The effects of aminoguanidine on renal changes in a baboon model of Type 1 diabetes.
BACKGROUND
The efficacy of aminoguanidine (AG) on primary prevention of diabetic nephropathy was investigated in a nonhuman primate model of Type 1 diabetes over a period of 4 years.


METHODS
Adolescent male baboons (Papio hamadryas) were assigned to four groups: control, diabetic, and control and diabetic treated with AG. Diabetes was induced with streptozocin (60 mg/kg) and treated with insulin to maintain a mean HbA1c level of about 9%. AG was given subcutaneously (10 mg/kg) each day. All animals had annual renal biopsies and 24-h urine collections for measurements of glomerular basement membrane (GBM) thickness, fractional mesangium volume (FMV), albumin excretion rate (AER), and creatinine clearance. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were also determined.


RESULTS
The diabetic animals had increased GBM after 2 years of diabetes, but there was no increase in FMV over the study period. AG prevented the thickening of GBM at the 3- and 4-year time points. AG and diabetes synergistically increased the GFR. All diabetic animals developed increased albuminuria during the study although lower than the conventionally accepted microalbuminuria range. AG was not able to prevent this and, in fact, led to the nondiabetic animals also developing albuminuria.


CONCLUSIONS
This is the first study to investigate the early use of AG in ameliorating renal damage in a primate model of Type 1 diabetes. The structural and functional changes in the kidney of these animals resemble those seen in the early stages of the human disease. AG was able to significantly reduce the thickening of GBM due to diabetes. This may suggest a potential role for this in primary prevention of diabetic nephropathy in the future.
Birrell
Alex M
AM
Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia
Heffernan
Scott J
SJ
Kirwan
Paul
P
McLennan
Sue
S
Gillin
Adrian G
AG
Yue
Dennis K
DK
D000419:Albuminuria; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010215:Papio; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D003404:Creatinine; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine