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Endokrinologie 13. Juni 2017

Management of secondary hyperparathyroidism: practice patterns and outcomes of cinacalcet treatment with or without active vitamin D in Austria and Switzerland – the observational TRANSIT Study

Secondary hyperparathyroidism (SHPT) is a severe and progressive disorder frequently observed in patients from an early stage of chronic kidney disease (CKD) onwards. At the time this study was planned and initiated, in the years 2009/2010, the principles of therapy of SHPT were profoundly questioned and changed. A new theory of the pathogenesis of SHPT placed more emphasis on the control of serum phosphorus levels [ 1 ]. This newer theory views the CKD-induced impaired activation of vitamin D not as the cause of SHPT but as an adaptive reaction to processes occurring much earlier in the cascade of events. According to this theory phosphorus retention in the failing kidney leads to increases in circulating fibroblast growth factor 23 (FGF-23) levels. Together with the Klotho protein FGF-23 tries to restore effective renal phosphorus clearance. In addition, FGF-23 blocks the production of active vitamin D. Only in the very late stages of CKD, when no sufficient renal function remains and phosphorus clearance can no longer be supported by intrinsic mechanisms, the PTH-calcium-vitamin D axis as described in the “trade-off” comes into play [ 2 ]. Following this reasoning, SHPT treatment should primarily be based on phosphorus restriction in combination with physiologic doses of active vitamin D analogues. In patients where phosphate binders and physiologic vitamin D doses alone are insufficient to control parathyroid hormone (PTH), calcimimetics should be considered as first-line therapy to control serum PTH [ 1 ]. On the other hand, the Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD) guidelines issued in 2009 [ 3 ] were less stringent with respect to PTH target levels than the previously used National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI™) guidelines [ 4 ]. The 2003 NKF-KDOQI™ clinical practice guidelines for bone mineral metabolism and disease in CKD defined stringent target ranges for the key parameters of bone mineral metabolism (iPTH: 16.5–33.0 pmol/l; serum phosphorus: 1.1–1.78 mmol/l; serum calcium: 2.1–2.37 mmol/l; corrected calcium-phosphorus product <4.4 mmol²/l²) [ 4 ]. In 2009, the KDIGO clinical practice guidelines for the diagnosis, evaluation, prevention and treatment of CKD-MBD changed their focus towards defining ranges of extreme risk that should be avoided [ 3 ]. For intact PTH (iPTH), the recommended safe range was defined as 2–9 times the upper limit of normal (ULN) of the assay used; calcium is recommended to be maintained in the normal range and elevated phosphorus should be lowered toward the normal range. These recommendations allow some individualization of treatment much welcomed by the medical community.

At the time this study was planned a survey evaluating the quality of CKD-MBD treatment in Austria (Austrian Dialysis and Transplant Registry; “QUASI” 2008,www.nephro.athttp://www.nephro.at" TargetType="URL"/>), revealed that approximately 30% of Austrian patients received cinacalcet as a monotherapy, without concomitant administration of active vitamin D compounds. From the survey, however, it was not clear, whether cinacalcet was used as a monotherapy already at cinacalcet initiation or if active vitamin D was initially co-administered and discontinued later. One aim of this study therefore was to determine the proportion of patients where cinacalcet was initiated as a monotherapy or in combination with active vitamin D. Another aim of this study was to identify treatment combinations used in clinical practice and their potential to control CKD-MBD.

Dr. Wolfgang Pronai, Alexander Rosenkranz, Andreas Bock, Renate Klauser-Braun, Christine Jäger, Gunther Pendl, Margit Hemetsberger, Karl Lhotta, Wiener klinische Wochenschrift 9/10/2017

Volltext dieses Beitrags / entire article auf SpringerLink

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