What could explain a 3 L/24 h urine output in a patient who has already been evaluated and ruled out for diabetes insipidus?

Differential Diagnosis of 3 L/24h Urine Output Without Diabetes Insipidus

Your 3 L/24h urine output most likely represents polyuria from primary polydipsia (excessive fluid intake), medication effects, or early chronic kidney disease—not diabetes insipidus, which has been appropriately ruled out by your normal urine concentrating ability.

Why Diabetes Insipidus Is Excluded

Your evaluation has definitively ruled out diabetes insipidus through multiple converging lines of evidence:

• Urine osmolality >300 mOsm/kg rules out diabetes insipidus, and a value of 498 mOsm/kg indicates completely normal kidney concentrating ability 1
• Normal serum sodium (143 mEq/L) combined with appropriately concentrated urine is inconsistent with diabetes insipidus, which requires the pathognomonic triad of polyuria, inappropriately dilute urine (<200 mOsm/kg), and high-normal or elevated serum sodium 1, 2
• Normal copeptin level (4.6 pmol/L) falls well below the 21.4 pmol/L threshold that would suggest nephrogenic diabetes insipidus, confirming your ADH system functions normally 1

Most Likely Alternative Causes

Primary Polydipsia (Excessive Fluid Intake)

This is the most common explanation when diabetes insipidus is excluded:

• Many patients develop habitual excessive water drinking based on health beliefs, misguided hydration advice, or anxiety about dehydration 3, 4
• The European Society of Endocrinology notes that urine osmolality in the 200-300 mOsm/kg range (and even higher) can occur with primary polydipsia without representing true diabetes insipidus 1
• Your kidneys are appropriately responding to high fluid intake by producing dilute urine to maintain fluid balance, but your concentrating ability remains intact when tested 4

Critical distinction: In primary polydipsia, you can concentrate urine normally when you reduce fluid intake, whereas true diabetes insipidus patients cannot concentrate urine regardless of hydration status 2, 4.

Medication-Induced Polyuria

Review your current medications for contributors:

• Diuretics (including thiazides, loop diuretics, or combination products) are the most obvious cause 3
• Losartan and other ARBs do not cause diabetes insipidus but may occasionally affect electrolyte balance 5
• Proton-pump inhibitors (pantoprazole), statins (atorvastatin), DOACs (apixaban), and levothyroxine do not affect ADH pathways or cause polyuria 5

Early Chronic Kidney Disease or Renal Concentrating Defect

• Chronic kidney disease and inherited kidney disorders can impair concentrating ability without causing frank diabetes insipidus 3, 1
• Your eGFR of 78 mL/min/1.73m² represents mild reduction (CKD stage G2 if confirmed), which can subtly affect urine concentration 3
• Check for albuminuria (albumin-to-creatinine ratio) to assess for early diabetic or hypertensive kidney disease 3

Metabolic and Electrolyte Causes

• Hypercalcemia and hypokalemia both impair renal concentrating ability and should be measured if not already done 1
• Hyperglycemia causes osmotic diuresis through glucosuria, but your normal glucose (96 mg/dL) and HbA1c rule out diabetes mellitus 1, 5

Recommended Diagnostic Approach

Step 1: Quantify Actual Fluid Intake

• Measure your total fluid intake over 24 hours (including all beverages, soups, and high-water-content foods) to determine if intake exceeds 3 L/day 3
• If fluid intake substantially exceeds 3 L/day, this confirms primary polydipsia as the cause of your polyuria 4

Step 2: Trial of Fluid Restriction

• Reduce fluid intake to approximately 1 L/24 hours (as recommended for patients with predominant nocturia) and monitor urine output 3
• If urine output decreases proportionally with reduced intake, this confirms primary polydipsia rather than pathologic polyuria 4
• Your demonstrated ability to concentrate urine to 498 mOsm/kg indicates this approach is safe and will not cause dehydration 1

Step 3: Additional Laboratory Evaluation

• Measure serum calcium, potassium, and magnesium to exclude metabolic causes of impaired concentration 1
• Check albumin-to-creatinine ratio (ACR) to assess for early kidney disease given your borderline eGFR 3
• Repeat serum creatinine and calculate eGFR in 3 months to confirm stability 3

Step 4: Medication Review

• Review all prescription and over-the-counter medications with your physician, particularly any diuretics or supplements 3
• Consider discontinuing or adjusting any medications that may contribute to increased urine output 3

Common Pitfalls to Avoid

• Do not proceed with water deprivation testing when baseline evaluation shows urine osmolality >300 mOsm/kg with normal serum osmolality, as this would be uncomfortable and potentially dangerous without adding diagnostic value 1
• Do not confuse polyuria from high fluid intake with pathologic polyuria—the former is behavioral and reversible, while the latter requires medical treatment 4
• Do not assume all polyuria represents diabetes insipidus—many conditions cause urine osmolality in the 200-300 mOsm/kg range without representing true diabetes insipidus 1

When to Seek Further Evaluation

Return to your physician if you develop:

• New onset of excessive thirst that feels uncontrollable (suggesting possible dipsogenic diabetes insipidus) 2, 4
• Inability to reduce urine output despite restricting fluid intake (suggesting acquired nephrogenic diabetes insipidus) 2
• Rising serum sodium levels or symptoms of dehydration when attempting fluid restriction 1
• Worsening kidney function (rising creatinine or declining eGFR) 3