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Diabetes 54:228-233, 2005
© 2005 by the American Diabetes Association, Inc.

Altered Transcapillary Escape of Albumin and Microalbuminuria Reflects Two Different Pathogenetic Mechanisms

Romano Nosadini1, Mario Velussi2, Enrico Brocco3, Cataldo Abaterusso4, Francesco Piarulli5, Giuseppe Morgia6, Andrea Satta7, Rossana Faedda7, Avinash Abhyankar8, Holger Luthman8, and Giancarlo Tonolo9

1 Department of Endocrinology and Metabolic Diseases, University of Sassari, Sassari, Italy
2 Ospedale Civile, Centro Antidiabetico of Monfalcone, Monfalcone, Italy
3 Diabetic Clinic of Abano, Padova, Italy
4 Department of Nephrology, Castelfranco Veneto, Veneto, Italy
5 Diabetic Clinic, Porto Viro, Rovigo, Italy
6 Department of Urology, Università of Sassari, Sassari, Italy
7 Patologia Medica, Dipartimento di Medicina Interna, Specialization School of Nephrology, Università of Sassari, Sassari, Italy
8 Wallenberg Laboratory, Department of Endocrinology, University Hospital MAS, Lund, Malmo, Sweden
9 Diabetic Clinic, Clinica Medica, University of Sassari, Sassari, Italy

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 125I-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.


Address correspondence and reprint requests to R. Nosadini, Via C. De Brosses 1, 35128 Padova, Italy. E-mail: noscia{at}tin.it or nosadini{at}libero.it


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