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The Structure of Human Diabetic Nephropathy

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The Diabetic Kidney

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

This chapter outlines the histopathology of human diabetic nephropathy (DN). The classical structural changes of DN have been well described and demonstrated in general renal and renal pathology textbooks. The emphasis here is on current and evolving studies and concepts in this field. As renal lesions in type 1 diabetes are believed to be more unique to DN and more uniform and as lesions in type 2 diabetes are more heterogeneous and, perhaps, more frequently complicated by renal diseases other than diabetes, this chapter primarily focuses on the structural changes in type 1 diabetes. We will, however, discuss nephropathy of type 2 diabetes and its differences from type 1 diabetes at the end of this chapter.

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References

  1. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003;348:2285–2293.

    Article  PubMed  CAS  Google Scholar 

  2. Østerby R. Early phases in the development of diabetic glomerulopathy. Acta Med Scand Suppl 1974;574:3–82.

    PubMed  Google Scholar 

  3. Steffes MW, Sutherland DE, Goetz FC, Rich SS, Mauer SM. Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus. N Engl J Med 1985;312:1282–1287.

    Article  PubMed  CAS  Google Scholar 

  4. Brito PL, Fioretto P, Drummond K, et al. Proximal tubular basement membrane width in insulindependent diabetes mellitus. Kidney Int 1998;53:754–761.

    Article  PubMed  CAS  Google Scholar 

  5. Mauer SM, Barbosa J, Vernier RL, et al. Development of diabetic vascular lesions in normal kidneys transplanted into patients with diabetes mellitus. N Engl J Med 1976;295:916–920.

    Article  PubMed  CAS  Google Scholar 

  6. Burkholder PM. Immunohistopathologic study of localized plasma proteins and fixation of guinea pig complement in renal lesions of diabetic glomerulosclerosis. Diabetes 1965;14:755–770.

    PubMed  CAS  Google Scholar 

  7. Steffes MW, Bilous RW, Sutherland DE, Mauer SM. Cell and matrix components of the glomerular mesangium in type I diabetes. Diabetes 1992;41:679–684.

    Article  PubMed  CAS  Google Scholar 

  8. Steffes MW, Barbosa J, Basgen JM, Sutherland DE, Najarian JS, Mauer SM. Quantitative glomerular morphology of the normal human kidney. Lab Invest 1983;49:82–86.

    PubMed  CAS  Google Scholar 

  9. Drummond KN, Kramer MS, Suissa S, et al. International diabetic nephropathy study group. Effects of duration and age at onset of type 1 diabetes on preclinical manifestations of nephropathy. Diabetes 2003;52:1818–1824.

    Article  PubMed  CAS  Google Scholar 

  10. Drummond K, Mauer M. International diabetic nephropathy study group. The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes. Diabetes 2002;51:1580–1587.

    Article  PubMed  CAS  Google Scholar 

  11. Katz A, Caramori ML, Sisson-Ross S, Groppoli T, Basgen JM, Mauer M. An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients. Kidney Int 2002;61:2058–2066.

    Article  PubMed  Google Scholar 

  12. Stout LC, Kumar S, Whorton EB. Focal mesangiolysis and the pathogenesis of the Kimmelstiel-Wilson nodule. Hum Pathol 1993;24:77–89.

    Article  PubMed  CAS  Google Scholar 

  13. Saito Y, Kida H, Takeda S, et al. Mesangiolysis in diabetic glomeruli: its role in the formation of nodular lesions. Kidney Int 1988;34:389–396.

    Article  PubMed  CAS  Google Scholar 

  14. Kim Y, Kleppel MM, Butkowski R, Mauer SM, Wieslander J, Michael AF. Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol 1991;138:413–420.

    PubMed  CAS  Google Scholar 

  15. Zhu D, Kim Y, Steffes MW, Groppoli TJ, Butkowski RJ, Mauer SM. Glomerular distribution of type IV collagen in diabetes by high resolution quantitative immunochemistry. Kidney Int 1994;45:425–433.

    Article  PubMed  CAS  Google Scholar 

  16. Moriya T, Groppoli TJ, Kim Y, Mauer M. Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients. Kidney Int 2001;59:317–323.

    Article  PubMed  CAS  Google Scholar 

  17. Falk RJ, Scheinman JI, Mauer SM, Michael AF. Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes 1983;32(2):34–39.

    PubMed  Google Scholar 

  18. Hørlyck A, Gundersen HJ, Østerby R. The cortical distribution pattern of diabetic glomerulopathy. Diabetologia 1986;29:146–150.

    Article  PubMed  Google Scholar 

  19. Harris RD, Steffes MW, Bilous RW, Sutherland DE, Mauer SM. Global glomerular sclerosis and glomerular arteriolar hyalinosis in insulin dependent diabetes. Kidney Int 1991;40:107–114.

