What are the top differential diagnoses for a 58-year-old female with hypertension (HTN) and diabetes mellitus (DM) presenting with fever, left flank pain, oliguria, costovertebral angle (CVA) tenderness, leukocytosis, acute kidney injury (elevated creatinine), hyponatremia, hypoalbuminemia, anemia, and a urine culture growing Escherichia coli (E. coli)?

Top Differential Diagnoses

The most likely diagnosis in this patient is acute pyelonephritis (complicated urinary tract infection) with acute kidney injury, given the constellation of fever, left flank pain with CVA tenderness, oliguria, elevated creatinine (222.9 μmol/L), leukocytosis, and urine culture growing E. coli. 1

Primary Differential: Acute Pyelonephritis with Acute Kidney Injury

This patient meets diagnostic criteria for complicated UTI/pyelonephritis requiring urgent treatment: she has both pyuria (abundant WBCs on urinalysis) and acute urinary symptoms (dysuria, fever 38°C, left flank pain, oliguria), plus systemic signs of infection (fever, leukocytosis 13.35 × 10⁹/L with 75.2% neutrophils). 1, 2

Key Supporting Features:

• Left CVA tenderness is the hallmark localizing sign of pyelonephritis, distinguishing upper from lower UTI 3
• E. coli growth (moderate) with pyuria (abundant WBCs, numerous pus cells) confirms bacterial infection rather than asymptomatic bacteriuria 1
• Acute kidney injury (creatinine 222.9 μmol/L) in the setting of pyelonephritis suggests either acute tubular necrosis from sepsis, volume depletion, or possible developing pyonephrosis/renal abscess 2, 3
• Oliguria with fever and flank pain raises concern for obstructive uropathy or pyonephrosis, which carries 10-20% mortality without prompt intervention 2

Critical Management Steps:

• Obtain blood cultures immediately before antibiotics, as bacteremia is common in pyelonephritis 3
• Urgent renal imaging (CT with contrast or ultrasound) is mandatory to exclude pyonephrosis, renal abscess, or obstructive uropathy, especially given the acute kidney injury and diabetes 2, 3
• Start empiric IV antibiotics immediately after cultures: ceftriaxone 1-2g IV daily plus gentamicin 5-7mg/kg (dose-adjusted for renal impairment) pending susceptibilities 2, 3
• The urine culture shows resistance to ceftriaxone, so switch to piperacillin-tazobactam or ertapenem based on reported susceptibilities 1

Secondary Differentials to Consider

2. Pyonephrosis (Infected Hydronephrosis)

Pyonephrosis is a urological emergency that must be excluded in any diabetic patient with pyelonephritis, acute kidney injury, and oliguria. 2

• Requires urgent urological decompression (percutaneous nephrostomy or ureteral stent) to prevent mortality 2
• CT imaging is essential to diagnose—look for hydronephrosis with debris/fluid levels and perinephric fat stranding 2, 3
• Mortality approaches 10-20% without prompt drainage, making this the most critical diagnosis not to miss 2

3. Renal Abscess

Renal abscess presents similarly to pyelonephritis but with more severe systemic toxicity and requires longer antibiotic duration (2-4 weeks) plus possible percutaneous drainage. 3

• Diabetic patients have atypical presentations and higher risk of emphysematous complications 3
• CT with contrast is the gold standard for diagnosis 3
• Abscesses >3-5cm typically require percutaneous drainage in addition to antibiotics 3
• Blood cultures are critical as bacteremia is common, particularly with gram-negative organisms 3

4. Acute Tubular Necrosis (ATN) Secondary to Sepsis/Volume Depletion

The acute kidney injury (creatinine 222.9 μmol/L) with oliguria may represent ATN from sepsis-induced hypoperfusion or volume depletion from fever/vomiting. 4

• Hypoalbuminemia (29 g/L) and hyponatremia (133 mmol/L) suggest volume depletion 5
• Anemia (Hgb 10.8 g/dL) in acute kidney injury is unusual and warrants investigation 4
• Urine sediment showing few epithelial cells and 0-1 RBC/HPF argues against acute glomerulonephritis 1

5. Nephrolithiasis with Superimposed Infection (Obstructive Pyelonephritis)

Renal stones with infection constitute a urological emergency requiring urgent decompression. 6

• Stones appear as echogenic foci with acoustic shadowing on ultrasound 6
• Calcium oxalate crystals noted on urinalysis raise suspicion for stones 6
• However, absence of hematuria (0-1 RBC/HPF) makes stones less likely as the primary pathology 7, 6

6. Less Likely but Important Differentials

Acute pancreatitis can present with isolated left flank pain mimicking pyelonephritis, but absence of epigastric pain, normal amylase/lipase (not reported), and positive urine culture make this unlikely 8

Page kidney (subcapsular hematoma) presents with flank pain and hematuria but this patient lacks hematuria and has no trauma history 7

Ovarian vein thrombosis causes right lower quadrant/flank pain in postpartum women but this patient is not postpartum 9

Common Pitfalls to Avoid

• Do not delay imaging in diabetic patients with pyelonephritis and acute kidney injury—they require urgent CT to exclude pyonephrosis or abscess 2, 3
• Do not assume all flank pain with pyuria is simple pyelonephritis—oliguria and acute kidney injury mandate imaging to exclude obstruction 2
• Do not use aminoglycosides without dose adjustment in renal impairment—calculate CrCl and adjust gentamicin dose accordingly 2, 3
• Do not treat based on initial empiric regimen alone—adjust antibiotics based on culture susceptibilities (this patient's E. coli is resistant to ceftriaxone) 1
• Do not miss the need for urological consultation if imaging shows obstruction, abscess, or pyonephrosis 2