Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition

@article{Wihler2005RenalAA,
  title={Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition},
  author={Cornelia Wihler and Stefan Sch{\"a}fer and Karin Schmid and E. K. Deemer and Gerald M{\"u}nch and Markus Bleich and Andreas E. Busch and Theodor Dingermann and Veronika Somoza and John W. Baynes and Jochen Huber},
  journal={Diabetologia},
  year={2005},
  volume={48},
  pages={1645-1653}
}
Aims/hypothesisRenal accumulation of AGEs may contribute to the progression of diabetic nephropathy. We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes.MethodsMale Zucker diabetic fatty rats (ZDF, Gmi-fa/fa) rats were treated from age 10 to 37… 

Inhibition of renin angiotensin system decreases renal protein oxidative damage in diabetic rats.

LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat

The results of this study provide further evidence that LR-90, an AGE inhibitor with pleiotrophic effects, may also be beneficial for the prevention of type 2 diabetic nephropathy, where multiple risk factors, such as hyperglycaemia, dyslipidaemia, obesity, insulin resistance and hypertension, contribute to renal injury.

New therapeutic agents for diabetic kidney disease

Iron chelators, as antioxidant agents, work in reducing cellular damage by reactive oxygen species that are part of common final pathways in diabetic kidney disease.

Glycation End-Products and their Receptors: Pathophysiology and Therapeutic Targeting in Diabetes Mellitus

Some of the clinical outcomes of DM in cellular metabolism and organ function through the AGE-RAGE signaling pathway are revealed and recombinant sRAGE cannot be translated into clinical practice due to its limitations.

Serum levels of RBP4 might not be determined by diabetes mellitus but by kidney function and renal replacement therapy

The study results demonstrated that the serum level of RBP4 was negatively related to the eGFR, whether diabetes mellitus (DM) affected the blood concentration ofRBP4 or not, and the serumlevel of RBp4 exhibited significant difference in different renal replacement therapies.

Serum levels of RBP4 might not be determined by diabetes mellitus but by kidney function and renal replacement therapy

The study results demonstrated that the serum level of RBP4 was negatively related to the eGFR, whether diabetes mellitus (DM) affected the blood concentration ofRBP4 or not, and the serumlevel of RBp4 exhibited significant difference in different renal replacement therapies.

References

SHOWING 1-10 OF 46 REFERENCES

Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy.

A relationship between the renin-angiotensin system and the accumulation of AGEs in experimental diabetic nephropathy that may be linked through oxidative stress is identified.

Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model.

It is concluded that AGE inhibition should be included in the therapeutic strategy of DN after a strain of spontaneously hypertensive/NIH-corpulent rats was used as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs.

Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms.

It is demonstrated for the first time that widely used hypotensive agents, AIIR antagonists and ACE inhibitors, significantly attenuate AGE production.

Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease.

CML is a major AGE in renal basement membranes in diabetic nephropathy, and its accumulation involves upregulation of RAGE on podocytes, as assessed pathologically.

Attenuation of extracellular matrix accumulation in diabetic nephropathy by the advanced glycation end product cross-link breaker ALT-711 via a protein kinase C-alpha-dependent pathway.

Findings implicate AGEs as important stimuli for the activation of PKC, particularly PKC-alpha, in the diabetic kidney, which can be directly inhibited by ALT-711.

ALT-946 and aminoguanidine, inhibitors of advanced glycation, improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat.

Findings indicate that even in the context of renal injury presumed to be primarily blood pressure- and/or angiotensin II-dependent, approaches that interfere with metabolic pathways such as inhibitors of AGE formation can confer renal protection in experimental diabetes.

Mechanisms for the formation of glycoxidation products in end-stage renal disease.

The formation of the two glycoxidation products, pentosidine and CML, proceeds by different pathways and is enhanced by different precursors in the uremic milieu, evidence for the presence of increased metal-ion mediated oxidant stress in uremia.

Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy

Findings suggest that other vasoactive mechanisms in addition to angiotensin II are important in the prevention of diabetic nephropathy, and that vasopeptidase inhibition might confer an advantage over blockade of the RAS alone in the treatment of diabetic renal disease.

Advanced glycation end products and the progressive course of renal disease.

In experimental and human diabetic nephropathy (DN), it has been shown that advanced glycation end products (AGEs), in particular, carboxymethyl-lysine and pentosidine, accumulate with

Renoprotective effects of a novel inhibitor of advanced glycation

The ALT-946 inhibitor was more potent than aminoguanidine in inhibiting AGE-protein cross-linking both in vitro and in vivo and should be considered as a treatment for preventing or retarding diabetic nephropathy.