Hyperfiltration hypothesis in children with a solitary functioning kidney: an assessment of glomerular function by single shot inulin clearance - THE KIMONO-STUDY

The hyperfiltration hypothesis is designed by Brenner and co-workers around
1980 and states that a reduction in renal mass and therefore a lower number of
nephrons triggers a pathological vicious cycle. In the long run, this cycle
may result in hyperfiltration injury clinically coming to expression as
hypertension, proteinuria and chronic kidney disease. However due to
methodological limitations a different approach is required to study the
phenomenom of hyperfiltration in humans.
One such an approach is to study children with a solitary functioning kidney.
Not only these children have a reduction in renal mass, but also this condition
is present from childhood onwards. This implies a long time exposure to the
vicious cycle of hyperfiltration in these children. Several studies report
about hyperfiltration in man with a solitary kidney from childhood onwards,
with inconclusive results. However, only two studies are known that used an
inuline clearance to evaluate glomerular filtration rate.
Two reports with a retrospective design from our research group have shown that
more than half of all children with a solitary functioning kidney have
hypertension, (micro)albuminuria or chronic kidney disease. Furthermore a
developed prediction model showed that glomerular filtration begins to decline
progressively in these children from 10 yrs of age onwards. These results can
be interpreted as possible hyperfiltration injury, implying that these children
are at risk for chronic renal disease in later life. However our retrospective
studies, as many other reports, used the Schwartz-formula to estimate
glomerular function in these children. The KIMONO-STUDY is designed to assess
exact glomerular function by inulin clearance, which is known as the gold
standard technique for glomerular filtration rate.

This study evaluates glomerular function in children with a solitary
functioning kidney. Furthermore anthropometric data is gathered about waist-hip
ratio and subscapular skinfold thickness. Anthropometric characteristics can be
both a cause as an effect of impaired glomerular function in hyperfiltration
hypothesis. To evaluate early renal dysfunction, recently discovered markers
are assessed in blood and urine.
The KIMONO-STUDY serves the purpose to study the hyperfiltration hypothesis in
humans and evaluates the results from our earlier retrospective studies. The
main aim of this study is to answer the question whether or not children with a
solitary kidney are truly at risk for developing chronic renal disease in later
life.

The KIMONO-STUDY contains the following tests:

1. Inulin clearance by single shot injection method
2. Anthropometric data about waist-hip ratio and subscapular skinfold thickness.
3. Extended blood- and urine evaluation on parameters for renal dysfunction:
plasma-renin activity, ACE-polymorphisms, aldosterone, cystatin C, HbA1C, Von
Willebrand-factor, cholesterol and homocystein.

The inulin clearance requires an intravenous line. To reduce the burden of
multiple injections to a minimum, all other actions will be done from this
intravenous line. A bolus of inulin is given at the start of the test and blood
is drawn from the intravenous line at five marked times.

Patients will get an intravenous line. Inulin will be given by single shot
method to prevent the child from multiple injections to draw blood. Inulin is
an inert sugarpolymer, which can cause only slight hypersensitivity reactions;
there are very little other complications. Hypersensitivity is prevented by
admission of a antihistaminic agent (clemastine) before the start of the test.
At the Pediatric Renal Center the single shot inulin clearance is performed
routinely by trained nurses for clinical purposes, who have experience with
children in a medical setting. The subscapular skinfold thickness is measured
by the scientifically known method.

The KIMONO-STUDY is especially designed to reduce the burden and risks for the
participating children to a minimum. In respect to the standard hospital
appointment, the study requires an extension at the following points:

• The children have to to stay all morning.

• Blood is drawn from an intravenous line (from which inulin will be
adminstrated) in stead of the standard intravenous punction. One more tube of
blood will be drawn.

• The inulin clearance requires an intravenous line

• Waist-hip ratio and scapular skinfold thickness will be measured.