    Article  PubMed  CAS  Google Scholar 

  20. Mauer SM, Sutherland DE, Steffes MW. Relationship of systemic blood pressure to nephropathology in insulin-dependent diabetes mellitus. Kidney Int 1992;41:736–740.

    Article  PubMed  CAS  Google Scholar 

  21. Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 1998;54:687–697.

    Article  PubMed  CAS  Google Scholar 

  22. Pätäri A, Forsblom C, Havana M, Taipale H, Groop PH, Holthofer H. Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes 2003;52:2969–2974.

    Article  PubMed  Google Scholar 

  23. Nakamura T, Ushiyama C, Suzuki S, et al. Urinary excretion of podocytes in patients with diabetic nephropathy. Nephrol Dial Transplant 2000;15:1379–1383.

    Article  PubMed  CAS  Google Scholar 

  24. Pagtalunan ME, Miller PL, Jumping-Eagle S, et al. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 1997;99:342–348.

    PubMed  CAS  Google Scholar 

  25. Meyer TW, Bennett PH, Nelson RG. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with type II diabetes and microalbuminuria. Diabetologia 1999;42:1341–1344.

    Article  PubMed  CAS  Google Scholar 

  26. White KE, Bilous RW, Marshall SM, et al. Podocyte number in normotensive type 1 diabetic patients with albuminuria. Diabetes 2002;51:3083–3089.

    Article  PubMed  CAS  Google Scholar 

  27. Dalla Vestra M, Masiero A, Roiter AM, Saller A, Crepaldi G, Fioretto P. Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes 2003;52:1031–1035.

    Article  PubMed  CAS  Google Scholar 

  28. Weibel ER, Gomez DM. A principle for counting tissue structures on random sections. J Appl Physiol 1962;17:343–348.

    PubMed  CAS  Google Scholar 

  29. Steffes MW, Schmidt D, McCrery R, Basgen JM. International diabetic nephropathy study group. Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney Int 2001;59:2104–2113.

    PubMed  CAS  Google Scholar 

  30. White KE, Bilous RW. Diabiopsies study group. Structural alterations to the podocyte are related to proteinuria in type 2 diabetic patients. Nephrol Dial Transplant 2004;19:1437–1440.

    Article  PubMed  Google Scholar 

  31. Toyoda M, Najafian B, Groppoli T, Basgen J, Kim Y, Mauer M. Problems in the measurement of podocyte structural parameters in proteinuric type 1 diabetic patients. J Am Soc Nephrol 2003;14:597A.

    Google Scholar 

  32. Kriz W, LeHir M. Pathways to nephron loss starting from glomerular diseases-insights from animal models. Kidney Int 2005;67:404–419.

    Article  PubMed  Google Scholar 

  33. Najafian B, Kim Y, Crosson JT, Mauer M. Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy. J Am Soc Nephrol 2003;14:908–917.

    Article  PubMed  Google Scholar 

  34. Tomlanovich S, Deen WM, Jones HW 3rd, Schwartz HC, Myers BD. Functional nature of glomerular injury in progressive diabetic glomerulopathy. Diabetes 1987;36:556–565.

    Article  PubMed  CAS  Google Scholar 

  35. Brown DM, Mauer SM. Diabetes Mellitus. In: Pediatric Nephrology. Holliday M, Barrat M, Vernier RL (eds.), Baltimore: Williams & Wilkins, 1987, 513–519.

    Google Scholar 

  36. Mauer SM, Miller K, Goetz FC, et al. Immunopathology of renal extracellular membranes in kidneys transplanted into patients with diabetes mellitus. Diabetes 1976;25:709–712.

    Article  PubMed  CAS  Google Scholar 

  37. Fioretto P, Steffes MW, Mihatsch MJ, Strom EH, Sutherland DE, Mauer M. Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients. Kidney Int 1995;48:489–495.

    Article  PubMed  CAS  Google Scholar 

  38. Østerby R, Hartmann A, Bangstad HJ. Structural changes in renal arterioles in Type I diabetic patients. Diabetologia 2002;45:542–549.

    Article  PubMed  CAS  Google Scholar 

  39. Østerby R, Hartmann A, Nyengaard JR, Bangstad HJ. Development of renal structural lesions in type 1 diabetic patients with microalbuminuria. Observations by light microscopy in 8-year follow-up biopsies. Virchows Arch 2002;440:94–101.

    Article  PubMed  CAS  Google Scholar 

  40. Paulsen EP, Burke BA, Vernier RL, Mallare MJ, Innes DJ Jr, Sturgill BC. Juxtaglomerular body abnormalities in youth-onset diabetic subjects. Kidney Int 1994;45:1132–1139.

