What could be causing my frequent urination, given that I have normal kidney function, no proteinuria, and have ruled out diabetes insipidus (DI) and diabetes mellitus (DM)?

Differential Diagnosis for Frequent Urination Without DM, DI, Hypercalcemia, Proteinuria, or Kidney Dysfunction

Your frequent urination is most likely caused by overactive bladder syndrome, which affects the bladder muscle's ability to control contractions, leading to urgency, frequency, and potentially urge incontinence. 1

Primary Consideration: Overactive Bladder

Overactive bladder occurs when you cannot control your bladder muscle—when the muscle contracts too often or cannot be controlled, you experience leakage of urine (urge urinary incontinence), needing to urinate right away (urgency), and needing to urinate often (frequency). 1

Key Diagnostic Features to Assess:

• Urgency: Do you experience a sudden, compelling need to urinate that is difficult to defer? 1
• Frequency: Are you urinating more than 8 times per 24 hours? 1
• Nocturia: Are you waking at night specifically to urinate (not just urinating when you happen to wake up)? 1, 2
• Urge incontinence: Do you experience leaking or wetting accidents associated with the strong urge? 1

Treatment Options for Overactive Bladder:

Anticholinergic medications are first-line pharmacologic therapy, with tolterodine 2-4 mg daily or oxybutynin 5-20 mg/day as established options. 1, 2

• Tolterodine causes dry mouth in 71.4% of patients (dose-related), constipation in 15.1%, and blurred vision in 9.6% 2
• Oxybutynin has similar anticholinergic side effects including dry mouth, urinary hesitation (8.5%), and urinary retention (6.0%) 2

Important Contraindications:

Do not use anticholinergic medications if you have urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. 1

Secondary Considerations

Polyuria from Other Causes:

If your 24-hour urine output exceeds 3 liters per day, this represents true polyuria rather than just frequency, and requires different evaluation. 3, 4

Medication-Induced Polyuria:

• Review all current medications, as drug-induced polyuria is a well-known entity with an extensive medication list, particularly lithium. 5, 4
• Thiazide diuretics, loop diuretics, and other medications can cause increased urination 5

Primary Polydipsia:

• Excessive water intake from abnormal thirst regulation can cause polyuria with dilute urine, but this is a diagnosis of exclusion after ruling out DI. 4
• Patients compensate for polyuria by excessive water intake but show marked decreases in urine specific gravity and osmolality 5

Incomplete Bladder Emptying:

Assess for post-void residual volume, as incomplete emptying leads to frequent small voids rather than true polyuria. 1, 2

• Urinary hesitation and weak urine stream suggest this possibility 1, 2
• Post-void residual >100-150 mL is abnormal and requires further evaluation 1

Diagnostic Algorithm

Step 1: Quantify the Problem

• Maintain a 24-hour voiding diary documenting time, volume of each void, and fluid intake. 3, 4
• Distinguish between high-frequency/low-volume voids (overactive bladder) versus high-volume polyuria (>3L/day) 3, 4

Step 2: Assess Bladder Function

• Evaluate for urgency symptoms and measure post-void residual urine volume by bladder scan or catheterization. 1, 2
• Check for urinary tract infection with urinalysis and culture 2

Step 3: Medication Review

Systematically review all medications for agents that can cause polyuria or urinary frequency. 5, 4

Step 4: Consider Urine Concentration Ability

• If true polyuria (>3L/day) is confirmed, measure urine osmolality on a random sample. 5, 4
• Urine osmolality <250 mOsmol/kg with normal serum sodium suggests you may have missed a diagnosis of partial DI 4
• Urine osmolality between 250-750 mOsmol/kg requires water deprivation testing 4

Common Pitfalls to Avoid

Do not assume all frequent urination is overactive bladder without quantifying actual urine output and ruling out incomplete bladder emptying. 1, 3

Do not overlook medication-induced causes, particularly if symptoms began after starting new medications. 5, 4

Do not initiate anticholinergic therapy without first confirming the patient can empty their bladder completely, as these medications can precipitate urinary retention. 1, 2

Recognize that partial forms of diabetes insipidus can present with urine osmolality between 250-750 mOsmol/kg and may require water deprivation testing for diagnosis. 4