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properties such as binding cholesterol, uraemic toxins or other their respective cohorts and will yield important results within the next
pro-inflammatory factors three years.
Cincalcet and Other ‘Suspects’ Nicotinamide, originally prescribed in the treatment of dyslipidaemias
Cinacalcet, the allosteric modulator of the Ca-sensing receptor (CaSR), due to its low-density lipoprotein (LDL)-lowering and high-density
lowers both serum Ca and P concentrations in addition to suppressing lipoprotein (HDL)-increasing properties, is an inhibitor of active
immunoreactive PTH (iPTH) secretion.
This highly reproducible and transcellular P absorption. This mechanism of action requires
persistent effect may be due to an improved bone turnover and thus appropriate pre-clinical and clinical trials in order to evaluate the
an increased ion uptake into the bone, but potentially also by effects potency and the tolerability of the drug compared to the available
on the ion efflux from the intracellular into the extracellular treatment options.
Last but not least, one should not forget about the
compartment. Cinacalcet also suppresses parathyroid hyperplasia value of increasing the dialysis dose, either by increasing the length of
when administered and prevents calcitriol-induced vascular each session (e.g. 3x8h per week, ‘nocturnal dialysis’) or frequency (e.g.
calcifications in experimental models.
The new developments 6x3h per week), both of which will normalise phosphate levels in most
concerning the value of cinacalcet in the current treatment of patients if on a reasonable diet.
The missing pieces in this therapeutic
According to epidemiological data, hyperphosphataemia appears to
be one of the key threats to the event-free survival of dialysis, and
puzzle are prospective, hard-outcome
potentially to a considerable part of CKD stage 3 and 4 patients. The
data showing clear-cut superiority of
mainstay of therapy is the use of P binders, while management of
hyperphosphataemia by balanced diets should be used in conjunction.
the available treatment options, while
Combinations of the different P binders may improve P control and
sevelamer hydrochloride probably still
consequently limit side effects (e.g., Ca load, gastrointestinal complaints).
The missing pieces in this therapeutic puzzle are prospective, hard-
has the most solid dataset available.
outcome data showing clear-cut superiority of the available treatment
options, while SEV probably still has the most solid dataset available.
However, it must be kept in mind that all data that demonstrated harmful
secondary hyperparathyroidism and CKD-associated mineral disorders effects of hyperphosphataemia are obtained from observational studies.
are related to the launch of two large, prospective, randomised, For example, there is no prospective randomised, controlled trial showing
controlled trials observing the effects of cinacalcet on coronary artery that a serum phosphate target level of 1.8mmol/l leads to improved
calcification and cardiovascular survival. These studies are: Study to survival versus a serum phosphate of 2.4mmol/l. The recent anaemia
Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification trials – Cardiovascular Reduction Early Anemia Treatment Epoetin Beta
in Subjects With Chronic Kidney Disease Receiving Hemodialysis (CREATE) trial and the Correction of Hemoglobin and Outcomes in Renal
(ADVANCE) and EValuation Of Cinacalcet HCl Therapy to Lower Insufficiency (CHOIR) trial – should warn us against making too definite
CardioVascular Events (EVOLVE). Both studies are currently recruiting assumptions from epidemiology. ■
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