Pediatric Nephrology

, Volume 20, Issue 6, pp 750–758

Widening of foot processes in normoalbuminuric adolescents with type 1 diabetes

  • Torun Birgitta Torbjörnsdotter
  • Nina Elisabeth Staffansdotter Sohlman Perrin
  • Georg Alexander Jaremko
  • Ulla Birgitta Berg
Original Article


We compared renal morphology in normoalbuminuric adolescents with type 1 diabetes with age-and sex-matched controls. Renal morphological measurements in 46 unselected adolescents with diabetes for approx. 10 years were compared with those in 20 healthy kidney donors. Renal volume estimated by ultra-sound, renal function determined by clearances of inulin and para-aminohippurate, and long-term mean HbA1c were measured in the patient group. Basement membrane thickness (BMT), mesangial matrix and capillary volume fractions per glomerulus [VV(matrix/glom), VV(cap/glom)] were significantly greater in patients than in controls (505 nm, 10.5%, 46.7% vs. 320 nm, 7.9% and 39.3%). The foot processes were wider in patients than in living donors (414 nm vs. 372 nm). There was no difference in mean kidney volume of patients with diabetes and healthy subjects. Glomerular filtration rate, body weight, and slit pore length density explained 60% of the variance in renal volume. After about 10 years’ duration of type 1 diabetes, BMT, VV(matrix/glom), VV(cap/glom), and foot process width were greater in normoalbuminuric adolescents than in healthy controls. This increase in foot processes of normoalbuminuric patients has not been reported before.


Kidney biopsy Insulin-dependent diabetes mellitus Adolescents Diabetic nephropathy Kidney morphology Foot processes Basement membrane thickness 


