The Effective of Potassium Sodium Hydrogen Citrate in Treating Uric Acid Stones Using Gut Microbiota and Metabolomics.

The Clinical Study Utilizing Gut Microbiota and Metabolomics to Investigate the Efficacy of Potassium Sodium Hydrogen Citrate Therapy in the Treatment of Uric Acid Kidney Stones.

The goal of this observational study is to investigate the alterations in gut microbiota and metabolites among patients with uric acid stones following the administration of potassium sodium hydrogen citrate. The main question it aims to predict the potential metabolic mechanism and therapeutic target of potassium sodium hydrogen citrate in treating uric acid stones through analysis of gut microbiota and metabolomics. The participants were required to undergo a 3-month drug intervention, providing blood, urine, and stool samples before and after treatment. No additional interventions were implemented for the subjects.

Study Overview

• Status: Recruiting
• Conditions: Uric Acid Stones
• Intervention / Treatment: Drug: Potassium sodium hydrogen citrate

Detailed Description

The objectives of this study were to investigate the association between the presence of bacterial genera and short-chain fatty acids (SCFAs) in stool, as well as biochemical elements in blood and urine, among patients with uric acid nephrolithiasis. The sensitivity difference of potassium sodium hydrogen citrate in treating uric acid kidney stones was examined through gut microbiota analysis and metabolomics to predict potential metabolic mechanisms and sensitive targets for treatment. Blood biochemistry, 24-hour urine composition analysis, and other indicators were collected from the subjects. Fecal samples were obtained for 16S ribosomal RNA sequencing to analyze the characteristics of gut microbiota in relation to blood and urine biochemical metabolism indicators. Subjects received treatment with potassium sodium hydrogen citrate granules for a duration of 3 months. Blood and urine biochemical indexes, fecal samples, 16S ribosomal RNA sequencing data, and short-chain fatty acid levels in fecal samples were collected before and after treatment. The care of the enrolled patients will not be subject to any intervention.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Ping Zhu, MD; Phone Number: +86 15150374982; Email: zhuping5262@163.com

Study Locations

• China
  • Jiangsu
    • Changshu City, Jiangsu, China, 215500
      • Recruiting
      • Changshu Hospital Affiliated to Soochow University
      • Contact: Ping Zhu, MD; Phone Number: +86 15150374982; Email: zhuping5262@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All stone patients were diagnosed using urologic ultrasonography, kidney-ureter-bladder (KUB) X-ray, or abdominal computed tomography (CT). Stone samples were obtained through ureteroscopic lithotripsy (URSL), percutaneous nephrolithotomy (PCNL), or extracorporeal shock wave lithotripsy (ESWL). Stones were analyzed using an automated infrared spectroscopy system, LIIR-20 (Lanmode Scientific Instrument Co., Ltd., Tianjin, China), and the main components were determined based on the most abundant substances listed in the report, which were classified as pure or mixed uric acid stones (anhydrous uric acid content >50%).

Description

Inclusion Criteria:

All stone patients were diagnosed using urologic ultrasonography, kidney-ureter-bladder (KUB) X-ray, or abdominal computed tomography (CT). Stone samples were obtained through ureteroscopic lithotripsy (URSL), percutaneous nephrolithotomy (PCNL), or extracorporeal shock wave lithotripsy (ESWL). Stones were analyzed using an automated infrared spectroscopy system, LIIR-20 (Lanmode Scientific Instrument Co., Ltd., Tianjin, China), and the main components were determined based on the most abundant substances listed in the report, which were classified as pure or mixed uric acid stones (anhydrous uric acid content >50%).

Exclusion Criteria:

Patients with malignancy, chronic liver insufficiency, a history of statin use, and thyroid or parathyroid disease were excluded from the study. Similarly, individuals with a history of urolithiasis or dyslipidemia as well as those who had used statins were excluded from the control group. Participants were also excluded if they had taken antibiotics or immune suppressants within one month prior to fecal sampling, or had a history of chronic diarrhea or constipation, chronic enteritis, irritable bowel syndrome, gastrointestinal tumors or intestinal surgery.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Drug treatment group of uric acid stones（DT group）; Potassium sodium hydrogen citrate granules (MADAUS GMBH, Germany, 2.5g/packet) were administered to patients with residual stones (>5 mm in diameter) after surgery or difficult-to-remove stones in the infrarenal calyces for a three-month intervention period. The medication was taken as follows: one packet after breakfast, one packet after lunch, and two packets after dinner. Participants were instructed to abstain from alcohol consumption, smoking, and the use of any probiotics or medications that lower uric acid levels during the therapeutic period.They were also instructed to monitor preprandial urine pH levels to maintain an effective range of 6.2-6.8.

Drug: Potassium sodium hydrogen citrate; Medication: Potassium sodium hydrogen citrate granules (MADAUS GMBH, Germany, 2.5g/package). Method: Preprandial urine pH was monitored to maintain an effective range of 6.2 to 6.8. One package should be taken after breakfast, one after lunch, and two after dinner. If the pH falls below 6.2, a half-package dose should be added; if it exceeds 6.8, a half-package dose should be reduced accordingly. Oral medication will be administered for a duration of three months. Medication requirements: Abstain from alcohol and smoking during treatment period and avoid using any probiotics or drugs that lower uric acid levels.; Other Names: PSHC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum diameter of stone	The patients underwent pre- and post-drug intervention abdominal CT examinations, enabling determination of the stone's maximum diameter（mm） through analysis of CT images.	From enrollment to the end of treatment at 3 months
Gut microbiota analysis	The fecal samples were collected pre- and post-intervention for the analysis of gut microbiota.	From enrollment to the end of treatment at 3 months
Short chain fatty acid contents	The collection of fecal samples was conducted both pre- and post-intervention in order to assess the levels of short-chain fatty acids.	From enrollment to the end of treatment at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum triglycerides	The peripheral venous blood was collected pre- and post-intervention, and the serum triglyceride level (mmol/L) was measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum cholesterol	The peripheral venous blood was collected pre- and post-intervention, and the serum cholesterol level (mmol/L) was measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum high density lipoprotein cholesterol	The peripheral venous blood was collected pre- and post-intervention, and the serum high density lipoprotein cholesterol level (mmol/L) was measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum low density lipoprotein cholesterol	The peripheral venous blood was collected pre- and post-intervention, and the serum low density lipoprotein cholesterol level (mmol/L) was measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum creatinine	The peripheral venous blood samples were collected from the subjects both before and after the intervention, and the serum creatinine levels（μmol/L） were measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum uric acid	The peripheral venous blood samples were collected from the subjects both before and after the intervention, and the serum uric acid levels（μmol/L） were measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum potassium	The peripheral venous blood samples were collected from the subjects both before and after the intervention, and the serum potassium levels（mmol/L） were measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Serum magnesium	The peripheral venous blood samples were collected from the subjects both before and after the intervention, and the serum magnesium levels（mmol/L） were measured by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months
Urine pH	The urine pH value was assessed by collecting mid-stream urine samples before and after the intervention by automatic biochemical analyzer.	From enrollment to the end of treatment at 3 months

Collaborators and Investigators

• Sponsor: Cheng Cao
• Investigators: Principal Investigator: Cheng Cao, MD, The Changshu Hospital Affiliated to Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): March 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 26, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: gut microbiota; 16S rRNA; short chain fatty acid; renal uric acid stone; potassium sodium hydrogen citrate
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Urolithiasis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephrolithiasis
• Other Study ID Numbers: ChangshuAHSU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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