Redistribution of renal flow and tubular inflammation

Renal artery stenosis is a common cause of secondary hypertension, which is
associated with progressive renal decline and an increased cardiovascular risk.
The critical element promoting hypertension in this disorder is a reduced
arterial perfusion to the post-stenotic kidney, which initiates the
Renin-Angiotensine-Aldosteron system and increases efferent arteriolar
resistance. Although, an causal association between decreased renal blood flow
and renal functional decay is clinically well-accepted, recent research
indicated that alteration of intrarenal hemodynamics and ensuing renal damage
are not explained by a globally decreased renal blood flow per se.
Hypothesis: Alteration in the intrarenal flow-distribution may precede overt
renal deterioration and results in a decreased peritubular capillary flow,
decreased tubular oxygen supply and tubulo-interstitial inflammation.

The main goal of the study is evaluation of the effects from renal artery
stenosis on intrarenal flow-distribution and tubular function. Assumed and
measured effects are alterations of medullary flow, inflammatory markers and
overall tubular function.

Longitudinal study design with 9 months follow-up after PTRA, which compares
the intrarenal effects of clinical treatment in patients with hemodynamically
significant unilateral artery stenosis.

Participating patients won*t obtain direct benefits, but results from the study
could influence future clinical treatment decisions. Participation requires
three site visits (total time spent in research facility: 12-15 hours), all
three visits are preceded by a pharmacological wash-out (first visit: 3 weeks;
second visit 9 days; third visit 9 months after PTRA: 3 weeks) and
salt-restriction during seven days (before all three visits; total duration of
salt restriction 21 days in 9 months). During each visit a maximum of 60mL of
blood will be drawn (sampling from venous line, 6 samples of 10mL) for
measurement of renal inulin/PAH clearance and characterisation of biochemical
risk factors. Moreover, an intrarenal flow distribution will be assessed using
a dynamic MRI. Although MRI is a safe and non-invasive technique, the
intravenous administering of gadolinium contrast has been associated with a
small risk of contrast induced nephrotoxicity (< 1%).