Intestinal Phosphate Transporter Expression in CKD Patients

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Joint Study on Intestinal Phosphate-TRAnsporter Expression in CKD Patients

Conditions
-----------------
Chronic Kidney Diseases

Intervention / Treatment
-----------------
* Procedure: endoscopy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Upper endoscopy for suspected or known esophageal or gastric pathology Upper endoscopy for screening purposes Written consent to take part in the study Exclusion Criteria: Food intake within 8 hours prior to the endoscopy Major duodenal pathology, in particular duodenitis or duodenal ulcers or tumor Contraindication to duodenal biopsy such as bleeding disorder Treatment with medication known to regulate the expression or activity of intestinal phosphate transporters (e.g. nicotinamide) Kidney transplant patients Alcohol or drug abuse Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study Participation in a parallel clinical trial Subjects who are in any state of dependency to the sponsor or the investigators Employees of the sponsor or the investigators Subjects who have been committed to an institution by legal or regulatory order

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: normal renal function<br>Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level. | Procedure: endoscopy<br>* duodenal biopsies<br>|
| Experimental: CKD stage 3-5 (not on dialysis)<br>Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level. | Procedure: endoscopy<br>* duodenal biopsies<br>|
| Experimental: on dialysis<br>Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level. | Procedure: endoscopy<br>* duodenal biopsies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in the expression level of phosphate transporters in the duodenal of the populations |  | 5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phosphate transporter, CKD, duodenal biopsies