Urinary podocyte mRNA excretion in children with D+HUS: a potential marker of long-term outcome.
BACKGROUND
Diarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure and may lead to podocyte loss. Objective. To determine if the urinary mRNA excretion of podocyte proteins is detectable in children with D+HUS and if it is a biomarker of a poor long-term outcome.


METHODS
Patients were randomly selected from participants in the SYNSORB Pk trial. Urine samples were collected daily during the first week of hospitalization. Specimens were also obtained in healthy volunteers. Synaptopodin and nephrin mRNA levels were measured using real-time PCR.


RESULTS
Fifteen children, aged 4.9+/-2.8 years, were studied. Patients were categorized based on urinary mRNA levels into normal (marker:GAPDH<or=mean + SD) or high (marker:GAPDH>mean + SD) in controls. Twelve patients (80%) had increased urinary podocyte mRNA excretion; 11 (73%) had high synaptopodin and 5 (33%) had high nephrin mRNA levels. Follow-up data were available in 13/15 patients, all of whom had normal blood pressure, urinalysis, and serum creatinine concentration.


CONCLUSIONS
The isolation of podocyte mRNA from routine urine samples is feasible in children with D+HUS. Most patients have podocyturia based on synaptopodin and nephrin mRNA excretion. Larger studies with extended follow-up are required to determine the relationship of these biomarkers to long-term renal prognosis in D+HUS.
De Petris
Laura
L
Department of Pediatrics, Washington University, St. Louis, Missouri, USA.
Patrick
Jilma
J
Christen
Erica
E
Trachtman
Howard
H
D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000150:complications / Q000188:drug therapy / Q000652:urine*; D006463:Hemolytic-Uremic Syndrome / Q000150:complications / Q000188:drug therapy / Q000652:urine*; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics / Q000652:urine; D008840:Microfilament Proteins / Q000235:genetics / Q000652:urine; D017646:Organosilicon Compounds / Q000627:therapeutic use; D050199:Podocytes / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000652:urine*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014312:Trisaccharides / Q000627:therapeutic use
D015415:Biomarkers; D008565:Membrane Proteins; D008840:Microfilament Proteins; D017646:Organosilicon Compounds; D012333:RNA, Messenger; C503967:SYNPO protein, human; C119238:SYNSORB Pk; D014312:Trisaccharides; C113267:nephrin