Summary
Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18–29) years, duration of diabetes 12 (8–15) years, mean blood pressure 93 (87–115) mm Hg, glomerular filtration rate 132 (101–209) ml·min−1·1.73 m2−2, albumin excretion rate (mean over 1 year) 32 (15–194) μg/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549–641 nm) vs 305 nm (287–325 nm),p=0.0001; mesangial volume fraction 0.22 (0.21–0.23) vs 0.19 (0.18–0.21),p=0.04, and matrix volume fraction 0.13 (0.12–0.13 vs 0.09 (0.08–0.10),p=0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively. Increment of basement membrane thickness and matrix volume fraction per year were significantly correlated with mean 1-year HbAlc (r=0.55 andr=0.51, respectively). We conclude that microalbuminuria in Type 1 diabetes is associated with increased basement membrane thickness and also mesangial matrix expansion. This increment seems to correlate with glycaemic control.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H (1982) Microalbuminuria is a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet I:1430–1432
Parving HH, Oxenbøll B, Svendsen PAa, Sandahl Christiansen J, Andersen AR (1982) Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol 100: 500–505
Mogensen CE (1987) Microalbuminuria is a predictor of clinical diabetic nephropathy. Kidney Int 31: 673–689
Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32: 219–226
Chavers MB, 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: 966–970
Østerby R, Andersen AR, Gundersen HJG, Jørgensen HE, Mogensen CE, Parving H-H (1984) Quantitative studies of glomerular ultra structure in type 1 diabetics with incipient nephropathy. Diabetic Nephropathy 3: 95–100
Inomata S, Oosawa Y, Itoh M, Masamune O (1987) Analysis of urinary proteins in diabetes mellitus—with reference to the relationship between microalbuminuria and diabetic lesions. J Jpn Diabetes Soc 30: 429–435
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
Østerby R (1992) Glomerular structural changes in type 1 (insulin-dependent) diabetes. Consequences, causes, and prevention. Diabetologia 35: 803–812
Nyberg G, Hedman L, Blohme I, Svalander C (1992) Morphological findings in baseline kidney biopsies from living related donors. Transpl Proc 24: 355–356
Brøchner-Mortensen J (1972) A simple method for the determination of glomerular filtration rate. Scand J Clin Invest 30: 271–274
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 Ultrastruc Res 15: 283–309
Østerby R, Parving H-H, Nyberg G et al. (1988) A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy. Diabetologia 31: 265–270
Østerby R (1973) Morphometric studies of the peripheral glomerular basement membrane in early juvenile diabetes II. Topography of the initial lesions. Diabetologia 9: 108–114
Gundersen HJG, Bendtsen TF, Korbo L et al. (1989) Some new simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96: 379–394
Ellis EN, Mauer SM, Sutherland DER, Steffes MW (1989) Glomerular capillary morphology in normal humans. Lab Invest 60: 231–236
Ellis EN, Steffes MW, Goetz FC, Sutherland DE, Mauer SM (1986) Glomerular filtration surface in type 1 diabetes mellitus. Kidney Int 29: 889–894
Steffes MW, Barbosa J, Basgen JM, Sutherland DER, Najarian JS, Mauer SM (1983) Quantitative glomerular morphology of the normal human kidney. Lab Invest 49: 82–85
Østerby R (1973) A quantitative electron microscopic study of mesangial regions in glomeruli from patients with short term juvenile diabetes mellitus. Lab Invest 29: 99–110
Steffes MW, Sutherland DER, Goetz FC, Rich SS, Mauer SM (1985) Studies of kidney and muscle biopsies in identical twins discordant for type I diabetes mellitus. N Engl J Med 312: 1281–1287
Mauer SM, Goetz FC, McHugh LE et al. (1989) Long-term study of normal kidneys transplanted into patients with type 1 diabetes. Diabetes 38: 516–523
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
Kanwar YS (1984) Biology of disease. Biophysiology of glomerular filtration and proteinuria. Lab Invest 5: 7–21
Sakai T, Kriz W (1987) The structural relationship between mesangial cells and basement membrane of the renal glomerulus. Anat Embryol 176: 373–385
Michael AF, Keane WF, Raij L, Vernier RL, Mauer SM (1980) The glomerular mesangium. Kidney Int 17: 141–154
Mathiesen ER, Hommel E, Giese J, Parving HH (1991) Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. Br Med J 303: 81–87
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bangstad, H.J., Østerby, R., Dahl-Jørgensen, K. et al. Early glomerulopathy is present in young, Type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 36, 523–529 (1993). https://doi.org/10.1007/BF02743268
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02743268