Faculty Collaboration Database

Progression of diabetic kidney disease in T2DN rats. Am J Physiol Renal Physiol 2019 Dec 01;317(6):F1450-F1461

Date

10/01/2019

Pubmed ID

31566426

Pubmed Central ID

PMC6960784

DOI

10.1152/ajprenal.00246.2019

Scopus ID

2-s2.0-85075960951 (requires institutional sign-in at Scopus site)   52 Citations

Abstract

Diabetic kidney disease (DKD) is one of the leading pathological causes of decreased renal function and progression to end-stage kidney failure. To explore and characterize age-related changes in DKD and associated glomerular damage, we used a rat model of type 2 diabetic nephropathy (T2DN) at 12 wk and older than 48 wk. We compared their disease progression with control nondiabetic Wistar and diabetic Goto-Kakizaki (GK) rats. During the early stages of DKD, T2DN and GK animals revealed significant increases in blood glucose and kidney-to-body weight ratio. Both diabetic groups had significantly altered renin-angiotensin-aldosterone system function. Thereafter, during the later stages of disease progression, T2DN rats demonstrated a remarkable increase in renal damage compared with GK and Wistar rats, as indicated by renal hypertrophy, polyuria accompanied by a decrease in urine osmolarity, high cholesterol, a significant prevalence of medullary protein casts, and severe forms of glomerular injury. Urinary nephrin shedding indicated loss of the glomerular slit diaphragm, which also correlates with the dramatic elevation in albuminuria and loss of podocin staining in aged T2DN rats. Furthermore, we used scanning ion microscopy topographical analyses to detect and quantify the pathological remodeling in podocyte foot projections of isolated glomeruli from T2DN animals. In summary, T2DN rats developed renal and physiological abnormalities similar to clinical observations in human patients with DKD, including progressive glomerular damage and a significant decrease in renin-angiotensin-aldosterone system plasma levels, indicating these rats are an excellent model for studying the progression of renal damage in type 2 DKD.

Author List

Palygin O, Spires D, Levchenko V, Bohovyk R, Fedoriuk M, Klemens CA, Sykes O, Bukowy JD, Cowley AW Jr, Lazar J, Ilatovskaya DV, Staruschenko A

Author

Allen W. Cowley PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aging
Albuminuria
Animals
Blood Glucose
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Disease Progression
Hypertrophy
Kidney Glomerulus
Male
Membrane Proteins
Organ Size
Polyuria
Rats
Rats, Wistar
Renin-Angiotensin System
Water-Electrolyte Imbalance