Nephrinuria in diabetic nephropathy of type 1 diabetes.

Diabetic nephropathy is the leading cause of end-stage renal disease. Because early diagnosis and treatment may prevent the complication, new tools for an early detection are needed. One of the key components of the glomerular filtration slit spanning between neighboring podocytes is nephrin. Its expression is altered in experimental models of diabetes and also in various human proteinuric diseases, including diabetes. We studied whether type 1 diabetic patients with or without nephropathy exhibit immunoreactive nephrin in the urine, reflecting early damage of the filtration barrier. Diabetic patients with normoalbuminuria (n = 40), with microalbuminuria (n = 41), and with macroalbuminuria (n = 39) and patients previously normoalbuminuric but now testing positive for microalbuminuria (newMicro, n = 39) were screened for nephrinuria with Western blotting using two affinity-purified anti-nephrin antibodies. Nondiabetic healthy subjects (n = 29) were also studied. Nephrinuria was present in 30% of normoalbuminuric, 17% of microalbuminuric, 28% of macroalbuminuric, and 28% of newMicro patients. Of female patients, 35% were nephrinuric compared with only 19% of male patients (P = 0.02). None of the control subjects was nephrinuric. In conclusion, glomerular filtration barrier may be affected in one-third of diabetic patients manifesting as early nephrinuria. Nephrinuria may have prognostic value and become a marker of susceptibility for kidney complications in diabetes.

[1]  M. Cooper,et al.  Disparate effects of angiotensin II antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension: potential role of nephrin , 2003, Journal of hypertension.

[2]  U. Berg,et al.  Altered ultrastructural distribution of nephrin in minimal change nephrotic syndrome. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  S. Shankland,et al.  Podocyte biology and response to injury. , 2002, Journal of the American Society of Nephrology : JASN.

[4]  H. Holthöfer,et al.  Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition , 2002, Diabetologia.

[5]  G. Remuzzi,et al.  Podocyte number in normotensive type 1 diabetic patients with albuminuria. , 2002, Diabetes.

[6]  M. Cooper,et al.  Role of nephrin in renal disease including diabetic nephropathy. , 2002, Seminars in nephrology.

[7]  G. Jerums,et al.  Expression of the slit-diaphragm protein, nephrin, in experimental diabetic nephropathy: differing effects of anti-proteinuric therapies. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  G. Jerums,et al.  Modulation of nephrin in the diabetic kidney: association with systemic hypertension and increasing albuminuria , 2002, Journal of hypertension.

[9]  Mi-kyung Kim,et al.  Expression of nephrin in acquired human glomerular disease. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[10]  M. Rastaldi,et al.  Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases. , 2002, Kidney international.

[11]  M. Knip,et al.  Nephrin is expressed in the pancreatic beta cells , 2001, Diabetologia.

[12]  E. Lewis,et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. , 2001, The New England journal of medicine.

[13]  I. Tikkanen,et al.  Changes in the Expression of Nephrin Gene and Protein in Experimental Diabetic Nephropathy , 2001, Laboratory Investigation.

[14]  M. Cooper,et al.  Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade , 2001, Diabetologia.

[15]  M. Cooper,et al.  Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension , 2001, Diabetologia.

[16]  M. Steffes,et al.  Glomerular cell number in normal subjects and in type 1 diabetic patients. , 2001, Kidney international.

[17]  A. Brun,et al.  Frontal Dysfunction and Frontal Cortical Synapse Loss in Alcoholism –The Main Cause of Alcohol Dementia? , 2001, Dementia and Geriatric Cognitive Disorders.

[18]  K. Tryggvason,et al.  Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome , 2001, Human mutation.

[19]  G. Camussi,et al.  Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. , 2001, The American journal of pathology.

[20]  K. Tryggvason,et al.  Expression of nephrin in pediatric kidney diseases. , 2001, Journal of the American Society of Nephrology : JASN.

[21]  T. Nakamura,et al.  Urinary excretion of podocytes in patients with diabetic nephropathy. , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[22]  A. Saller,et al.  Structural involvement in type 1 and type 2 diabetic nephropathy. , 2000, Diabetes & metabolism.

[23]  D. Kerjaschki,et al.  Nephrin localizes at the podocyte filtration slit area and is characteristically spliced in the human kidney. , 1999, The American journal of pathology.

[24]  L. Holzman,et al.  Cloning and expression of the rat nephrin homolog. , 1999, The American journal of pathology.

[25]  K. Tryggvason,et al.  Nephrin is specifically located at the slit diaphragm of glomerular podocytes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Pringle,et al.  Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[27]  L Peltonen,et al.  Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. , 1998, Molecular cell.

[28]  G. Jerums,et al.  Fractional clearance of albumin is influenced by its degradation during renal passage. , 1997, Clinical science.

[29]  T. Meyer,et al.  Podocyte loss and progressive glomerular injury in type II diabetes. , 1997, The Journal of clinical investigation.

[30]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. , 1993 .

[31]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. , 1993, The New England journal of medicine.

[32]  S. Nielsen,et al.  Structural and functional features of protein handling in the kidney proximal tubule. , 1991, Seminars in nephrology.

[33]  J. Kastrup,et al.  Microalbuminuria: an early marker of renal involvement in diabetes. , 1985, Uremia investigation.

[34]  M. Steffes,et al.  Structural-functional relationships in diabetic nephropathy. , 1984, The Journal of clinical investigation.

[35]  H. Parving,et al.  Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. , 1982, Acta endocrinologica.

[36]  H. Keen,et al.  MICROALBUMINURIA AS A PREDICTOR OF CLINICAL NEPHROPATHY IN INSULIN-DEPENDENT DIABETES MELLITUS , 1982, The Lancet.

[37]  M. Abbal,et al.  Letter: Factor-VIII complex and endothelial damage. , 1975, Lancet.

[38]  M. Karnovsky,et al.  POROUS SUBSTRUCTURE OF THE GLOMERULAR SLIT DIAPHRAGM IN THE RAT AND MOUSE , 1974, The Journal of cell biology.

[39]  P. Kimmelstiel,et al.  Intercapillary Lesions in the Glomeruli of the Kidney. , 1936, The American journal of pathology.