Kidneys can be injured by a number of reasons. In the United States alone, more than 26 million people are estimated to have chronic kidney disease (CKD), 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 CKD severe enough to require renal replacement therapy,” says Dr. Burgess, founder of the EndoTool Glucose Management System.

Irrespective of the cause of CKD or Acute Kidney Disease (AKD), the clearance of insulin from the body is altered when the patient has kidney dysfunction leading to difficult insulin management problems when intravenous insulin is used to control a patient’s elevated blood glucose level.

Insulin Stacks in Patients With Any Decrease in Kidney Filtration

“With kidney dysfunction, insulin tends to stack,” Dr. Burgess notes. “Typically, the half-life of IV administered insulin is five to six minutes. This means that if a change is made in the insulin infusion rate, it takes about roughly 20 minutes for the insulin concentration in body fluids to reach equilibrium at the new infusion rate. By understanding the physiology insulin metabolism, the physician 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 the term applied to the excess insulin activity that occurs following a decrease in the insulin infusion that is strongly related to kidney filtration. Without accounting for EREI, excess insulin occurs and can result in an undesirable decrease in the blood sugar level.

In a healthy patient, 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 rate decrease in patients with kidney dysfunction results in more residual insulin activity than the physician intended.

Because the majority of insulin is excreted by the kidneys, for patients with kidney dysfunction it is critical that adjustments in dosing occur on a timely and accurate basis. One dosing regimen does not fit all patients and must be adjusted for the many clinical parameters that affect insulin metabolism– including kidney filtration.

The Secretion 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 excreted through the kidneys, while the remainder is excreted through other bodily mechanisms.

“It is important to include the method of excretion of the insulin in the patient dosing algorithm,” says Dr. Burgess. “When 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 depressed eGFR to adjust the starting insulin to a lower dose of insulin and increases the dose less rapidly than would occur in patients with normal or high rates of excretion. If someone has kidney dysfunction, less insulin dosing is required compared to the exact same patient with normal kidney filtration.”

Computerized Glucose Management System for Glycemic Control

“With regard to how EndoTool recommends insulin, we are not concerned with the diagnosis of kidney failure,” says Dr. Burgess. “We are focused on the patient’s physiological response to insulin over the recent past few glucose readings and the fact that the filtration of the blood is diminished, which results in a diminished clearance of the insulin.”

EndoTool manages the dosing of insulin and by taking into consideration the clinical parameters that impact insulin effectiveness in the dosing algorithms. The math is adjusted when there is renal dysfunction. 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.

EndoTool is effective in regulating glucose. This is important because infections – especially in a hospital setting – are more likely when glucose levels remain elevated. When a patient is in a hospital with high sugar levels, their immune system is weaker and the risk for other complications like diminished healing and AKD are known to be related to poor glycemic control.

“We have incorporated these complicated EREI calculations in the EndoTool software. The algorithm adjusts the next dose based on this EREI amount resulting in a more appropriate, precise dose,” Dr. Burgess notes. “With this software, data collected in a 13-hospital system with thousands of patient-days of treatment showed clinical and statistically significant reductions in all ranges of hypoglycemia with the same mean glucose in the range of the 130s mg/dL with the time to control remaining unchanged. Without EREI, the reduced hypoglycemic result could only occur by raising the target goal range and resulting higher mean glucose.”