The assessment of microvascular alterations in renal-pancreas transplant recipients before and after transplantation.

Diabetic nephropathy is currently one of the most serious complications of
longstanding diabetes and has emerged as the most common cause of end-stage
renal disease worldwide. A common feature of early-stage diabetic nephropathy
is the development of albuminuria, which is associated with glomerular
hypertrophy, thickening of glomerular basement membrane, and expansion of
mesangial extracellular matrix. Advanced diabetic nephropathy is characterized
by glomerulosclerosis, vascular and capillary loss, tubulointerstitial
degeneration, and fibrosis that is associated with renal function impairment
and substantial proteinuria. The loss of the microvasculature and endothelial
damage correlates directly with the development of glomerular and
tubulointerstitial scarring.
Considerable laboratory and clinical evidence indicates that endothelial
dysfunction, due to hyperglycaemia induced oxidative stress, is a critical part
of the pathogenesis of microvascular and macrovascular complications in
diabetes. It has been well described that these lesions can be largely
prevented when control of blood sugar can be achieved . Combined kidney and
pancreas transplantation is an effective treatment option for diabetic
nephropathy aiming at insulin independency, long-term normoglycemia and
amelioration of secondary complications related to chronic diabetes. Current
1-year patient and graft survival rates are 90% and 80%, respectively, and
evidence is accumulating that improvements occur in microvascular and
neuropathic complications as well.
To visualize the microvasculature, capillary microscopy was used to demonstrate
that there is microvascluar capillary loss in nail fold, skin and conjunctiva
in essential hypertension, diabetes mellitus, autoimmune rheumatic diseases and
cardio vascular diseases Similarly, it was shown that the labial capillary
density has increased in patients with systemic sclerosis and in smokers and
nail fold capillary density has increased in treated hypertensive patients.
Recently, orthogonal polarization spectral (OPS) imaging, which is a non
invasive technique, has been used to visualize the human circulation in
patients with sepsis and microvascular structure in many animal tissues. We
expect that kidney-pancreas transplantation, which leads to normalization of
glucose levels, will improve the microvascular damage visualized by OPS.

Assessment of the effect of kidney-pancreas transplantation in diabetic
nephropathy patients on microvascular alterations using orthogonal spectral
polarization and correlate this effect with markers for endothelial cell
dysfunction and fibrosis

The study is designed as a prospective observational pilot study. We will
include patients who are on the waiting list for combined kidney-pancreas
transplantation. Per year approximately 15 patients undergo combined
kidney-pancreas transplantation at the LUMC.

Study visits for the patients will be planned at outpatient follow-up controls.
The visits will take 1 hour extra for the OPS measurement.