EARLIER: an observational study to evaluate the use of cinacalcet in incident hemodialysis patients with secondary hyperparathyroidism in daily clinical practice.

The EARLIER (Evaluation of MimpARa in incident hemodiaLysis patIEnts with secondaRy hyperparathyroidism; SHPT) observational postmarketing surveillance study evaluated incident hemodialysis patients (< 1 year dialysis vintage; n = 146) receiving cinacalcet in Austrian clinical practice. Despite intervention with vitamin D sterols and phosphate binders, 24 % had already developed severe SHPT (intact parathyroid hormone (iPTH) > 800 pg/mL) at baseline. After cinacalcet was started, median iPTH decreased substantially, from 611 pg/mL to 251 pg/mL (median decrease 58 % [IQR - 36 to - 78 %] at 12 months. Overall, 36 % of patients achieved the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range (150-300 pg/mL) for iPTH; this included 35 % of those with severe SHPT at baseline. Serum phosphorus (P), calcium (Ca) (corr), and Ca (corr) × P also decreased, with 43, 34, and 62 % of patients, respectively, reaching K/DOQI targets at 12 months. Thus, in this observational study, mineral metabolism in incident dialysis patients with SHPT improved after starting cinacalcet.

Darbepoetin alfa once every 2 weeks effectively maintained hemoglobin in dialysis patients in an observational study: Austrian cohort of ALTERNATE.

ALTERNATE is an international observational study evaluating biweekly darbepoetin alfa (DA) in adult dialysis patients in clinical practice. Austrian ALTERNATE results are presented here (n = 505). The follow-up study ALTERNATE follow-up (AFU) followed Austrian ALTERNATE patients for an additional 12 months (n = 135). Data were collected 6 months before and 12 months after conversion to biweekly dosing and during 12 months of follow-up. The primary measures were hemoglobin concentration 12 months after conversion and at the end of AFU, respectively. Mean (95 % CI) hemoglobin (g/dL) was 11.87 (11.75-11.99) at conversion, 11.71 (11.58-11.83) at month 12, and 11.66 (11.45-11.86) at end of AFU. Geometric mean (95 % CI) weekly dose (µg/wk) was 32.97 (30.80-35.30) at conversion, 29.90 (26.71-33.46) 12 months after conversion, and 24.38 (18.40-30.35) at end of AFU. The studies show that hemoglobin and dose could be effectively maintained over an extended period of time after conversion from higher frequency erythropoiesis-stimulating agents to biweekly DA.

Extended dosing of darbepoetin alfa in peritoneal dialysis patients.

BACKGROUND: Anemia is common among peritoneal dialysis (PD) patients, and most patients require erythropoiesis-stimulating agents (ESA) to maintain their hemoglobin concentrations within current guideline recommendations. Darbepoetin alfa is an ESA with a 3-fold longer half-life and greater in vivo biological activity than recombinant human erythropoietin, allowing less frequent dosing that may simplify anemia management in these patients, providing benefits to patients, care givers and health care providers. Clinical studies have confirmed the efficacy and safety of darbepoetin alfa administered at extended dosing intervals. However, there are limited data on the management of anemia with ESAs in PD patients in routine clinical practice. The aim of this multicenter observational study in European and Australian dialysis patients was to evaluate darbepoetin alfa administered once every 2 weeks (Q2W) in routine clinical practice for 12 months. METHODS: PD patients ≥18 years old and converting to treatment with darbepoetin alfa Q2W were eligible for enrollment regardless of previous or current ESA use. Patients enrolled in the study were treated according to local usual clinical practice. Data were collected up to 6 months prior to and 12 months after conversion to darbepoetin alfa Q2W. The primary endpoint was hemoglobin concentration 12 months after conversion to darbepoetin alfa Q2W. RESULTS: Of the 741 eligible PD patients (mean age, 61 years; male, 57%), 640 (86%) completed the study. Mean hemoglobin concentration (g/dL) was 11.69 (95% CI, 11.53-11.86) 6 months before the conversion, 12.25 (95% CI, 12.13-12.38) at conversion, and 11.88 (95% CI, 11.74-12.02) 12 months after conversion to darbepoetin alfa Q2W. The weekly equivalent ESA dose (µg/wk) was a geometric mean of 25.24 (95% CI, 23.46-27.15) 6 months before conversion, 20.90 (95% CI, 19.13-22.83) immediately before conversion, 18.89 (95% CI, 18.13-19.68) at conversion and 19.04 (95% CI, 17.69-20.49) 12 months after conversion. Twelve months after conversion, 70% of patients were receiving darbepoetin alfa Q2W and 73% had hemoglobin concentrations >11.0 g/dL. CONCLUSION: In this large observational study, PD patients were able to maintain mean hemoglobin concentrations >11.0 g/dL after conversion to extended dosing of darbepoetin alfa Q2W, with no mean dose increase.

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 is a complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. A total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of a cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitamin D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented. Overall, the mean intact parathyroid hormone (iPTH) increased from 64.2 pmol/l to 79.6 pmol/l under conventional therapy and decreased after cinacalcet initiation to 44.0 pmol/l after 12 months (mean decrease between baseline and 12 months -45%). Calcium remained within the normal range throughout the study and phosphorus ranged around the upper limit of normal. The Kidney Disease: Improving Global Outcomes (KDIGO) target achievement for iPTH increased from 44.5% of patients at baseline to 65.7% at 12 months, corrected calcium from 58.9% to 51.9% and phosphorus from 18.4% to 24.4%. On average, approximately 30% of patients adapted their regimen from one observation period to the next. The reasons for changing a given regimen were to attain or maintain any of the bone mineral markers within recommended targets and to avoid developments to extreme values. Some regional differences in practice patterns were identified. No new safety signals emerged. In conclusion, cinacalcet appears to be a necessary treatment component to achieve recommended targets. The detailed composition of the treatment mix should be adapted to patient requirements and reassessed on a regular basis.

Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for alpha-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.