DE
T50 EXPLAINED
T50 DIRECTLY MEASURES THE DRIVER
OF CARDIOVASCULAR DISEASE PROGRESSION
The T50 blood test is a new modifiable cardiovascular risk factor: poor T50 values are strongly associated with poor cardiovascular prognosis. Optimized therapies can improve the T50, and thus patient prognosis.

The T50 measures the Calcification Propensity, and thus the endogenous defense capacity against calcification. The measurement also reflects Phosphate Toxicity, as the calcifications are linked to dysregulation of phosphate in diseased patients.

Advantages of T50:
• Unique assessment/identification of cardiovascular high-risk patients
• Helps obtain the full potential of existing therapies
• Helps achieve best outcome
T50 MEASUREMENT PRINCIPLE
The T50 test measures how quickly toxic calcified particles are formed in vitro in the patient serum.

The body naturally converts phosphate and calcium into calcified particles called primary calciprotein particles (CPP1). Over time the CPP1 convert into secondary calciprotein particles (CPP2), which are known to be physiologically toxic and responsible for the progression of calcification in tissues.
The assay relies on the formation of CPP1 by addition of exogenous calcium and phosphate to a human serum sample. The newly formed CPP1 undergo spontaneous transformation to the more toxic CPP2, a process which is optically monitored by the T50 analyzer. The reported T50 value is the time necessary for the serum to convert 50% of the CPP1 into CPP2.
STUDIES
Clinical researchers worldwide are using the T50 test (and the underlying physiological role of CPP) and have published over 30 studies, including over 18'000 patients so far.
UNDERLYING PATHOPHYSIOLOGICAL TOXICITY
OF CPP2 MEASURED BY T50


Human vascular smooth muscle cells (VSMC) are the
cells in the vascular system that are predominantly
affected by calcification in CKD. VSMC exposed in vitro
to CPP1 do not develop calcification, but exposure to
CPP2 result in rapid calcification, inflammation
(TNF-alpha) and oxidative stress. (Figure 1). [1]
THE T50 TEST CAN PREDICT MULTIPLE
IMPORTANT CLINICAL ENDPOINTS


Mortality. Lower T50 values in kidney patients were associated with the progression of vascular stiffness and shorter life expectancy, see Figure 2. No other in vitro tests could statistically predict difference in survival (calcium, phosphate, magnesium, pyrophosphate and fetuin-A). [2]

Cardiovascular complications. In a study with 2785 patients, each 84 minutes (or 1 standard deviation) lower T50 value was associated with an 38% increase in myocardial infarctions. [3]

Progression of calcification. In a cohort of 460 patients with CKD stage 2-4, the T50 was associated with progression of coronary artery calcification (CAC): each 77-minute (or 1 standard deviation) lower T50 value was associated with a 28% increase of CAC progression of ≥100 Agatston units per year. [4]
EXISTING THERAPIES CAN BE OPTIMIZED TO IMPROVE CALCIFICATION PROPENSITY (T50) IN THE PATIENT

A low T50 value is consistently associated with poor outcome. Therapies can be personalized with the aim to increase the T50, and thus expect improved outcome. For example, an intervention trial demonstrated immediate improvement in T50 in the arm subjected to the therapy (increased Mg2+ concentration in dialysate, see Figure 3). [5]
STUDIES WITH T50 IN NON-RENAL PATIENTS UNDERLINE THE BROAD CLINICAL VALUE OF T50:

In lupus erythematosus T50 is associated with disease activity and cardiovascular events. [6]
In pregnancy, amniotic fluid T50 is associated with premature rupture of the membrane. [7]
In the general population, T50 is associated with incident cardiovascular events. [8]
References:
[1] Aghagolzadeh et al, Atherosclerosis 2016; [2] Smith et al, J Am Soc Nephrol 2014; [3] Pasch et al., CJASN 2016; [4] Bundy et al, Am J Kidney Dis 2019; [5] Bressendorff et al, Clin J Am Soc Nephrol 2018; [6] Dahdal, S. et al., Plos one, 2018; [7] Shook, L. et al., Sci Translat Med, 2016; [8] Eelderink, C. et al., Arterioscler Thromb Vasc Biol, 2020.
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