A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR).

Abstract:

BACKGROUND:The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS:Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic) at six weeks of age, and sacrificed 4 and 12 weeks later. Further groups were treated for 12 weeks post-STZ or vehicle with the angiotensin converting enzyme inhibitor, perindopril. Comparisons were made with 18-week-old non-diabetic and diabetic spontaneously hypertensive rats (SHR). RESULTS:In diabetic TGR, the most florid lesion was seen after 12 weeks of STZ, with kidneys exhibiting vacuolated tubules, hylanized arterioles, medullary fibrosis and necrosis and severe glomerulosclerosis. In contrast, only mild glomerulosclerosis was seen in non-diabetic TGR and diabetic SHR. Glomerular filtration rate was increased after four weeks of diabetes in TGR and 12 weeks of diabetes in SHR, but declined by greater than 50% after 12 weeks of diabetes in TGR. In both TGR and SHR, diabetes increased albuminuria but did not modify systolic blood pressure. Renal renin content increased progressively in diabetic TGR, and this was associated with increased renin immunolabeling in the juxtaglomerular apparatus (JGA) and the appearance of renin in proximal convoluted tubules. In contrast, renal renin content and JGA renin immunolabeling were unchanged in diabetic SHR. Perindopril attenuated renal pathology, improved renal function and abolished proximal tubular renin immunolabeling in diabetic TGR. CONCLUSIONS:This is the first report of a diabetic rodent model developing rapid onset renal impairment. Furthermore, this study suggests a role for an activated renal RAS in the acceleration of diabetic renal disease and confirms the benefit of drugs that inhibit this system.

journal_name

Kidney Int

journal_title

Kidney international

authors

Kelly DJ,Wilkinson-Berka JL,Allen TJ,Cooper ME,Skinner SL

doi

10.1046/j.1523-1755.1998.00019.x

subject

Has Abstract

pub_date

1998-08-01 00:00:00

pages

343-52

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)30648-7

journal_volume

54

pub_type

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