compared to NCCaAc or Phos-ex (2.38 +/- 0.04, 2.47 +/- 0.04 and 2.48 +/- 0.04 mmol/l, P < 0.05). There were less hypercalcemic and more hyperphosphatemic events in the ECCaAc period, compared to the other periods. The daily CaAc dose and dietary intake of calcium, phosphate, protein and calories were comparable in all three periods. With Phos-ex, patients noticed more gastro-intestinal complaints than with to NCCaAc and ECCaAc. Two patients stopped taking Phos-ex because of side effects. CONCLUSIONS: In hemodialysis patients, phosphate control and tolerance were both influenced by the formulation of CaAc. Although phosphate control was adequate with all three formulations of CaAc, ECCaAc was less effective compared to NCCaAc or Phos-ex. NCCaAc and ECCaAc were better tolerated than Phos-ex. Regarding efficacy and tolerance, NCCaAc was the best calcium acetate formulation.