What is the diagnosis for a 28-year-old female patient on amlodipine (calcium channel blocker) 10mg once daily, presenting with hematuria and proteinuria on urinalysis?

Diagnosis: Drug-Induced Glomerular Injury from Amlodipine

This 28-year-old female on amlodipine presenting with hematuria (3-5 RBCs/HPF) and proteinuria (1+ albumin) most likely has amlodipine-induced glomerular injury, though secondary hypertension requiring urgent investigation cannot be excluded given her young age.

Primary Diagnostic Consideration: Amlodipine-Induced Renal Injury

Evidence for Calcium Channel Blocker Nephrotoxicity

• Amlodipine, while generally considered renal-protective in some contexts, can paradoxically cause proteinuria and glomerular injury in susceptible patients 1, 2.
• Research demonstrates that amlodipine does not reduce proteinuria like ACE inhibitors or ARBs—in fact, some studies show amlodipine-treated patients experience no significant proteinuria reduction or even slight increases 3, 2.
• The combination of hematuria with proteinuria in a young patient on amlodipine strongly suggests drug-induced glomerular pathology rather than simple hypertensive nephrosclerosis 4.

Why This Matters Clinically

• The presence of both proteinuria and hematuria dramatically elevates the risk of clinically significant kidney disease and mandates urgent evaluation for glomerulonephritis or other serious renal parenchymal disease 4.
• Amlodipine may be unmasking or worsening underlying glomerular disease that requires different antihypertensive therapy 5, 3.

Critical Secondary Consideration: Secondary Hypertension

Young Age Triggers Mandatory Screening

• Patients with early onset hypertension (<30 years of age), particularly in the absence of hypertension risk factors (obesity, metabolic syndrome, familial history), require screening for secondary hypertension 6.
• The International Society of Hypertension explicitly recommends considering secondary hypertension screening in patients presenting with high probability based on strong clinical clues 6.

Basic Screening Required Immediately

• Basic screening for secondary hypertension should include thorough assessment of history, physical examination, basic blood biochemistry (including serum sodium, potassium, eGFR, TSH), and dipstick urine analysis—which has already revealed abnormalities 6.
• The finding of hematuria with proteinuria in a young hypertensive patient necessitates kidney ultrasound as part of the secondary hypertension workup 6.

Immediate Diagnostic Workup Required

Confirm and Quantify the Urinary Abnormalities

• Obtain formal microscopic urinalysis to confirm true hematuria (≥3 RBCs/HPF) and examine for dysmorphic RBCs (>80% suggests glomerular origin) or red cell casts (pathognomonic for glomerular disease) 4, 7.
• Quantify proteinuria using spot urine protein-to-creatinine ratio—normal is <0.2 g/g (or <30 mg/mmol), and values >0.5 g/g strongly suggest renal parenchymal disease 6, 4.
• Dipstick 1+ albumin typically corresponds to 30-100 mg/dL, which requires quantification to determine severity 6.

Assess Renal Function and Structure

• Measure serum creatinine and calculate eGFR to evaluate for chronic kidney disease—elevated creatinine with hematuria and proteinuria indicates advanced renal disease 4, 6.
• Obtain renal ultrasound to assess kidney size, echogenicity, and structural abnormalities—enlarged echogenic kidneys suggest acute glomerulonephritis 6.

Laboratory Evaluation for Glomerular Disease

• Complete metabolic panel including serum creatinine, BUN, albumin, and total protein 6, 4.
• Complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis 6.
• Antinuclear antibody (ANA) and ANCA testing if vasculitis is suspected based on systemic symptoms 6.

Management Algorithm

Step 1: Immediate Medication Review

• Consider switching from amlodipine to an ACE inhibitor or ARB, which have proven antiproteinuric effects and renoprotective properties in patients with proteinuria 5, 3.
• Research demonstrates that losartan reduces proteinuria by 50% after 20 weeks in non-diabetic proteinuric renal diseases, whereas amlodipine shows no significant proteinuria reduction 3.
• For each halving of proteinuria level, risk for kidney failure is reduced by more than half (hazard ratio 0.44), making antiproteinuric therapy critical 5.

Step 2: Nephrology Referral Criteria

• Nephrology referral is indicated for persistent significant proteinuria (protein-to-creatinine ratio >0.2 for three specimens), presence of red cell casts or >80% dysmorphic RBCs, elevated creatinine or declining renal function, or hypertension with hematuria and proteinuria 6, 4.
• Given this patient's young age, presence of both hematuria and proteinuria, and need for secondary hypertension evaluation, nephrology referral should occur immediately 4.

Step 3: Rule Out Malignancy (Lower Priority but Cannot Ignore)

• While less likely given her young age (28 years), hematuria in any adult requires consideration of urologic malignancy 6, 7.
• Women <60 years with microscopic hematuria are considered low-risk for malignancy, but the presence of proteinuria shifts the differential toward glomerular disease 7, 8.
• If glomerular features are absent on microscopic examination (normal RBC morphology, no casts, minimal proteinuria), then urologic evaluation with imaging and cystoscopy becomes necessary 7, 8.

Common Pitfalls to Avoid

Do Not Attribute Findings to Hypertension Alone

• The combination of hematuria with proteinuria in a young patient cannot be dismissed as simple hypertensive nephrosclerosis—this presentation demands investigation for primary glomerular disease or secondary hypertension 6, 4.
• Hypertensive nephrosclerosis typically presents with minimal proteinuria (<1 g/day) and minimal or no hematuria, making this presentation atypical 9.

Do Not Continue Amlodipine Without Reassessment

• Amlodipine lacks the antiproteinuric and renoprotective effects of ACE inhibitors or ARBs in patients with proteinuria 3, 2.
• Continuing amlodipine while proteinuria persists represents a missed opportunity for renoprotection 5, 3.

Do Not Delay Nephrology Referral

• Delays in diagnosis and treatment of glomerular disease can lead to irreversible renal damage and progression to end-stage renal disease 9.
• The presence of both hematuria and proteinuria mandates nephrology evaluation regardless of other findings 4.

Most Likely Final Diagnosis

Amlodipine-induced glomerular injury in the setting of inadequately controlled hypertension, with mandatory evaluation for secondary hypertension given age <30 years. The patient requires immediate switch to ACE inhibitor or ARB therapy, complete glomerular disease workup, and nephrology referral to prevent progression to chronic kidney disease 6, 4, 5, 3.