AC/DC Study: Acidification Test in Patients With Chronic Kidney Disease and Healthy Controls (AC/DC)

In this study the effect of an acute acid load on the intrarenal renin angiotensin-system is evaluated in patients with chronic kidney disease and healthy controls

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease stage4
• Intervention / Treatment: Diagnostic test: Urinary acidification test

Detailed Description

Metabolic acidosis is one of the metabolic complications of chronic kidney disease (CKD). Correction of metabolic acidosis in CKD has been shown to prevent further loss of kidney function over time. Currently, a clinical trial (the BIC-study, MEC-2013-332) is conducted in which patients with CKD and metabolic acidosis receive sodium bicarbonate, sodium chloride, or no treatment (time control) to address the hypothesis that the beneficial effects of acidosis correction are mediated through inhibition of the intrarenal renin-angiotensin system (RAS). It is unknown, however, if and how acute changes in acid-base status affect the intrarenal RAS during CKD. In the present study it is hypothesized that an acute acid load increases the activity of the intrarenal RAS, and that this response is exaggerated in patients with CKD compared with healthy controls.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015CN
      • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Patients with CKD:

• Male or female adults (≥18 years)
• Chronic kidney disease stage 4 (eGFR: 15-30 ml/min/1.73 m2, calculated using the CKD-EPI equation)

Healthy controls:

• Healthy male or female adults (≥ 18 years)
• Normal kidney function (eGFR > 90 ml/min/1.73 m2, calculated using the CKD-EPI equation)

Exclusion Criteria:

• CKD patients
• Plasma bicarbonate level < 20.0 mmol/l
• Serum potassium >5.5 mmol/l
• Sodium bicarbonate use in the month preceding the test
• Heart failure (NYHA III or IV)
• Liver cirrhosis (Child Pugh B or C)
• Blood pressure >140/90 mmHg despite the use of 3 different anti-hypertensive drugs
• Kidney transplantation
• Use of calcineurin inhibitors (these immunosuppressive drugs affect acid-base balance)
• Known urea cycle disorder
• Alcoholism or drug use
• Pregnancy
• Current use of antibiotics, NSAIDS or alkalizing drugs (sodium-bicarbonate, citric acid, potassium citrate, acetazolamide)
• Inability to adhere to the study protocol (due to language barrier or intellectual disability)

Healthy controls:

• eGFR < 90 ml/min/1.73 m2 (calculated using the CKD-EPI equation)
• Plasma bicarbonate < 20 mmol/l
• History of, or drugs for, diabetes mellitus
• History of chronic diarrheal disease
• Ileostomy/colostomy
• Known urea cycle disorder
• Alcoholism or drug use
• Pregnancy
• Current use of antibiotics, antihypertensive drugs, NSAIDS or alkalizing drugs (sodium-bicarbonate, citric acid, potassium citrate, acetazolamide)
• Inability to adhere to the study protocol (due to language barrier or intellectual disability)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy controls	Diagnostic test: Urinary acidification test; Urinary acidification by administration of ammonium chloride (100 mg/kg body weight, given orally) during a single-day hospital admission.
Experimental: Patients with chronic kidney disease	Diagnostic test: Urinary acidification test; Urinary acidification by administration of ammonium chloride (100 mg/kg body weight, given orally) during a single-day hospital admission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Urinary renin	up to 6 hours

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2016
• Primary Completion (Actual): November 11, 2018
• Study Completion (Actual): November 11, 2018

Study Registration Dates

• First Submitted: September 20, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): June 20, 2019
• Last Update Submitted That Met QC Criteria: June 19, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: NL57148.078.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No