Summary
Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p<0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p<0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p<0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r=0.65, p<0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients.
Article PDF
Similar content being viewed by others
Abbreviations
- IDDM:
-
Insulin-dependent diabetes mellitus
- GFR:
-
glomerular filtration rate
- AER:
-
albumin excretion rate
- HbA1c :
-
glycated haemoglobin
- ND:
-
non-diabetic control subjects
- DNA :
-
diabetic patients with normal albumin excretion rate
- DMI :
-
diabetic patients with microalbuminuria
- DP :
-
diabetic patients with proteinuria
- CV:
-
coefficient of variation (SD/mean)
- FPWPBM :
-
width of foot processes on peripheral basement membrane
- FPWMES :
-
width of foot processes on glomerular mesangium
- ANOVA:
-
analysis of variance
- PBM:
-
peripheral basement membrane
References
Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet I: 1430–1432
Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 89–93
Mogensen CE (1990) Prediction of clinical diabetic nephropathy in IDDM patients. Alternatives to microalbuminuria? Diabetes 39: 761–767
Mauer SM, Steffes MW, Ellis EN, Sutherland DER, Brown DM, Goetz FC (1984) Structural-functional relationships in diabetic nephropathy. J Clin Invest 74: 1143–1155
Østerby R, Gundersen HJG, Nyberg G, Aurell M (1987) Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli. Diabetes 36: 612–619
Østerby R, Parving HH, Hommel E, JØrgensen HE, LØkkegaard H (1990) Glomerular structure and function in diabetic nephropathy. Early to advanced stages. Diabetes 39: 1057–1063
Walker JD, Close CF, Jones SL et al. (1992) Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria. Kidney Int 41: 741–748
Bangstad HJ, Østerby R, Dahl-JØrgensen K et al. (1993) Early glomerulopathy is present in young, type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 36: 523–529
Bangstad HJ, Østerby R, Dahl-JØrgensen K, Berg KJ, Hartmann A, Hanssen KF (1994) Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia 37: 483–490
Bohman SO, Jaremko G, Bohlin AB, Berg U (1984) Foot process fusion and glomerular filtration rate in minimal change nephrotic syndrome. Kidney Int 25: 696–700
Seefeldt T, Bohman SO, Gundersen HJG, Maunsbach AB, Petersen VP, Olsen S (1981) Quantitative relationship between glomerular foot process width and proteinuria in glomerulonephritis. Lab Invest 44: 541–546
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: 736–741
Østerby R, Andersen AR, Gundersen HJ, JØrgensen HE, Mogensen CE, Parving HH (1984) Quantitative studies of glomerular ultrastructure in type I diabetics with incipient nephropathy. Diabetic Nephropathy 3: 95–100
Farquhar MG (1975) The primary glomerular filtration barrier-basement membrane or epithelial slits? Kidney Int 8: 197–211
Daniels BS, Deen WM, Mayer G, Meyer T, Hostetter TH (1993) Glomerular permeability barrier in the rat. Functional assessment by in vitro methods. J Clin Invest 92: 929–936
Drumond MC, Deen WM (1992) Structural determinants of glomerular capillary hydraulic permeability. J Am Soc Nephrol 3: 560 (Abstract)
Mogensen CE (1988) Definition of diabetic renal disease in insulin-dependent diabetes mellitus based on renal function tests. In: Mogensen CE (ed) The kidney and hypertension in diabetes mellitus. Martinus Nijhoff Publishing, Boston Dordrecht Lancaster, pp 7–16
Maunsbach AB (1966) The influence of different fixatives and fixation methods on the ultrastructure of rat kidney proximal tubule cells. II. Effects of varying osmolality, ionic strength, buffer system and fixative concentration of glutaraldehyde solutions. J Ultrastruct Res 15: 283–309
Østerby R, Gundersen HJG (1978) Sampling problems in the kidney. In: Miles RE, Serra J (eds) Lecture notes in biomathematics, vol 23. Springer, Berlin Heidelberg New York, pp 185–191
Weibel ER (1980) Stereological methods. Practical methods for biological morphometry, vol 1. Academic Press, New York
Microalbuminuria Collaborative Study Group (1993) Risk factors for development of microalbuminuria in insulin dependent diabetic patients: a cohort study. BMJ 306: 1235–1239
Gundersen HJG, Seefeldt T, Østerby R (1980) Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation. Cell Tissue Res 205: 147–155
Steffes MW, Leffert JD, Basgen JM, Brown DM, Mauer SM (1980) Epithelial cell foot process width in intact and uninephrectomized diabetic and nondiabetic rats. Lab Invest 43: 225–230
Østerby R, Nyberg G, Hedman L, Karlberg I, Persson H, Svalander C (1991) Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy. Diabetologia 34: 668–674
Furukawa T, Ohno S, Oguchi H, Hora K, Tokunaga S, Furuta S (1991) Morphometric study of glomerular slit diaphragms fixed by rapid-freezing and freeze-substitution. Kidney Int 40: 621–624
Mogensen CE, Østerby R, Gundersen HJ (1979) Early functional and morphologic vascular renal consequences of the diabetic state. Diabetologia 17: 71–76
Shea SM, Morrison AB (1975) A Stereological study of the glomerular filtre in the rat. Morphometry of the slit diaphragm and basement membrane. J Cell Biol 67: 436–443
Schneeberger EE, Levey RH, McCluskey RT, Karnowsky MJ (1975) The isoporous substructure of the human glomerular slit diaphragm. Kidney Int 8: 48–52
Ohno S, Hora K, Furukawa T, Oguchi H (1992) Ultrastructural study of the glomerular slit diaphragm in fresh unfixed kidneys by a quick-freezing method. Virchows Arch B Cell Pathol 61: 351–358
Drenckhahn D, Franke RP (1988) Ultrastructural organization of contractile and cytoskeletal proteins in glomerular podocytes of chicken, rat, and man. Lab Invest 59: 673–682
Tisher CC, Brenner BM (1989) Structure and function of the renal glomerulus. In: Tisher CC, Brenner BM (eds) Renal pathology with clinical and functional correlations. Publishing House, Philadelphia London Mexico New York, pp 92–110
Heptinstall RH (1983) Pathology of the kidney. Vol. II. The nephrotic syndrome, filtration of macromolecules. Little, Brown, Boston Toronto, pp 638–650
Dekan G, Gabel C, Farquhar MG (1991) Sulphate contributes to the negative charge of podocalyxin, the major sialoglycoprotein of the glomerular filtration slits. Proc Natl Acad Sci USA 88: 5398–5402
Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32: 219–226
Deckert T, Kofoed-Enevoldsen A, Vidal P, NØrgaard K, Andreasen HB, Feldt-Rasmussen B (1993) Size- and charge selectivity of glomerular filtration in type 1 (insulin-dependent) diabetic patients with and without albuminuria. Diabetologia 36: 244–251
Vernier RL, Steffes MW, Sisson-Ross S, Mauer SM (1992) Heparan sulphate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. Kidney Int 41: 1070–1080
Shiromura H, Spiro RG (1987) Studies on macromolecular components of human glomerular basement membrane and alterations in diabetes. Decreased levels of heparan sulphate proteoglycan and laminin. Diabetes 36: 374–381
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
BjØrn, S.F., Bangstad, H.J., Hanssen, K.F. et al. Glomerular epithelial foot processes and filtration slits in IDDM patients. Diabetologia 38, 1197–1204 (1995). https://doi.org/10.1007/BF00422369
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00422369