Familial Juvenile Hyperuricaemic Nephropathy (FJHN)

Familial juvenile hyperuricemic nephropathy (FJHN) is a rare kidney disease with an autosomal dominant inheritance pattern. It is characterized by early onset hyperuricemia and gout in conjunction with progressive chronic kidney disease (CKD). Protheragen offers end-to-end preclinical development services to accelerate therapeutic innovation for familial juvenile hyperuricemic nephropathy.

Introduction to Familial Juvenile Hyperuricemic Nephropathy

Familial Juvenile Hyperuricemic Nephropathy (FJHN) is a rare genetic disorder that manifests early in life, often during the childhood or adolescent years. This disorder leads to the production of abnormally high levels of serum uric acid (hyperuricemia) which may cause the formation of urate crystals that build up in the kidneys and other tissues. FJHN is linked to mutations in the URAT1 gene (SLC22A12) which codes for a renal urate transporter. This disorder hampers effective urate reabsorption in the kidneys and hence, leads to hyperuricemia and kidney damage. The disorder is considered rare with only a few documented cases, most of which exist in familial clusters.

Pathogenesis of Familial Juvenile Hyperuricemic Nephropathy

Mutations in the "UMOD" gene which encodes the protein uromodulin (or Tamm-Horsfall protein), are the primary causes of FJHN. In healthy people, uromodulin is the most abundant protein in urine, and is secreted mainly by the renal tubular epithelial cells located in the thick ascending limb of the loop of Henle. Uromodulin performs a number of functions within the kidney, such as lowering the risk of urinary tract infection and controlling the balance of salt and water in the body.

Fig.1 Proposed model of pathogenesis and treatment for FJHN. (Fraser and Davey, 2020)

In FJHN some mutations in the UMOD gene results in the production of uromodulin which is misfolded. This causes for uromodulin to be retained in the endoplasmic reticulum and not secreted into the urine as is the norm. The toxic renal tubular cell dump leads to cell stress and apoptosis which results in chronic tubular and interstitial fibrosis. There is also functional impairment of the uromodulin which leads to the kidneys inability to urinate uric acid declining leading to hyperuricemia and gout flares.

Therapeutic Development for Familial Juvenile Hyperuricemic Nephropathy

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 comprehensive preclinical service provider dedicated to the discovery and development of novel therapeutics for familial juvenile hyperuricemic nephropathy. Our expertise spans therapeutic development and disease model development, which supports the journey from therapeutic discovery to preclinical validation for FJHN-specific therapeutics.

Therapeutic Development Platform for Familial Juvenile Hyperuricemic Nephropathy

Protheragen offers a versatile suite of therapeutic development platforms, adaptable to the unique challenges of familial juvenile hyperuricemic nephropathy and other rare kidney diseases. Our integrated approach supports the discovery and optimization of diverse therapeutic modalities.

Disease Models Development for Familial Juvenile Hyperuricemic Nephropathy

Protheragen offers a range of specialized disease models designed to accelerate preclinical research and therapy development for FJHN. These models, including cell-based models, kidney organoids, and animal models, are essential for understanding the genetic and biochemical underpinnings of FJHN and testing potential drug candidates for safety and efficacy.

Cell-based & Organoid Models

• UMOD-mutant renal tubular epithelial cells
• ER stress-primed podocytes
• 3D proximal tubule dysfunction co-culture
• Hyperuricemic stress kidney tubuloid
• Tubulointerstitial fibrosis simulator

Animal Models Development

• Tubule-specific Umod mutant mouse
• Hyperuricemia-accelerated rat model
• Umod morpholino knockdown zebrafish
• Humanized UMOD p.Trp226Arg rabbit
• Double-hit Umod/Hprt1 KO mouse

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

Drug Safety Evaluation

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation

• Immunogenicity and Immunotoxicity Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation

• Tissue Cross-Reactivity Evaluation
• Safety Pharmacology Evaluation
• Toxicokinetic Evaluation

Protheragen offers comprehensive, end-to-end preclinical development services specifically designed to address the unique challenges of familial juvenile hyperuricemic nephropathy. 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. We are committed to accelerating the journey of novel therapies for rare kidney diseases like FJHN.

If you are interested in our services, please don't hesitate to contact us.

References

1. Fraser, A. M., and M. G. Davey. "Talpid3 in Familial Juvenile Hyperuricemic Nephropathy and Related Ciliopathy Disorders." Curr Opin Genet Dev 56 (2019): 41-48.
2. Tran, A. M., A. J. Jnah, and M. J. De Castro Pretelt. "Genetics Review: Familial Juvenile Hyperuricemic Nephropathy." Neonatal Netw 44.3 (2025): 159-66.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.