What history questions should be asked to establish a differential diagnosis in a patient with intractable nausea and Acute Kidney Injury (AKI), a past medical history (PMHx) of amputation, and an Ejection Fraction (EF) of 15%, who was on doxycycline?

Critical History Questions for Differential Diagnosis

In this patient with intractable nausea, AKI, severe heart failure (EF 15%), and recent doxycycline use, your history must immediately focus on identifying volume status, nephrotoxic exposures, cardiac decompensation triggers, and infection sources to distinguish between cardiorenal syndrome, drug-induced nephrotoxicity, prerenal azotemia, and sepsis-related AKI. 1

Volume Status and Cardiac Function Assessment

Fluid Balance History:

• Document recent weight changes over the past week—rapid weight gain suggests volume overload and cardiorenal syndrome, while weight loss suggests hypovolemia 1
• Quantify recent diuretic use, including doses, frequency, and any recent changes or discontinuation 1
• Assess for orthopnea, paroxysmal nocturnal dyspnea, and increased lower extremity edema indicating worsening heart failure 2
• Determine if patient has been taking medications as prescribed, particularly ACE inhibitors, ARBs, or beta-blockers 1

Cardiac Decompensation Triggers:

• Identify any recent dietary sodium indiscretion or fluid intake changes 2
• Ask about medication non-adherence, particularly diuretics and heart failure medications 1
• Assess for chest pain, palpitations, or syncope suggesting acute cardiac events 1

Nephrotoxic Medication Exposure

Doxycycline-Specific History:

• Determine exact duration of doxycycline therapy and total cumulative dose 3, 4
• Ask about timing of medication administration relative to meals and bedtime—doxycycline taken immediately before bed increases risk of esophageal injury and associated complications 3
• Document indication for doxycycline use to assess if infection could be contributing to AKI 4

Other Nephrotoxic Agents:

• Systematically inquire about NSAIDs (including over-the-counter ibuprofen, naproxen), which are a leading cause of drug-induced AKI and should be specifically asked about 1, 5
• Ask about recent contrast media exposure within the past 7 days 1
• Document use of aminoglycosides, vancomycin, or other antibiotics 4, 5
• Inquire about herbal supplements, over-the-counter medications, and "natural remedies" 1

Infection and Sepsis Screening

Infectious Symptoms:

• Document fever, chills, or rigors suggesting systemic infection 1
• Ask about dysuria, urinary frequency, or flank pain indicating urinary tract infection 1
• Assess for cough, dyspnea, or sputum production suggesting pneumonia 1
• In the context of amputation history, specifically ask about wound drainage, erythema, or pain at the amputation site 1

Gastrointestinal Infection:

• Determine if diarrhea is present, particularly watery or bloody diarrhea, which could indicate Clostridium difficile infection given recent antibiotic use 3
• Ask about recent gastrointestinal bleeding or melena 1

Prerenal vs. Intrinsic AKI Differentiation

Hypovolemia Assessment:

• Quantify recent vomiting episodes—frequency, volume, and duration 1, 6
• Document oral intake over the past 48-72 hours 1
• Ask about diarrhea, which combined with nausea/vomiting suggests significant volume depletion 1, 6
• Determine if patient has been able to take oral medications 1

Hypotension History:

• Ask about lightheadedness, dizziness, or near-syncope suggesting hypotension 1
• Document any recent blood pressure readings if patient monitors at home 1

Urinary Obstruction Screening

Obstructive Symptoms:

• Ask about decreased urine output, straining to void, or sensation of incomplete bladder emptying 1, 7
• Document urinary hesitancy, weak stream, or nocturia 1
• Inquire about suprapubic or flank pain 1
• In context of amputation, ask about any pelvic surgery or radiation that could cause obstruction 1

Baseline Renal Function

Chronic Kidney Disease History:

• Obtain most recent baseline creatinine values—ideally within the past 3 months 1
• Ask about known history of CKD, proteinuria, or hematuria 1
• Document any previous episodes of AKI and their causes 1

Cirrhosis and Hepatorenal Considerations

Liver Disease Assessment:

• Although not explicitly mentioned in this patient, ask about history of liver disease, alcohol use, or ascites, as the nausea and AKI combination could suggest hepatorenal syndrome 1
• Document any history of variceal bleeding or spontaneous bacterial peritonitis 1

Critical Timing Information

Temporal Relationship:

• Establish precise timeline: when did nausea begin relative to doxycycline initiation 3, 4
• Determine when patient last felt well and had normal urine output 1
• Document any recent hospitalizations or procedures within the past 7 days 1

Common Pitfalls to Avoid

The most critical error is failing to ask specifically about NSAID use, as patients often do not consider over-the-counter medications as "real drugs" and will not volunteer this information unless directly asked 1, 5. In a patient with severe heart failure (EF 15%), distinguishing between cardiorenal syndrome from volume overload versus prerenal AKI from overdiuresis is essential, as management is diametrically opposed 2. The recent doxycycline use raises concern for drug-induced AKI, but doxycycline is generally considered less nephrotoxic than other tetracyclines and rarely causes AKI in isolation 3, 4. However, the rise in BUN associated with tetracyclines is dose-related and should be considered 3.