DN
Streptozotocin (STZ)-induced diabetic nephropathy
Type 1 diabetes model with hyperglycaemia, glomerular hypertrophy and progressive albuminuria.
Background and rationale
Streptozotocin destroys pancreatic beta cells, producing insulin-deficient diabetes. Sustained hyperglycaemia leads to glomerular hypertrophy, mesangial expansion, basement membrane thickening and albuminuria, reproducing early and intermediate diabetic kidney disease. Protocols use either a single high dose or multiple low doses to balance nephrotoxicity against beta-cell specificity.
Typical study design
- Single high-dose or multiple low-dose induction, with citrate vehicle controls
- Confirmation of stable hyperglycaemia before randomisation
- Optional insulin implants to keep glucose in a defined range
- Serial glucose, HbA1c, body weight and albuminuria monitoring
Readouts
- Blood glucose, HbA1c and plasma insulin
- Urinary albumin-creatinine ratio; plasma creatinine, BUN and cystatin C
- Transdermal GFR measurement to capture hyperfiltration
- PAS histology with AI-assisted mesangial expansion and glomerular size quantification
- Electron microscopy of glomerular basement membrane thickness
- Bulk and single nuclei RNA sequencing, spatial transcriptomics
Interested in this model?
We will walk you through severity levels, group sizes, dosing windows and endpoints, and propose a design matched to your compound.