Glomerular podocytes in kidney health and disease

• Published in: The Lancet (British edition) Vol. 393; no. 10174; pp. 856 - 858
• Main Authors: Assady, Suheir, Benzing, Thomas, Kretzler, Matthias, Skorecki, Karl L
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 02.03.2019; Elsevier Limited
• Subjects: Biological properties; Biological samples; Biomarkers; Biopsy; Calcium channels; Cell injury; Clinical decision making; Clinical trials; Consortia; Decision making; Diabetes mellitus; Gene mapping; Genomics; Genotypes; Glomerulonephritis; Kidney diseases; Kidney transplantation; Kidneys; Mapping; Medical research; Metabolomics; Morphology; Nephrotic syndrome; Organic chemistry; Patients; Population; Proteinuria; Proteomics; Transcription; Urine; Israel
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(18)33000-9

Activation of calcium channels leads to cell injury and proteinuria, while blocking of TRPC5 by novel small molecules (eg, ML204 [Merck] or AC1903 [Cayman Chemical]) has been suggested to prevent disease progression by preclinical studies, providing new opportunities for future treatment.7 Population disparity in chronic kidney disease has long been a troubling concern. Population-based gene mapping led to the identification of high-frequency variants at the APOL1 genetic locus, which account for much of the disparity in non-diabetic chronic kidney disease of glomerular origin in the African ancestry population.8 This discovery is already impacting day-to-day clinical decision-making regarding kidney donation, and in the assessment of outcomes when transplanting kidneys of high-risk genotype.9 To what extent is this progress decreasing the need for kidney biopsy or transforming the way pathologists examine kidney biopsy samples from pure morphological to molecular analysis? Productive observational global consortia (like PodoNet, the Nephrotic Syndrome Study Network [NEPTUNE], the SPOR Canadian Glomerulonephritis Registry and Translational Research Initiative, and others), wherein patient biological samples (kidney biopsy, serum, plasma, and urine) are systematically collected and analysed, are using these investigational platforms.13 Differential transcriptional, proteomic, metabolomic, and epigenomic signatures (such as non-coding RNAs), among others, are being investigated to understand their potential utility in the clinical care of patients with nephrotic syndrome, mainly in terms of identification of novel pathophysiological pathways and molecules, variability of disease progression, prognostic biomarkers, and response to therapy.13 Could this approach lead to mechanism-based interventional clinical trials? A survey of registered clinical trials at ClinicalTrials.gov shows that this is already the case.