|
 |
|
|||||||
|
|||||||||
© 2002 by the American Diabetes Association, Inc.
The Early Natural History of Nephropathy in Type 1 Diabetes
II. Early Renal Structural Changes in Type 1 Diabetes
1 McGill University, Montreal, Quebec, Canada
2 University of Minnesota, Minneapolis, Minnesota
Renal structural abnormalities are known to precede the development of proteinuria, hypertension, and reduced renal function in patients with type 1 diabetes. The determinants of these early structural abnormalities are, however, largely unknown. The International Diabetic Nephropathy Study (IDNS) has recruited 243 children and adults (aged 10–40 years) in Montreal, Minneapolis, and Paris to identify and quantify these determinants. All study subjects were normotensive and had normal-to-high glomerular filtration rates (GFRs) and urinary albumin excretion rates (AERs) <100 µg/min at study entry. Only 8 of 243 had an AER 
20 µg/min (microalbuminuria). Two renal biopsies are obtained at a 5-year intervals, with baseline and follow-up measures of renal function, blood pressure (BP), HbA1c, plasma lipids, and AER. Herein, we examine the baseline renal biopsy morphometric findings in these subjects and in 87 kidney donor control subjects and explore the associations between findings and clinical and demographic variables. The principal morphometric abnormalities were increased glomerular basement membrane (GBM) width and fractional volume of mesangium [Vv(Mes/glom)] and mesangial matrix [Vv(MM/glom)]. The frequency of these abnormalities increased with increasing duration of diabetes but was observed as early as 2–8 years after onset. Diastolic BP (DBP), but not HbA1c, was directly associated with these abnormalities. Elevated GFR was associated with only a small increase in peripheral glomerular capillary basement membrane filtration surface density. Center differences were detected in renal structural, renal functional, and BP parameters, especially between the Paris and North American centers. GBM width, Vv(Mes/glom), and Vv(MM/glom) are significantly increased even within a few years of onset of type 1 diabetes. These changes are detectable in normoalbuminuric patients and are related to duration, BP, and study site. Changes in these and other morphometric measures over 5-year follow-up should help clarify the roles of glycemia and other determinants of the rates of development of diabetic nephropathy lesions, as well as their relationships to early changes in BP, albumin excretion, and renal function.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Chang, M. L. Caramori, R. Moriya, and M. Mauer Having One Kidney Does Not Accelerate the Rate of Development of Diabetic Nephropathy Lesions in Type 1 Diabetic Patients Diabetes, June 1, 2008; 57(6): 1707 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tan, J.-S. Keum, B. Wang, M. B. McHenry, S. R. Lipsitz, and A. A. Jaffa Targeted deletion of B2-kinin receptors protects against the development of diabetic nephropathy Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1026 - F1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yuan, J. Deng, T. Wang, C. Zhao, X. Xu, P. Wang, J. W. Voltz, M. L. Edin, X. Xiao, L. Chao, et al. Tissue Kallikrein Reverses Insulin Resistance and Attenuates Nephropathy in Diabetic Rats by Activation of Phosphatidylinositol 3-Kinase/Protein Kinase B and Adenosine 5'-Monophosphate-Activated Protein Kinase Signaling Pathways Endocrinology, May 1, 2007; 148(5): 2016 - 2026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Perkins, L. H. Ficociello, B. E. Ostrander, K. H. Silva, J. Weinberg, J. H. Warram, and A. S. Krolewski Microalbuminuria and the Risk for Early Progressive Renal Function Decline in Type 1 Diabetes J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1353 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K O Alsaad and A M Herzenberg Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update J. Clin. Pathol., January 1, 2007; 60(1): 18 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Sochett, D. Z.I. Cherney, J. R. Curtis, M. G. Dekker, J. W. Scholey, and J. A. Miller Impact of Renin Angiotensin System Modulation on the Hyperfiltration State in Type 1 Diabetes J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1703 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Caramori, P. Fioretto, and M. Mauer Enhancing the Predictive Value of Urinary Albumin for Diabetic Nephropathy J. Am. Soc. Nephrol., February 1, 2006; 17(2): 339 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Briggs and T. H. Hostetter Opening Words for CJASN Clin. J. Am. Soc. Nephrol., January 1, 2006; 1(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
|
|
K. Susztak, A. C. Raff, M. Schiffer, and E. P. Bottinger Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy Diabetes, January 1, 2006; 55(1): 225 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Gurley, S. E. Clare, K. P. Snow, A. Hu, T. W. Meyer, and T. M. Coffman Impact of genetic background on nephropathy in diabetic mice Am J Physiol Renal Physiol, January 1, 2006; 290(1): F214 - F222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Beisswenger, K. S. Drummond, R. G. Nelson, S. K. Howell, B. S. Szwergold, and M. Mauer Susceptibility to Diabetic Nephropathy Is Related to Dicarbonyl and Oxidative Stress Diabetes, November 1, 2005; 54(11): 3274 - 3281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Steinke, A. R. Sinaiko, M. S. Kramer, S. Suissa, B. M. Chavers, M. Mauer, and for the International Diabetic Nephropathy Study G The Early Natural History of Nephropathy in Type 1 Diabetes: III. Predictors of 5-Year Urinary Albumin Excretion Rate Patterns in Initially Normoalbuminuric Patients Diabetes, July 1, 2005; 54(7): 2164 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Coppelli, R. Giannarelli, F. Vistoli, S. Del Prato, G. Rizzo, F. Mosca, U. Boggi, and P. Marchetti The Beneficial Effects of Pancreas Transplant Alone on Diabetic Nephropathy Diabetes Care, June 1, 2005; 28(6): 1366 - 1370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tan, B. Wang, J.-S. Keum, and A. A. Jaffa Mechanisms through which bradykinin promotes glomerular injury in diabetes Am J Physiol Renal Physiol, March 1, 2005; 288(3): F483 - F492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Hudson The Molecular Basis of Goodpasture and Alport Syndromes: Beacons for the Discovery of the Collagen IV Family J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2514 - 2527. [Full Text] [PDF]
|
|
|
|
|
|
K. N. Drummond, M. S. Kramer, S. Suissa, C. Levy-Marchal, S. Dell'Aniello, A. Sinaiko, and M. Mauer Effects of Duration and Age at Onset of Type 1 Diabetes on Preclinical Manifestations of Nephropathy Diabetes, July 1, 2003; 52(7): 1818 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Jaffa, R. Durazo-Arvizu, D. Zheng, D. T. Lackland, S. Srikanth, W. T. Garvey, and A. H. Schmaier Plasma Prekallikrein: A Risk Marker for Hypertension and Nephropathy in Type 1 Diabetes Diabetes, May 1, 2003; 52(5): 1215 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Lane Diabetic kidney disease: impact of puberty Am J Physiol Renal Physiol, October 1, 2002; 283(4): F589 - F600. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |