The Effect of Furosemide on Protein-Bound Uremic Toxin Plasma Levels and Excretion in Patients with Chronic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- UMC Utrecht
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Plasma levels of the PBUT indoxyl sulfate
研究概览
简要总结
The goal of this observational study is to examine the interaction between the diuretic furosemide and certain toxins called protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD). The main question it aims to answer is: what is the effect of furosemide on plasma levels of PBUTs in patients with CKD? Besides, the investigators will also look at the effect of furosemide on the excretion of PBUTs via the urine.
Participants will be included in the study once they will be prescribed furosemide as part of routine patient care. Before they start with the furosemide treatment, patients will undergo the following:
- Blood pressure measurement
- Blood sample withdrawal
- Urine sample collection
- 12-hour urine collection
Then, one to four weeks after starting with furosemide treatment, patients will undergo the following:
- Blood pressure measurement
- Blood sample prior to furosemide intake (Tmin)
- Blood sample withdrawal 90 minutes after furosemide intake (Tmax: time at which the highest furosemide plasma level is expected)
- Urine sample collection 60-120 minutes after furosemide intake
- 12-hour urine collection
The investigators expect furosemide to increase plasma levels of PBUTs by decreasing the renal excretion of the toxins.
详细描述
Protein-bound uremic toxins are known to accumulate in chronic kidney disease (CKD) and are associated with increased morbidity and mortality. It is therefore crucial to maintain the PBUT levels low in this patient group. Furosemide is often prescribed to CKD patients. However, based on preclinical data, furosemide could affect the renal excretion of PBUTs, either by competing for binding to albumin or by competing for the secretory system in the kidney. It is important to examine the effect of furosemide on the excretion and plasma concentration PBUTs as this might have harmful consequences for patients with CKD.
This study aims to examine the effect of furosemide PBUT plasma levels in patients with CKD as well as the renal PBUT excretion. The investigators expect furosemide to increase plasma levels of PBUTs by decreasing the renal excretion of the toxins.
This study is observational and includes invasive measurements; a prospective repeated measures cohort study design will be used in which PBUT plasma concentrations and excretion will be determined before and after the start of furosemide treatment.
The study population consists of patients with CKD stage 3-5 (<60 mL/min/1.73m2 for at least three months) who have an indication for furosemide treatment as part of routine patient care. Participants will receive furosemide in a dosage prescribed by their nephrologist as part of their routine patient care; this treatment is not changed by the participation of patients in the study.
A power analysis for a paired samples T-Test was done using GPower (version 3.1.9.4). Data regarding PBUT plasma levels from the study of Tang et al. in 2021 was used in order to calculate the sample size; PCS plasma levels before (average ± standard deviation: 13,481 ± 12,642 nM) and after (average ± standard deviation: 23,000 ± 24,900 nM) furosemide intake were chosen, since PCS is one of the main PBUTs of interest. This calculation showed a required sample size of 34 (one-tail, power = 80%, α = 0.05, d = 0.44, correlation between samples 0.5 based on assumption).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •An age of 18 years or older
- •An eGFR <60 mL/min/1.73m2 for at least three months (diagnosis of CKD stage 3-5)
- •An indication for the start of treatment with furosemide as part of routine patient care
- •Willingness to participate in the study and a signed informed consent
排除标准
- •Patients who are already on furosemide treatment
- •Patients with a liver disease with hyperbilirubinemia
- •Patients who receive any type of renal replacement therapy (peritoneal dialysis, haemodialysis)
- •Patients with end-stage renal failure without residual diuresis
- •Patients who will start with medication simultaneously with start of furosemide treatment that might interfere with PBUT excretion or PBUT protein binding
- •Patients who are incapacitated
结局指标
主要结局
Plasma levels of the PBUT indoxyl sulfate
时间窗: This will be assessed three times during the study participation period (between 1-4 weeks).
Indoxyl sulfate plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
Plasma levels of the PBUT p-cresyl sulfate
时间窗: This will be assessed three time during the study participation period (between 1-4 weeks).
P-cresyl sulfate plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
Plasma levels of the PBUT indole-3-acetic acid
时间窗: This will be assessed three times during the study participation period (between 1-4 weeks).
Indole-3-acetic acid plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
Plasma levels of the PBUT kynurenic acid
时间窗: This will be assessed three times during the study participation period (between 1-4 weeks).
Kynurenic acid plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
Plasma levels of the PBUT L-kynurenine
时间窗: This will be assessed three times during the study participation period (between 1-4 weeks).
L-kynurenine plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
Plasma levels of the PBUT hippuric acid
时间窗: This will be assessed three times during the study participation period (between 1-4 weeks).
Hippuric acid plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
Plasma levels of the PBUT p-cresyl glucuronide
时间窗: This will be assessed three times during the study participation period (between 1-4 weeks).
P-cresyl glucuronide plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.
次要结局
- Surrogate for PBUT clearance(This will be assessed three times during the study participation period (between 1-4 weeks).)
- Fractional PBUT excretion(This will be assessed three times during the study participation period (between 1-4 weeks).)
- PBUT protein binding(This will be assessed three times during the study participation period (between 1-4 weeks).)
- Ratio of the surrogate PBUT clearance / CKD-EPI creatinine equation(This will be assessed three times during the study participation period (between 1-4 weeks).)
- Ratio of the surrogate PBUT clearance / CKD-EPI cystatin C equation(This will be assessed three times during the study participation period (between 1-4 weeks).)
- Ratio of the surrogate PBUT clearance / CKD-EPI creatinine-cystatin C equation(This will be assessed three times during the study participation period (between 1-4 weeks).)
研究者
Karin G.F. Gerritsen
Associate professor, MD
UMC Utrecht