Sepsis
Conditions
Keywords
kidney dysfunction, chronic critical illness, sepsis, Glomerular filtration rate
Brief summary
This study investigates the mechanism by which kidney dysfunction perpetuates inflammation, immunosuppression, and catabolism (PICS) in chronic critical illness. The investigators will test the hypothesis that persistent kidney dysfunction in sepsis associated by chronic critical illness contributes to decreased survival through the development of PICS. In chronic critical illness, the persistence of the inflammatory state may lead to capillary rarefication in the kidney causing accelerated chronic kidney disease. Progression of chronic kidney disease during chronic critical illness can drive PICS. Indeed, many of the features of chronic critical illness are consistent with the protein-energy malnutrition and muscle wasting associated with chronic kidney disease. Thus, the kidney can play a contributory role in chronic critical illness and PICS.
Detailed description
The main goal of this project is to measure kidney filtration function at day 14 or the day of discharge from hospital (whichever occurs first), in order to determine the presence and magnitude of persistent kidney dysfunction after sepsis episode and to longitudinally assess further decline of kidney function at one year follow-up. The measure of the glomerular filtration rate (GRF) in patients with chronic critical illness and controls (sepsis patients discharged from ICU before day 14) will be used to determine to what degree of kidney dysfunction contributes to decreased survival and increase in chronic kidney disease at year one after sepsis onset. GFR assessment will be determined at approximately day 14 or approximately at the day of discharge from the ICU and at the one-year follow-up: 1. Determine GFR by Iohexol clearance and/or 2. Estimated GFR by urea concentration and creatinine clearance 3. Estimated GFR using calculations with serum creatinine
Interventions
DIAGNOSTIC_TESTGFR by Iohexol
Participants may receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected and measured to determine glomerular filtration rate measurements. This test will be repeated in one year.
DIAGNOSTIC_TESTUrine Collection
Both groups of sepsis participants will have urine collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine and urea concentration. This test will be repeated in one year.
DIAGNOSTIC_TESTBlood samples
Both groups of sepsis participants will provide peripheral blood samples to the research staff. The samples will be sent to the laboratory for serum creatinine results. This test will be repeated in one year.
Sponsors
National Institutes of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
University of Florida
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence in the surgery or trauma ICU * Age of ≥18 years * Entrance into our sepsis protocol * Ability to obtain informed consent.
Exclusion criteria
* Expected lifespan of the patient is less than 3 months due to severe pre-existing comorbidities (ex. recurrent, advanced or metastatic cancer) * Severe traumatic brain injury (evidence of neurologic injury on CT scan and a GCS \<8) * Refractory shock (i.e., patients who die within 12 hours) * Uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel) * Patient or patient's family are not committed to aggressive management of the patient's condition and/or the patient has a DNR/DNI on file. * Severe CHF (NY Heart Association Class IV) * Child-Pugh C liver disease or pre-liver transplant. * Known HIV infection with CD4 count \<200 cells/mm3 * Organ transplant recipient on immunosuppressive agents * Known pregnancy and mother's that are breastfeeding * Prisoners * Institutionalized patients * Inability to obtain informed consent. * Chemotherapy or radiotherapy within 30 days prior to sepsis. * End stage renal disease on admission.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline | For Arm 1 baseline is measured GFR at 14 days inhospital with sepsis or sepsis diagnosis. For Arm 2 baseline is measured GFR at discharge date prior to day 14 of hospitalizaton with sepsis or sepsis diagnosis. | The difference between a measured GFR with Iohexol and calculated GFR from creatinine. |
| Delta Curve Between Calculated GFR and GFR Measured by Iohexol at 1 Year Follow-up. | one year follow up for both arms | The difference between a measured GFR with Iohexol and calculated GFR from creatinine This was a one-time determination at 1 year follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated GFR by Serum Creatinine | at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization | The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups. |
| Calculated GFR by Urea Concentration and Creatinine Clearance | at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization | The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine and urea concentration |
Countries
United States
Participant flow
Recruitment details
73 subjects enrolled and 41 completed.
