What is the most likely cause of acute kidney injury in a 76‑year‑old woman with hypertension and diabetes on valsartan who had severe vomiting and diarrhea, resulting in a creatinine rise from 0.6 to 1.6 mg/dL, low BUN/creatinine ratio, urine sodium 60 mEq/L, low specific gravity, and urine osmolality 220 mOsm/kg?

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Acute Tubular Necrosis (ATN)

This patient has acute tubular necrosis (ATN), not prerenal azotemia, despite the clinical history of volume depletion from vomiting and diarrhea. The urinary indices definitively indicate established tubular injury that has progressed beyond reversible prerenal physiology.

Diagnostic Reasoning

Urinary Indices Point to ATN

The laboratory values are pathognomonic for ATN and exclude prerenal azotemia 1, 2:

  • Urine sodium 60 mEq/L: Values >40 mEq/L indicate tubular dysfunction and loss of sodium reabsorptive capacity, which is diagnostic for ATN 1, 2, 3
  • Urine osmolality 220 mOsm/kg: This low osmolality (<350 mOsm/kg) confirms complete loss of concentrating ability, inconsistent with preserved tubular function seen in prerenal states 1, 2
  • Low specific gravity (900): Further confirms inability to concentrate urine, supporting ATN 3

In contrast, prerenal azotemia would show urine sodium <20 mEq/L, urine osmolality >500 mOsm/kg, and preserved concentrating ability 4, 5, 2.

Low BUN/Creatinine Ratio

The urea of 11 mmol/L (approximately 31 mg/dL) with creatinine 160 μmol/L (1.8 mg/dL) yields a BUN/creatinine ratio of approximately 17:1, which is below the typical 20:1 ratio expected in prerenal azotemia 6. This low ratio occurs because damaged tubules in ATN cannot reabsorb urea effectively 7.

Clinical Context Supporting ATN Progression

While the patient initially had volume depletion from vomiting and diarrhea (a prerenal insult), several factors promoted progression to established ATN 7, 1:

  • Age (70s) with diabetes and hypertension: These conditions impair renal autoregulation and increase susceptibility to ischemic tubular injury 1, 6
  • Continued valsartan use during illness: RAAS inhibitors during volume depletion exacerbate renal hypoperfusion by preventing compensatory efferent arteriolar vasoconstriction, converting prerenal injury to ATN 7, 4
  • One-week duration: Prolonged hypoperfusion (from appointment to presentation) allowed progression from reversible prerenal physiology to structural tubular damage 8, 9

Why Not Prerenal Azotemia?

Prerenal azotemia requires preserved tubular function with appropriate compensatory responses 4, 5:

  • Urine sodium should be <20 mEq/L (not 60) 5, 2
  • Urine osmolality should be >500 mOsm/kg (not 220) 5, 2
  • FENa should be <1% (calculable from these values, would be elevated here) 5, 6

The distinction between prerenal and ATN is ultimately confirmed by response to volume resuscitation 5. However, the urinary indices here are so definitively consistent with ATN that therapeutic trial is diagnostic rather than therapeutic 1, 3.

Why Not Acute-on-Chronic Kidney Disease?

The baseline creatinine of 60 μmol/L (0.67 mg/dL) one week prior indicates preserved baseline renal function, making chronic kidney disease unlikely 4, 6. The acute rise represents KDIGO Stage 2 AKI (>2.0 times baseline) superimposed on normal kidneys 1.

Management Priorities

Immediate Actions

  • Discontinue valsartan and all nephrotoxic medications (NSAIDs, metformin if applicable) until recovery 1, 4
  • Volume resuscitation with isotonic crystalloids: Even in established ATN, some prerenal component may be reversible 1, 6
  • Monitor for dialysis indications: Hyperkalemia, metabolic acidosis, uremia, or volume overload 1, 6

Critical Pitfall to Avoid

Do not assume this is simple prerenal azotemia based solely on the clinical history of volume depletion 7, 5. Up to 86% of patients with intrinsic kidney disease can initially present with volume depletion 5. The urinary indices are the definitive discriminator, and this patient's indices unequivocally indicate ATN 1, 2, 3.

Long-Term Follow-Up

Even with complete creatinine recovery, this patient faces significantly increased risks of recurrent AKI, progression to chronic kidney disease, and cardiovascular events 1, 5. Mandatory follow-up includes creatinine monitoring every 2-4 weeks for 6 months, with nephrology referral if creatinine fails to return to within 115% of baseline 1, 5.

References

Guideline

Acute Tubular Necrosis Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Acute Kidney Injury: Pre-Renal Azotemia Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Assessment of Prerenal Acute Kidney Injury in Post-Operative Elderly Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Acute kidney injury: a guide to diagnosis and management.

American family physician, 2012

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Immune mechanisms in the different phases of acute tubular necrosis.

Kidney research and clinical practice, 2018

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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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