Quite excited about this latest paper of ours just published in NDT.
What did we find? And what is a calciprotein particle?
I'll walk you through the results (thread) 1/12
What did we find? And what is a calciprotein particle?
I'll walk you through the results (thread) 1/12
In blood Ca and PO4 exist in a metastable state and will spontaneously form more thermodynamically stable mineral leading to deposition of Ca/PO4 in soft tissue and ectopic calcification. 2/12
Amorphous Ca/PO4 binds to fetuin-A and forms a spherical primary calciprotein particle (CPP-1), thus acting as a buffer for Ca/PO4 and chaperoning it to sites of mineral degradation and preventing ectopic calcification. 3/12
With time CPP-1 accumulate Ca/PO4, the core becoming crystalline and containing hydroxyapatite. The CPP undergoes a conformational change to a needle-like shape and is now termed CPP-2. This is particularly prevalent in conditions of PO4 excess, e.g. ESKD. 4/12
While CPP-1 is benign CPP-2 induces massive oxidative stress, inflammation and calcification of vascular smooth muscle cells. The transition from CPP-1 to CPP-2 is believed to be an important component of the so-called PO4 toxicity. 5/12
Mg delays the transition from CPP-1 to CPP-2. We hypothesised that increasing dialysate Mg for 28 days would prevent transition from CPP-1 to CPP-2 resulting in more CPP-1 and less CPP-2. What we found surprised us quite a bit... 6/12
Increasing Mg reduced CPP-2 by 68%, but CPP-1 was also reduced by 42% and thus total CPP was reduced by 52%. Also, TNF-alpha and IL-6 were both reduced by about 20% each. 7/12
CPPs are believed to be formed in the gut or released from bone, and since increasing dialysate Mg should not affect formation of CPP in the gut, we reasoned that Mg might affect bone turnover... 8/12
Indeed, we found a 33% reduction in osteoclast activity (bone resorption) and a 17% increase in osteoblast activity (bone formation). This suggests a previously unknown beneficial effect of Mg on bone turnover. 9/12
We speculate the following: Mg affects bone resorption and formation leading to a reduction in the release of CPP into circulation. The reduced CPP burden lessens the CPP-2 load and consequently reduces systemic inflammation. Lower risk of calcification and fractures? 10/12
Limitations - post hoc exploratory analysis, short trial duration, surrogate markers of bone turnover, unknown clinical correlation. 11/12
This is the superficial presentation of the data. For more details and nuances, check out the full paper out now in NDT (end thread) 12/12
CKD-MBD doesn't get a lot of traction on Twitter, but hope people find this interesting and become aware of the concept of CPPs and its link to calcification in CKD/ESKD @hswapnil @drpaddymark @rkramann @hjanders_hans @jennifer_s_lees @jeroendebaaij
