An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome

Abstract

Idiopathic nephrotic syndrome is the most common childhood glomerular disease. Most forms of this syndrome respond to corticosteroids at standard doses and are, therefore, defined as steroid-sensitive nephrotic syndrome (SSNS). Immunological mechanisms and subsequent podocyte disorders play a pivotal role in SSNS and have been studied for years; however, the precise pathogenesis remains unclear. With recent advances in genetic techniques, an exhaustive hypothesis-free approach called a genome-wide association study (GWAS) has been conducted in various populations. GWASs in pediatric SSNS peaked in the human leukocyte antigen class II region in various populations. Additionally, an association of immune-related CALHM6/FAM26F, PARM1, BTNL2, and TNFSF15 genes, as well as NPHS1, which encodes nephrin expressed in podocytes, has been identified as a locus that achieves genome-wide significance in pediatric SSNS. However, the specific mechanism of SSNS development requires elucidation. This review describes an updated view of SSNS pathogenesis from immunological and genetic aspects, including interactions with infections or allergies, production of circulating factors, and an autoantibody hypothesis.

Intrinsic Kidney Pathology in Children and Adolescents Following COVID-19 Vaccination: A Systematic Review

“…Prior to the COVID-19 pandemic, onset of MCD secondary to vaccination has been reported following the administration of influenza, hepatitis B, pneumococcal, and measles to tetanus–diphtheria–poliomyelitis vaccines [ 52 , 53 , 54 , 55 ]. The current theory of MCD pathogenesis is that the condition manifests from complex interactions between T-cells, B-cells, circulating factors, and podocytes [ 56 ]. Dysregulation of T-cell mediated immunity is widely speculated to be the main cause of COVID-19 vaccine-induced MCD, with enhanced type 2 T-helper cell activity causing release of cytokines such as interferon-γ and IL-2 leading to increased permeability factor formation [ 12 , 57 ].…”

Predictive Parameters of Steroid Dependency in Minimal Change Disease

“…Nephrotic syndrome is the most common childhood chronic glomerular disease. 1,2 Steroid dependency is one of the major difficulties in the treatment of patients with NS. The long-term steroid administration in patients with SDNS can cause complications such as diabetes, hypertension, obesity, osteoporosis, short stature, susceptibility to infections, gastritis, and posterior subcapsular cataracts, and therefore the use of alternative immunosuppressant agents is necessary in these patients.…”

“…Nephrotic syndrome (NS) is the most frequent pediatric glomerulopathy characterized by proteinuria, hypoalbuminemia, and edema. 1 The most common type of childhood NS is minimal change disease (MCD)accounting for up to 90% of cases. 2 As the main treatment of MCD is immunosuppression with corticosteroids, immune system dysregulation strongly indicates a pathogenic role in disease development.…”

Therapeutic trials in difficult to treat steroid sensitive nephrotic syndrome: challenges and future directions

“…Pathogenesis of nephrotic syndrome is not fully understood and likely results from complex interactions between genetic, immune, and environmental factors. Detailed reviews of SSNS pathogenesis [9] and SSNS genetics were recently published [10]. Human leukocyte antigen (HLA) risk alleles and mutations in immune regulatory genes increase the risk of SSNS but appear insufficient to cause disease alone.…”