title: Altered transcapillary escape of albumin and microalbuminuria reflects two different pathogenetic mechanisms.
abstract: We studied the following in normo- and microalbuminuric hypertensive type 2 diabetic patients: 1) transcapillary escape rate of albumin (TERalb) and 2) expression of mRNA slit diaphragm and podocyte proteins in renal biopsies. Normoalbuminuric subjects had renal cancer, and kidney biopsy was performed during surgery. TERalb was evaluated by clearance of (125)I-albumin. Real-time PCR of mRNA slit diaphragm was measured in kidney specimens. Albumin excretion rate (AER) was by definition lower in normoalbuminuric subjects than in microalbuminuric subjects with typical diabetic glomerulopathy (group 1), in microalbuminuric subjects with normal or near-normal glomerular structure (group 2), and in microalbuminuric subjects with atypical diabetic nephropathy (group 3). This classification was based on light microscopy analysis of renal tissue. TERalb (%/h) was similar in normoalbuminuric and microalbuminuric group 1, 2, and 3 diabetic patients (medians: 14.1 vs. 14.4 vs. 15.7 vs. 14.9, respectively) (ANOVA, NS). mRNA expression of slit diaphragm proteins CD2AP, FAT, Actn 4, NPHS1, and NPHS2 was higher in normoalbuminuric patients than in microalbuminuric patients (groups 1, 2, and 3) (ANOVA, P < 0.001). All diabetic patients had greater carotid artery intimal thickness than normal control subjects using ultrasound technique (ANOVA, P < 0.01). In conclusion, the present study suggests that microalbuminuria identifies a subgroup of hypertensive type 2 diabetic patients who have altered mRNA expression of slit diaphragm and podocyte proteins, even before glomerular structure shows abnormalities using light microscopy analysis. On the contrary, altered TERalb and increased carotid artery intimal thickness are shown by all hypertensive type 2 diabetic patients, both with normal and altered patterns of AER.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, University of Sassari, Sassari, Italy. noscia@tin.it
authors.forename: Romano
authors.initials: R
authors.lastname: Nosadini
authors.forename: Mario
authors.initials: M
authors.lastname: Velussi
authors.forename: Enrico
authors.initials: E
authors.lastname: Brocco
authors.forename: Cataldo
authors.initials: C
authors.lastname: Abaterusso
authors.forename: Francesco
authors.initials: F
authors.lastname: Piarulli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morgia
authors.forename: Andrea
authors.initials: A
authors.lastname: Satta
authors.forename: Rossana
authors.initials: R
authors.lastname: Faedda
authors.forename: Avinash
authors.initials: A
authors.lastname: Abhyankar
authors.forename: Holger
authors.initials: H
authors.lastname: Luthman
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tonolo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000419:Albuminuria / Q000503:physiopathology*; D001706:Biopsy; D002196:Capillaries / Q000503:physiopathology*; D002339:Carotid Arteries / Q000473:pathology; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012709:Serum Albumin; D003404:Creatinine