Single Cell Data-derived European Study for Personalised Management of Chronic Kidney Disease (CKD) in Children and Adolescents

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Minimal-change disease (MCD) is a renal pathology primarily affecting glomerular podocytes. MCD represents the most frequent chronic kidney disease (CKD) in children and adolescents, leading to nephrotic syndrome and potentially to kidney failure. Conventional treatment of the disease involves steroid therapy. However, children and adolescents with MCD may be resistant to steroids, and also depending on therapeutic response, the disease may show a stable or relapsing course. Thus, an adequate prediction of the individual type of MCD development would allow a more personal allocation of immunosuppressive therapy preventing under- and overtreatment. Unfortunately, the initial diagnostic kidney biopsy has no intrinsic prognostic power. These issues raise the need to add prognostic value to the kidney biopsy and to design a reliable non-invasive MCD test allowing serial patient monitoring. We start to approach these challenges by the first-time, cutting-edge application of podocyte single-cell RNA sequencing and proteomics from microdissected glomerular podocytes obtained from archival kidney biopsies with MCD of a local detection cohort and of two external validation cohorts from Bristol, UK, and Stockholm, Sweden. Thereby, we will investigate which omics-derived features of MCD i) add prognostic value to the renal biopsy, and ii) can also be detected and subsequently be validated in serum and/or urine specimens of our young MCD patients. Thereafter, statistical machine learning methods will be developed and applied to integrate key omics-based findings of serum and/or urine samples with more routine clinical (e.g. blood pressure), laboratory (e.g. serum creatinine, albuminuria, and anti-nephrin antibodies) and personal (e.g. sex, age) patient features to define a prognostic non-invasive MCD test. Finally, a prospective national - possibly international including UK/Sweden - multicentric clinical trial to validate the prognostic MCD test will be initiated in Bergen.