Will insulin needs increase in a critically ill patient with pre-existing diabetes or stress-induced hyperglycemia if Continuous Renal Replacement Therapy (CRRT) is not given?

Will Insulin Needs Increase Without CRRT?

Yes, insulin needs may paradoxically increase if CRRT is not provided, primarily due to worsening uremia-induced insulin resistance and accumulation of uremic toxins, though the relationship is complex and bidirectional. 1, 2

The Metabolic Impact of Acute Kidney Injury on Insulin Requirements

Insulin Resistance in AKI

• AKI creates profound insulin resistance through peripheral mechanisms and activation of hepatic gluconeogenesis that cannot be suppressed by exogenous nutrient supply, unlike in stable chronic kidney disease 1
• Hyperglycemia in AKI is caused by both peripheral insulin resistance and increased hepatic glucose production, which may worsen as renal function deteriorates 1, 2
• Insulin resistance is highly prevalent among AKI patients and is independently associated with increased mortality risk 2

Uremic Toxin Accumulation Without CRRT

• Without CRRT, accumulation of gut microbiota-derived uremic toxins (particularly phenyl sulfate) increases insulin resistance in adipocytes while paradoxically enhancing pancreatic insulin secretion 3
• This creates a vicious cycle where more insulin is secreted but tissues become increasingly resistant to its effects, potentially requiring higher exogenous insulin doses to achieve glycemic control 3

How CRRT Affects Insulin Metabolism

Energy Substrate Provision by CRRT

• CRRT solutions can provide substantial energy substrates that may reduce apparent insulin needs: citrate (3 kcal/g), glucose (3.4 kcal/g), and lactate (3.62 kcal/g) 1
• Energy gain from CRRT can be substantial, ranging from 115-1300 kcal/day depending on the type and rate of fluids used, with high lactate replacement fluids and ACD-A anticoagulation providing the most 1
• This exogenous glucose and energy provision may mask underlying insulin resistance and reduce the apparent need for insulin therapy 1

Clearance of Uremic Toxins

• CRRT removes uremic toxins that contribute to insulin resistance, potentially improving insulin sensitivity compared to no renal replacement therapy 3
• However, CRRT also causes significant amino acid losses (10-15 g/day) and protein losses (5-10 g/day), which can affect overall metabolic balance 1

Clinical Implications for Insulin Management

Without CRRT

• Expect worsening insulin resistance as uremic toxins accumulate, potentially requiring higher insulin doses to maintain target glucose levels of 140-180 mg/dL 1, 2
• However, simultaneously be vigilant for hypoglycemia risk, as impaired renal insulin clearance prolongs insulin half-life and reduces renal gluconeogenesis 2, 4
• This creates a dangerous paradox: patients may need more insulin due to resistance but are at higher risk of severe hypoglycemia due to impaired clearance 2, 4

With CRRT

• Insulin requirements may appear lower due to glucose provision from dialysate (up to 300 kcal/day with glucose-containing solutions) and improved clearance of insulin-resistance-inducing uremic toxins 1, 3
• Monitor for hypoglycemia if using glucose-free replacement fluids, as this removes an energy source 5
• Factor in citrate-based anticoagulation energy provision (potentially 100-300 kcal/day) when calculating total insulin needs 1

Practical Management Algorithm

Target Glucose Levels

• Maintain serum glucose between 140-180 mg/dL in all hospitalized AKI patients, regardless of CRRT status (Grade A recommendation) 1, 2
• Never pursue tight glucose control (80-110 mg/dL) due to dramatically increased hypoglycemia risk 1, 2

Insulin Dose Adjustments

• If initiating CRRT: Consider reducing insulin doses by 25% initially due to improved uremic toxin clearance and potential glucose provision from dialysate 4
• If CRRT is discontinued or not initiated: Anticipate potentially higher insulin requirements due to worsening insulin resistance, but simultaneously reduce doses by 25% to account for impaired insulin clearance 4
• This seemingly contradictory guidance reflects the complex bidirectional effects of AKI on glucose metabolism 1, 2

Monitoring Strategy

• Check glucose every 6-12 hours in critically ill AKI patients, with more frequent monitoring during CRRT initiation or discontinuation 2
• Monitor for both hyperglycemia (>180 mg/dL) and hypoglycemia (<100 mg/dL), as both risks are elevated 2, 4

Critical Pitfalls to Avoid

• Do not assume insulin needs will simply decrease without CRRT—the relationship is complex, with competing forces of increased resistance (favoring higher doses) and decreased clearance (favoring lower doses) 1, 2, 3
• Avoid oral sulfonylureas (like gliclazide) entirely in AKI, as they carry a 5-fold increased risk of severe hypoglycemia regardless of CRRT status 4, 6
• Account for hidden glucose sources from CRRT solutions when calculating insulin requirements—failure to do so may lead to overtreatment and hypoglycemia 1, 5
• Recognize that glycemic variability increases dramatically in AKI patients, requiring frequent reassessment rather than fixed insulin protocols 2