Does insulin cause kidney failure?

Does Insulin Cause Kidney Failure?

No, insulin does not cause kidney failure; in fact, insulin metabolism is altered by kidney disease, and patients with advanced chronic kidney disease (CKD) often require reduced insulin doses due to decreased insulin clearance.

Relationship Between Insulin and Kidney Function

Normal Insulin Metabolism and the Kidneys

• The kidneys play a significant role in insulin metabolism, clearing approximately 30-80% of systemic insulin 1
• Under normal conditions, the kidney also contributes to glucose homeostasis, accounting for up to 20% of glucose uptake during fed states and producing up to 20-25% of blood glucose via gluconeogenesis during fasting 1
• Only about 1% of insulin is excreted unchanged in the urine 1

How Kidney Disease Affects Insulin Metabolism

• In chronic kidney disease, insulin clearance is reduced, leading to prolonged half-life of insulin in the circulation 1
• Advanced CKD is associated with impaired insulin degradation due to uremia 1
• Patients with end-stage kidney disease (ESKD) are prone to hypoglycemia due to decreased insulin clearance 1
• An interesting phenomenon called "burn-out diabetes" occurs in approximately 15-30% of patients with advanced CKD (GFR < 20 mL/min/1.73 m²), where they require less or no medications for glycemic control as kidney disease progresses 1

Insulin Use in Patients with Kidney Disease

Insulin Dosing Considerations in CKD

• Patients with substantial decreases in eGFR (CKD stages 4 and 5) have increased risk of hypoglycemia due to decreased insulin clearance and impaired renal gluconeogenesis 1
• Patients with type 1 diabetes receiving insulin who have significant creatinine elevations have a 5-fold increase in the frequency of severe hypoglycemia 1
• Progressive kidney failure necessitates dose reductions of insulin to avoid hypoglycemia 1

Mechanisms of Hypoglycemia Risk in CKD

• Multiple factors increase hypoglycemia risk in advanced CKD 1:
  • Failure of kidney gluconeogenesis
  • Impaired insulin clearance by the kidney
  • Defective insulin degradation due to uremia
  • Increased erythrocyte glucose uptake during hemodialysis
  • Impaired counterregulatory hormone responses
  • Nutritional deprivation

Diabetes and Kidney Disease Relationship

Diabetes as a Cause of Kidney Disease

• Diabetes is the leading cause of chronic kidney disease and is responsible for approximately half of all cases of end-stage kidney disease worldwide 1
• Uncontrolled diabetes is associated with long-term complications, including chronic kidney disease 1
• The chronic hyperglycemia of diabetes is associated with long-term damage to various organs, especially the kidneys 1

Glycemic Control in CKD

• Based on observational data, an HbA1c range of 7% to 8% appears to be the most favorable for patients with diabetes and advanced CKD 1
• Preferred medications for glucose management in individuals with CKD are GLP-1 receptor agonists and SGLT2 inhibitors, which can be initiated if eGFR is above 20 mL/min/1.73 m² 1
• SGLT2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin) have shown beneficial effects on slowing progression of CKD and cardiovascular outcomes in people with CKD and type 2 diabetes 1

Common Pitfalls in Managing Diabetes with CKD

Monitoring Challenges

• Assessment of glycemia by HbA1c is hampered by various CKD-associated conditions that can bias the measure either to the low or high range 1
• Despite its limitations, HbA1c remains the preferred glycemic biomarker in CKD patients 1
• Continuous glucose monitoring shows promise for more precise monitoring and treatment adjustments in patients with diabetes and advanced CKD 1

Medication Adjustments

• Metformin should not be started in patients whose eGFR is <45 mL/min/1.73 m² and should be stopped once eGFR is <30 mL/min/1.73 m² 1
• First-generation sulfonylureas should be avoided altogether in patients with CKD due to increased risk of hypoglycemia 1
• Among second-generation sulfonylureas, glipizide is preferred as it does not have active metabolites and does not increase the risk of hypoglycemia in CKD patients 1

In conclusion, insulin itself does not cause kidney failure. Rather, diabetes—which often requires insulin treatment—is a major cause of kidney disease. As kidney function declines, insulin metabolism is altered, requiring careful dose adjustments to prevent hypoglycemia.