Dear Partners,

As you well know, in the CLIgAN study, the renal biopsy is the cornerstone for the enrollment of patients with a documented diagnosis of IgA nephropathy. This aspect, illustrated at the Rimini meeting, differentiates our clinical trial from those previously carried out and published in which patients who had undergone a kidney biopsy long time (months or a few years) before enrollment and randomisation were reformed. Waiting to start with the CLIgAN' project, I'm sending you

1.   Questionnaire on the execution of the kidney biopsy to see potential differences that may be present between the participating Centers.
2.   Biopsy processing protocol for light microscopy with a scheme on the preparation of the slides containing the sections of kidney tissue (thickness 2-3 micron) which will be distributed on the slides numbered in order to have different sections which can study the kidney biopsy on different layers. The progressive number and the arrows indicate the order that is advisable to follow. Therefore 24 sections of the kidney biopsy will be examined to have a broad view of the histological lesions. In addition, each staining will be performed on two slides and the biopsy reading will be carried out on all the slides of which the first set (A1,B1,C1,D1) remains on site while the second set (A2,B2,C2,D2) will be sent to the Pathological Anatomy Center of Monza to be scanned with Aperio viewing software at 40x magnification. The slides can be sent every 6 months in the presence of an adequate number of performed kideny biopsies. This procedure will make it possible to create a picture database containing all the kidney biopsies of the CLIgAN study which will be used, in the first instance by the three centers for the Peer Review process, established by the project, and subsequently it will be available to all partners to carry out ancillary studies. The database (2 terabytes in size) will be located in the National Institute of Nuclear Physics, partner of the project. Surely all the attached procedures are already adopted in many Centers but we have described them to standardize the methodology and reduce potential bias. Thus, Peer Review will be performed once a year.
3.    Instructions for the kidney biopsy report. It has been used in the implementation of the MEST-C classification in Oxford and subsequently revised. It will be filled in electronic form on the website https://bio-d.ba.infn.it/Omniacare-Nefrologia which will be available to CLIgAN study participants with the password assigned to each Centre. The aim of using all the same model reduces the reading bias between Centers and will make easier the Peer Review process established by the protocol approved by AIFA.
4.   AIFA Authorization for the clinical study. It has been sent separately. The prescription of Dapagliflozine for non-diabetic patients with chronic kidney disease will be cpossible by the end of this year. You will shortly receive the documentation of the clinical study from the CRO (CRT of Naples). The task of the CRO is to help the Centers to prepare and submit the documentation to the Local Ethics Committees.

F.P. Schena
E-mail:paolo.schena@uniba.it
Bari 28.10.2022