  1. 1.
    Viberti G, Keen H (1984) The patterns of proteinuria in diabetes mellitus. Relevance to pathogenesis and prevention of diabetic nephropathy. Diabetes 33:686–692Google Scholar
  2. 2.
    Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93PubMedGoogle Scholar
  3. 3.
    Caramori ML, Fioretto P, Mauer M (2000) The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 49:1399–1408PubMedGoogle Scholar
  4. 4.
    Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS (2003) Regression of microalbuminuria in type 1 diabetes. N Engl J Med 348:2285–2293Google Scholar
  5. 5.
    Mauer SM, Steffes MW, Goetz FC, Sutherland DE, Brown DM (1983) Diabetic nephropathy. A perspective. Diabetes 32 [Suppl 2]:52–55Google Scholar
  6. 6.
    Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC (1984) Structural-functional relationships in diabetic nephropathy. J Clin Invest 74:1143–1155PubMedGoogle Scholar
  7. 7.
    Østerby R, Gundersen HJ, Nyberg G, Aurell M (1987) Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli. Diabetes 36:612–619Google Scholar
  8. 8.
    Chavers BM, Bilous RW, Ellis EN, Steffes MW, Mauer SM (1989) Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria. N Engl J Med 320:966–970PubMedGoogle Scholar
  9. 9.
    Bangstad HJ, Østerby R, Dahl-Jorgensen K, Berg KJ, Hartmann A, Nyberg G, Frahm Bjorn S, Hanssen KF (1993) Early glomerulopathy is present in young, type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 36:523–529Google Scholar
  10. 10.
    Walker JD, Close CF, Jones SL, Rafftery M, Keen H, Viberti G, Østerby R (1992) Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria. Kidney Int 41:741–748Google Scholar
  11. 11.
    Berg UB, Torbjörnsdotter TB, Jaremko G, Thalme B (1998) Kidney morphological changes in relation to long-term renal function and metabolic control in adolescents with IDDM. Diabetologia 41:1047–1056Google Scholar
  12. 12.
    Drummond K, Mauer M (2002) The early natural history of nephropathy in type 1 diabetes. II. Early renal structural changes in type 1 diabetes. Diabetes 51:1580–1587Google Scholar
  13. 13.
    Mauer SM, Bilous RW, Ellis E, Harris R, Steffes MW (1988) Some lessons from the studies of renal biopsies in patients with insulin-dependent diabetes mellitus. J Diabetes Complications 2:197–202Google Scholar
  14. 14.
    Torbjörnsdotter TB, Jaremko GA, Berg UB (2004) Nondipping and its relation to glomerulopathy and hyperfiltration in adolescents with type 1 diabetes. Diabetes Care 27:510–516Google Scholar
  15. 15.
    Torbjörnsdotter TB, Jaremko GA, Berg UB (2001) Ambulatory blood pressure and heart rate in relation to kidney structure and metabolic control in adolescents with type I diabetes. Diabetologia 44:865–873Google Scholar
  16. 16.
    Jeppsson JO, Jerntorp P, Sundkvist G, Englund H, Nylund V (1986) Measurement of hemoglobin A1c by a new liquid-chromatographic assay: methodology, clinical utility, and relation to glucose tolerance evaluated. Clin Chem 32:1867–1872PubMedGoogle Scholar
  17. 17.
    DCCT (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329:977–986CrossRefPubMedGoogle Scholar
  18. 18.
    Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, Hoshino T, John WG, Kobold U, Little R, Mosca A, Mauri P, Paroni R, Susanto F, Takei I, Thienpont L, Umemoto M, Wiedmeyer HM (2004) IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem 50:166–174CrossRefPubMedGoogle Scholar
  19. 19.
    Dinkel E, Ertel M, Dittrich M, Peters H, Berres M, Schulte-Wissermann H (1985) Kidney size in childhood. Sonographical growth charts for kidney length and volume. Pediatr Radiol 15:38–43PubMedGoogle Scholar
  20. 20.
    Hilger HH, Klümper JD, Ullrich KJ (1958) Wasserrückresorption und ionentransport durch die sammelrohrzellen der Säugetiernieren. Pflugers Arch 267:218–237Google Scholar
  21. 21.
    Smith HW, Fingelstein N, Aliminosa L, Crawford B, Graber M (1945) The renal clearances of substituted hippuric acid derivates and other aromatic acids in dog and man. J Clin Invest 24:388–404Google Scholar
  22. 22.
    Berg UB, Thalme B (1984) Early renal functional changes in children with insulin-dependent diabetes mellitus-their relation to metabolic control. Int J Pediatr Nephrol 5:16–21Google Scholar
  23. 23.
    Østerby R, Gundersen HJG (1980) Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy. Diabetologia 18:493–500Google Scholar
  24. 24.
    Jensen EB, Gundersen HJG, Østerby R (1979) Determination of membrane thickness distribution from orthogonal intercepts. J Microsc 115:19–33Google Scholar
  25. 25.
    Ellis EN, Warady BA, Wood EG, Hassanein R, Richardson WP, Lane PH, Howard C, Kemp SF, Aceto T, Garibaldi L, Wiegmann TB, Savin VJ (1997) Renal structural-functional relationships in early diabetes mellitus. Pediatr Nephrol 11:584–591Google Scholar
  26. 26.
    Østerby R (1975) Early phases in the development of diabetic glomerulopathy. A quantitative electron microscopic study. Acta Med Scand Suppl 574Google Scholar
  27. 27.
    Steffes MW, Barbosa J, Basgen JM, Sutherland DER, Najarian JS, Mauer SM (1983) Quantitative glomerular morphology of the normal human kidney. Lab Invest 49:82–86Google Scholar
  28. 28.
