Klotho Gene Polymorphism in Dialyzed Patients With Hyperphosphatemia

Chronic Kidney Disease Clinical Trial

Official title:

Study of Klotho Gene Polymorphisms in the Regulation of Serum Phosphate Levels in Hemodialysis Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00374712
• Other study ID #: P031010
• Secondary ID: CRC 03161
• Status: Terminated
• Phase: N/A
• First received: September 12, 2005
• Last updated: November 6, 2007
• Start date: January 2005
• Est. completion date: November 2007

Study information

• Verified date: November 2007
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Observational

Clinical Trial Summary

Patients with chronic kidney disease (CKD) and those with end-stage renal disease (ESRD) undergoing renal replacement therapies show elevated serum phosphate levels which predispose them to cardiovascular calcifications and high risks of death from cardiovascular diseases. However, in certain patients hyperphosphatemia is not related to dialysis insufficiency, excessive daily dietary phosphorus intake or high serum parathyroid hormone (PTH) levels, suggesting that other mechanisms could be involved. Transgenic mice lacking the klotho gene showed a phenotype which resembles that of dialyzed ESRD patients, in the sense that they have hyperphosphatemia, vascular calcifications, and a short lifespan. This study will analyze whether functional polymorphisms or variants in the human klotho gene are associated with hyperphosphatemia in these patients.

Description:

The entire coding region of the klotho gene will be sequenced looking for functional variants and polymorphisms that differentiate two groups of adult dialyzed ESRD patients, matched for age and gender, and with comparable values for dialysis dose and daily protein intake. These two groups consist of one group of 20 adult, dialyzed patients with serum phosphate levels > 2.50 mM compared to another group of 20 adult, dialyzed ESRD patients with serum phosphate levels < 1.50 mM. The results of this study will allow to determine whether there is a relationship between extreme hyperphosphatemia and klotho gene polymorphisms in dialysed ESRD patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Group 1

• Stable hemodialysis patients for at least 3 months

• Phosphatemia > 2.5 mM

• Kt/V > 1.2

• Total weekly phosphate removal > 75 millimoles

Group 2

• Stable hemodialysis patients for at least 3 months

• Phosphatemia < 1.5 mM

• Kt/V > 1.2

• Total weekly phosphate removal > 25 millimoles

Exclusion Criteria:

• Age > 80 years

• Insufficient dialysis dose (Kt/V < 1.2)

• Total weekly phosphate removal < 25 mM

• Problems with vascular access for hemodialysis (central catheter, arteriovenous [A-V] fistula dysfunction)

• Methods of dialysis different than the classical hemodialysis (peritoneal, hemofiltration, or hemodiafiltration with or without acetate)

• Intolerance or allergy to ARYLANE M9 dialyzers

• Hypocalcemia < 2.0 mmol/liter

• Hypophosphatemia < 0.6 mmol/liter

• Daily protein intake < 0.6 g/kg/j

• Parathyroidectomy at least 3 months prior to the study

• Evolutive neoplasia with or without secondary lytic bone lesions

• Intestinal malabsorption

• Alcoholism

• Corticotherapy

• Treatment by bisphosphonates, fluor or recombinant PTH

• Malnutrition (body mass index [BMI] < 15)

• Amputation of lower members (> 10% of total body)

• Prolonged immobilization

• Secondary hyperparathyroidism (PTH > 1400 pg/ml)

• Vitamin D deficiency (25OHD3 < 10 ng/ml)

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Kidney Disease
• End Stage Renal Disease
• Hyperphosphatemia
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic
• Renal Osteodystrophy

Locations

Country	Name	City	State
France	Clinique de l'Orangerie - Service de Néphrologie et Dialyse	Aubervilliers

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (1)

Prié D, Beck L, Urena P, Friedlander G. Recent findings in phosphate homeostasis. Curr Opin Nephrol Hypertens. 2005 Jul;14(4):318-24. Review. — View Citation