Early diagnosis in children with Alport syndrome (AS) with isolated hematuria opens a
"window of opportunity" for early intervention. In the Alport mouse-model, this early
intervention with the ACE-inhibitor Ramipril let to a delay of kidney failure by 111%. In
order to observe treatment approaches for AS in humans, this registry has been
established in 2006 to collect data over several generations of Alport families across
Europe. In the meantime, this registry has been expanded to "Alport XXL" via the
International Alport Alliance as a global effort across all continents.
Small children with AS first develop microscopic hematuria (stage 0), proceeding to
microalbuminuria (stage I), overt proteinuria (stage II), impaired kidney function (stage
III) and finally can end up with kidney failure (stage IV), leading to impaired quality
of life and premature death (stage V). This registry uses these stages to assess if
earlier initiation of medications such as ACE-inhibition at earlier stages of disease is
more effective than later therapy in delaying the time to disease progression (doubeling
or tripeling of albuminuria), delaying loss of estimated glomerular filtration rate
(eGFR), and if therapy improves life-expectancy.
Untreated children with autosomal-recessive AS, digenic AS, and boys with X-linked AS
typically all develop kidney failure early in life. Untreated girls with X-linked AS have
a 30-40% risk of kidney failure, typically later in life (40 years or older). Untreated
heterozygous patients with COL4A3/COL4A4 variants typically have a less severe phenotype
(in former times also called "familial benign hematuria" or "thin basement membrane
nephropathy" (TBMN)) and a 1-2% risk of kidney failure.
Several interim results of this registry have been published since 2012.
Alport XXL is designed and conducted as strictly observational, non-interventional data
acquisition with prospective (and in parts retrospective) data analysis. Young patients
with AS in disease stages 0,I,II from all over the world are included. The renewed
version from 2021 has been re-approved by the Ethics Committee of the University Medical
Center Göttingen as "Alport XXL", a further development of the former European Alport
Therapy Registry (AZ 10/11/06). "Alport XXL" registry and data storage are in conformity
with Good Clinical Practice guidelines.
ICH-GCP-conform patient information and data exchange is secured by data transfer and
cooperation agreements between all international trial centers and the coordinating
principal investigator at University Medical Center Goettingen. At baseline, data
collection including retrospective data is performed using a standardized,
ICH-GCP-conform and pseudonymized questionnaire assessing age, sex, weight, height, mode
of inheritance (X-linked, autosomal, compound heterozygous/homozygous, number of missense
variants), family history, albumin in 24-hour or spontaneous urine, serum-creatinine,
RAS-blockade with preparation and dose. Follow-up visits include same data than baseline
plus blood-pressure, smoking-status, serum-potassium, eGFR, hearing loss and eye
involvement, other symptoms such as leiomyomatosis, comorbidities and adverse events
(adverse events of special interest defined as hyperkalemia, cough, hypotension, acute
renal failure, malignancy, death).