Intestinal Phosphate Transporter Expression in CKD Patients (PeTRA)

RWTH Aachen University

Status: Terminated

Conditions: Chronic Kidney Diseases

Treatments: Procedure: endoscopy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02539680

14-145

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

normal renal function

Experimental group

Description:

Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.

Treatment:

Procedure: endoscopy

CKD stage 3-5 (not on dialysis)

Experimental group

Description:

Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.

Treatment:

Procedure: endoscopy

on dialysis

Experimental group

Description:

Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.

Treatment:

Procedure: endoscopy