Kidneys can be injured by a number of reasons. In the United States, more than 10% of adults are estimated to have kidney disease, although most don’t know it because early signs are often missed.
While diabetes is the leading cause of kidney failure that does not mean that everyone with diabetes will develop kidney disease severe enough to require renal replacement therapy.
Irrespective of the cause of Chronic Kidney Disease (CKD) or Acute Kidney Disease (AKD), the clearance of insulin from the body is altered when a patient has kidney dysfunction, which can lead to complications when insulin is used to control a patient’s elevated blood glucose level. Because of this altered metabolism and clearance of insulin, dosing algorithms need to include an estimate of kidney function to reach the goal of controlling elevated glucose levels effectively without the risk of hypoglycemia.
Insulin Stacks in Patients with Any Decrease in Kidney Filtration
With kidney dysfunction, insulin tends to ‘stack’, i.e. accumulate. Normally, the half-life of IV administered insulin is four to five minutes. This means that if a change is made in the insulin infusion rate, it can take up to 20 minutes for the insulin concentration in body fluids to reach equilibrium with the new infusion rate. By understanding the physiology of insulin metabolism, physicians can better adjust the next action required to treat an elevated glucose and avoid hypoglycemia.
A major factor that affects intravenous insulin dosing is Estimated Residual Extracellular Insulin (EREI) – a new term in medicine. EREI is defined as the excess insulin activity that occurs following a decrease in the insulin infusion and is strongly related to kidney filtration. Without accounting for EREI, excess insulin activity occurs and can result in an undesirable decrease in a future blood sugar level.
In a healthy patient with normal kidney filtration, the insulin concentration equilibrium is established quickly following changes in the insulin infusion rate. However, in a patient with advanced kidney dysfunction, it might take an hour or more for this to happen. Thus an insulin infusion rate decrease in patients with kidney dysfunction results in a larger EREI and more residual insulin activity resulting in a lower than expect future glucose level unless that EREI is used as a dose attenuation.
The majority of administered insulin is cleared by the kidneys, thus for patients with kidney dysfunction it is critical that adjustments in dosing occur on a timely and accurate basis. A dosing regimen must be adjusted for the many clinical parameters that affect insulin metabolism– including kidney filtration.
The Clearance of Insulin is Critical to Dosing
Insulin is a hormone which regulates the glucose level in the body’s fluids that surround the body’s cells. Insulin promotes glucose entry into cells where glucose is utilized as a fuel or stored for later use. During this process, 60 percent or more of the administered insulin is cleared by the kidneys, while the remainder is removed through other bodily mechanisms.
It is important to include the estimated clearance of the insulin in the patient dosing algorithm. For example, Monarch Medical Technologies EndoTool® calculates the estimated kidney filtration, abbreviated eGFR (estimated Glomerular Filtration Rate), from the patient’s weight, age, gender, and serum creatinine. The software uses the eGFR to adjust the starting insulin to a lower dose and increases the dose less rapidly than would occur in patients with normal clearance. If someone has kidney dysfunction, less insulin is required compared to the exact same patient with normal kidney filtration. Additionally, the eGFR strongly influences the calculation of EREI dose adjustment following a decrease in the insulin infusion.
Computerized Glucose Management System for Glycemic Control
EndoTool manages the dosing of insulin by taking into consideration all of the clinical parameters that impact insulin activity. These clinical parameters include age, weight, serum creatinine, height, gender, and glucose responses to the previous four doses of insulin, changes in carbohydrate administration, and clinical changes which impact insulin needs like steroids or sudden loss of a carbohydrate source. We have incorporated complex EREI calculations in the FDA cleared EndoTool software. The algorithm adjusts the next dose based on this EREI amount resulting in a more appropriate, precise dose.
When EndoTool recommends insulin, it is not concerned with the diagnosis of kidney failure. EndoTool is focused on the patient’s responses to insulin over the recent glucose readings, the patient’s physiology, and the pharma-kinetics of insulin based on the patient’s eGFR. This combination results in the best possible subsequent insulin infusion dose recommendation.
About the Author: Founding the technology in 2003, Dr. Patrick Burgess remains an active contributor to the development and advancement of EndoTool. Beginning his healthcare career at Carolinas Medical Center, Dr. Burgess founded EndoTool with the goal to improve glucose management for all patients in hospitalized care. After receiving his Bachelors degree from Ohio State University and PhD from Princeton University in Chemical Engineering, Dr. Burgess then earned his Doctorate of Medicine from the University of Miami.
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