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Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition
- Source :
- Diabetologia. 45(11)
- Publication Year :
- 2002
-
Abstract
- AIMS/HYPOTHESIS: Proteinuria, reflecting increased glomerular permeability to macromolecules is a characteristic feature of diabetic nephropathy. Nephrin, a 1241-residue transmembrane protein is a key component of the podocyte slit pore membrane and a major contributor of the glomerular filtration barrier. We investigated the expression of nephrin in human kidney tissue from patients with diabetic nephropathy to elucidate its relationship with proteinuria and the effects of anti-proteinuric therapy with angiotensin converting enzyme inhibition. METHODS: Renal biopsies were examined from 14 patients with Type II (non-insulin-dependent) diabetes mellitus and proteinuria who had been randomised to receive treatment with the ACE inhibitor, perindopril (4 mg/day) or placebo for the preceding 2 years. These specimens were compared with control human tissue sections, obtained from areas of normal renal cortex following nephrectomy for malignancy. Proteinuria was measured, specimens were examined histologically for injury and the expression of nephrin messenger RNA was assessed by quantitative in situ hybridisation. RESULTS: Glomeruli from placebo-treated patients with diabetic nephropathy, showed a 62% reduction in nephrin expression compared with control subjects (p=0.0003). In contrast, nephrin RNA in glomeruli from perindopril treated patients was similar to that in the non-diabetic control group. In both placebo and perindopril treated patients, a close inverse correlation was noted between the magnitude of nephrin gene expression and the degree of proteinuria (placebo: r=0.86, p=0.013, perindopril: r=0.91, p=0.004). CONCLUSION/INTERPRETATION: Modulation in nephrin expression is related to the extent of proteinuria in diabetic nephropathy. These changes define, at a molecular level alterations in the glomerulus that occur in relation to proteinuria in diabetes and the effects of anti-proteinuric treatment with ACE inhibition.
- Subjects :
- medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Biopsy
030232 urology & nephrology
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
030204 cardiovascular system & hematology
urologic and male genital diseases
Nephropathy
Podocyte
Diabetic nephropathy
Nephrin
Placebos
03 medical and health sciences
0302 clinical medicine
Internal medicine
Internal Medicine
medicine
Perindopril
Humans
Diabetic Nephropathies
In Situ Hybridization
Glycated Hemoglobin
biology
urogenital system
business.industry
Glomerulosclerosis
Membrane Proteins
Proteins
medicine.disease
female genital diseases and pregnancy complications
3. Good health
Proteinuria
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Creatinine
ACE inhibitor
biology.protein
business
Nephrotic syndrome
medicine.drug
Subjects
Details
- ISSN :
- 0012186X
- Volume :
- 45
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Diabetologia
- Accession number :
- edsair.doi.dedup.....6e353350f6cb9e51c0989f723558ba38