Chronic Kidney Diseases Clinical Trial
Official title:
Joint Study on Intestinal Phosphate-TRAnsporter Expression in CKD Patients
The aim of the present study is to study the expression of the various phosphate transporters in patients with normal or moderately impaired renal function or in patients on dialysis. In particular, the investigators want to clarify whether NaPi-IIb expression level decreases in CKD patients, which would render it a potentially inadequate pharmaceutical target in these patients.
Elevated serum phosphate is a potent predictor of death and cardiovascular events in patients
with renal disease. Control of serum-phosphate to desired target ranges is insufficient in
many patients with advanced chronic kidney disease (CKD), in particular dialysis patients
despite dietary restrictions, optimized dialysis regimens and the use of phosphate binders.
One reason why for example, phosphate binders are insufficient to control phosphate uptake in
the intestine or why they even loose efficacy, is a compensatory upregulation of phosphate
transporters in the gut wall.
Thus, several companies attempt to specifically interfere with intestinal phosphate
transporters, in particular the NaPi-IIb transporter. However, recent Chugai data obtained in
experimental CKD challenge the assumption that NaPi-IIb is the major therapeutic target in
this situation. In addition to NaPi-IIb, PiT-1 and -2 also might contribute to phosphate
transport.
In normal human intestinal mucosa the most prominent expression of all 3 transporters is
observed in the duodenum, i.e. an area, which can easily be assessed by endoscopy.
During endoscopy a biopsy for research purposes will be obtained. Chugai will evaluate the
expression level of NaPi-IIb, PiT-1, PiT-2, and villin1 at the mRNA and, if possible, the
protein level.
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