Histopathological assessment

Patients will be recruited in the study based on local kidney pathology assessments. The assessment will include findings from light microscopy and immunofluorescence and/or immunohistochemistry, as per local clinical practice. Procedural recommendations will be provided to the participating centres to ensure standardised evaluations. Reports will be made available to the coordinating centre. Information should include 2003 ISN/RPS class and NIH activity index and chronicity index (including items).

Baseline and repeat kidney biopsy slides containing the most representative lesions will be pseudonymised and sent to the coordinating centre for digitalisation. The digital micrographs will be posted on a secure website allowing access to accredited REBIOLUP investigators and renal pathologists involved in the central pathology review. The following stains should be sent: haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Masson’s Trichrome (Ladewig), and Jones Methenamine Silver (JMS) stain. The biopsy slides will thereafter be shipped back to the respective site.

Histopathological response will be defined as follows:

• Complete response: NIH activity index score = 0.
• Partial response: ≥ 50% decrease in NIH activity index score, resulting in a score 1–3. 
• Non-response: residual activity (NIH activity index score > 3) prompting intensification of immunosuppression. 

Renal immunological assessment  

For the purpose of electron microscopy studies (a major scope of this study), two very small fragments of the kidney cortex will be isolated from the freshly obtained biopsy core before any other procedure. Each one of these two fragments should ideally contain at least one glomerulus. These two fragments, no larger than a pinhead, must immediately be dropped into a 2.5% glutaraldehyde solution (together). Samples will then be stored at 4 °C until shipment to the coordinating centre UCLouvain.

Electron micrographs will be used to assess the renal immunological response at the level of tissue. This assessment will include intensity (e.g. on a scale graded from 0 to 3) and amount (e.g. using ordinal grading scores: occasional, scarce, moderate, profuse) of immune deposits assessed. Collaborations will be established to implement computerised assessment algorithms.

Renal immunological response will be defined as follows:

• Complete response: disappearance or trace positivity of immune deposits.
• Partial response: ≥ 50% decrease of immune deposits in terms of both intensity and amount.