What is the likely cause of acute kidney injury in a 68-year-old male with a history of hypertension, Type 2 diabetes mellitus, osteoarthritis, and benign prostatic hyperplasia (BPH), who presents with generalized weakness, poor appetite, and decreased urine output, and has been taking ibuprofen (ibuprofen) and lisinopril (lisinopril), with lab results showing impaired renal function and volume depletion?

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Pertinent Negatives in This AKI Scenario

Three critical pertinent negatives in this case are: (1) no fever or signs of infection, (2) no urinary obstruction symptoms, and (3) no rash or systemic illness indicators.

These absences help narrow the differential diagnosis and guide management by ruling out specific etiologies of AKI that would require different interventions.


1. Absence of Fever or Signs of Infection

  • No fever, chills, or infectious symptoms excludes sepsis as a primary driver of AKI, which is critical since infection is a predominant cause of AKI globally and requires immediate antibiotic therapy 1
  • The absence of infection means the AKI is less likely to be related to septic acute tubular necrosis or inflammatory processes requiring antimicrobial intervention 2
  • This negative finding supports a prerenal etiology (volume depletion) rather than intrinsic renal injury from sepsis-related mechanisms 1, 3

Clinical significance: Without infection, the focus shifts to correcting volume status and discontinuing nephrotoxic medications rather than pursuing infectious workup or empirical antibiotics 1, 4


2. Absence of Urinary Obstruction Symptoms

  • No symptoms of urinary retention, suprapubic pain, or complete anuria makes postrenal obstruction less likely despite his BPH history 4, 2
  • While BPH is present in the history, the patient has been producing some urine (though decreased), which argues against complete obstruction 2
  • The absence of flank pain, hematuria, or complete anuria reduces suspicion for bilateral ureteral obstruction or bladder outlet obstruction 1, 2

Clinical significance: Although kidney ultrasound should still be obtained to definitively exclude obstruction (particularly after correcting hypovolemia), the lack of obstructive symptoms makes prerenal azotemia from volume depletion and nephrotoxic medications the more likely diagnosis 4, 2

Common pitfall: Do not assume obstruction is ruled out without imaging—ultrasound remains indicated in older men with BPH and AKI, but the clinical presentation suggests this is not the primary etiology 4


3. Absence of Rash or Systemic Illness Indicators

  • No skin rash, arthralgias, or signs of vasculitis makes acute interstitial nephritis (AIN) from allergic drug reaction less likely, though NSAIDs can still cause AIN without a rash 5, 2
  • The absence of systemic symptoms (no hemoptysis, no purpura) argues against glomerulonephritis or vasculitis as causes of intrinsic renal injury 2, 3
  • No evidence of rhabdomyolysis symptoms (severe muscle pain, dark urine) reduces concern for myoglobin-induced tubular injury 1, 3

Clinical significance: The bland presentation without systemic features supports a diagnosis of prerenal AKI from the "triple whammy" combination of volume depletion + NSAID (ibuprofen 800mg TID) + ACE inhibitor (lisinopril), rather than intrinsic kidney disease requiring kidney biopsy or immunosuppression 1, 5, 6


Why These Pertinent Negatives Matter

The absence of these findings creates a clinical picture consistent with prerenal AKI from:

  • Volume depletion (poor oral intake, nausea, dry mucous membranes, sluggish capillary refill) 6, 2
  • Nephrotoxic medication exposure: NSAIDs cause both direct tubular toxicity and renovasoconstriction, while ACE inhibitors impair autoregulation in volume-depleted states 5, 7
  • The combination creates the dangerous "triple whammy" when volume depletion is present 5, 6

Immediate management priorities based on these negatives:

  • Discontinue ibuprofen immediately (causes both dysfunction and injury) 5
  • Temporarily hold lisinopril during acute illness and volume depletion 4, 7
  • Initiate volume resuscitation with isotonic crystalloids while monitoring for fluid overload 4, 8
  • Obtain kidney ultrasound to definitively exclude obstruction despite low clinical suspicion 4, 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute kidney injury: a guide to diagnosis and management.

American family physician, 2012

Research

Acute kidney injury.

Nature reviews. Disease primers, 2021

Guideline

Acute Kidney Injury Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Drug-Induced Acute Kidney Injury

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Causes of Severe Intravascular Volume Depletion

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Fluid balance and acute kidney injury.

Nature reviews. Nephrology, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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