NON-OXIDIZED, BIOLOGICAL ACTIVE PARATHYROID HORMONE DETERMINES MORTALITY IN HEMODIALYSIS PATIENTS

摘要

A new method of in vitro monitoring and assessing the need of a medication which interferes with the regulation of the parathyroid hormone level in a kidney patient subject to oxidative stress, notably hemodialysis patients. FIG. 1 shows the distribution of n-oxPTH concentrations in 340 hemodialysis patients (224 men and 116 women) with a median age of 66 years (IQR, 56 to 75 years), a median time since initiation of dialysis (dialysis vintage) of 266 days (IQR, 31 to 1209 days), and a median dialysis dose (kt/V) of 1.2 (IQR, 1.1 to 1.3). The cause of chronic kidney disease was nephrosclerosis in 113 cases (33%), diabetic nephropathy in 107 cases (31%), chronic glomerular nephritis in 29 cases (9%), polycystic kidney disease in 9 cases (3%) and other/unknown in 82 cases (24%). The median n-oxPTH concentration was 5.9 ng/L (IQR, 2.4 to 14.0 ng/L). n-oxPTH concentrations were not different in men and women (5.9 ng/L; IQR, 2.4 to 14.2 ng/L; n=224; vs. 5.5 ng/L; IQR, 2.4 to 14.0 ng/L; n=1 16; p=0.915).

主权项

1. Method of in vitro monitoring and assessing the need of a medication which interferes with the regulation of the parathyroid hormone level in a kidney patient subject to oxidative stress comprising the steps of:
purifying a sample of plasma or serum from said kidney patient from human PTH peptides oxidized at either methionine 8 or 18 or both or at tryptophan 22 by contacting said sample with an antibody which recognizes and specifically binds a three-dimensional epitope located between amino acids 3 to 34 of oxidized human PTH peptides but which antibody does not bind non-oxidized human PTH (1-84) and fragments thereof; determining the amount of immunoreactive human PTH (iPTH) peptides in said sample by an immunoassay based on antibodies against human PTH(1-84) and fragments thereof that contain at least the domains responsible for receptor binding and activation of the cAMP-cyclase located between amino acids 3 to 34 of the human PTH sequence; and obtaining a PTH status value (n-oxPTH value) for said kidney patient which includes the rate of immunoreactive human PTH fiPTH) peptides secreted by cells of the parathyroid gland into the circulation and the rate by which immunoreactive human PTH (iPTH) peptides are oxidized by the oxidative stress suffered by said patient; and comparing the PTH status value (n-oxPTH) with a reference value at which the morbidity and ali-cause mortality is low to determine the need of a medication with respect to a regulation of the PTH status value or for supplementation of the patient with human parathyroid hormone or active fragments thereof or both.