Claudia Friedl1, Gilbert Reibnegger2, Reinhard Kramar3, Emanuel Zitt4, Stefan Pilz5, Johannes F E Mann6, Alexander R Rosenkranz7. 1. Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Auenbruggerplatz 27, A-8036 Graz, Austria. Electronic address: claudia.friedl@medunigraz.at. 2. Institute of Physiological Chemistry, Medical University of Graz, Harrachgasse 21, A-8010 Graz, Austria. Electronic address: gilbert.reibnegger@medunigraz.at. 3. Austrian Dialysis and Transplant Registry, Brandstatt 37, A-4532 Rohr, Austria. Electronic address: rkramar@aon.at. 4. Department of Nephrology and Dialysis, Academic Teaching Hospital, Carinagasse 47, A-6870 Feldkirch, Austria. Electronic address: emanuel.zitt@lkhf.at. 5. Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria. Electronic address: stefan.pilz@medunigraz.at. 6. Department of Nephrology, University of Erlangen-Nürnberg, Maximiliansplatz 2, D-91054 Erlangen, Germany; KfH Kidney Center, Munich, Isoldenstraße 15, D-80804 München, Germany. Electronic address: prof.j.mann@googlemail.com. 7. Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Auenbruggerplatz 27, A-8036 Graz, Austria. Electronic address: alexander.rosenkranz@medunigraz.at.
Abstract
BACKGROUND: Secondary hyperparathyroidism (sHPT) is associated with higher mortality in dialysis patients. The calcimimetic cinacalcet reduces intact parathyroid hormone (iPTH) in dialysis patients. The randomized controlled EVOLVE trial failed to unequivocally prove survival advantage of cinacalcet in dialysis patients. However, recent post hoc analyses suggested a benefit in subgroups of dialysis patients. Large observational cohort studies may represent an option to better determine such subgroups. METHODS: Data from the nationwide Austrian registry of dialysis patients between January 2004 and December 2009 were analyzed with follow-up until December 2010. All-cause and cardiovascular mortality analyses were performed using the Kaplan-Meier and Cox proportional hazards regression. To reduce confounding effects a propensity score (PS) based method (matching by stratification) was used for group comparison. RESULTS: The cohort included 7983 dialysis patients, 1572 (19.7%) were prescribed cinacalcet. During a median follow-up of 2.7years, 3574 (44.8%) patients died, including 1342 (16.8%) deaths from cardiovascular causes. Survival analyses in the PS-matched study population (n=6109) showed lower all-cause mortality for cinacalcet-treated as compared to untreated patients only in subsets characterized by younger age, low prevalence of diabetes, iPTH levels between 300 and 599pg/mL, concomitant therapy with vitamin D and phosphate binders. CONCLUSIONS: Our data suggest that a subgroup of dialysis patients, namely those with moderate sHPT, younger age and without diabetes benefit from cinacalcet with reduced overall and cardiovascular mortality. These findings may help to identify populations for further controlled trials and may allow a more individualized sHPT treatment using cinacalcet in specific patient subgroups.
BACKGROUND: Secondary hyperparathyroidism (sHPT) is associated with higher mortality in dialysis patients. The calcimimetic cinacalcet reduces intact parathyroid hormone (iPTH) in dialysis patients. The randomized controlled EVOLVE trial failed to unequivocally prove survival advantage of cinacalcet in dialysis patients. However, recent post hoc analyses suggested a benefit in subgroups of dialysis patients. Large observational cohort studies may represent an option to better determine such subgroups. METHODS: Data from the nationwide Austrian registry of dialysis patients between January 2004 and December 2009 were analyzed with follow-up until December 2010. All-cause and cardiovascular mortality analyses were performed using the Kaplan-Meier and Cox proportional hazards regression. To reduce confounding effects a propensity score (PS) based method (matching by stratification) was used for group comparison. RESULTS: The cohort included 7983 dialysis patients, 1572 (19.7%) were prescribed cinacalcet. During a median follow-up of 2.7years, 3574 (44.8%) patients died, including 1342 (16.8%) deaths from cardiovascular causes. Survival analyses in the PS-matched study population (n=6109) showed lower all-cause mortality for cinacalcet-treated as compared to untreated patients only in subsets characterized by younger age, low prevalence of diabetes, iPTH levels between 300 and 599pg/mL, concomitant therapy with vitamin D and phosphate binders. CONCLUSIONS: Our data suggest that a subgroup of dialysis patients, namely those with moderate sHPT, younger age and without diabetes benefit from cinacalcet with reduced overall and cardiovascular mortality. These findings may help to identify populations for further controlled trials and may allow a more individualized sHPT treatment using cinacalcet in specific patient subgroups.
Authors: Bradley A Warady; Eric Ng; Laura Bloss; May Mo; Franz Schaefer; Justine Bacchetta Journal: Pediatr Nephrol Date: 2020-05-04 Impact factor: 3.714
Authors: Andras T Deak; Francesca Ionita; Alexander H Kirsch; Balazs Odler; Peter P Rainer; Reinhard Kramar; Michael P Kubatzki; Katharina Eberhard; Andrea Berghold; Alexander R Rosenkranz Journal: Nephrol Dial Transplant Date: 2020-10-01 Impact factor: 5.992