Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived sideeffects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 ± 48 lmol/L to 157 ± 62 lmol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 ± 4.3 to 4.8 ± 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated.

To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with varying degrees of renal dysfunction. After administration of cimetidine for three to six days, serum creatinine level rose in all participants, while CEDTA and CIn remained stable in a subgroup of 14 subjects in whom they were measured before as well as after the administration of cimetidine. The mean (+/- SD) ratios of CCr to CEDTA (N = 39) and of CCr to CIn (N = 19) after ingestion of cimetidine were 1.02 +/- 0.13 and 1.01 +/- 0.13, respectively, and did not differ significantly from unity. This high degree of accuracy of the cimetidine-aided CCr was present over the entire range of renal function in the study population. Our results also indicated an improved precision of the cimetidine-aided measurement of CCr, resulting in a variability that did not differ significantly from that of the measurement of CEDTA or CIn. We conclude that after oral administration of cimetidine, the creatinine clearance can be used as a reliable measure of GFR within a broad range of renal function.

Abstract. Cyclosporine is considered to contribute to the high cardiovascular morbidity and mortality in patients after renal transplantation. Tacrolimus may be more favorable in this respect, but controlled data are scarce. In this prospective randomized study in 124 stable renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on cardiovascular risk factors and renal function were investigated. Follow-up was 6 mo. Statistical analysis was performed by ANOVA for repeated measurements. The serum creatinine level decreased from 137 Ϯ 30 mol/L to 131 Ϯ 29 mol/L (P Ͻ 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 Ϯ 13 to 99 Ϯ 12 mmHg (P Ͻ 0.001). Serum LDL cholesterol decreased from 3.48 Ϯ 0.80 to 3.11 Ϯ 0.74 mmol/L (P Ͻ 0.001,) and serum apolipoprotein B decreased from 1018 Ϯ 189 to 935 Ϯ 174 mg/L (P Ͻ 0.001). Serum triglycerides decreased from 2.11 Ϯ 1.12 to 1.72 Ϯ 0.94 mmol/L (P Ͻ 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 Ϯ 857 to 3417 Ϯ 751 mg/L (P Ͻ 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 Ϯ 1.3 mmol/L to 5.8 Ϯ 1.9 mmol/L (P Ͻ 0.05). Conversion to tacrolimus resulted in a significant reduction of the Framingham risk score. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients has a beneficial effect on renal function, BP, serum concentration and atherogenic properties of serum lipids, and fibrinogen.During the past two decades, cyclosporine has proved to be a valuable immunosuppressive drug that has contributed to a significant reduction in the incidence of acute rejection after renal transplantation. However, cyclosporine also increases cardiovascular risk profiles (1). Ultimately, up to 63% of renal transplant patients die of cardiovascular disease (2). The increased cardiovascular risk profile as a result of cyclosporine is ascribed to both a quantitative increase in LDL particles and an increased oxidizability of the LDL particles (3-5). Use of cyclosporine is also associated with increased plasma lipoprotein(a) (Lp[a]) (6) and homocysteine levels (7), but these effects are not unequivocal (8). In addition, unfavorable effects on the fibrinolytic system by cyclosporine have been described (9). Apart from these disadvantageous effects of cyclosporine on several metabolic cardiovascular risk factors, cyclosporine leads to an elevation of BP (4). These side effects not only contribute to the high cardiovascular morbidity in renal transplant patients but also may lead to an accelerated loss of graft function (10 -12).Tacrolimus is like cyclosporine, a calcineurin inhibitor, with even more potent immunosuppressive properties. The use of tacrolimus after renal transplantation is associated with a less unfavorable effect on BP and serum lipid levels, but evidence from controlled studies is scarce (4,13). L...

In adult-onset HUS, the recurrence rate and the incidence of acute rejections are high, resulting in a detrimental graft survival. In childhood-onset HUS, the recurrence rate is low, but the posttransplantation course is complicated by an increased incidence of acute rejections.

RAS blockade increases graft survival in CAN. In view of the limited treatment options for CAN, this finding is of importance and needs confirmation by a prospective randomized trial.