The use of cinacalcet for the treatment of calciphylaxis in patients with chronic kidney disease: A comprehensive review

Abstract

Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists so far. In an attempt to avoid surgical intervention with parathyroidectomy, which is of questionable efficacy and carries several risks, a number of noninvasive treatments have been trialled with variable success. These treatments are aimed at modifying risk factors for calciphylaxis, in particular hypercalcaemia, hyperphosphataemia and hyperparathyroidism. The aim of this review was to summarise the available evidence to determine the potential role of cinacalcet in the treatment of calciphylaxis in patients with chronic kidney disease. Demographic, clinical and laboratory data were retrospectively collected from the available English and non-English literature. Overall, there was a very high response rate (partial or complete) of calciphylaxis lesions to both cinacalcet monotherapy and cinacalcet as part of a combination therapy (83.4% and 82.8%, respectively). When examining complete response to treatment specifically, combination therapy with cinacalcet proved more efficacious than monotherapy (62.1% versus 41.7%). There was also an associated rapid reduction of intact parathyroid hormone over a period of 2-33 months in both groups. While there are limitations as to how our data can be interpreted due to the heterogeneity of the methods and follow-up of the included case reports and case series, prompt and consistent therapy including cinacalcet may help improve the disease outcome. Additional research needs to be performed in this area, to further define the optimal use of cinacalcet for the treatment of calciphylaxis.

Calciphylaxis in end-stage kidney disease: outcome data from the United Kingdom Calciphylaxis Study

“…The increased use of cinacalcet at baseline (19%) in the UKCS cohort may therefore represent underlying SHPT rather than a causative association. Deen et al have suggested the beneficial effects of cinacalcet as a treatment for CUA in a recent review [ 26 ]. The EVOLVE study also suggested that patients receiving cinacalcet for SHPT were less likely to develop calciphylaxis; 18 patients assigned to placebo developed calciphylaxis versus six assigned to cinacalcet [ 27 ].…”

Risk factors for calciphylaxis in Chinese hemodialysis patients: a matched case-control study

“…Excessive calcium and phosphate would deposit in the vascular wall, making the medial membrane and soft tissues prone to calcification that may aggravate or induce calciphylaxis [24,25]. Therefore, cinacalcet, which could improve bone markers and stabilize vascular calcification, may be preferable to PTX for calciphylaxis patients with SHPT, and PTX is reserved for refractory cases [26][27][28][29].…”

Actinomycetes-derived imine reductases with a preference towards bulky amine substrates

“…3c and Supplementary Fig. 5), a treatment for secondary hyperparathyroidism 23 . Given aromatic conjugated ketones being challenged substrates for IREDs 20,24 , we applied kinetic resolution to synthesize bulky N-alkylated benzylamines.…”