    Article  PubMed  CAS  Google Scholar 

  41. Moriya R, Manivel JC, Mauer M. Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients. Diabetologia 2004;47:82–88.

    Article  PubMed  CAS  Google Scholar 

  42. Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC. Structural-functional relationships in diabetic nephropathy. J Clin Invest 1984;74:1143–1155.

    Article  PubMed  CAS  Google Scholar 

  43. Ellis EN, Steffes MW, Goetz FC, Sutherland DE, Mauer SM. Glomerular filtration surface in type I diabetes mellitus. Kidney Int 1986;29:889–894.

    Article  PubMed  CAS  Google Scholar 

  44. Østerby R, Gundersen HJ, Nyberg G, Aurell M. Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli. Diabetes 1987;36:612–619.

    Article  PubMed  Google Scholar 

  45. Hirose K, Tsuchida H, Østerby R, Gundersen HJ. A strong correlation between glomerular filtration rate and filtration surface in diabetic kidney hyperfunction. Lab Invest 1980;43:434–437.

    PubMed  CAS  Google Scholar 

  46. Caramori ML, Kim Y, Huang C, et al. Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes. Diabetes 2002;51:506–513. Erratum in: Diabetes 2002;51:1294.

    Article  PubMed  CAS  Google Scholar 

  47. Mauer SM. Structural-functional correlations of diabetic nephropathy. Kidney Int 1994;45:612–622. Erratum in: Kidney Int 1994;46:285.

    Article  PubMed  CAS  Google Scholar 

  48. Lane PH, Steffes MW, Fioretto P, Mauer SM. Renal interstitial expansion in insulin-dependent diabetes mellitus. Kidney Int 1993;43:661–667.

    Article  PubMed  CAS  Google Scholar 

  49. Fioretto P, Steffes MW, Sutherland DE, Mauer M. Sequential renal biopsies in insulin-dependent diabetic patients: structural factors associated with clinical progression. Kidney Int 1995;48:1929–1935.

    Article  PubMed  CAS  Google Scholar 

  50. Taft JL, Nolan CJ, Yeung SP, Hewitson TD, Martin FI. Clinical and histological correlations of decline in renal function in diabetic patients with proteinuria. Diabetes 1994;43:1046–1051.

    Article  PubMed  CAS  Google Scholar 

  51. Fioretto P, Steffes MW, Mauer M. Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria. Diabetes 1994;43:1358–1364.

    Article  PubMed  CAS  Google Scholar 

  52. Bilous RW, Mauer SM, Sutherland DE, Steffes MW. Mean glomerular volume and rate of development of diabetic nephropathy. Diabetes 1989;38:1142–1147.

    Article  PubMed  CAS  Google Scholar 

  53. Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 1992;232:194–201.

    Article  PubMed  CAS  Google Scholar 

  54. Bendtsen TF, Nyengaard JR. Glomerutubular junction abnormalities are associated with proteinuria in type 1 diabetes. J Am Soc Nephrol, in press.

    Google Scholar 

  55. Najafian B, Crosson JT, Kim Y, Mauer M. The frequency of glomerulotubular junction abnormalities and atubular glomeruli in relation to albumin excretion rtae in type 1 diabetic patients. J Am Soc Nephrol 2003;14:597A.

    Article  Google Scholar 

  56. Najafian B, Crosson JT, Kim Y, Mauer M. Predilection of tuft to Bowman’s capsule adhesions for glomerulotubular junction area in type 1 diabetes mellitus. J Am Soc Nephrol 2004;15:729A.

    Google Scholar 

  57. Howie AJ, Ferreira MA, Majumdar A, Lipkin GW. Glomerular prolapse as precursor of one type of segmental sclerosing lesions. J Pathol 2000;190:478–483.

    Article  PubMed  CAS  Google Scholar 

  58. Kriz W, Elger M, Hosser H, et al. How does podocyte damage result in tubular damage? Kidney Blood Press Res 1999;22:26–36.

    Article  PubMed  CAS  Google Scholar 

  59. Howie AJ. Epithelial membrane antigen in normal and proteinuric glomeruli and in damaged proximal tubules. J Pathol 1986;148:55–60.

    Article  PubMed  CAS  Google Scholar 

  60. Brenner BM, Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA. The role of glomerular hyperfiltration in the initiation and progression of diabetic nephropathy. Acta Endocrinol Suppl (Copenh) 1981;242:7–10.

    CAS  Google Scholar 

  61. Paueksakon P, Revelo MP, Ma LJ, Marcantoni C, Fogo AB. Microangiopathic injury and augmented PAI-1 in human diabetic nephropathy. Kidney Int 2002;61:2142–2148.

