Kidney Dial., Volume 3, Issue 4 (December 2023) – 3 articles

Nephrotic syndrome (NS) is a complex clinical entity characterized by proteinuria, hypoalbuminemia, and edema. In this review, we propose the view of NS as a podocytopathy, highlighting the importance of understanding the role of podocytes in the development of this condition. We discuss the various etiologies of NS, ranging from congenital to primary renal diseases, as well as secondary forms due to systemic diseases. We also delve into the mechanisms underlying podocyte injury, which plays a crucial role in the development of NS. By viewing NS as a podocytopathy, we suggest potential implications for the diagnosis and treatment of this condition, including the use of podocyte-specific biomarkers and targeted therapies. Our review provides a comprehensive overview of NS and its underlying mechanisms, emphasizing the importance of a multidisciplinary approach to the diagnosis and management of this condition. Further research is essential to better understand the complex interplay between podocyte injury and the development of NS, with the ultimate goal of improving patient outcomes. Full article

ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials. Full article

Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes. Full article