Calciphylaxis in Patients With Chronic Kidney Disease - A Study of the Danish Calciphylaxis Research Initiative (DanCaRI)

Calciphylaxis is a rare yet life-threatening condition involving pronounced calcification in small blood vessels of the skin.

Knowledge about its underlying mechanisms and contributing risk factors remains limited. Chronic kidney disease is one of the strongest disease predictors. No evidence based effective therapy is currently available. Research on the topic is mainly hindered by the condition's rarity.

The study Calciphylaxis in patients with chronic kidney disease - A study of the Danish Calciphylaxis Research Initiative (DanCaRI) is set up to facilitate the systematic retrospective (two years) and prospective (three years follow-up period) comparison of patients with chronic kidney disease and calciphylaxis (cases) to matched patients with chronic kidney disease who did not develop calciphylaxis (controls) thereby providing new knowledge that can support prevention, early detection, and new treatment approaches.

The study collects clinical data and biological samples. A healthy group is part of the study to enable comparison to reference parameters.

Primary outcomes

• All-cause mortality [3 year follow up period]: Associations between disease status (case or control), clinical and laboratory variables, molecular parameters, and all-cause mortality will be evaluated.

Secondary outcomes

• Pain severity [3 year follow up period]: Associations between disease status (case or control), clinical and laboratory variables, molecular parameters, and pain severity (determined using Wong-Baker Faces scale) will be evaluated
• Quality of life (QoL) [3 year follow up period]: Associations between disease status (case or control), clinical and laboratory variables, molecular parameters, and QoL (determined using the Edmonton Symptom Assessment System-Revised: Renal (ESAS-r: Renal)) will be evaluated.
• Hospitalizations [3 year follow up period]: Associations between disease status (case or control), clinical and laboratory variables, molecular parameters, and hospitalizations (inpatient-days of any cause) will be evaluated
• Calciphylaxis Wound Status [3 year follow up period]: Associations between clinical and laboratory variables, as well as molecular parameters, and calciphylaxis wound status (determined using the Bates-Jensen Wound Assessment Tool (BWAT) modified for DanCaRI) will be evaluated

Other outcomes

• Retrospective and cross-sectional: Development of calciphylaxis skin lesions [2 years retrospective and at inclusion]: To determine clinical, laboratory, and molecular predictors of skin lesion development through comparison with a matched control population

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

Cases

* Age ≥18 years.
* CKD.
* Suspicion of calciphylaxis or newly diagnosed calciphylaxis episode. The suspicion or diagnosis of calciphylaxis is a mutual decision of the involved medical specialties (nephrologist, dermatologist, pathologist, other).
* Ability to give informed consent.
* Ability to participate in a clinical study as assessed by the local investigator.
* Provides written informed consent.

Controls

* Age ≥18 years.
* CKD
* Ability to give informed consent.
* Ability to participate in a clinical study as assessed by the local investigator.
* Provides written informed consent.

Healthy reference group

* Age ≥18 years.
* Self-assessed as healthy, confirmed by local investigators at inclusion

Exclusion Criteria:

Cases

\- the calciphylaxis diagnosis becomes excluded

Controls - Being diagnosed with calciphylaxis

Healthy controls Up to 60 years of age: eGFR below 60 ml/min/1.72m2.

\- Over 60 years of age: eGFR below the 95% confidence interval for eGFR adjusted for age (Danish Society of Nephrology references ranges)

• Subagini Nagarajah, PhD, Principal investigator, Odense University Hospital
• Alexandra Scholze, Dr.med, PhD, Principal investigator, Odense University Hospital