作者: Kline, Myriam ; Christen, Erica ; Emlen, Woodruff ; Hoffman, Cathy ; Wood, Susan ; Lesser, Martin ; Holers, V. Michael ; Akana, Hillary ; Thurman, Joshua M. ; Smith, Christopher ; Marians, Russell ; Trachtman, Howard

BACKGROUND AND OBJECTIVESDiarrhea-associated hemolytic uremic syndrome (D+HUS) is a common cause of acute kidney injury in children. Mutations in alternative pathway (AP) complement regulatory proteins have been identified in severe cases of thrombotic microangiopathy, but the role of the AP in D+HUS has not been studied. Therefore, we determined whether plasma levels of markers of activation of the AP are increased in D+HUS and are biomarkers of the severity of renal injury that predict the need for dialysis.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSPatients were randomly selected from among participants in the HUS-SYNSORB Pk trial. Plasma samples were collected on days 1, 4, 7, and 10 after enrollment and day 28 after discharge from the hospital. Levels of two complement pathway products, Bb and SC5b-9, were determined by ELISA.RESULTSSeventeen children (6 boys and 11 girls; age, 5.4 +/- 3.5 yr) were studied. Eight (47%) required dialysis support, and two had serious extrarenal events. On the day of enrollment, plasma levels of Bb and SC5b-9 were significantly increased in all patients compared with healthy controls (P < 0.01). The elevated concentrations normalized by day 28 after discharge. Circulating levels of complement pathway fragments did not correlate with severity of renal injury or occurrence of complications.CONCLUSIONSPatients with acute-onset D+HUS manifest activation of the AP of complement that is temporally related to the onset of disease and that resolves within 1 mo. Therapies to inhibit the AP of complement may be useful in attenuating the severity of renal injury and extrarenal complications.

2006-07-01·Pediatric Nephrology3区 · 医学

Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury

3区 · 医学

Article

作者: Nathan Bullington ; Volker Mai ; Jaya Mishra ; Avital Cnaan ; Howard Trachtman ; Prasad Devarajan ; Erica Christen ; Jilma Patrick ; Aditya Jain

BACKGROUNDDiarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure. Neutrophil gelatinase-associated lipocalcin (NGAL) is an early indicator of kidney injury.OBJECTIVETo determine if urinary NGAL excretion is a biomarker of severe renal injury and predicts the need for dialysis in D+HUS.METHODSPatients were randomly selected from among participants in the SYNSORB Pk trial. Urine samples were collected daily if available during the first week of hospitalization. NGAL levels were determined by ELISA.RESULTS34 children, age 5.9+/-3.9 yr, were studied; ten (29%) required dialysis. Patients were categorized based on urinary NGAL concentration within five days of hospitalization - <200 ng/ml and >or=200 ng/ml. Twenty patients (58%) had increased urinary NGAL excretion. The severity of D+HUS at enrollment was similar in the two groups. However, children with increased urinary NGAL levels had higher peak BUN and creatinine concentrations (P<0.01) and required dialysis more often, 9/20 versus 1/14 (P=0.024) compared to children with normal excretion.CONCLUSIONThe majority of patients with D+HUS have renal tubular epithelial injury, as evidenced by elevated urinary NGAL excretion. Urinary NGAL levels below 200 ng/ml within five days of hospitalization may be an adjunctive marker that defines less severe renal involvement.

2006-01-01·Renal Failure4区 · 医学

Urinary Podocyte mRNA Excretion in Children with D+HUS: A Potential Marker of Long-Term Outcome

4区 · 医学

ArticleOA

作者: Howard Trachtman ; Jilma Patrick ; Erica Christen ; Laura De Petris

BACKGROUNDDiarrhea-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.METHODSPatients 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.RESULTSFifteen children, aged 4.9+/-2.8 years, were studied. Patients were categorized based on urinary mRNA levels into normal (marker:GAPDHmean + 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.CONCLUSIONThe 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.

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适应症	最高研发状态	国家/地区	公司	日期
梭菌感染	临床3期	阿根廷	-	-
梭菌感染	临床3期	加拿大	-	-
梭菌感染	临床3期	-	Hawker Resources, Inc.	-
梭菌感染	临床3期	波多黎各	-	-
梭菌感染	临床2期	墨西哥	-	-
梭菌感染	临床2期	-	Omnicare LLC	-
梭菌感染	临床2期	美国	-	-
梭菌感染	临床2期	-	Paladin Labs, Inc.	-