How to manage ketoacidosis in a patient with Chronic Kidney Disease (CKD) on Hemodialysis (HD)?

Management of Ketoacidosis in CKD Patients on Hemodialysis

Hemodialysis is the definitive treatment for ketoacidosis in anuric or oliguric CKD patients on chronic HD, as it simultaneously corrects severe acidemia, removes ketones, manages volume status, and addresses electrolyte abnormalities that cannot be adequately managed with standard DKA protocols alone. 1, 2

Critical Differences from Standard DKA Management

Patients with ESRD on hemodialysis present unique challenges that fundamentally alter DKA management:

• Absence of osmotic diuresis and glycosuria means these patients are partially protected from the severe dehydration typical of DKA, though substantial volume loss can still occur from decreased oral intake, tachypnea, and fever 1
• Higher admission glucose levels (mean 804 mg/dL vs 472 mg/dL in preserved renal function) but paradoxically lower HbA1c (9.6% vs 12.0%) are characteristic 2
• Dramatically increased risk of hypoglycemia (34% vs 14% for glucose <70 mg/dL) and volume overload (28% vs 3%) compared to patients with normal renal function 2
• Three-fold higher odds of hypoglycemia (OR 3.3) and four-fold higher odds of volume overload (OR 4.22) after adjusting for covariates 2

Initial Assessment and Stabilization

Diagnostic Workup

• Confirm DKA with standard criteria: glucose >250 mg/dL, pH <7.3, bicarbonate <15 mEq/L, and ketonemia/ketonuria 3
• Obtain plasma glucose, BUN/creatinine, serum ketones, electrolytes with anion gap, arterial blood gases, CBC, ECG, and cultures if infection suspected 3
• Critical: Check potassium immediately - if K+ <3.3 mEq/L, delay insulin therapy and aggressively replace potassium first to prevent life-threatening arrhythmias 3

Identify Precipitating Factors

• Search for infection, myocardial infarction, stroke, pancreatitis, trauma, or insulin omission 3
• Discontinue SGLT2 inhibitors immediately if the patient is taking them, as they promote ketogenesis and cause euglycemic DKA 4
• Discontinue metformin due to lactic acidosis risk in the setting of renal impairment and tissue hypoperfusion 4

Fluid Management: Modified Approach for HD Patients

Fluid resuscitation must be dramatically more conservative than standard DKA protocols due to anuria/oliguria and high risk of volume overload:

• Start with isotonic saline (0.9% NaCl) at 5-10 mL/kg/hour (approximately 500-750 mL in the first hour) rather than the standard 15-20 mL/kg/hour used in patients with normal renal function 3, 2
• Monitor closely for signs of volume overload: jugular venous distension, pulmonary edema, peripheral edema, and respiratory distress 2
• Total fluid administration should be limited to 1-2 liters over 24 hours unless the patient has documented significant volume depletion from vomiting or decreased intake 1, 2
• When glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45% saline at reduced rates to prevent hypoglycemia while continuing insulin 3

Insulin Therapy: Lower Doses Required

Use reduced insulin doses compared to standard protocols due to impaired insulin clearance and increased hypoglycemia risk:

• Start continuous IV regular insulin at 0.05-0.075 units/kg/hour (half the standard dose) for critically ill patients 3, 5, 2
• Target a slower glucose decline of 25-50 mg/dL per hour rather than the standard 50-75 mg/dL per hour to minimize hypoglycemia risk 3, 2
• If glucose does not decline adequately in the first hour and hydration is acceptable, increase insulin cautiously by 50% increments rather than doubling 3
• Continue insulin infusion until ketoacidosis resolves (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 3
• Monitor glucose hourly with point-of-care testing to detect hypoglycemia early 2

Hemodialysis: The Definitive Intervention

Urgent hemodialysis should be initiated early in the treatment course rather than waiting for medical management to fail:

