Abstract
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) micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
Adolescent
Adult
Albuminuria
Basement Membrane/pathology
Biomarkers/urine
Biopsy, Needle/methods
Blood Glucose/metabolism
Blood Pressure
Child
Diabetes Mellitus, Type 1/pathology,physiopathology,urine
Diabetic Nephropathies/pathology,physiopathology,urine
Extracellular Matrix/pathology
Female
Glomerular Filtration Rate
Glomerular Mesangium/pathology
Glycated Hemoglobin A/analysis
Humans
Kidney Glomerulus/pathology
Male
Prospective Studies
Chemicals
Biomarkers
Blood Glucose
Glycated Hemoglobin A
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bangstad H J
Aker Diabetes Research Center, Aker University Hospital, Oslo, Norway.
Osterby R
Dahl-Jørgensen K
Berg K J
Hartmann A
Nyberg G
Frahm Bjørn S
Hanssen K F
References (24)
24 references, click to expand
-
Albuminuria reflects widespread vascular damage. The Steno hypothesis.
Diabetologia. 1989 Apr;32(4):219-26
PMID: 2668076
-
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. 1966 Jun;15(3):283-309
PMID: 5328615
-
Glomerular filtration surface in type I diabetes mellitus.
Kidney Int. 1986 Apr;29(4):889-94
PMID: 3712971
-
Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria.
Kidney Int. 1992 Apr;41(4):741-8
PMID: 1513096
-
Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus.
N Engl J Med. 1985 May 16;312(20):1282-7
PMID: 4039409
-
A simple method for the determination of glomerular filtration rate.
Scand J Clin Lab Invest. 1972 Nov;30(3):271-4
PMID: 4629674
-
Microalbuminuria as a predictor of clinical diabetic nephropathy.
Kidney Int. 1987 Feb;31(2):673-89
PMID: 3550239
-
Morphologic findings in baseline kidney biopsies from living related donors.
Transplant Proc. 1992 Feb;24(1):355-6
PMID: 1539315
-
Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion.
Acta Endocrinol (Copenh). 1982 Aug;100(4):550-5
PMID: 6812342
-
Long-term study of normal kidneys transplanted into patients with type I diabetes.
Diabetes. 1989 Apr;38(4):516-23
PMID: 2647558
-
Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.
BMJ. 1991 Jul 13;303(6794):81-7
PMID: 1860008
-
Some new, simple and efficient stereological methods and their use in pathological research and diagnosis.
APMIS. 1988 May;96(5):379-94
PMID: 3288247
-
A quantitative electron microscopic study of mesangial regions in glomeruli from patients with short term juvenile diabetes mellitus.
Lab Invest. 1973 Jul;29(1):99-110
PMID: 4728359
-
A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.
Diabetologia. 1988 May;31(5):265-70
PMID: 3396784
-
Glomerular capillary morphology in normal humans.
Lab Invest. 1989 Feb;60(2):231-6
PMID: 2915517
-
The glomerular mesangium.
Kidney Int. 1980 Feb;17(2):141-54
PMID: 6991772
-
Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria.
N Engl J Med. 1989 Apr 13;320(15):966-70
PMID: 2784542
-
The structural relationship between mesangial cells and basement membrane of the renal glomerulus.
Anat Embryol (Berl). 1987;176(3):373-86
PMID: 3631536
-
Quantitative glomerular morphology of the normal human kidney.
Lab Invest. 1983 Jul;49(1):82-6
PMID: 6865334
-
Biophysiology of glomerular filtration and proteinuria.
Lab Invest. 1984 Jul;51(1):7-21
PMID: 6376945
-
Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus.
Lancet. 1982 Jun 26;1(8287):1430-2
PMID: 6123720
-
Morphometric studies of the peripheral glomerular basement membrane. II. Topography of the initial lesions.
Diabetologia. 1973 Apr;9(2):108-14
PMID: 4716114
-
Glomerular structural changes in type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention.
Diabetologia. 1992 Sep;35(9):803-12
PMID: 1397774
-
Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy.
Diabetologia. 1991 Sep;34(9):668-74
PMID: 1955100