What is the likely cause of frequent urination in a patient with normal kidney function, normal eGFR, and normal creatinine level, and without diabetes mellitus or diabetes insipidus?

Frequent Urination Without Diabetes: Differential Diagnosis

Your frequent urination with normal kidney function (eGFR 78, creatinine 0.80) and no diabetes requires immediate evaluation for several common causes: overactive bladder, excessive fluid intake (primary polydipsia), urinary tract infection, medications (especially diuretics), benign prostatic hyperplasia (if male), or early-stage conditions not yet detected by standard testing.

Immediate Diagnostic Steps Required

Essential Laboratory Testing

• Measure urinary albumin-to-creatinine ratio (UACR) on a spot urine sample, as early kidney disease can present with normal eGFR and creatinine but elevated albuminuria (UACR ≥30 mg/g), which affects 20-40% of patients who develop chronic kidney disease 1, 2.
• Obtain urinalysis with microscopy to detect urinary tract infection, hematuria, pyuria, or casts that suggest alternative diagnoses such as glomerulonephritis or interstitial nephritis 3, 4.
• Check fasting glucose and hemoglobin A1c to definitively exclude prediabetes or early diabetes, as 6.5% of newly diagnosed type 2 diabetes patients already have kidney involvement at diagnosis 2.

Clinical History Details to Assess

• Quantify actual urine volume over 24 hours - true polyuria is defined as >3 liters/day; many patients perceive frequent urination (urinary frequency) without actual polyuria 5.
• Review all medications including over-the-counter drugs, particularly diuretics, NSAIDs, lithium, and supplements that can cause polyuria or bladder irritation 2.
• Assess fluid intake patterns - primary polydipsia (excessive water drinking) is a common cause of frequent urination with normal kidney function and no diabetes 5.
• Evaluate for nocturia specifically - waking ≥2 times per night to urinate suggests different etiologies than daytime frequency alone 5.

Common Causes With Normal Kidney Function

Urological Conditions

• Overactive bladder syndrome is extremely common, affecting 15-20% of adults, characterized by urgency with or without urge incontinence, usually with frequency and nocturia, without infection or metabolic cause 6.
• Benign prostatic hyperplasia (if male) causes urinary frequency, urgency, weak stream, and nocturia due to bladder outlet obstruction 6.
• Urinary tract infection presents with frequency, urgency, dysuria, and should be excluded with urinalysis 3, 4.

Metabolic and Endocrine Causes

• Primary polydipsia (excessive fluid intake) causes polyuria with dilute urine but normal kidney function; patients often drink >3-4 liters daily 5.
• Hypercalcemia impairs renal concentrating ability and causes polyuria; check serum calcium if not recently measured 6.
• Hypokalemia similarly impairs concentrating ability; verify potassium is normal 6.

Medication-Related Causes

• Diuretics are an obvious but often overlooked cause when patients don't recognize them as such (including combination antihypertensives) 2.
• Caffeine and alcohol act as bladder irritants and mild diuretics, contributing to frequency 6.

Critical Pitfalls to Avoid

Don't Assume Normal Creatinine Equals Normal Kidneys

• Early chronic kidney disease presents with normal eGFR (60-89 mL/min/1.73 m²) but abnormal UACR in Stage 1-2 CKD; your eGFR of 78 is technically Stage 2 if albuminuria is present 1, 2.
• Up to 63% of patients with reduced eGFR have normoalbuminuria, meaning CKD can exist without traditional albuminuria progression, but UACR must still be checked 7.
• Two of three UACR specimens over 3-6 months must be abnormal before confirming persistent albuminuria, as biological variability exceeds 20% between measurements 1, 3.

Recognize Transient Causes of Elevated Albuminuria

• Exercise within 24 hours, fever, infection, marked hyperglycemia, menstruation, marked hypertension, and congestive heart failure can transiently elevate urinary albumin independent of kidney damage 1, 3.
• Repeat testing after excluding these factors before concluding kidney disease is present 3.

Consider Partial or Evolving Diabetes Insipidus

• Partial central diabetes insipidus can present with polyuria despite normal initial testing, particularly if there's history of head trauma, pituitary surgery, or autoimmune conditions 5.
• Nephrogenic diabetes insipidus can be acquired from chronic lithium use, hypercalcemia, hypokalemia, or certain medications even with normal baseline kidney function 8.

When to Refer to Specialists

Nephrology Referral Indications

• UACR ≥30 mg/g on repeated testing warrants nephrology evaluation even with normal eGFR 1, 2.
• Continuously increasing UACR or decreasing eGFR despite optimal management requires specialist input 1, 2.
• Active urinary sediment (red cells, white cells, casts) suggesting glomerulonephritis needs urgent nephrology referral 1, 3.

Urology Referral Indications

• Persistent urinary frequency with negative metabolic workup suggests primary urological pathology requiring cystoscopy or urodynamic studies 6.
• Hematuria without infection requires urological evaluation to exclude malignancy 4.
• Male patients with obstructive symptoms (weak stream, hesitancy, incomplete emptying) need prostate evaluation 6.

Algorithmic Approach to Your Situation

1. Obtain UACR, urinalysis with microscopy, fasting glucose, and HbA1c immediately 1, 2, 3
2. If UACR ≥30 mg/g: Repeat twice over 3-6 months; if 2/3 abnormal, diagnose early CKD and initiate appropriate management 1, 3
3. If urinalysis shows infection: Treat and recheck after resolution 3
4. If all testing normal: Consider 24-hour urine volume measurement to distinguish true polyuria from urinary frequency 5
5. If true polyuria (>3L/day) with normal labs: Consider primary polydipsia, partial diabetes insipidus, or medication effects 5, 8
6. If urinary frequency without polyuria: Likely overactive bladder or urological cause requiring urology referral 6