    Article  PubMed  CAS  Google Scholar 

  62. Mazzucco G, Bertani T, Fortunato M, et al. Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. Am J Kidney Dis 2002;39:713–720.

    PubMed  Google Scholar 

  63. Carpenter AM, Goetz FC, LeCompte PM, Williamson JR. Glomerulosclerosis in type 2 (non-insulindependent) diabetes mellitus: relationship to glycaemia in the University Group Diabetes Program (UGDP). Diabetologia 1993;36:1057–1063.

    Article  PubMed  CAS  Google Scholar 

  64. Fioretto P, Stehouwer CD, Mauer M, et al. Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. Diabetologia 1998;41:233–236.

    Article  PubMed  CAS  Google Scholar 

  65. Fioretto P, Mauer M, Brocco E, et al. Patterns of renal injury in NIDDM patients with microalbuminuria. Diabetologia 1996;39:1569–1576.

    Article  PubMed  CAS  Google Scholar 

  66. Østerby R, Gall MA, Schmitz A, Nielsen FS, Nyberg G, Parving HH. Glomerular structure and function in proteinuric type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:1064–1070.

    Article  PubMed  Google Scholar 

  67. Rasch R. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. The mesangial regions. Diabetologia 1979;17:243–248.

    Article  PubMed  CAS  Google Scholar 

  68. Rasch R. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Diabetologia 1979;16:319–324.

    Article  PubMed  CAS  Google Scholar 

  69. Steffes MW, Brown DM, Basgen JM, Mauer SM. Amelioration of mesangial volume and surface alterations following islet transplantation in diabetic rats. Diabetes 1980;29:509–515.

    PubMed  CAS  Google Scholar 

  70. Mauer SM, Goetz FC, McHugh LE, et al. Long-term study of normal kidneys transplanted into patients with type I diabetes. Diabetes 1989;38:516–523.

    Article  PubMed  CAS  Google Scholar 

  71. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003;290:2159–2167.

    Article  Google Scholar 

  72. Bangstad HJ, Østerby R, Dahl-Jorgensen K, Berg KJ, Hartmann A, Hanssen KF. Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia 1994;37:483–490.

    Article  PubMed  CAS  Google Scholar 

  73. Barbosa J, Steffes MW, Sutherland DE, Connett JE, Rao KV, Mauer SM. Effect of glycemic control on early diabetic renal lesions. A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients. JAMA 1994;272:600–606.

    Article  PubMed  CAS  Google Scholar 

  74. Bilous RW, Mauer SM, Sutherland DE, Najarian JS, Goetz FC, Steffes MW. The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 1989;321:80–85.

    Article  PubMed  CAS  Google Scholar 

  75. Bohman SO, Wilczek H, Tyden G, Jaremko G, Lundgren G, Groth CG. Recurrent diabetic nephropathy in renal allografts placed in diabetic patients and protective effect of simultaneous pancreatic transplantation. Transplant Proc 1987;19:2290–2293.

    PubMed  CAS  Google Scholar 

  76. Fioretto P, Mauer SM, Bilous RW, Goetz FC, Sutherland DE, Steffes MW. Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 1993;342:1193–1196.

    Article  PubMed  CAS  Google Scholar 

  77. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998;339:69–75.

    Article  PubMed  CAS  Google Scholar 

  78. Lubec G, Pollak A. Reduced susceptibility of nonenzymatically glucosylated glomerular basement membrane to proteases: is thickening of diabetic glomerular basement membranes due to reduced proteolytic degradation? Ren Physiol 1980;3:4–8.

    PubMed  CAS  Google Scholar 

  79. Roy S, Sala R, Cagliero E, Lorenzi M. Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 1990;87:404–408.

    Article  PubMed  CAS  Google Scholar 

  80. Susztak K, Sharma K, Schiffer M, McCue P, Ciccone E, Bottinger EP Genomic strategies for diabetic nephropathy. J Am Soc Nephrol 2003;14:S271–S278.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN

    Michael Mauer MD

  2. Department of Pediatrics and Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN

    Behzad Najafian MD

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  1. Michael Mauer MD
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  2. Behzad Najafian MD
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Editors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, MI

    Pedro Cortes MD

  2. Department of Internal Medicine M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark

    Carl Erik Mogensen MD

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© 2006 Humana Press Inc., Totowa, NJ

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Mauer, M., Najafian, B. (2006). The Structure of Human Diabetic Nephropathy. In: Cortes, P., Mogensen, C.E. (eds) The Diabetic Kidney. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-59745-153-6_21

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  • DOI: https://doi.org/10.1007/978-1-59745-153-6_21

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-624-5

  • Online ISBN: 978-1-59745-153-6

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