Steroid-Resistant Nephrotic Syndrome (SRNS) is a severe kidney disease marked by persistent proteinuria that does not respond to standard corticosteroid treatment, usually resulting in end-stage renal disease. Protheragen offers a full spectrum of end-to-end preclinical development services to accelerate therapeutic innovation in steroid-resistant nephrotic syndrome.
Overview of Steroid-Resistant Nephrotic Syndrome
Steroid-Resistant Nephrotic Syndrome (SRNS) is an incomplete response to steroid therapy for nephrotic syndrome, defined by persistent proteinuria. It is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children and adults, often with rapid progression. Clinically, it is characterized by varying degrees of proteinuria, reduced serum albumin levels (hypoalbuminemia), swelling (edema), and fat in the blood (hyperlipidemia) and is often associated with focal segmental glomerulosclerosis (FSGS), which is defined by the scarring of parts of the glomeruli. Given the disease burden due to the high morbidity and mortality associated with SRNS and limited effective treatment, there is a pressing need for treatment innovation and advanced research.
Pathogenesis of Steroid-Resistant Nephrotic Syndrome
SRNS is primarily caused by genetic mutations that disrupt the relaxation and contractile functions of podocytes and immune mechanisms that result in podocyte damage. Glomeruli are made of highly specialized cells called podocytes that serve to protect glomerular capillaries and are crucial for the maintenance of the glomerular filtration barrier.
Fig.1 (a) Role of NPHS1 and NPHS2 in glomerular filtration in normal kidney and (b) impact of NPHS1 and NPHS2 mutations in SRNS/CNS pediatric patients. (Lee, Tan and Ismail, 2024)
- Genetic Factors: A notable number of SRNS cases, especially in children, are monogenic due to mutations in genes that encode structural or signaling proteins critical for the maintenance and function of podocytes. Over sixty genes have been implicated including NPHS1, NPHS2, WT1, TRPC6, INF2, and ACTN4. Moreover, high-risk variants of the APOL1 gene are known to be strongly linked with SRNS and FSGS in individuals of African descent.
- Immune-Mediated and Circulating Factors: Many non-genetic SRNS cases are believed to be immune-mediated, caused by some form of immune system circulation that directly harms podocytes. While the precise factors are unclear, some include soluble urokinase-type plasminogen receptor (suPAR), cardiotrophin-like cytokine 1 (CLC-1), and anti-CD40 antibodies that are known to podocytes and can lead to protein loss.
Acquired or genetic, the disruptive alteration of podocyte structure and function caused leads to effacement of foot processes, narrowed the filtration slits within the podocyte cellular layer, and leads to glomerulosclerosis and progressive kidney failure.
Therapeutics Development for Steroid-Resistant Nephrotic Syndrome
| Drug/Technology |
Therapeutic Target |
Key Evidence |
Development Stage |
| Obinutuzumab |
CD20 protein |
35% response rate in rituximab-resistant patients |
Phase II |
| Eculizumab |
C5 protein (complement) |
Reduces proteinuria in C3 glomerulopathy patients |
Phase II |
| Telitacicept |
BAFF (TNFSF13B) + APRIL (TNFSF13) |
Attenuates podocyte injury in FSGS murine models |
Preclinical |
| Abatacept |
B7-1 (CD80) on podocytes |
50% complete remission in B7-1(+) patients vs. 8% placebo (B7-1-guided therapy) |
Phase II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is a dedicated provider of preclinical research services focused on therapeutic development for steroid-resistant nephrotic syndrome. We leverage advanced disease models that capture the complex genetic and immune-mediated aspects of SRNS, including its severe podocyte injury and progressive renal manifestations, to facilitate mechanism-based drug discovery for this challenging kidney disease.
Therapeutic Development Platforms for Steroid-Resistant Nephrotic Syndrome
Disease Models Development for Steroid-Resistant Nephrotic Syndrome
Protheragen provides specialized disease models to accelerate preclinical research on steroid-resistant nephrotic syndrome. Our platform integrates advanced cell-based models, kidney organoids, and animal models. These models can support robust target identification and comprehensive therapeutic efficacy testing for SRNS-specific pathways.
Cell-based & Organoid Models
- Patient-derived iPSCs differentiated into podocytes
- SRNS gene mutant podocyte cell lines
- iPSC-based kidney organoids
- Kidney organoids modeling specific SRNS mutations
Animal Models
- Nphs2 knockout mice
- APOL1 transgenic mice
- Trpc6 gain-of-function mice
- Adriamycin/Doxorubicin-induced nephropathy models
- Puromycin aminonucleoside (PAN) nephrosis models
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Metabolic Stability Assay
- Plasma Protein Binding
- Renal Tubular Epithelial Cell Uptake & Efflux
- Drug-Transporter Interaction Profiling
- Cellular Permeability
In Vivo Pharmacokinetics Services
- Systemic Pharmacokinetics
- Kidney Tissue Distribution and Retention
- Renal Clearance and Excretion Studies
- Urinary Metabolite Profiling
- Blood-to-Plasma Ratio
Protheragen offers comprehensive, end-to-end preclinical development services specifically designed to address the unique challenges of steroid-resistant nephrotic syndrome. Our expertise spans disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your therapeutic investigations from initial target identification through to preclinical validation.
If you are interested in our specialized services, please do not hesitate to contact us.
References
- Guo, H. L., et al. "Steroid-Resistant Nephrotic Syndrome in Children: A Mini-Review on Genetic Mechanisms, Predictive Biomarkers and Pharmacotherapy Strategies." Curr Pharm Des 27.2 (2021): 319-29.
- Lee, J. X., Y. J. Tan, and N. A. S. Ismail. "Nphs Mutations in Pediatric Patients with Congenital and Steroid-Resistant Nephrotic Syndrome." Int J Mol Sci 25.22 (2024).
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
