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Clinical Trial
. 2010 Aug;53(8):1638-46.
doi: 10.1007/s00125-010-1763-3. Epub 2010 May 1.

The relationship of retinal vessel diameter to changes in diabetic nephropathy structural variables in patients with type 1 diabetes

R Klein  1 , M D Knudtson, B E K Klein, B Zinman, R Gardiner, S Suissa, A R Sinaiko, S M Donnelly, P Goodyer, T Strand, M Mauer
Affiliations
Clinical Trial

The relationship of retinal vessel diameter to changes in diabetic nephropathy structural variables in patients with type 1 diabetes

R Klein et al. Diabetologia. 2010 Aug.

Abstract

Aims/hypothesis: We examined whether retinal vessel diameter in persons with type 1 diabetes mellitus is associated with changes in subclinical anatomical and functional indicators of diabetic nephropathy.

Methods: Persons with type 1 diabetes mellitus had gradable fundus photographs and renal biopsy data at baseline and 5-year follow-up (n = 234). Retinal arteriolar and venular diameters were measured at baseline and follow-up. Central retinal arteriole equivalent (CRAE) and central retinal venule equivalent (CRVE) were computed. Baseline and 5-year follow-up renal structural variables were assessed by masked electron microscopic morphometric analyses from percutaneous renal biopsy specimens. Variables assessed included: mesangial fractional volume, glomerular basement membrane width, mesangial matrix fractional volume and glomerular basement membrane width composite glomerulopathy index.

Results: While controlling for other covariates, baseline CRAE was positively associated with change in the glomerulopathy index over the 5-year period. Change in CRAE was inversely related to a change in mesangial matrix fractional volume and abnormal mesangial matrix fractional volume, while change in CRVE was directly related to change in the volume fraction of cortex that was interstitium [Vv((Int/cortex))] over the 5-year period. Baseline CRAE or CRVE or changes in these diameters were not related to changes in other anatomical or functional renal endpoints.

Conclusions/interpretation: Independently of other factors, baseline CRAE correlated with changes in glomerulopathy index, a composite measure of extracellular matrix accumulation in the mesangium and glomerular basement membrane. A narrowing of the CRAE was related to mesangial matrix accumulation. Changes in CRVE were related to changes in Vv((Int/cortex),) a measure of interstitial expansion in persons with type 1 diabetes mellitus.

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Conflict of interest statement

Duality of Interest:

Dr. Zinman, lecture fees, consulting fees, and research grants from Merck; and Dr. Klein reports being an advisory board member for AstraZeneca (through the DIRECT study), Pfizer, Lilly, and Novartis.

No other dualities of interest relevant to this article were reported.

Figures

Figure 1
Figure 1
Three photomicrographs from three separate baseline biopsies of glomerular tissues for light microscopy that were fixed in Zenker’s solution and embedded in paraffin and stained with periodic acid Schiff (PAS): a. glomerulus in which the mesangium appears normal; b. shows a glomerulus with mild mesangial expansion with increased PAS positive matrix material between the capillary loops and branching from the base of the glomerulus (hilus) to the periphery (black arrows); c. shows a glomerulus with moderate mesangial expansion (black arrows).
Figure 1
Figure 1
Three photomicrographs from three separate baseline biopsies of glomerular tissues for light microscopy that were fixed in Zenker’s solution and embedded in paraffin and stained with periodic acid Schiff (PAS): a. glomerulus in which the mesangium appears normal; b. shows a glomerulus with mild mesangial expansion with increased PAS positive matrix material between the capillary loops and branching from the base of the glomerulus (hilus) to the periphery (black arrows); c. shows a glomerulus with moderate mesangial expansion (black arrows).
Figure 1
Figure 1
Three photomicrographs from three separate baseline biopsies of glomerular tissues for light microscopy that were fixed in Zenker’s solution and embedded in paraffin and stained with periodic acid Schiff (PAS): a. glomerulus in which the mesangium appears normal; b. shows a glomerulus with mild mesangial expansion with increased PAS positive matrix material between the capillary loops and branching from the base of the glomerulus (hilus) to the periphery (black arrows); c. shows a glomerulus with moderate mesangial expansion (black arrows).
Figure 2
Figure 2
a. Retinal image of left eye showing narrow retinal arterioles (white arrows, CRAE 99:m, mean and standard deviation in the RASS 159±13:m) and normal retinal venules (CRVE 222:m, mean and standard deviation in the RASS 228±22:m) and b. Retinal image of a left eye showing wide retinal venules (black arrows, CRAE 177 :m, CRVE 304 :m) and normal retinal arterioles.
Figure 2
Figure 2
a. Retinal image of left eye showing narrow retinal arterioles (white arrows, CRAE 99:m, mean and standard deviation in the RASS 159±13:m) and normal retinal venules (CRVE 222:m, mean and standard deviation in the RASS 228±22:m) and b. Retinal image of a left eye showing wide retinal venules (black arrows, CRAE 177 :m, CRVE 304 :m) and normal retinal arterioles.
See this image and copyright information in PMC

References

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