Parathyroid Hormone Level and Growth in Pediatric Patients With ESRD on Regular Hemodialysis
Condition: Drug Effect
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic kidney disease (CKD) is defined as either renal damage and/ or a glomerular
      filtration rate (GFR) below 60 mL/min/1.73 m2 for more than 3 months. End stage renal disease
      (ESRD) is defined as GFR below 15 mL/min/1.73 m2.

      Secondary hyperparathyroidism (SHPT) is an insidious disease that develops early in the
      course of CKD and increase in severity as the GFR deteriorates. High serum levels of intact
      parathyroid hormone (iPTH) are known to cause high turnover bone disease, i.e. osteitis
      fibrosa and have also been reported to increase the mortality risk in patients undergoing
      hemodialysis (HD).

      Standard therapy for SHPT includes dietary calcium supplementation, active vitamin D, and
      phosphate binders; however, these are often insufficient to allow patients to achieve their
      serum parathyroid hormone (PTH), calcium and calcium-phosphorus product (Ca × P) targets.

      Recent preclinical studies have demonstrated that treatment with calcimimetics that increase
      the sensitivity of the calcium-sensing receptor (CaR) to calcium can reverse the alterations
      in CaR and vitamin D receptor expression and parathyroid cell proliferation that are
      associated with SHPT.

      Calcimimetics such as cinacalect are positive allosteric modulators of the calcium-sensing
      receptor that increase its sensitivity by lowering the threshold for activation by
      extracellular calcium ions. The calcimimetic cinacalcet mainly increases the sensitivity of
      the CaR to extracellular Ca, thus inhibiting the release of PTH, although, as recently shown,
      it also decreases PTH synthesis.

      Growth hormone (GH) indirectly promotes the growth of child by stimulating the production of
      insulin like growth factor (IGF-1), many children with renal disease have normal or elevated
      level of GH in their blood otherwise the levels of IGF-1 are low because the approximately
      98% of IGF-1 is always bound to one of binding proteins (BP) inside the liver, so this
      accumulated protein will reduce the function of IGF-1.

      Using cinacalcet in controlling hyperparathyroidism may reduce growth problems in children
      with ESRD with regular hemodialysis.
    

Detailed description: 
      This interventional study will be conducted at Nephrology Unit Pediatric Department Tanta
      University Hospital (TUH) for a period of 6 months starting from August 2023.

      Study duration 6 months from August 2023 to February 2024. Place of the study: Nephrology
      Unit at TUH. Study sample: This study will be conducted on 35 children and adolescents with
      end stage renal disease on regular hemodialysis for three to four times weekly at our
      nephrology Unit at TUH during the period of the study.

      Inclusion criteria:

      Pediatric patients with end stage renal disease aged from 8 to 18 years on regular
      hemodialysis.

      Exclusion criteria:

        -  Controlled hyperparathyroidism- PTH <300 pg/ml.

        -  Children < 8y.

        -  Previous parathyroidectomy

        -  children on growth hormone therapy

      All patients included in the study will be subjected to:

        1. History taking including duration of dialysis and regular drugs that are taken.

        2. Clinical examination including anthropometric measurements and blood pressure
           estimation. All measurements will be taken in the dialysis free day

        3. Investigations A- Routine investigations: including

             -  Complete blood picture

             -  Serum albumin Serum creatinine, blood urea level●

             -  Serum CRP B- Specific investigations: including

                  -  Serum insulin growth factor-1 using ELIZA kits.

                  -  Serum parathyroid hormone.

                  -  Serum calcium.

                  -  Serum phosphorus.

                  -  Serum alkaline phosphatase.

           Sample collection:

           Seven millilitres of venous blood will be collected under complete aseptic precautions
           at 8 AM and before dialysis session before and after one month of cinacalcet treatment.
           Five millilitres will be put in a plain test tube without anticoagulant, and the
           remaining two millilitres will be put in a test tube with ethylene diamine tetra-acetic
           acid (EDTA) as an anticoagulant, to be used for performing complete blood count. After
           clotting, the samples will be centrifuged at 1500 xg for 15 minutes. Part of the
           separated serum will be used to perform serum creatinine, urea, albumin and blood urea
           nitrogen (BUN). The rest of the serum will be separated and will be used for the
           subsequent assay of IGF-1 serum level by enzyme-linked immunosorbent assay (ELISA).
           Hemolysed samples will be discarded. Repeated thawing and freezing will be avoided.

        4. treatment received: All children will receive cinacalcet in a dose of 30 mg/day taken
           with food for 3 months, in addition to their supportive treatment including
           erythropoietin injection, oral calcium, one alpha, folic acid and antihypertensive drugs
           to hypertensive patients.
    

Intervention name(s): Cinacalcet
Intervention type(s): Drug
Intervention description(s): calcimimetic
Other intervention name(s): Mimpara
Intervention MeSH terms: Cinacalcet
Intervention model: Sequential Assignment
Intervention model description: evaluate the effect of cinacalcet on insulin like growth factor-1 in pediatric patients with ESRD on regular hemodialysis
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: cinacalcet; insulin like growth factor-1