Transplant reno-vascular stenoses associated with early erythropoietin use.
OBJECTIVE
This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use.


METHODS
To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls.


RESULTS
Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid-free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post-transplant) was significantly associated with the combinatory findings of new-onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury.


CONCLUSIONS
This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia.
Nagarajan
Suja
S
Department of Pediatrics (Nephrology) Stanford University, Palo Alto, CA 94305-5208, USA.
Mansfield
Elaine
E
Hsieh
Sue
S
Liu
Rosa
R
Hsieh
Frank
F
Li
Li
L
Salvatierra
Oscar
O
Sarwal
Minnie M
MM
D000293:Adolescent; D002648:Child; D003251:Constriction, Pathologic / Q000235:genetics*; D004921:Erythropoietin / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D006397:Hematinics / Q000009:adverse effects*; D006801:Humans; D006978:Hypertension, Renovascular / Q000235:genetics* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins; D012189:Retrospective Studies
D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin