Global heterogeneity of glomerular volume distribution in early diabetic nephropathy.
BACKGROUND
Morphologic characteristics in early stage of nephropathy of noninsulin-dependent diabetes mellitus (NIDDM) have not been determined despite the fact thatdiagnosis in this stage of the disease is important for the prognosis. We hypothesized that heterogeneity in glomerular volume-distribution may be a sensitive index of early stage of diabetic nephropathy in NIDDM.


METHODS
In spontaneous diabetic rats [Otsuka Long-Evans Tokushima Fatty (OLETF) rat (N= 5)] of 27 to 28 weeks, an experimental model of early diabetic nephropathy in human NIDDDM and age-matched control rats [Long Evans Tokushima Lean (LETO) rat (N= 5)], we completely filled the kidney with contrast medium. Glomeruli were visualized as three-dimensional images using x-ray micro-computed tomography (micro-CT). Glomerular volumes (N= 400 in each kidney) were directly measured and evaluated as absolute volume and normalized values to kidney weight and body weight. Scattering of glomerular volume-distribution was evaluated as coefficient variation (CV) (SD/mean).


RESULTS
The CV was significantly larger in OLETF rat (0.195) comparing to LETO rat (0.146, P < 0.01). This difference was even consistent under the normalization to kidney weight and body weight. Absolute glomerular volume was larger in OLETF rat compared to LETO rat (P < 0.005); however, when glomerular volume was normalized, this variable was comparable between two groups.


CONCLUSIONS
We visualized three-dimensional glomerular images in the early stages of diabetic nephropathy using micro-CT and quantified the heterogeneity in glomerular volume distribution throughout the cortex by direct measurement of the individual. We propose that heterogeneity in glomerular volume distribution is a sensitive parameter to ascertain early diabetic nephropathy in NIDDM.
Toyota
Eiji
E
Department of Medical Engineering, Department of Anatomy, Kawasaki Medical School, Kurashiki, Japan. etoyota@med.kawasaki-m.ac.jp
Ogasawara
Yasuo
Y
Fujimoto
Katsukui
K
Kajita
Tatsuya
T
Shigeto
Fumiyuki
F
Asano
Takahisa
T
Watanabe
Nozomi
N
Kajiya
Fumihiko
F
D000818:Animals; D003928:Diabetic Nephropathies / Q000000981:diagnostic imaging* / Q000473:pathology; D042241:Early Diagnosis; D021621:Imaging, Three-Dimensional; D007678:Kidney Glomerulus / Q000000981:diagnostic imaging* / Q000473:pathology; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods* / Q000592:standards