What could be the cause of dysuria in an elderly male patient with chronic kidney disease (CKD) and impaired renal function, with a negative urine culture and no evidence of leukocytes or red blood cells (RBCs)?

Dysuria in Elderly Male with Advanced CKD and Negative Urine Studies

In an elderly male with advanced CKD (eGFR 23) presenting with dysuria but negative urine culture, absent leukocytes, and absent RBCs, the most likely causes are non-infectious urethral irritation, medication-related effects, uremic toxicity affecting the bladder mucosa, or interstitial cystitis/bladder pain syndrome.

Primary Non-Infectious Etiologies to Consider

Uremic Bladder Irritation and Fluid Dysregulation

• Advanced CKD (Stage 4 with eGFR 23) causes impaired salt and water homeostasis, leading to uremic toxicity that can directly irritate bladder mucosa 1
• Patients with severe renal impairment develop fluid overload and accumulation of uremic toxins that affect the urinary tract, causing dysuria without infection 2
• The loss of residual renal function impairs both fluid removal and clearance of solutes, leading to uremic toxicity and inflammatory activation in the bladder 2

Medication-Related Causes

• Review all current medications, particularly diuretics, calcium channel antagonists, and nonsteroidal anti-inflammatory drugs (NSAIDs), as these commonly cause urethral and bladder irritation in CKD patients 3
• Medications used in CKD management can cause non-inflammatory dysuria through direct mucosal irritation 4

Interstitial Cystitis/Bladder Pain Syndrome

• This chronic inflammatory bladder condition presents with dysuria, negative cultures, and absence of pyuria or hematuria 4, 5
• Interstitial cystitis is a diagnosis of exclusion that should be considered when infection is ruled out 5
• The condition may have higher prevalence of low-concentration microorganisms in urine that don't grow on standard cultures 5

Secondary Considerations

Prostatic Disease

• Elderly males have increased incidence of prostatic hyperplasia with accompanying inflammation, which causes dysuria without bacteriuria 6
• Benign prostatic hyperplasia with urethral obstruction and voiding dysfunction is common after age 60 and can present with dysuria independent of infection 1, 6

Urethral Trauma or Anatomic Abnormalities

• Local urethral trauma from catheterization or instrumentation can cause dysuria without infection 4
• Urethral anatomic abnormalities related to prostatic disease may contribute to symptoms 4

Diagnostic Approach

Essential Immediate Assessments

• Obtain detailed history focusing on: timing of symptoms relative to voiding, presence of obstructive symptoms, recent instrumentation, complete medication review, and fluid intake patterns 4, 3
• Physical examination should assess for suprapubic tenderness, prostatic enlargement on digital rectal exam, and signs of fluid overload (edema, elevated blood pressure) 3
• Verify urinalysis was performed correctly with microscopic examination, not just dipstick, as pyuria can be absent in non-infectious causes 1, 4

Additional Testing if Initial Evaluation Unrevealing

• Consider post-void residual volume measurement to assess for urinary retention from prostatic obstruction 6
• Renal ultrasound to evaluate for hydronephrosis or structural abnormalities if not recently performed 3
• Review recent trends in serum creatinine, blood urea nitrogen, and electrolytes to assess degree of uremic toxicity 3

Management Strategy

Initial Therapeutic Interventions

• Optimize blood pressure control and review diuretic timing, as nocturnal polyuria from CKD can worsen bladder irritation 3
• Implement dietary salt restriction and fluid management advice to reduce uremic burden on the bladder 3
• Discontinue or adjust nephrotoxic medications including NSAIDs if being used 3

When to Refer

• Refer to urology if symptoms persist despite conservative management, if post-void residual is significantly elevated (>200 mL), or if there is concern for bladder outlet obstruction 4
• Consider nephrology referral given eGFR <30 mL/min/1.73 m² per standard CKD guidelines, as this patient requires evaluation for progression and potential need for renal replacement therapy planning 1

Critical Pitfalls to Avoid

• Do not empirically treat with antibiotics given negative culture and absence of pyuria, as this is inappropriate and contributes to resistance 1
• Do not assume asymptomatic bacteriuria requires treatment in this population—pyuria accompanying asymptomatic bacteriuria is not an indication for antimicrobial treatment 1
• Do not overlook medication review, as this is a reversible cause frequently missed in elderly patients with CKD 3
• Recognize that standard urine cultures may miss fastidious organisms or low-concentration bacteria that could contribute to symptoms in interstitial cystitis 5