Hypertension accelerates the development of a diabetic nephropathy model with more relevant clinical features in Dahl salt-sensitive rat.

Abstract

Objective: Diabetic nephropathy is becoming an increasing health problem and the major cause of chronic kidney disease. The lack of experimental models that reproduce all structural and functional alterations of human diabetic nephropathy is one of the barriers to solve these clinical needs in basic research. We aimed to establish a simple and rapid method for diabetic nephropathy induction in Dahl salt-sensitive rats and achieved more clinical relevant features.

Methods and results: Six or seven-week-old male Dahl salt-sensitive rats were used to induce diabetes by a single injection of streptozotocin (STZ; 45 mg/kg, intraperitoneally). After 7 days, rats with diabetes (will refer as STZ-DS rats) will be used for further studies. STZ-DS rats will be grouped and were fed with water or water containing 0.3%/0.9%/2% NaCl and a regular chow throughout the study. We found that STZ-treated Dahl salt-sensitive rat fed with 0.9% NaCl in drinking water (STZ-DS + 0.9% NaCl) displayed most of the characteristics of human diabetic nephropathy and the model meets the criteria of the diabetic nephropathy standards proposed by Animal Models of Diabetic Complications Consortium (AMDCC); which includes a 10-fold increase in albuminuria, more than 50% decline in estimated glomerular filtration rate over the lifetime, hypertrophy, thickening of the glomerular basement membrane, expansion of the mesangial matrix, any degree of arteriolar hyalinosis, severe glomerulosclerosis, and tubulointerstitial fibrosis.

Conclusion: STZ-DS + 0.9% NaCl is an improved diabetes nephropathy model and more suited for the study of the signaling pathways and mechanisms in the progression of diabetes-induced renal disease. The model will facilitate the development of new therapies for diabetes nephropathy.