Furosemide Stress Test as a Predictor of Tubular Function in Chronic Kidney Disease

Overview

In kidney diseases, tubule-interstitium has become much more relevant, as formerly only the glomerulus was considered to have the main importance. Kidney's tubular atrophy and interstitital fibrosis is now recognized as long term prognostic value. We aim to evaluate the function of the kidney's tubule-interstitium through furosemide excretion after intravenous administration of this drug, and correlate the rate of excretion of furosemide with interstitial fibrosis findings in scheduled kidney biopsy for patients with chronic kidney disease.

Full Title of Study: “Furosemide Stress Test as a Predictor of Tubular Atrophy and Interstitial Fibrosis in Patients With Chronic Kidney Disease”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Diagnostic
  • Masking: None (Open Label)
• Study Primary Completion Date: April 2016

Detailed Description

All patients scheduled for kidney biopsy will be invited to participate in a standard isovolemic furosemide stress test before the biopsy procedure. The latter will consist in 1.5 miligrams per kilogram of weight of intravenous furosemide administration, with urinary output follow up and measurement. The urinary output will be replaced intravenously with normal saline to avoid dehydration and/or hypotension. A standard 5ml sample of blood will be taken before the test and aliquots of urine before and after furosemide administration will be frozen. After completion of the formely mentioned test, patients will proceed to their scheduled kidney biopsy along with interventions considered appropiate by their attending physician. Kidney biopsy sample will be examined by histopathology service and the degree of interstitial fibrosis will be described. The degree of fibrosis will be correlated with the degree furosemide excretion and urinary output.

Interventions

• Drug: Furosemide
  • Evaluate urinary excretion rate fo furosemide

Arms, Groups and Cohorts

• Experimental: Furosemide Stress Test
  • Furosemide stress test will be perform to patients scheduled for kidney bipsy. The test consist in 1.5 miligrams per kilogram of weight of intravenous furosemide administration, along with urinary output follow up and measurement for 6 hours. The urinary output will be replaced intravenously with normal saline to avoid dehydration and/or hypotension.

Clinical Trial Outcome Measures

Primary Measures

• Urinary Output
  • Time Frame: 6 hours
  • Cuantify urinary output after furosemide administration

Secondary Measures

• Furosemide excretion rate
  • Time Frame: 6hrs
  • Cuantify furosemide excretion in urine
• Interstitial Fibrosis
  • Time Frame: 3 days
  • Measure interstitial fibrosis in kidney biopsy

Participating in This Clinical Trial

Inclusion Criteria

• Accept to participate (informed consent) – Legal age or older – An estimated glomerular filtration rate greater than 15ml/min/1.73m2, calculated by CKD-EPI. Exclusion Criteria:

• Known Alergic reaction to furosemide – Contraindication to kidney biopsy – Patient already in renal replacement therapy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Instituto Nacional de Cardiologia Ignacio Chavez
• Provider of Information About this Clinical Study
  • Principal Investigator: Magdalena Madero, Chief of Nephrology Department, MD – Instituto Nacional de Cardiologia Ignacio Chavez
• Overall Official(s)
  • Magdalena Madero, MD, Principal Investigator, Chief of the Nephrology Department
• Overall Contact(s)
  • Magdalena Madero, MD, +55-5573-2911, madero.magdalena@gmail.com

References

Boor P, Ostendorf T, Floege J. Renal fibrosis: novel insights into mechanisms and therapeutic targets. Nat Rev Nephrol. 2010 Nov;6(11):643-56. doi: 10.1038/nrneph.2010.120. Epub 2010 Sep 14.

Burns WC, Kantharidis P, Thomas MC. The role of tubular epithelial-mesenchymal transition in progressive kidney disease. Cells Tissues Organs. 2007;185(1-3):222-31. doi: 10.1159/000101323.

Farris AB, Chan S, Climenhaga J, Adam B, Bellamy CO, Seron D, Colvin RB, Reeve J, Mengel M. Banff fibrosis study: multicenter visual assessment and computerized analysis of interstitial fibrosis in kidney biopsies. Am J Transplant. 2014 Apr;14(4):897-907. doi: 10.1111/ajt.12641. Epub 2014 Feb 20.

Farris AB, Colvin RB. Renal interstitial fibrosis: mechanisms and evaluation. Curr Opin Nephrol Hypertens. 2012 May;21(3):289-300. doi: 10.1097/MNH.0b013e3283521cfa.

van der Voort PH, Boerma EC, Pickkers P. The furosemide stress test to predict renal function after continuous renal replacement therapy. Crit Care. 2014 May 14;18(3):429. doi: 10.1186/cc13871. No abstract available.

Citations Reporting on Results

Chawla LS, Davison DL, Brasha-Mitchell E, Koyner JL, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Kimmel PL, Seneff MG. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013 Sep 20;17(5):R207. doi: 10.1186/cc13015.