Cystatin C as a Marker for Detecting Early Renal Dysfunction in a Pediatric Emergency Department
Condition: Acute Renal Failure; Gastroenteritis; Dehydration
MeSH terms: Gastroenteritis; Renal Insufficiency; Acute Kidney Injury; Dehydration; Emergencies
Study type: Observational

Summary: 
      Acute renal failure (ARF) is a rare but serious complication of gastroenteritis and
      dehydration, the most common reason for pediatric emergency visits. Renal function is
      determined by the glomerular filtration rate (GFR). Serum creatinine, the current marker of
      GFR, is insensitive and a late marker of ARF. Unfortunately, "gold standard" methods for
      measurement of GFR are impractical in the emergency setting. Recently, cystatin C (CysC) was
      introduced as superior marker for the measurement of GFR, particularly in children. A single
      random blood sample allows for accurate determination of GFR in the so-called
      "creatinine-blind" range and independent of the body composition. There is growing evidence
      that the determination of serum CysC concentration can detect ARF in adults earlier than
      serum creatinine or urinary fractional sodium excretion. No studies have examined this marker
      for the early detection of ARF in children at risk. We therefore propose a prospective study
      that compares CysC with other biomarkers of renal dysfunction for the early detection of ARF
      in children with dehydration due to gastroenteritis. Patients with minor trauma and a minimal
      likelihood of ARF will serve as a control. This study may establish CysC as an accurate and
      cost-effective marker for identifying patients at risk.
    

Detailed description: 
      -  Rationale and hypotheses: Acute renal failure is a relatively rare but serious illness
           in children. Early detection is important in preventing life threatening complications
           that can arise from acute renal failure. Presently, most methods of determining renal
           function are either too cumbersome, too invasion or too unreliable to be used in
           children. Current evidence has shown that serum cystatin C is more precise and
           cost-effective in determining renal function. Our objective is to compare serum cystatin
           C with other biomarkers as an early diagnostic detection for renal dysfunction in
           children with acute renal failure in an emergency setting.

        -  Study design and methods: This is a prospective double cohort control study to compare
           the serum creatinine and serum cystatin C in detecting early renal dysfunction in
           children presenting to the emergency department. The study will be conducted in CHEO
           emergency department. A study nurse will identify eligible patients and discuss whether
           to approach the families with either the bedside nurse or attending physician before
           meeting them. Interested families are than given an explanation of our study. Once
           written consent is obtained, a copy will be given to the family. Additional tests will
           than be requested from blood and urine samples of the patients. Only patients that
           already require an intravenous needling are eligible for this study. No additional
           needling is therefore needed as part of this study. Urine sample will only be obtained
           through bad or voiding samples. No catheter urine samples will be requested as part of
           this study.

        -  Subject selection: Our target population are patients presenting to the CHEO emergency
           department with the diagnoses of gastroenteritis and dehydration, and requiring
           intravenous rehydration. Our control group are patients with traumatic injury requiring
           conscious sedation and intravenous access. We will exclude patients who are known to
           have underlying kidney diseases, renal transplantation, thyroid dysfunction, chronic
           systematic steroid uses, genitourinary trauma and patients transferred from another
           hospitals for ongoing assessment and treatment.

        -  Specify the number of participants drawn from CHEO and other centres: CHEO is the only
           designated centre for the study. 464 patients will be recruited to complete the study,
           232 in each arm.

        -  Delineate the outcomes to be measured and analyzed: The primary outcome measures are to
           compare the sensitivity and the timing of detecting early renal dysfunction using either
           serum creatinine or serum cystatin C in the paediatric emergency setting. Our secondary
           outcome measures are to compare serum cystatin C to other surrogate renal markers for
           acute renal failure. Other renal markers include calculated Schwartz glomerular
           filtration rate, urine microprotein excretion, fractional excretions of sodium and urea,
           serum sodium, chloride, bicarbonate, urine Na/K ratio and regular urinalysis. Additional
           analysis will be conducted on the comparison of fractional excretion of urea to
           fractional excretion of sodium as an earlier marker of dehydration in children.

        -  Anticipated benefits/harms and how these will be addressed: Only patients who already
           require needling as part of their hospital care are eligible for the study. No
           additional needling is therefore requested. Additional tests will be requested that
           would otherwise not be part of the routine care of these patients. It is therefore
           possible that a kidney disorder will be identified in a child who was not yet diagnosed
           with this disease. We will discuss this possibility with the family before enrollment of
           the patient. All major abnormalities will be followed by both the attending physician
           and the principle investigators of the study and appropriate care will apply. We do not
           intervene with the ongoing care of the patients while the patients remain in hospital.
           The study will terminate when patients are discharged from the hospital.

        -  Data fields (if any) to be abstracted from the patient's health record: We will record
           patient's CHEO medical record number for the purpose of retrieving laboratory data; date
           of birth; biometric measurement (height, weight and sex). No other identifiable
           information will be record on the data sheet. No individual information will be used for
           publication or presentation.

      Informed consent documents and any advertisement notices must be appended to the application.
      Both English and French versions of the consent forms and information sheets are enclosed
      with this application.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children less than 18 years old who visit the treating pediatric emergency department.

        Gastro cohort: children suffer acute gastroenteritis with signs of dehydration and require
        intravenous fluid rehydration Injury cohort: children suffer musculoskeletal injury that
        require intravenous sedation for the repair
      
Keywords: Cystatin C; Acute renal failure; Gastroenteritis; Dehydration