Medullary Cystic Kidney Disease (MCKD) is a rare, inherited kidney disorder characterized by the progressive development of cysts primarily in the renal medulla, leading to interstitial fibrosis and ultimately, end-stage renal disease (ESRD). Protheragen provides comprehensive preclinical drug and therapy development services specifically tailored to address the unique mechanisms of MCKD, with a focused expertise on renal-related therapeutic strategies.
Introduction to Medullary Cystic Kidney Disease
Medullary Cystic Kidney Disease (MCKD) is a rare hereditary disorder passed on in an autosomal dominant pattern. It involves progressive damage to the kidneys, loss of the ability to retain salt, and the gradual formation of cysts in the kidney medulla. The condition affects roughly 1 to 5 people in every 100,000, usually becoming evident in adulthood between the ages of 30 and 50. Defects in the MUC1 gene (MCKD1) or the UMOD gene (MCKD2) disrupt the structure of the renal tubules, causing scarring and cyst growth. Emerging evidence indicates that MCKD is frequently underrecognized, as its clinical features resemble those of other cystic kidney disorders.
Pathogenesis of Medullary Cystic Kidney Disease
Fig.1 Renal biopsy findings in medullary cystic kidney disease individuals. (Hibino
et al., 2020)
In MCKD1, mutations in the UMOD gene cause the uromodulin protein to misfold and accumulate in the endoplasmic reticulum of tubular cells, where it is incapable of reaching the cell surface. This retention activates the unfolded protein response, inducing inflammation and scarring while also impairing tubular transport processes. The damage eventually results in tubular atrophy, persistent interstitial inflammation, and scarring that primarily affects the medullary region of the kidney, with cysts developing in a variable manner. In MCKD2, mutations in the REN gene lead to excess renin production and release, which causes sustained stimulation of the renin-angiotensin-aldosterone system. The ensuing hypertension, tubular injury, and progressive kidney damage reflect the combined effects of these mutations. Regardless of the genetic mechanism, both forms of the disease culminate in interstitial scarring and chronic loss of kidney function.
Therapeutics Development for Medullary Cystic Kidney Disease
| Drug Name |
Therapeutic Target |
Key Mechanisms/Advances |
Development Stage |
| Empagliflozin |
SLC5A2 (SGLT2 protein) |
Reduces intraglomerular pressure and fibrosis; slows CKD progression in diabetic patients |
Phase IV |
| Finerenone |
NR3C2 (Mineralocorticoid receptor) |
Blocks aldosterone-driven inflammation/fibrosis; reduces CKD progression |
Phase III |
| Sparsentan |
AGTR1 (AT1R) + EDNRA |
Reduces proteinuria and fibrosis; improved safety profile vs. earlier agents |
Phase III |
| UMOD-ASO |
UMOD |
Splice modulation to restore uromodulin function; validated in ciliopathy models |
Preclinical |
| CRISPR-MUC1/UMOD |
MUC1 or UMOD gene |
Repairs mutations in renal organoids; reduces cystogenesis |
Preclinical |
TGF-β1 Inhibitors
(e.g., Fresolimumab) |
TGF-β1 |
Suppresses fibrotic pathways in CKD models |
Preclinical/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 comprehensive preclinical service provider dedicated to the discovery and development of novel therapeutics for medullary cystic kidney disease. Our extensive therapeutic development services incorporate the use of sophisticated disease models that effectively capture important features of this inherited disorder, with particular emphasis on the renal pathology.
Therapeutic Development Platforms for Medullary Cystic Kidney Disease
Disease Models Development for Medullary Cystic Kidney Disease
Protheragen offers innovative and comprehensive disease models to advance preclinical research into medullary cystic kidney disease. Our platform integrates advanced cell-based models, sophisticated kidney organoids, and relevant animal models.
- UMOD or REN Mutant Renal Tubular Epithelial Cell Lines
- iPSC-derived Kidney Organoids
- Renal Tubuloid Models
- Three-dimensional (3D) Cell Culture Models
- Umod Mutant Mouse Models
- Ren Transgenic or Mutant Mouse Models
- Zebrafish umod or ren Mutant Models
- Humanized Kidney Disease Models
- Spontaneously Hypertensive Rats
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's integrated preclinical development solutions are specifically designed for research affecting renal systems, such as medullary cystic kidney disease. We specialize in comprehensive disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your therapeutic investigations from initial target validation to IND-enabling studies.
Contact us today to accelerate your medullary cystic kidney disease research with end-to-end solutions.
References
- Hibino, S., et al. "Medullary Cystic Kidney Disease and Focal Segmental Glomerulosclerosis Caused by a Compound Heterozygous Mutation in Ttc21b." Intern Med 59.14 (2020): 1735-38.
- Hildebrandt, F., and H. Omram. "New Insights: Nephronophthisis-Medullary Cystic Kidney Disease." Pediatr Nephrol 16.2 (2001): 168-76.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
