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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.

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.

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)

Adult, end-stage renal disease patients treated by standard hemodialysis