What is the appropriate workup for a patient with hypertension and increased creatinine (Impaired renal function)?

Workup for Increased Creatinine in Hypertensive Patients

Measure serum creatinine, calculate eGFR using the CKD-EPI equation, and obtain a urine albumin-to-creatinine ratio (UACR) immediately—these three tests form the essential foundation for evaluating renal impairment in hypertensive patients. 1

Initial Laboratory Assessment

The routine workup must include:

• Serum creatinine with eGFR calculation using the race-free CKD-EPI equation (preferred over MDRD or Cockcroft-Gault) 1, 2
• Urine albumin-to-creatinine ratio (UACR) on a spot urine sample to quantify proteinuria 1, 2
• Complete urinalysis with microscopy to evaluate for active sediment (RBC casts, dysmorphic RBCs suggesting glomerulonephritis) versus bland sediment typical of hypertensive nephrosclerosis 3
• Serum electrolytes including potassium, as hyperkalemia may develop with ACE inhibitor/ARB therapy 2, 4
• 12-lead ECG to assess for left ventricular hypertrophy and guide treatment choice 1

Chronic kidney disease (CKD) is defined as eGFR <60 mL/min/1.73 m² or albuminuria ≥30 mg/g (≥3 mg/mmol) present for at least 3 months. 1 The combination of reduced eGFR and proteinuria indicates greater cardiovascular and renal risk than either abnormality alone. 4

Albuminuria Classification

• Normal: UACR <30 mg/g 2
• Moderately elevated: UACR 30-299 mg/g 2
• Severely elevated: UACR ≥300 mg/g 2

Due to biological variability exceeding 20% between measurements, two out of three samples collected over 3-6 months must be abnormal before confirming elevated albuminuria. 2

Imaging Studies

Renal ultrasound with Doppler examination should be considered in hypertensive patients with CKD to assess kidney structure, determine causes of CKD, and exclude renoparenchymal and renovascular hypertension. 1 CT or magnetic resonance renal angiography are alternative options. 1

Renal imaging is particularly important when:

• There is unexplained renal insufficiency 1
• Unilateral smaller kidney or kidney size difference >1.5 cm is suspected 5
• Serum creatinine increases ≥50% within one week of starting ACE inhibitor or ARB therapy (suggests renovascular disease) 5
• Patient presents with recurrent flash pulmonary edema despite preserved systolic function 1
• Severe or resistant hypertension is present 5

Optional Advanced Testing

Echocardiography is recommended when the ECG is abnormal, murmurs are detected, or cardiac symptoms are present to assess for hypertension-mediated organ damage including left ventricular hypertrophy and diastolic dysfunction. 1

Fundoscopy is recommended if BP >180/110 mmHg to evaluate for hypertensive emergency, malignant hypertension (hemorrhages, exudates, papilloedema), or hypertensive retinopathy. 1

Screening for Secondary Hypertension

Secondary hypertension should be suspected when:

• Severe or resistant hypertension is present 5
• Age of onset <30 years (especially before puberty) 5
• Acute rise in BP from previously stable readings 5
• Serum creatinine increases ≥50% within one week of starting ACE inhibitor/ARB 5

When secondary hypertension is suspected based on clinical presentation, appropriate screening should include:

• Renovascular disease screening (renal artery stenosis): Renal Doppler ultrasound, CT angiography, or MR angiography, particularly in older patients, smokers, those with peripheral arterial disease, or unexplained renal insufficiency 1, 3
• Primary aldosteronism: Plasma aldosterone-to-renin ratio if hypokalemia or resistant hypertension is present 1
• Pheochromocytoma: Plasma free metanephrines (99% sensitivity, 89% specificity) if episodic hypertension, headaches, palpitations, or sweating occur 1
• Cushing's syndrome: 24-hour urinary free cortisol or overnight dexamethasone suppression test if cushingoid features present 1
• Thyroid disease: TSH level 1

Monitoring Schedule

If moderate-to-severe CKD is diagnosed (eGFR <60 mL/min/1.73 m² or UACR ≥30 mg/g), repeat measurements of serum creatinine, eGFR, and UACR at least annually. 1

After initiating ACE inhibitor or ARB therapy, recheck serum creatinine and potassium within 7-14 days. 2, 4, 3 A creatinine increase up to 20-30% is expected and reflects hemodynamic changes from reduced intraglomerular pressure, not progressive kidney damage—this should be tolerated. 4, 3 However, increases >30% warrant investigation for bilateral renal artery stenosis or volume depletion. 2

Nephrology Referral Criteria

Refer to nephrology when:

• eGFR <30 mL/min/1.73 m² 2
• Uncertainty about the etiology of kidney disease exists 2
• Rapidly progressive kidney disease is present 2
• Active urinary sediment suggests glomerulonephritis 3
• Difficult management issues arise 2

Common Pitfalls to Avoid

Do not rely on serum creatinine alone to assess renal function—patients can have significantly decreased GFR with normal-range creatinine values, particularly in elderly patients, women, and those with reduced muscle mass. 6, 7 Studies show that 18-25% of hypertensive patients have impaired renal function (CrCl <60 mL/min) despite only 4% having elevated serum creatinine by traditional cutoffs. 6

Do not discontinue ACE inhibitor or ARB therapy for minor creatinine increases (≤30%) in the absence of volume depletion, as these medications provide critical renoprotection in patients with proteinuria and CKD. 2, 4

Do not overlook the higher risk in Black patients—even with good blood pressure control, Black patients are twice as likely as White patients to experience deterioration in renal function (23% vs 11%). 8