Sirolimus-associated heavy proteinuria in a renal transplant recipient: evidence for a tubular mechanism.

Sirolimus is a new and potent immunosuppressive agent. Recently, increased proteinuria has been recognized as an important complication. However, the mechanism thereof has remained unclear. We describe a patient who received sirolimus as standard therapy after living donor kidney transplantation. Within 10 days the patient developed a severe proteinuria that disappeared completely after substituting tacrolimus for sirolimus. Renal biopsy disclosed normal glomeruli even without effacement of the podocytic foot processes. Using FITC labeled anti-albumin antibodies we noted complete absence of albumin in the proximal tubules, whereas an abundant albumin staining was observed in a control patient with a comparable level of proteinuria due to a recurrence of focal segmental glomerulosclerosis after transplantation. Our data suggest that sirolimus can induce severe proteinuria, and that reduced tubular protein reabsorption contributes to the protein loss.

Morbidity and mortality during renal replacement therapy: dialysis versus transplantation.

AIM: Many patients with end-stage renal disease are eligible for renal transplantation. To enable a patient to choose between transplantation or to remain on dialysis comparable data on morbidity and mortality should be available. METHODS: Data were collected retrospectively from the medical records of all patients on the waiting list for renal transplantation and of transplanted patients during the period January 1, 1990, to January 1, 1997. All patients were dialyzed in the Kennemer Gasthuis and renal transplantation was performed in the Leiden University Medical Center (LUMC). Morbidity and mortality in both groups were compared. Morbidity was assessed by studying number, length and cause of hospital admissions. RESULTS: During the study period 102 patients had been on the waiting list and 54 patients had been transplanted in the LUMC. Mean length of stay on the waiting list before transplantation was 37 months. During the follow-up period 11 patients (10.8%) died on the waiting list and 6 patients (11.1%) died after renal transplantation. The mean length of stay on the waiting list of these two groups was much longer, being 55 months and 62 months, respectively. Length of hospitalization was significantly different between both patient groups during the first 6 months of treatment (13.24 days for those on the waiting list versus 40.75 days transplanted patients) and after 6 months (32.4 days for those on the waiting list versus 13.1 days transplanted patients). The number of hospital admissions did not differ significantly. Dialysis-related admissions constituted 47% of the total of admissions in the waiting list group and transplantation-related admissions were 43% in the transplanted group. CONCLUSION: In the present study we revealed no difference in overall mortality. However, mortality was influenced by length of stay on the waiting list. Morbidity was increased during the first 6 months after transplantation. Therapy modality greatly influenced the specific cause of morbidity.