The IgA Nephropathy and IgA Vasculitis Subregistry

 

General information

IgA Nephropathy (IgAN) is the most prevalent primary chronic glomerular disease worldwide, with an estimated annual diagnosis rate of 2.5 per 100,000. The disease may present at any age, but the peak incidence is in the second and third decades of life.
Diagnosis is based on kidney biopsy demonstrating dominant or codominant deposition of IgA. Currently used pathologic classification is the 2009 Oxford classification.
Many patients with IgAN have chronic kidney disease (CKD). Among patients who develop overt proteinuria and/or elevated serum creatinine concentration, progression to end-stage kidney disease (ESKD) is approximately 15 to 25 percent at 10 years and 20 to 30 percent at 20 years.
Currently the mainstay of treatment is tight blood pressure control and minimization of proteinuria control using renin-angiotensin system inhibition (RASi).

Recently, new treatment modalities have been introduced (SGLT2 inhibitors) as well as new drugs are being developed (e.g., Iptacopan, Povetacicept, Felzartamab, Ravulizumab).

IgA Vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP), is the most common form of systemic vasculitis in children, with an incidence range of 3 to 27 per 100,000. Ninety percent of cases occur in the pediatric age group. Diagnosis is usually based on typical clinical findings.
Kidney involvement has been reported in 20 to 54 percent of children with IgAV.  The findings on kidney biopsy are identical to those in IgAN.
Adults are at increased risk for developing significant kidney involvement including end-stage kidney disease.
The treatment of IgAV depends upon the severity of kidney disease, most cases only require suppurative care, but some may mandate immunosuppression.

 

 

Objectives

The subregistry primary objectives are to establish a patient cohort for IgAN and IgAV, create a prospective registry for monitoring disease progression and impact of treatment on long-term outcome and to establish criteria for adequate treatment and monitoring.
A dedicated pathology image repository (Omero) will be used to collect images of biopsy slides.

The secondary objective is to compare IgAV with kidney involvement to the IgAN patients. Due to their similar pathological findings, a detailed comparison of their clinical presentations, treatment responses, and outcomes will be conducted.

 

 

Inclusion and Exclusion Criteria

Eligible are all patients with a clinical diagnosis of IgAN or IgAV as defined below:

  • IgAN is defined as having at least one of the following criteria: episodic gross hematuria, persistent microhematuria or progressive kidney function impairment; as well as a kidney biopsy demonstrating the presence of dominant or codominant deposition of IgA.
  • IgAV is defined based on a clinical presentation - palpable purpura and at least two of the following: arthritis/arthralgia, abdominal pain, and kidney disease (urine protein-to-creatinine ratio ≥ 0.2 or hematuria); or a skin/kidney biopsy demonstrating leukocytoclastic vasculitis with a predominance of IgA deposition.
    Patients without a kidney involvement are excluded.

Patients will be assigned a diagnosis based on their initial presentation.

Excluded are patients with a diagnosis of Lupus Nephritis or IgAV without kidney involvement.

 

 

Ethical aspects

Data entry in this subregistry is covered by the consent for ERKNet participation.

 

 

Data collection

Basic Data

General information which is collected for all patients in the ERKNet Registry: sex, birth date, ethnicity, date of first symptoms, date of first visit, date of diagnosis.

In addition, specific information regarding relevant comorbidities, smoking, tonsillectomy and information regarding disease presentation – clinical presentation, suspected trigger, serum creatinine, height, weight, blood pressure, pathology findings and fields for the IIgAN-PT prognosis score.

 

Visit Data

Information which is collected within every annual visit for all patients in the ERKNet registry: date of visit, treatment modality (conservative, dialysis, transplant), date of transplantation/dialysis initiation, weight, height, blood pressure, serum creatinine, serum cholesterol, serum bicarbonate, hemoglobin, proteinuria assessment, biopsy date (if performed), RAS inhibitor treatment.

In addition, the following information – hematuria, serum IgA and uric acid, number of blood pressure lowering medications, pathology classification (if biopsy performed), occurrence of systemic symptoms and suspected trigger (prior to the systemic symptoms).
For kidney transplant patients – time of recurrence, symptoms at the time of recurrence, worst proteinuria and creatinine since the last visit.

Visit information will be collected in the following intervals:

  • 3 Months – Patients with a rapidly-progressive disease course (defined as ≥50% decline in eGFR over three months or less) or first visit after transplantation.
  • 6 Months – Patients within the first year of diagnosis or first visit after the initiation of a new medication, or patients with a ≥25% decline in eGFR over a year or less or an increase of 0.5 in urine protein:creatinine over a year or less.
  • 1 Year – The default interval.
  • 2 Years – IgAV patients with eGFR > 90 ml/min/1.73m2 and at least two years without significant proteinuria (defined as urine protein:creatinine < 0.2 for children or < 0.5 for adults), hematuria or clinical features suggesting of IgAV (palpable purpuric rash, arthralgia/arthritis or episodic abdominal pain not otherwise explained).

 

Medication Data

 

Information on usage (including duration and dosage) for drugs classified within the following families: Renin-Angiotensin System (RAS) inhibitors, Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors, Endothelin (ET1) blockers, glucocorticoids, immunosuppressants and complement inhibitors.

 

Extracorporeal Treatments

Information regarding plasmapheresis – duration and number of sessions.

 

 

User manual

To view the user manual, click here.

 

Coordination Structure / Scientific Committee

The subregistry is overseen by the following steering committee members:

  • Dr. Licia Peruzzi – MD, PhD - Pediatric Nephrologist
    Dipartimento Patologia e Cura del Bambino
    Turin, AOU CSS di Torino - Regina Margherita Hospital
  • Prof. Dr. Jürgen Floege – MD – Nephrologist
    Division of Nephrology and Clinical Immunology
    University Hospital RWTH Aachen

 

 

Contact Person

For more information please contact:

Dr. Eyal Rahmani Eyal.Rahmani[at]med.uni-heidelberg.de