Klotho Gene Polymorphism in Dialyzed Patients With Hyperphosphatemia

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Terminated

CT.gov ID

NCT00374712

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other)

Enrollment

Location

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease End Stage Renal Disease Hyperphosphatemia Renal Osteodystrophy

Detailed 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.

Study Design

Study Type:

Observational

Actual Enrollment :

40 participants

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jan 1, 2005

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)