Tubular and glomerular damage markers in urine and blood samples in diabetic patients.

Tubular damage markers in urine and blood samples of diabetes mellitus patients

Their is a need for markers that reliably predict the progression of renal
diseases. Macro-albuminuria is at this moment the best predictor for future
decrease in renal function. Nevertheless, a part of patients with
macro-albuminuria does not get decline in renal function, where an other part
of patients with micro-albuminuria does decline in renal function.
A lot is yet unknown about the exact cause of albuminuria. It is not clear
whether albuminuria is caused by tubular or glomerular damage. When the
glomerulus is damaged, large proteins that normally would not be able to reach
the pre-urine, are being filtrered through de glomerular membrane. Certainly
when these large proteins are negatively charged, they shouldn't be filtrated,
because the glomerular membrane is also negatively charged. Presence of for
example IgG4 in urine is indicative of glomerular damage.

Recenty a number of urinary tubular damage markers have been discovered. Some
of these markers are located in the proximal tubulus in the cell cytoplasm,
lysosomes or the brush border. Other markers are located in the cytoplasm of
distal tubulus cells. These markers are in healthy persons not to be found (or
in very small quantities) in urine. Presence of these markers in urine is
indicative of renal tubular damage.

A lot is unclear about in what situation these markers are increased and what
it actually means. This is why in this study patients with diabetes mellitus
with different extent of renal damage are investigated at these biomarkers.

The primary question is whether certain tubular biomarkers are associated with
albuminuria. It is thougt that to much albumin in the pre-urine is toxic to the
proximal tubulus. By measuring different kind of damage markers of different
locations of the nephron, it can be determined to what extent albumin is toxic
to the tubulus.

This is a cross-sectional study, where 100 patients witg diabetes mellitus are
invated to participate. They are invated to visit the out-patient clinic to
hand over some urine and undergo a venapuncture to obtain some serum.
Patients are beforehand selected on the amount of albumin in their urine during
their last visit.
40 patients with normo-albuminuria, 40 patients with micro-albuminuria and 20
patients with macro-albuminuria are to be included.
Patients with micro- and macro-albuminuria are checked (in their medical file)
for retinopathy, to be sure that the albuminuria is the consequence of
diabetes. The samples are collected within 3 months.

In the urine samples 9 biomarkers, albumin and creatinine are measured. In the
blood samples will besides these 9 biomarkers also be measured albumin, BUN,
creatinin, glucose and HbA1c.
The first morning void is requested. For this all participants get by mail a
cup. Also inspection in the medical file is requested.

The researchers like to keep the option open to adress the same patients after
a few years. The urine and blood samples are also kept in the fridge for
maximum one year to measure new biomarkers if available.

The burden to participants is a sole extra visit to the out-patient-clinic. A
venapuncture is done and 20 cc of blood are taken. Risk of the venapuncture is
a local haematoma. Also patients are required to collect their first morning
void.