Calciphylaxis Registry. A rare disease as template for CKD-MBD?

Klinik für Kardiologie und Intensivmedizin

Vincent Brandenburg University Hospital RWTH Aachen

Dpt of Cardiology

© K. Zerres 2004

Istanbul, May 2013

CKD-MBD

cardiovascular disease

Accelerated Arteriosclerosis in Uremia: 3 Varieties

calcification

Chronic kidney disease

Heart Valves Large arteries Small arteries

Calciphylaxis (CUA) - rare, (Orpha.net # ORPHA280062)

- life-threatening syndrome,

- media calcifications of cutaneous vessels (~100µm)

- progressive, very painful lesions / ulcerations

- reduced quality of life, high mortality

Definition Calciphylaxis – calcific uremic arteriolopathy

Diagnostic criteria for CUA (Japan)

Diagnosis Calciphylaxis Matsuhiko Hayashi Clin Exp Nephrol 2012

- Missed cases? - Etiology and risk factors? - iatrogenic components? - trigger? - prevention? - different enteties? - treatment: good-clinical practice? - outcome? - prospective RCT: which endpoint(s)? - ….

Registry initiative since 2007

Calciphylaxis: (still) unsolved issues:

NDT survey about CUA - Undiagnosed cases?

The German Calciphylaxis Registry www.calciphylaxie.de

The German Calciphylaxis Registry www.calciphylaxis.eu

A) Baseline questions via online questionnaire: - patient data (age, sex, cv disease, kidney disease, PTex…) 15 - lab data (creatinine, phos., calc., PTH, CRP, Hb, albumin…) 12

- dialysis modality 9

- Medications (renal, cv) 24

- clinical data about CUA 6 + free text

66 items

The German Calciphylaxis Registry www.calciphylaxis.eu

B) Biobank: serum / plasma / full blood and tissue samples; C) picture documentation

Calciphylaxis Registry: outcome

STS-treatment

No STS-treatment

STS unknown

50%

516 days

Results

Calciphylaxis Registry: Co-medication [%]

01020304050607080

Vitamin D

PB

Coumadins

Cinacalcet ESA

Results

Role of vitamin K antagonist usage and CUA

Hayashi M et al; NDT 2012

Clear association between VKA usage and calciphylaxis: Causality?

Results

Calciphylaxis role of calcification inhibitors: serum MGP

Referenz PTCA Aortenstenose HD CUA

E. Cranenburg / V. Brandenburg et al. J Vasc Res 2008;45:427–436

Very low levels of circulating calcification inhibitors fetuin / MGP: cause versus effect?

Results

Calciphylaxis Registry: PTH levels [pg/mL]

0

10

20

30

40

50

60

1 2 3 4 0

5

10

15

20

25

30

35

1 2 3 4

Calciphylaxis registry March 2012

NDT educational online survey February 2012

0 – 150 150 - 300

300 - 600 > 600

0 – 150 150 - 300

300 - 600 > 600

Relevant differences between perception and registry data regarding PTH levels

PTH

Results

Calciphylaxis Registry: What´s new in 2013?

www.calciphylaxie.de

www.calciphylaxis.eu

WWW

Multilingual Online Registry System

„VHRegister“

• ONE Online Registry System, centrally hosted and professionally maintained • ONE Online Form in multiple languages, accessible from everywhere via WWW

VHRegister: Online Registry System - Basics

Participant

Participant

Participant

Participant

Participant

Multilingual Online Registry System

„VHRegister“

• The online form is integrated in a regular website or multiple international websites for a widespread usage • The registration process for participants takes only a few seconds • With the generated access code every participant = treating physician can enter new data or add data to existing cases from every computer with internet access • bidirectional data management and interaction administrator with participant

VHRegister: Example case entry (1)

(1) Visit www.calciphylaxis.net WWW

(2) Register or login with existing access code

Participant =

Treating MD with a case of CUA

• One online form is provided in multiple languages, freely switchable • The data is centrally stored as independent of language as possible

VHRegister: Example case entry (2)

Multilingual Online Registry System

„VHRegister“

WWW

(3) Enter and send data!

Participant

• The Administration Tool can be accessed by authorized users via an easy to use website from everywhere • All connections in the process and all stored data is highly encrypted (SSL/AES) • Case data can be viewed, edited, deleted and exported to EXCEL in any language • Every change in case data is logged, backed up and can be undone

VHRegister: Administration & Evaluation

Multilingual Online

Registry System „VHRegister“

WWW

Encrypted Data

Researcher

Researcher

Researcher

Researcher

Researcher

• VH Register 2.0 was used on the German Calciphylaxis Registry since 2006 very sucessfully, collecting over 30 cases per year of this very rare disease • VH Register 3.0 was used by the German Society of Nephrology (DGfN) in the 2011 EHEC/HUS outbreak for www.ehec-hus.net, collecting hundreds of cases very efficiently and quickly • VH Register 3.5 was just released and is now used on both projects, allowing multiple forms, follow-ups and languages • All software is centrally hosted and maintained professionaly in Nuremberg / Germany • Turn key solution! No programming skills or profound training necessary:

If you can surf a website, you can use VHRegister!

VHRegister: Details

• Local study centers collect and administrate cases from their country • One central study center reviews and consolidates all collected data

Perspective: www.calciphylaxis.eu

Multilingual Online

Registry System „VHRegister“

WWW

Local Study Center

Local Study Center Central Study Center

Participant Participant Participant Participant

Participant

Participant

Calciphylaxis registry – Perspectives and Summary

Registry characteristics: The nationwide registry is a suitable tool for data collection ca. 30 pts / year (May 2013 n=185) The registry allows central data collection, processing and analysis Strengths: central data quality control, central laboratory analyses Results: PTH lower than expected High rate of vitamin K antagonist treatment Mean survival rate about 1.5 yrs Role of calcification inhibitors to be determined: Cause or effect?

Perspectives: Prospective regular follow-up data collection plus On-side visits for detailed FU Pan-European?