What is the most likely diagnosis in a 56‑year‑old woman with diabetes mellitus, hypertension, hyperglycemia, normal blood urea nitrogen, elevated serum creatinine, and hyperuricemia, and what are the possible causes?

Diagnosis: Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD) – Most Likely Diabetic Nephropathy with Acute Decompensation

This 56-year-old woman with diabetes and hypertension presenting with markedly elevated creatinine (23.7 mg/dL) and relatively normal BUN (11.27 mg/dL) most likely has acute-on-chronic kidney disease, with diabetic nephropathy as the underlying chronic condition and a superimposed acute insult causing severe renal decompensation. 1, 2

Laboratory Interpretation

Serum Creatinine (23.7 mg/dL)

• Severely elevated – indicates profound reduction in glomerular filtration rate, consistent with either acute kidney injury or advanced chronic kidney disease 1
• This level suggests an estimated GFR well below 15 mL/min/1.73 m², placing her in Stage 5 CKD (kidney failure) if chronic, or severe AKI if acute 1
• The magnitude of elevation (>15-fold above normal for women) requires immediate nephrology referral and likely urgent dialysis 3

Blood Urea Nitrogen (11.27 mg/dL)

• Paradoxically normal-to-low despite severe creatinine elevation 4
• The BUN/Creatinine ratio is approximately 0.5:1 (normal is 10-20:1), which is markedly abnormal 2, 3
• This dissociation suggests:
  • Not pre-renal azotemia (which would show BUN/Cr ratio >20:1) 2, 3
  • Possible intrinsic kidney disease with selective impairment of creatinine clearance 4
  • Consider rhabdomyolysis (muscle breakdown releases creatinine disproportionately) 4
  • Possible severe malnutrition or liver disease (reduced urea production) 4
  • Dilutional effect from fluid overload or SIADH 4

Fasting Blood Sugar (10.57 mmol/L or ~190 mg/dL)

• Poorly controlled diabetes – increases risk for diabetic nephropathy progression 1
• Hyperglycemia is both a cause and consequence of kidney dysfunction 1

Uric Acid (0.741 mmol/L or ~12.5 mg/dL)

• Markedly elevated (normal <6-7 mg/dL) 5, 6
• Hyperuricemia in this context indicates:
  • Reduced renal clearance due to severe kidney dysfunction 5
  • Not the primary cause but a consequence of the kidney failure 5
  • Associated with increased cardiovascular risk in diabetic, hypertensive patients 5, 6

Most Likely Diagnosis

Diabetic nephropathy with acute decompensation, based on:

Supporting Evidence for Diabetic Nephropathy

• Diabetes is the leading cause of end-stage renal disease in the United States 3
• In type 2 diabetes, nephropathy may be present at diagnosis (unlike type 1 where it develops after 10 years) 3
• Hypertension accelerates diabetic kidney disease progression 1
• Poor glycemic control (FBS 190 mg/dL) increases risk of microvascular complications 1

Evidence for Acute Component

• The disproportionate creatinine elevation relative to BUN suggests an acute process superimposed on chronic disease 2, 4
• Acute kidney injury is diagnosed by sustained increase in serum creatinine over a short period 1
• People with diabetes are at higher risk of AKI than those without 1, 7
• Each AKI episode doubles the risk of progressing to advanced CKD in diabetic patients 7

Possible Acute Precipitants to Investigate

Medication-Related Causes

• ACE inhibitors or ARBs – can cause acute creatinine rise, especially with volume depletion 1, 2, 3
• Diuretics – most common avoidable cause of AKI in patients on RAAS inhibitors through volume depletion 2, 3
• NSAIDs – should be discontinued immediately as they reduce renal blood flow 1, 3
• Metformin – should be held given severe renal dysfunction (contraindicated at this GFR) 2

Volume Depletion

• Dehydration, vomiting, or diarrhea can precipitate pre-renal AKI, though the low BUN/Cr ratio argues against pure pre-renal azotemia 2, 8
• Assess for orthostatic hypotension, decreased skin turgor, dry mucous membranes, recent weight loss 3

Contrast or Nephrotoxin Exposure

• Contrast-induced nephropathy from recent imaging studies 3
• Other nephrotoxic exposures should be reviewed 1

Intrinsic Kidney Disease

• Acute tubular necrosis from hypotension, sepsis, or nephrotoxins 3
• Multiple myeloma with cast nephropathy – must be excluded given the severity and unusual BUN/Cr ratio 3, 9
• Glomerulonephritis – less likely but should be considered if urinalysis shows active sediment 3

Immediate Diagnostic Workup Required

Essential Tests

• Urinalysis with microscopy – to assess for proteinuria, hematuria, cellular casts (excellent negative predictive value for intrinsic kidney injury) 1, 3
• Urine albumin-to-creatinine ratio – persistent albuminuria ≥30 mg/g indicates kidney damage 1, 3
• Complete metabolic panel – assess potassium (risk of hyperkalemia), bicarbonate (metabolic acidosis), calcium, phosphorus 1
• Complete blood count – check for anemia (common in CKD and can indicate multiple myeloma) 9
• Serum protein electrophoresis and urine protein electrophoresis – to rule out multiple myeloma given the unusual presentation 3, 9
• Renal ultrasound – assess kidney size (small kidneys suggest chronic disease; normal size suggests acute or diabetic nephropathy) 9

Volume Status Assessment

• Clinical examination for signs of volume depletion or overload 3
• Serum osmolality – values >300 mOsm/kg confirm dehydration 3
• Urine sodium and fractional excretion of sodium – helps distinguish pre-renal from intrinsic causes 4

Immediate Management

Urgent Interventions

• Immediate nephrology referral – eGFR <30 mL/min/1.73 m² (this patient is likely <10) requires urgent specialist evaluation 1, 3
• Prepare for dialysis – creatinine of 23.7 mg/dL typically requires renal replacement therapy 9
• Hold all nephrotoxic medications immediately:
  • ACE inhibitors/ARBs 2, 3
  • Diuretics 2, 3
  • NSAIDs 1, 3
  • Metformin (contraindicated in severe renal dysfunction) 2

Monitoring

• Check serum potassium urgently – hyperkalemia is life-threatening at this level of renal dysfunction 1
• Monitor for uremic symptoms – altered mental status, pericarditis, bleeding 1
• Assess volume status carefully – avoid both dehydration and fluid overload 1, 2

Critical Clinical Pearls

The Unusual BUN/Creatinine Ratio

• This is the most striking abnormality – a ratio of 0.5:1 is highly unusual and demands explanation 4
• Consider rhabdomyolysis (check creatine kinase), severe malnutrition, liver disease, or dilutional states 4
• The low BUN relative to creatinine rules out simple pre-renal azotemia as the sole explanation 2, 3

Diabetic Nephropathy Confirmation

• Requires documentation of albuminuria (macro- or microalbuminuria) 3
• Ideally confirmed with diabetic retinopathy on ophthalmologic examination 3
• If proteinuria is absent or atypical features present, consider renal biopsy to identify alternative diagnoses 3, 9

Prognosis

• AKI episodes in diabetic patients carry cumulative risk – each episode doubles the risk of progressing to advanced CKD 7
• Even if this acute component is reversible, long-term prognosis is guarded given the severity of presentation 7