Participants by arm
| Arm | Count |
|---|---|
| In Hospital Group at Day 14 This group of sepsis participants remain hospitalized at day 14. A normal saline dilution of Iohexol 0.5-1 ml will be given IV push. | 41 |
| Discharged From Hospital Prior to Day 14 This group of sepsis participants were discharged prior to day 14 and iohexol determination of GFR was done at time of discharge. A normal saline dilution of Iohexol 0.5-1 ml will be given IV push. | 32 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 21 | 11 |
Baseline characteristics
| Characteristic | In Hospital Group at Day 14 | Discharged From Hospital Prior to Day 14 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 8 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 24 Participants | 55 Participants |
| GFR by iohexol | 91.5 ml/min/1.7m2 STANDARD_DEVIATION 46 | 88.3 ml/min/1.7m2 STANDARD_DEVIATION 39 | 90.3 ml/min/1.7m2 STANDARD_DEVIATION 43 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 8 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 24 Participants | 63 Participants |
| Region of Enrollment United States | 41 Participants | 32 Participants | 73 Participants |
| Sex: Female, Male Female | 21 Participants | 19 Participants | 40 Participants |
| Sex: Female, Male Male | 20 Participants | 13 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 41 | 1 / 32 |
| other Total, other adverse events | 0 / 41 | 0 / 32 |
| serious Total, serious adverse events | 24 / 41 | 15 / 32 |
Outcome results
Primary
Delta Curve Between Calculated GFR and GFR Measured by Iohexol at 1 Year Follow-up.
The difference between a measured GFR with Iohexol and calculated GFR from creatinine This was a one-time determination at 1 year follow-up
Time frame: one year follow up for both arms
Population: The iohexol could not be performed in many individuals because they could not come in to the clinic, would not come into the clinic, or the iohexol injection was contraindicated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhospital Group at Day 14 | Delta Curve Between Calculated GFR and GFR Measured by Iohexol at 1 Year Follow-up. | 71.4 mL/min/1.73m2 | Standard Deviation 38.6 |
| Discharged Prior to Day 14 GFR | Delta Curve Between Calculated GFR and GFR Measured by Iohexol at 1 Year Follow-up. | 58.8 mL/min/1.73m2 | Standard Deviation 40.9 |
Primary
Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline
The difference between a measured GFR with Iohexol and calculated GFR from creatinine.
Time frame: For Arm 1 baseline is measured GFR at 14 days inhospital with sepsis or sepsis diagnosis. For Arm 2 baseline is measured GFR at discharge date prior to day 14 of hospitalizaton with sepsis or sepsis diagnosis.
Population: GFR by iohexol and eGFR by CKD epi at baseline. The iohexol could not be performed on many patients because it was contraindicated
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhospital Group at Day 14 | Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline | Iohexol GFR | 91.5 ml/min/1.73m2 | Standard Deviation 46 |
| Inhospital Group at Day 14 | Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline | eGFR by epi formula | 93.6 ml/min/1.73m2 | Standard Deviation 26.6 |
| Discharged Prior to Day 14 GFR | Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline | Iohexol GFR | 88.3 ml/min/1.73m2 | Standard Deviation 39 |
| Discharged Prior to Day 14 GFR | Delta Curve Between Calculated GFR and GFR Measured by Iohexol at Baseline | eGFR by epi formula | 90.0 ml/min/1.73m2 | Standard Deviation 28.7 |
p-value: <0.05Delta analysis
Secondary
Calculated GFR by Urea Concentration and Creatinine Clearance
The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine and urea concentration
Time frame: at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization
Population: this outcome measure was not performed due to lack of funding prior to initiation of study
Secondary
Calculated GFR by Urea Concentration and Creatinine Clearance
The urine will be collected for at least 4 hours to as long as 24 hours or more. The urine volume determined and a sample sent to the lab for determination of creatinine and urea concentration
Time frame: at one year follow-up
Population: this outcome measure not performed due to funding cuts prior to initiation of study
Secondary
Estimated GFR by Serum Creatinine
The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.
Time frame: at 14 days inpatient hospitalization or at discharge date prior to day 14 inpatient hospitalization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhospital Group at Day 14 | Estimated GFR by Serum Creatinine | 96.14 mL/min/1.73m2 | Standard Deviation 24.77 |
| Discharged Prior to Day 14 GFR | Estimated GFR by Serum Creatinine | 90.0 mL/min/1.73m2 | Standard Deviation 28.7 |
Secondary
Estimated GFR by Serum Creatinine
The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.
Time frame: at 1 year follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhospital Group at Day 14 | Estimated GFR by Serum Creatinine | 83.0 ml/min/1.73m2 | Standard Deviation 25.3 |
| Discharged Prior to Day 14 GFR | Estimated GFR by Serum Creatinine | 83.2 ml/min/1.73m2 | Standard Deviation 29.2 |