Nephrinuria in Diabetic Nephropathy of Type 1 Diabetes

  1. Anu Pätäri1,
  2. Carol Forsblom2,
  3. Marika Havana1,
  4. Heidi Taipale1,
  5. Per-Henrik Groop2,
  6. Harry Holthöfer1 and
  7. the FinnDiane Study Group
  1. 1Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  2. 2Department of Medicine, Division of Nephrology, Helsinki University Central Hospital and Folkhälsan Research Centre, Biomedicum Helsinki, Helsinki, Finland
  1. Address correspondence and reprint requests to Harry Holthöfer, P.O. Box 63 FIN-00014, University of Helsinki, Finland. E-mail: harry.holthofer{at}helsinki.fi

Abstract

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.

Footnotes

    • Accepted September 5, 2003.
    • Received February 28, 2003.
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