The Relation Between the Renal Resistive Index and Glomerular Hyper Filtration

Sepsis Clinical Trial

Official title:

Relation Between Renal Resistive Index, Glomerular Hyperfiltration and Hyperdynamic Circulation in Critically Ill Patients With Trauma or Sepsis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02560402
• Other study ID #: METC-2014.563
• Status: Completed
• Phase: N/A
• First received: September 22, 2015
• Last updated: May 9, 2016
• Start date: August 2015
• Est. completion date: February 2016

Study information

• Verified date: May 2016
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial Summary

Aim of the present study is to determine whether

1. RRI can predict glomerular hyperfiltration;

2. glomerular hyperfiltration is associated with low renal resistive index;

3. glomerular hyperfiltration/low RRI are associated with accelerated flow in the sublingual microcirculation;

4. glomerular hyperfiltration/low RRI are related to fluid status as quantified with bioimpedance analysis.

Description:

Apart from acute kiddney injury (AKI), critically ill patients with sepsis or trauma can also exhibit glomerular hyperfiltration (2-4). Glomerular hyperfiltration is not easily recognized, because the decrease in serum creatinine is a late manifestation and generally interpreted as normal renal function. Glomerular hyperfiltration may have clinical consequences, because it leads to augmented renal clearance of water soluble drugs. This is especially relevant for antibiotics, because augmented clearance can lead to underdosing and therapeutic failure (5-9). Patients with glomerular hyperfiltration are generally younger patients with less severe disease (3) and often exhibit a hyperdynamic circulation. The mechanism of glomerular hyperfiltration is poorly understood. High catecholamine release with increased renal blood flow could play a role. Direct measurement of renal blood flow is not available in daily clinical practice.

Nowadays, the investigators can measure Renal Resistive Index (RRI) using renal Doppler ultrasound. The RRI is a sonographic index assessing resistance of the intrarenal arcuate or interlobar arteries and is normally used to assess renal arterial disease. The method has now become available at the bedside in the intensive care unit. RRI is calculated as: (peak systolic velocity - end diastolic velocity)/peak systolic velocity. Normal values are between 0.60 and 0.70. A mean value of 0.72 has been found in critically ill patients admitted to the intensive care unit (personal data).

The investigators hypothesize that high glomerular filtration rate as measured with creatinine clearance is associated with a low renal resistive index and accelerated microvascular blood flow.

To prove or reject this hypothesis, the following study measurements will be performed in critically ill patients with sepsis or trauma:

1. Renal ultrasound to measure renal resistive index (RRI) After visualising the kidney in ultrasound mode, checking for (chronic) renal damage, an arcuate or interlobar artery will be localized and three successive Doppler measurements at different positions in the kidney (high, middle and low) will be performed. This will be repeated 3 times in each kidney. So a total number of 9 RRI values will be obtained in each kidney.

2. Sublingual microcirculation using Sidestream Dark Field imaging (SDF) After removal of secretions with a gauze, the device will be applied below the tongue and three sequences of about 20 seconds from adjacent areas will be recorded and stored. The investigators will measure the perfused vessel density (PVD), the proportion of perfused vessels (PPV) and the microvascular flow index (MFI) for small vessels. Each image will be divided into four quadrants, and the predominant type of flow (0 = absent, 1 = intermittent, 2 = sluggish, 3 = normal, 4 = high) will be evaluated in each quadrant. The mean of the four quadrants will be used for analysis.

3. To assess fluid status, Bioelectrical impedance analysis (BIA) will be performedusing the Akern BIA 101 device.

BIA measures Resistance (R) and Reactance (Xc) reflecting extracellulair (R) and cellular (Xc) resistance to an alternating current of 400 μA with afrequency of 50 kHz. In previous studies the investigators found that (changes in) R are highely correlation with (changes in) fluid status.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Admission to the intensive or medium care unit

• Sepsis or trauma

• Age > 18 years

Exclusion Criteria:

Patients

• with chronic renal insufficiency (eGFR < 30 ml)

• with renal transplant kidney

• on chronic dialysis

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Sepsis
• Trauma

Locations

Country	Name	City	State
Netherlands	VU Medical Center	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (9)

Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012 Aug 25;380(9843):756-66. doi: 10.1016/S0140-6736(11)61454-2. Epub 2012 May 21. Review. — View Citation

Claus BO, Hoste EA, Colpaert K, Robays H, Decruyenaere J, De Waele JJ. Augmented renal clearance is a common finding with worse clinical outcome in critically ill patients receiving antimicrobial therapy. J Crit Care. 2013 Oct;28(5):695-700. doi: 10.1016/j.jcrc.2013.03.003. Epub 2013 May 14. — View Citation

Cook AM, Arora S, Davis J, Pittman T. Augmented renal clearance of vancomycin and levetiracetam in a traumatic brain injury patient. Neurocrit Care. 2013 Oct;19(2):210-4. doi: 10.1007/s12028-013-9837-y. — View Citation

Fuster-Lluch O, Gerónimo-Pardo M, Peyró-García R, Lizán-García M. Glomerular hyperfiltration and albuminuria in critically ill patients. Anaesth Intensive Care. 2008 Sep;36(5):674-80. — View Citation

Minkute R, Briedis V, Steponaviciute R, Vitkauskiene A, Maciulaitis R. Augmented renal clearance--an evolving risk factor to consider during the treatment with vancomycin. J Clin Pharm Ther. 2013 Dec;38(6):462-7. doi: 10.1111/jcpt.12088. Epub 2013 Aug 8. — View Citation

Udy A, Boots R, Senthuran S, Stuart J, Deans R, Lassig-Smith M, Lipman J. Augmented creatinine clearance in traumatic brain injury. Anesth Analg. 2010 Dec;111(6):1505-10. doi: 10.1213/ANE.0b013e3181f7107d. Epub 2010 Nov 3. — View Citation

Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi: 10.2165/11318140-000000000-00000. Review. — View Citation

Udy AA, Roberts JA, Shorr AF, Boots RJ, Lipman J. Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients. Crit Care. 2013 Feb 28;17(1):R35. doi: 10.1186/cc12544. — View Citation

Udy AA, Varghese JM, Altukroni M, Briscoe S, McWhinney BC, Ungerer JP, Lipman J, Roberts JA. Subtherapeutic initial ß-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2012 Jul;142(1):30-9. doi: 10.1378/chest.11-1671. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal Resistive Index (RRI)		1 week	No
Secondary	4-h Creatinine clearance		1 week	No
Secondary	Microvascular flow index of the sublingual microcirculation		1 week	No
Secondary	Resistance, as measured with bioimpedance as a marker of fluid status.		1 week	No