Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care Subtitle. Kidney Response to Sepsis Affects Angiogenic Balance and Likelihood of CCI and PICS

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.

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. One and/or all of the three ways for GFR assessment will be used, both at approximately day 14 or approximately at the day of discharge from the ICU and at the one year follow up : Determine clearance of Iohexol from blood after Iohexol injection and/or Determine apperance of Iohexol in urine after Iohexol injection (this would be the same injection as in one, and would not require two injections) and/or A timed urine collection to determine clearance of urea and creatinine and/or Estimated GFR using calculations with serum creatinine and cystatin C, This will provide an opportunity to validate the different measurements.

This group of sepsis participants will remain hospitalized after day 14. A normal saline dilution of Iohexol 0.5-1 ml will be given IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year. In addition to or as an option would be to have a timed urine collection to determine clearance of urea and creatinine can be performed instead of the saline dilution of Iohexol 0.5-1 ml and/or an estimated of GFR using serum creatinine and cystatin C measurement using calculations from blood samples.

This group of sepsis participants will be released from the hospital prior to day 14. A normal saline dilution of Iohexol 0.5-1 ml will be given IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year. In addition to or as an option would be to have a timed urine collection to determine clearance of urea and creatinine can be performed instead of the saline dilution of Iohexol 0.5-1 ml and/or an estimated of GFR using serum creatinine and cystatin C measurement using calculations from blood samples.

Both groups of sepsis participants will receive a normal saline dilution of Iohexol 0.5-1 ml given by IV push. Blood or urine will be collected prior to the injection and at approximately 1, 2, 3, and 4 hours after the injection for glomerular filtration rate measurements. This test will be repeated in one year.

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.

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 and cystatin C results.

The decline in iohexol glomerular filtration rate at day 14 and 1 year follow-up between chronic crucial illness and control groups.

The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.

The correlation between iohexol glomerular filtration rate and estimated glomerular filtration rate using previously validated equation applied to serum creatinine in both groups.

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 urea concentration.

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 urea concentration.

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.

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.

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.

Loftus TJ, Wu Q, Wang Z, Lysak N, Moore FA, Bihorac A, Efron PA, Mohr AM, Brakenridge SC. Delayed interhospital transfer of critically ill patients with surgical sepsis. J Trauma Acute Care Surg. 2020 Jan;88(1):169-175. doi: 10.1097/TA.0000000000002476.