CKD-MBD new indicators: non-oxidized parathyroid hormone

The prevalence and mortality of patients with chronic kidney disease with abnormal bone and calcium metabolism (CKD-MBD) remains high. One of the major reasons for the lack of progression of CKD-MBD in the past decade has been the lack of predictors of prognostic function, limiting the development of CKD-MBD inpidualized therapy.

The relationship between non-oxidized parathyroid hormone levels and vascular calcification in patients with CKD-MBD from the University of Potsdam, Germany, was published in the latest issue of the Kidney disease Journal The

Parathyroid hormone (PTH) plays an important role in the pathophysiology of CKD-MBD. However, the currently used PTH sandwich detection system often does not accurately describe the level of PTH in CKD-MBD. Many preclinical studies, including observational studies in the human body, suggest that PTH is too high or too low to cause bone and cardiovascular disease to occur.

Based on the above study, the clinical guidelines for CKD patients with PTH is too high or too low have developed a corresponding treatment measures, such as low PTH given PTH analog treatment. Therefore, for CKD-MBD treatment, reliable determination of PTH tools is particularly important.

However, at present we have not been able to determine how high or low PTH values ​​are defined as secondary hyperparathyroidism. The description of the PTH value that should be reached in the clinical guideline is complex (for example, the PTH of these patients should be between 2 and 9 times the upper limit of the inpidual test, and the physician should consider the trend of PTH in adjusting the treatment). This description clearly indicates that there is currently a shortage of tools for detecting PTH.

Figure 1 The current detection system is a positive signal when the antibody binds to two sites on the parathyroid hormone (PTH) molecule. This ensures that all degraded PTH is not tested. Such detection is therefore known as complete PTH (iPTH) detection. However, this detection method does not distinguish between oxidized and non-oxidized PTH. Mid / C-PTH: medium / carboxy terminal PTH; N-PTH: amino acid end PTH; RIA: radioimmunoassay

The reason for the inaccurate detection of PTH system is the post-transcriptional modification of PTH, especially the oxidation of Met8 and Met18 in PTH molecules. This modification is particularly evident in CKD patients with significant oxidative stress.

As early as 20 years ago, an independent research team had found that oxidized PTH (oxPTH) and non-oxidized PTH (n-oxPTH) had completely different biological activity. Only n-oxPTH is a ligand for PTH receptors, and oxPTH does not activate PTH receptors. However, in the open PTH detection system, and did not consider the PTH oxidation caused by the detection is not accurate.

A new PTH detection system developed by the author team to distinguish between oxPTH and n-oxPTH. Compared with adult CKD patients (including dialysis and kidney transplantation), children with CKD2 stage of the highest n-oxPTH. EVOLVE studies involving 2,867 patients suggest that only n-oxPTH, rather than oxPTH or full iPTH, predicts cardiovascular events and all-cause mortality.

Therefore, with the new CKD-MBD index of n-oxPTH, it can provide a new reference for the inpidualized treatment of CKD-MBD patients and improve the prognosis of CKD-MBD patients.