    Bjorn SF, Bangstad HJ, Hanssen KF, Nyberg G, Walker JD, Viberti GC, Østerby R (1995) Glomerular epithelial foot processes and filtration slits in IDDM patients. Diabetologia 38:1197–1204Google Scholar
  29. 29.
    Østerby R (1992) Glomerular structural changes in type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention. Diabetologia 35:803–812Google Scholar
  30. 30.
    Caramori ML, Basgen JM, Mauer M (2003) Glomerular structure in the normal human kidney: differences between living and cadaver donors. J Am Soc Nephrol 14:1901–1903Google Scholar
  31. 31.
    Østerby R, Asplund J, Bangstad HJ, Nyberg G, Rudberg S, Viberti G, Walker JD (1997) Glomerular volume and the glomerular vascular pole area in patients with insulin-dependent diabetes mellitus. Virchows Arch 431:351–357Google Scholar
  32. 32.
    Østerby R, Bangstad HJ, Nyberg G, Rudberg S (2001) On glomerular structural alterations in type-1 diabetes. Companions of early diabetic glomerulopathy. Virchows Arch 438:129–135Google Scholar
  33. 33.
    Steffes MW, Schmidt D, McCrery R, Basgen JM (2001) Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney Int 59:2104–2113Google Scholar
  34. 34.
    Pagtalunan ME, Miller PL, Jumping-Eagle S, Nelson RG, Myers BD, Rennke HG, Coplon NS, Sun L, Meyer TW (1997) Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 99:342–348Google Scholar
  35. 35.
    Ellis EN, Steffes MW, Chavers B, Mauer SM (1987) Observations of glomerular epithelial cell structure in patients with type I diabetes mellitus. Kidney Int 32:736–741Google Scholar
  36. 36.
    Fioretto P, Steffes MW, Mauer M (1994) Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria. Diabetes 43:1358–1364Google Scholar
  37. 37.
    Østerby R, Nyberg G, Andersson C, Frisk B (1988) Glomerular structural quantities in baseline biopsies from cadaveric donor kidney pairs. APMIS Suppl 4:134–140Google Scholar
  38. 38.
    Østerby R (1990) Basemant membrane morphology in diabetes mellitus. In: Rifkin H, Porte D Jr (eds) Diabetes mellitus: theory and practice, 4th edn. Elsevier, Amsterdam, pp 220–233Google Scholar
  39. 39.
    Perrin NE, Torbjornsdotter TB, Jaremko GA, Berg UB (2004) Follow-up of kidney biopsies in normoalbuminuric patients with type 1 diabetes. Pediatr Nephrol 19:1004–1013Google Scholar
  40. 40.
    Rudberg S, Østerby R, Dahlquist G, Nyberg G, Persson B (1997) Predictors of renal morphological changes in the early stage of microalbuminuria in adolescents with IDDM. Diabetes Care 20:265–271Google Scholar
  41. 41.
    Johansson BL, Berg U, Freyschuss U, Hall K, Troell S (1990) Factors related to renal haemodynamics in young type 1 diabetes mellitus patients. Pediatr Nephrol 4:589–592Google Scholar
  42. 42.
    Frazer FL, Palmer LJ, Clarey A, Thonell S, Byrne GC (2001) Relationship between renal volume and increased albumin excretion rates in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 14:875–881Google Scholar
  43. 43.
    Feldt-Rasmussen B, Hegedus L, Mathiesen ER, Deckert T (1991) Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion: effect of long-term improved metabolic control. Scand J Clin Lab Invest 51:31–36Google Scholar
  44. 44.
    Mogensen CE, Andersen MJ (1973) Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 22:706–712PubMedGoogle Scholar
  45. 45.
    Sandahl Christiansen J, Gammelgaard J, Frandsen M, Parving H-H (1981) Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia 20:451–456Google Scholar
  46. 46.
    Mogensen CE, Andersen MJ (1975) Increased kidney size and glomerular filtration rate in untreated juvenile diabetes: normalization by insulin-treatment. Diabetologia 11:221–224Google Scholar
  47. 47.
    Mogensen CE (1973) Elevated glomerular filtration rate in insulin-treated short-term diabetes. Non-dependence on blood sugar value. Acta Med Scand 194:559–561Google Scholar
  48. 48.
    Wiseman MJ, Saunders AJ, Keen H, Viberti G (1985) Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes. N Engl J Med 312:617–621Google Scholar
  49. 49.
    Kleinman KS, Fine LG (1988) Prognostic implications of renal hypertrophy in diabetes mellitus. Diabetes Metab Rev 4:179–189Google Scholar
  50. 50.
    Baumgartl HJ, Sigl G, Banholzer P, Haslbeck M, Standl E (1998) On the prognosis of IDDM patients with large kidneys. Nephrol Dial Transplant 13:630–634Google Scholar
  51. 51.
    Bangstad HJ, Østerby R, Hartmann A, Berg TJ, Hanssen KF (1999) Severity of glomerulopathy predicts long-term urinary albumin excretion rate in patients with type 1 diabetes and microalbuminuria. Diabetes Care 22:314–319Google Scholar
  52. 52.
    Østerby R, Parving HH, Hommel E, Jorgensen HE, Lokkegaard H (1990) Glomerular structure and function in diabetic nephropathy. Early to advanced stages. Diabetes 39:1057–1063Google Scholar

Copyright information

© IPNA 2005

Authors and Affiliations

  • Torun Birgitta Torbjörnsdotter
    • 1
  • Nina Elisabeth Staffansdotter Sohlman Perrin
    • 1
  • Georg Alexander Jaremko
    • 2
  • Ulla Birgitta Berg
    • 1
  1. 1.Department of Pediatrics Karolinska InstitutetKarolinska University Hospital HuddingeStockholmSweden
  2. 2.Department of Pathology, Karolinska InstitutetKarolinska University Hospital SolnaSolnaSweden

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