How to manage an elderly female patient with Chronic Kidney Disease (CKD) and a significantly elevated white blood cell count, indicating a potential infection or inflammatory process, with normal Computed Tomography (CT) scans of the thorax and abdomen?

Management of Elderly Female with CKD and Leukocytosis (WBC 30,000) with Normal CT Imaging

In an elderly female with CKD presenting with marked leukocytosis (WBC 30,000) and normal CT thorax and abdomen, immediately obtain blood cultures, urinalysis with culture, and peripheral blood smear with manual differential to assess for left shift, then initiate empiric broad-spectrum antibiotics if infection is suspected while pursuing additional diagnostic workup for occult infection or hematologic disorder. 1, 2

Immediate Diagnostic Workup

Essential Laboratory Tests

• Obtain blood cultures from at least two sites before initiating antibiotics to identify bacteremia, as recommended for all patients with suspected infection and significant leukocytosis 1
• Perform manual differential count with peripheral blood smear to assess for left shift (band neutrophils ≥16% or absolute band count ≥1,500 cells/mm³), which has a likelihood ratio of 14.5 for bacterial infection 2
• Complete urinalysis with microscopy and urine culture if not already done, as urinary tract infections are common in elderly patients with CKD and may present without typical symptoms 2
• Measure inflammatory markers including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to assess degree of systemic inflammation 3
• Check serum albumin and prealbumin to assess nutritional status and degree of inflammation 3

Additional Infection Workup

• Test stool for Clostridium difficile toxin if any gastrointestinal symptoms are present, as this is a mandatory exclusion in patients with inflammatory conditions 3, 2
• Consider blood cultures even without fever, as WBC >14,000 cells/mm³ warrants careful assessment for bacterial infection with a likelihood ratio of 3.7 1
• Evaluate for occult sources: skin examination for cellulitis/abscess, cardiac auscultation for new murmurs (endocarditis), and joint examination for septic arthritis 2

Imaging Considerations Beyond Initial CT

When Normal CT is Insufficient

• Echocardiography should be performed if cardiac murmurs are detected or if endocarditis is suspected, as this is recommended for patients with unexplained leukocytosis and risk factors 3
• Consider pericardiocentesis or surgical drainage if pericardial effusion is identified on echocardiography, particularly if bacterial or neoplastic pericarditis is suspected 3
• Renal ultrasound with Doppler examination should be performed to assess kidney structure, exclude obstruction, and evaluate for renal abscess or pyelonephritis that may not be evident on CT without contrast 3
• MRI abdomen without contrast may be considered if CT with IV contrast is contraindicated due to advanced CKD and additional imaging is needed to characterize renal abnormalities 3

Contrast Administration in CKD

• The risk of contrast-induced acute kidney injury (CI-AKI) should not automatically preclude CT with IV contrast in this clinical scenario, as recent meta-analyses have failed to show higher risk of CI-AKI after CT in patients with chronic kidney disease 3
• If CT with contrast is deemed necessary for diagnosis, the benefit of prompt diagnosis and treatment in this frail elderly population may justify the risk, particularly with concurrent crystalloid resuscitation 3

Empiric Antibiotic Therapy

Initiation Criteria

• Start empiric broad-spectrum antimicrobial therapy immediately if bacterial infection is suspected based on clinical presentation, even before culture results are available 1
• Do not delay antibiotics while awaiting imaging or culture results in an elderly patient with CKD and marked leukocytosis, as mortality increases with delayed treatment 1

Antibiotic Selection with Renal Adjustment

• Cefepime requires dose adjustment in patients with creatinine clearance ≤60 mL/min to compensate for slower renal elimination; failure to adjust dosing can lead to serious adverse events including encephalopathy, myoclonus, and seizures 4
• Meropenem dosage adjustment is necessary in patients with creatinine clearance ≤50 mL/min 5
• Consider empiric coverage for urinary pathogens with renally-adjusted dosing of fluoroquinolones or third-generation cephalosporins if urinary source is suspected 1, 2

Hematologic Evaluation

When to Suspect Non-Infectious Causes

• If left shift is absent or minimal despite WBC 30,000, consider hematologic disorders including acute leukemia, chronic myeloproliferative disorders, or leukemoid reaction 2
• Peripheral blood smear examination is essential to identify blast cells, immature myeloid forms, or dysplastic features that would indicate primary hematologic disease 2
• Urgent hematology consultation is warranted if blast cells are identified, as prompt institution of definitive therapy is essential after measures to rapidly reduce white blood cell count 1

Special Considerations in Elderly CKD Patients

Age-Related Factors

• Elderly patients with CKD are at higher risk of toxic reactions to medications that are renally excreted, requiring careful dose selection and renal function monitoring 4, 5
• Atypical presentations are common in elderly patients, who may lack fever or typical infection symptoms despite serious bacterial infection 2
• Decreased basal body temperature in older adults makes left shift particularly important diagnostically, as fever may be absent even with significant infection 2

CKD-Specific Concerns

• Systemic inflammation is characteristic of CKD and elevated peripheral leukocyte count may reflect both acute infection and chronic inflammatory state 6, 7
• Peripheral neutrophil count >2,760/mm³ is associated with rapid renal progression in CKD patients, with an area under the curve of 0.813 for predicting rapid decline 7
• Monitor for CKD complications including hyperkalemia, metabolic acidosis, and anemia during acute illness 8, 9

Monitoring and Follow-Up

Response to Treatment

• Serial WBC counts should be obtained to assess response to antibiotic therapy, with normalization expected within 48-72 hours if appropriate treatment is initiated 10
• Persistent or worsening leukocytosis despite appropriate treatment indicates complications requiring further intervention, including imaging for occult abscess or consideration of resistant organisms 10, 1
• Reassess renal function after resolution of acute illness, as acute kidney injury superimposed on CKD may occur and requires adjustment of long-term management 8, 9

When to Escalate Care

• If no source is identified after initial workup, consider advanced imaging (MRI, PET scan if autoimmune condition suspected), bone marrow biopsy if hematologic disorder suspected, or infectious disease consultation 3, 1
• Nephrology referral is indicated for patients with eGFR <30 mL/min/1.73 m², particularly if acute deterioration occurs during this illness 8, 9