Assessing the vascular effects of early erythropoietin use in pediatric renal transplant recipients.

PALO Alto (Calif.); CALIFORNIA

BACKGROUND A cluster of four cases of severe hypertension secondary to renovascular abnormalities was noted soon after renal transplantation among children receiving steroid-free immunosuppression at Stanford University, Palo Alto, CA. OBJECTIVE To investigate factors associated with (and potential mechanisms underlying) the observed cases. DESIGN AND INTERVENTION A retrospective case-control study was conducted. A total of 50 consecutive patients aged 0-21 years who had received steroid-free, tacrolimus-based immunosuppression following renal transplantation at Stanford University during 1999-2002 (including the four cases of renovascular hypertension) were matched with 50 controls who had received steroid-containing, tacrolimus-based immunosuppression. Clinical histories of all patients were reviewed for relevant associations (including erythropoietin use), and blood samples obtained in the first week after transplantation were subjected to transcriptional analysis. OUTCOME MEASURE Renovascular abnormality causing severe hypertension, as detected by Doppler ultrasound, was the end point. RESULTS The incidence of post-transplantation hypertension was greater in the patients who received steroid-containing immunosuppression than in the patients who received steroid-free immunosuppression at 6 months, 12 months, 18 months and 24 months (P<0.001, P<0.001, P= 0.009 and P= 0.002, respectively), but none of the patients who received steroid-containing immunosuppression had renovascular abnormalities. Results of biochemical analyses were normal in all patients with severe hypertension. A higher proportion of patients in the steroid-free group than in the steroid-treated group developed anemia (hematocrit <25%) in the first year after transplantation (P<0.001). Of the 11 steroid-free patients who developed hypertension in the first year after transplantation, 6 (67%) had received erythropoietin in the first week after transplantation; of these, 4 had renovascular abnormalities. The anomalies were confirmed by gadolinium-based magnetic resonance angiography as renal artery stenosis in three cases, and the location of the stenoses indicated they were unlikely to be iatrogenic. All the lesions improved without surgery. No patient who received erythropoietin after the first week developed renovascular anomalies. Of the risk factors for renovascular hypertension analyzed, only erythropoietin therapy in the first week showed an association (P= 0.007). Transcriptional analysis revealed increased expression of vascular and growth-response-related genes (including some regulated by erythropoietin) in the patients with renovascular hypertension compared with steroid-free controls of the same age and sex and with the same cause of end-stage renal disease. As a result of these findings, Stanford University decided to abolish early or pre-emptive use of erythropoietin after renal transplantation and to reduce dosing of mycophenolate mofetil, which had been found to correlate with the presence of anemia. No renovascular abnormalities were observed in the subsequent 3 years. CONCLUSION Use of erythropoietin soon after renal transplantation should be avoided if possible. [ABSTRACT FROM AUTHOR]

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