Renal transplantation in patients with hemolytic uremic syndrome: high rate of recurrence and increased incidence of acute rejections.

BACKGROUND: The reported outcome of renal transplantation in patients with the hemolytic uremic syndrome (HUS) varies greatly, probably related to the diverse causes of HUS. In this single-center retrospective study, we have analyzed the recurrence rate, the incidence of acute rejections, and graft survival in patients suffering from adult-onset and childhood-onset HUS. METHODS: The medical records of 35 patients with end-stage renal disease caused by HUS, who received 50 renal allografts, were reviewed. A definite recurrence of HUS was diagnosed if both clinical and histologic signs of thrombotic microangiopathy (TMA) were present in the absence of any endovasculitis. If there were signs of mild endovasculitis, a probable recurrence was diagnosed. RESULTS: After first renal transplantation, 0 definite and 1 (6%) probable recurrence occurred in 18 patients with childhood-onset HUS, as opposed to 7 (41%) definite and 3 (18%) probable recurrences in 17 adult-onset HUS patients (odds ratio [OR], 13.4; 95% confidence interval [CI], 1.7-105.7). In the latter patients, early use of cyclosporine A increased the risk for recurrence. The incidence of acute rejections was increased compared with matched controls (OR, 1.52; 95% CI, 1.05-2.19 for adult-onset HUS and OR, 1.88; 95% CI, 1.34-2.62 for childhood-onset HUS). One-year graft survival in adult-onset HUS was poor (29%), whereas 1-year graft survival in childhood-onset HUS was comparable to matched controls. CONCLUSIONS: 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.

Outcome of renal transplantation in patients with systemic lupus erythematosus.

Renal transplantation is considered to be a good treatment option for patients with systemic lupus erythematosus (SLE) and end-stage renal disease. However, in patients with glomerular diseases, the outcome of renal transplantation can be adversely affected by recurrence of the original disease. Furthermore, the post-transplant course might be complicated by pre-transplant morbidity and treatment history. We studied the outcome of renal transplantation in patients with SLE who underwent transplantations in our center between 1968 and 2001. Patient and graft survival were compared with a matched control group. We specifically looked for any evidence of recurrent disease. There were 23 patients (two male, 21 female) with a mean +/-SD age of 34+/-12 years at transplantation. One patient developed renal failure with serological evidence of SLE activity at 61 months after transplantation. In the absence of urine abnormalities we favored the diagnosis of rejection, although recurrence of lupus nephritis could not formally be excluded. This was the only case of a possible recurrence of lupus nephritis. Two other patients developed extra-renal manifestations of SLE at 6 and 17 months after transplantation. Patient and graft survival rates at 5 years after transplantation were 86% and 68%, respectively. Survival rates were not significantly different from those of a matched control group, 95% and 78%, respectively. Recurrence of SLE after transplantation is rare. The results of renal transplantation in patients with SLE do not differ significantly from a matched control group. Renal transplantation is a good alternative for renal replacement therapy in patients with lupus nephritis.

Blockade of the renin-angiotensin system increases graft survival in patients with chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the leading cause of late allograft failure, with only limited treatment options. Blockade of the renin-angiotensin system (RAS) decreases progression in diabetic and non-diabetic renal disease, but the effect on CAN is as yet unclear. Therefore, we have studied retrospectively the effect of RAS blockade on renal survival in patients with biopsy-proven CAN. METHODS: The medical records of 72 patients with biopsy-proven CAN were evaluated with regard to time course of graft function, proteinuria, blood pressure, and antihypertensive and immunosuppressive treatment. Cox's proportional hazards model was used for analysing renal graft survival after the index biopsy. RESULTS: On univariate analysis, histological determinants influencing renal survival were the chronic interstitial and chronic tubular score, and clinical parameters were the serum creatinine level at the time of the biopsy, the relative change in serum creatinine level between 12 months post-transplantation and at the time of the biopsy, mean systolic and diastolic blood pressure after the biopsy, and RAS blockade by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. On multivariate analysis, graft outcome was influenced by the relative change in serum creatinine level between 12 months post-transplantation and the time of the index biopsy, the urinary protein excretion, the mean diastolic blood pressure after the index biopsy, and RAS blockade. Renal graft survival after treatment with RAS blockade was 6.3 (0.9-10.9) years as opposed to 1.8 (0.1-6.7) years in untreated patients (P = 0.003). CONCLUSION: 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.

Conversion from cyclosporine to tacrolimus improves quality-of-life indices, renal graft function and cardiovascular risk profile.

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 side-effects 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 micromol/L to 157 +/- 62 micromol/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.

Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus.

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 +/- 30 micromol/L to 131 +/- 29 micromol/L (P < 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 +/- 13 to 99 +/- 12 mmHg (P < 0.001). Serum LDL cholesterol decreased from 3.48 +/- 0.80 to 3.11 +/- 0.74 mmol/L (P < 0.001,) and serum apolipoprotein B decreased from 1018 +/- 189 to 935 +/- 174 mg/L (P < 0.001). Serum triglycerides decreased from 2.11 +/- 1.12 to 1.72 +/- 0.94 mmol/L (P < 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 +/- 857 to 3417 +/- 751 mg/L (P < 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 +/- 1.3 mmol/L to 5.8 +/- 1.9 mmol/L (P < 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.