Analysis of NO-synthase expression and clinical risk factors in human diabetic nephropathy.
BACKGROUND
Changes of renal nitric oxide (NO) production have been associated with glomerular hyperfiltration, vascular permeability, albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Several studies demonstrated an up- as well as downregulated expression of NO-synthases (NOS) in experimental diabetic nephropathy. It is still not yet specified whether the regulation and activity of NOS is changed in human diabetic nephropathy.


METHODS
Renal biopsies and clinical data of 45 patients with diabetic nephropathy and of 10 control subjects were investigated. Glomerular and cortical endothelial NOS (eNOS) and inducible NOS (iNOS) expression were assessed by immunohistochemical staining and related to clinical data such as the duration of diabetes, insulin therapy and arterial hypertension, albuminuria/proteinuria, eGFR according to the formula modification of diet in renal disease (MDRD), presence of vascular complications or diabetic retinopathy.


RESULTS
The mean age of patients at biopsy was 60.3 years and the mean duration of diabetes 12.9 years. Expression of cortical and glomerular eNOS was increased in type 2 diabetes (P < 0.05). Increased expression of glomerular and cortical eNOS correlated with more severe vascular complications (r = 0.44; P < 0.05). Glomerular eNOS was strongly increased among different degrees of proteinuria (P < 0.01). In contrast to expression levels of eNOS, the glomerular expression pattern of iNOS changed from an endothelial pattern in glomeruli with preserved morphology towards expression predominantly by inflammatory cells.


CONCLUSIONS
Thus, increased eNOS expression by the renal endothelium could be demonstrated in type 2 diabetic nephropathy, whereas iNOS was unchanged but spatially differentially expressed. The eNOS expression was related to vascular lesions and the degree of proteinuria.
Roland E. Schmieder, Department of Nephrology and Hypertension, University Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. Tel: +49-9131-8536245; Fax: +49-9131-8539209; E-mail: roland.schmieder@rzmail.uni-erlangen.de.
Bernd
B
Hohenstein
Christian P M
CP
Hugo
Birgit
B
Hausknecht
Kirsten P
KP
Boehmer
Regine H
RH
Riess
Roland E
RE
Schmieder
D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III