• Indications for urgent HD in DKA with ESRD: severe acidemia (pH <7.1), refractory hyperkalemia (K+ >6.5 mEq/L), volume overload, or failure to improve with initial conservative management 6, 1
• Use bicarbonate-based dialysate with concentration of 35-40 mEq/L to correct acidosis while avoiding overly rapid pH correction 7, 8
• Continuous renal replacement therapy (CRRT) or prolonged intermittent dialysis may be preferred over standard intermittent HD in hemodynamically unstable patients to avoid rapid fluid and electrolyte shifts 7, 5
• Dialysis simultaneously removes ketones, corrects acidemia, manages hyperkalemia, and removes excess fluid - addressing multiple problems that cannot be adequately managed medically in anuric patients 6, 1

Electrolyte Management: Critical Monitoring

Potassium Replacement

• Total body potassium depletion averages 3-5 mEq/kg despite potentially normal or elevated initial serum levels 3
• If K+ <3.3 mEq/L: Hold insulin, give 20-40 mEq/hour IV potassium until K+ ≥3.3 mEq/L 3
• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (2/3 KCl, 1/3 KPO₄) once urine output confirmed 3
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor every 2 hours, as levels will drop rapidly with insulin 3
• In anuric HD patients, potassium repletion must be more cautious - consider nephrology consultation and use dialysis to manage severe hyperkalemia 3

Bicarbonate Administration

• Bicarbonate is NOT recommended for pH >6.9-7.0 as it does not improve outcomes and may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 3, 6, 5
• For pH <6.9, consider 50-100 mEq sodium bicarbonate in 200 mL sterile water over 1 hour, but hemodialysis is preferred in ESRD patients 3, 6

Monitoring Protocol

• Check electrolytes, glucose, BUN, creatinine, and venous pH every 2 hours during active treatment 3
• Monitor for hypoglycemia aggressively - check glucose hourly given the 3-fold increased risk 2
• Assess volume status continuously: lung sounds, jugular venous pressure, peripheral edema, oxygen saturation 2
• Target glucose 150-200 mg/dL until DKA resolution parameters met 3
• Measure β-hydroxybutyrate directly if available, as it is more accurate than nitroprusside methods 3

Transition to Subcutaneous Insulin

Once DKA resolves (glucose <200 mg/dL, bicarbonate ≥18 mEq/L, pH >7.3, anion gap ≤12 mEq/L):

• Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin to prevent rebound ketoacidosis and hyperglycemia 3, 5
• Consider adding low-dose basal insulin analog during IV insulin infusion to prevent rebound hyperglycemia 3
• Start with reduced total daily insulin dose (approximately 20% less) than pre-admission regimen to account for impaired clearance 4
• Initiate multiple-dose regimen with combination of rapid-acting and long-acting insulin once patient can eat 3

Critical Pitfalls to Avoid

• Excessive fluid administration leading to volume overload, pulmonary edema, and need for mechanical ventilation (24% risk in ESRD patients) 2
• Standard insulin dosing without adjustment for impaired clearance, causing severe hypoglycemia 2
• Premature discontinuation of IV insulin before complete ketoacidosis resolution 3
• Failure to initiate hemodialysis early when medical management is inadequate 6, 1
• Inadequate potassium monitoring in the setting of anuria and dialysis dependence 3
• Stopping IV insulin without prior basal insulin administration, causing rebound hyperglycemia and ketoacidosis 3

Expected Outcomes and Disposition

• Longer hospital stays (median 7 days vs 3 days) compared to DKA patients with normal renal function 2
• Higher rates of mechanical ventilation (24% vs 3%) due to volume overload and respiratory compromise 2
• Maintain serum bicarbonate ≥22 mEq/L long-term through dialysate bicarbonate adjustment (40-42 mEq/L) 7, 8
• All patients require ICU-level care with nephrology consultation 6
• Ensure appropriate insulin regimen at discharge with attention to medication access and affordability 3