Our project aims to individualise the treatment for children and young adults with chronic kidney disease.
Children and young people who suffer from the disease "minimal change nephropathy" often have reduced functional capacity as a result of side effects from glucocorticoids and other anti-inflammatory medications. Minimal change nephropathy (also named "minimal change disease") is not a common disease like e.g. diabetes. The reported incidence globally is around 10–50 cases per 100,000 children and teenagers. Our project will contribute to a more personalized treatment for minimal change nephropathy, which is the most frequent chronic kidney disease in this age group.
As of today, there is initially a "one fits all" treatment with glucocorticoids. We aim for a more individualized and targeted therapy to avoid unnecessary side effects. A challenge with this treatment strategy is that patients are either sensitive, or else primary resistant from the beginning or become secondary resistant during disease course to prescribed steroids (e.g. prednisolone). We want to develop a comprehensive test with help of artificial intelligence to find this out before starting a treatment plan. The test will include a kidney biopsy (tissue sample), which has been carried out independently of this project to establish the diagnosis, as well as corresponding clinical findings and analyses from urine and blood samples. The aim of tissue sample studies is to find kidney cell markers based on advanced single cell RNA sequencing of glomerular podocytes from formalin-fixed and paraffin-embedded kidney biopsies that can help to predict whether a patient at the time of diagnosis will respond to therapy.
The kidney research environment in Bergen will collaborate with researchers from Bristol in England, Helsinki in Finland and Stockholm in Sweden. Our predictive test will be validated through a clinical study that includes patients from Norway and, if possible, also from England and Sweden.
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.
BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering