What could be causing my frequent daytime urination despite normal renal function, no albuminuria, euthyroid status, and normocalcemia while taking losartan, escitalopram, and clonazepam?

Evaluation of Frequent Daytime Urination with Normal Renal Parameters

Direct Answer

Your frequent daytime urination is most likely medication-related, particularly from losartan, which can cause polyuria as a side effect, or from clonazepam, which may alter bladder function through central nervous system effects. Given your normal albumin:creatinine ratio, preserved kidney function (eGFR 78 mL/min/1.73 m²), normal thyroid function, and normocalcemia, intrinsic renal, endocrine, or metabolic causes are effectively ruled out.

Systematic Evaluation of Your Laboratory Results

Renal Function Assessment

• Your eGFR of 78 mL/min/1.73 m² is Stage G2 (mildly decreased) but does not explain urinary frequency, as symptomatic polyuria from reduced concentrating ability typically occurs when eGFR falls below 60 mL/min/1.73 m² 1
• Your normal albumin:creatinine ratio (<30 mg/g) excludes diabetic kidney disease or other glomerular pathology as a cause 1
• Serum creatinine of 80 μmol/L (approximately 0.9 mg/dL) is within normal range and does not suggest acute kidney injury or significant chronic kidney disease 1

Metabolic Parameters

• Your serum calcium of 9.6 mg/dL is normal (reference range 8.5-10.5 mg/dL), effectively excluding hypercalcemia as a cause of polyuria 1
• Normal TSH excludes both hyperthyroidism (which causes polyuria) and hypothyroidism 1

Medication-Related Causes (Most Likely)

Losartan Effects

• Losartan can cause polyuria through multiple mechanisms: natriuresis from angiotensin II receptor blockade, altered renal hemodynamics, and increased distal tubular sodium delivery 2, 3
• ARBs like losartan reduce urinary albumin excretion but may transiently increase urine volume during the initial weeks of therapy 2, 4, 3
• The antiproteinuric effect of losartan is independent of blood pressure changes, suggesting direct renal tubular effects that could alter fluid handling 3

Psychotropic Medication Effects

• Escitalopram (SSRI) can cause urinary frequency through serotonergic effects on bladder function, though this is less common than with other SSRIs
• Clonazepam may cause urinary frequency or incontinence through central nervous system depression affecting bladder control mechanisms
• Benzodiazepines like clonazepam can reduce bladder capacity and increase urgency in some patients

Recommended Diagnostic Approach

Immediate Steps

1. Obtain a 3-day voiding diary documenting fluid intake, urine output volume, and frequency to quantify the problem objectively
2. Measure post-void residual urine volume by bladder ultrasound to exclude urinary retention with overflow
3. Perform urinalysis with microscopy to exclude urinary tract infection, which can cause transient proteinuria and frequency 5, 6
4. Check fasting glucose and hemoglobin A1c if not recently done, as undiagnosed diabetes remains a common cause of polyuria 6

If Initial Workup is Negative

• Consider a trial of losartan dose reduction or temporary discontinuation (under physician supervision) to assess whether symptoms improve, as the antialbuminuric effect persists even at lower doses 3
• Evaluate for overactive bladder syndrome if voiding diary shows frequent small-volume voids (<200 mL) rather than true polyuria
• Review timing of clonazepam administration relative to urinary symptoms, as dose adjustment or timing changes may help

Common Pitfalls to Avoid

• Do not assume normal albumin:creatinine ratio means no kidney involvement—reduced eGFR without albuminuria occurs in 30-40% of diabetic kidney disease cases, though your eGFR is not low enough to cause symptoms 1
• Do not rely on single measurements—biological variability in urinary parameters requires confirmation over 3-6 months for persistent abnormalities 1
• Do not discontinue losartan without physician guidance if you have hypertension or diabetes, as the cardiovascular and renal protective benefits outweigh urinary frequency in most cases 1
• Avoid 24-hour urine collections for initial evaluation, as spot urine samples provide equivalent information with less burden 1, 6

When to Refer to Nephrology

Nephrology referral is NOT indicated based on your current parameters, as referral criteria include: eGFR <30 mL/min/1.73 m², continuously increasing albuminuria despite treatment, rapidly declining kidney function, or uncertainty about kidney disease etiology 1, 5