How to manage a patient with hypertension, impaired renal function (elevated creatinine), thrombocytopenia, anemia, and hypoalbuminemia?

Management of Hypertension with Renal Impairment, Thrombocytopenia, Anemia, and Hypoalbuminemia

This patient requires immediate evaluation for thrombotic microangiopathy (TMA) or atypical hemolytic uremic syndrome (aHUS) given the constellation of hypertension, renal failure (creatinine 3), thrombocytopenia, anemia, and hypoalbuminemia—this is a medical emergency that may require plasma exchange and complement blockade, not simply routine hypertension management. 1

Immediate Diagnostic Priorities

Rule out TMA/aHUS first before attributing findings solely to hypertensive nephrosclerosis:

• Examine peripheral blood smear for schistocytes to confirm microangiopathic hemolytic anemia 1
• Check LDH, haptoglobin, indirect bilirubin to document hemolysis 1
• Measure ADAMTS13 activity to exclude thrombotic thrombocytopenic purpura 1
• Assess complement levels (C3, C4) and consider genetic testing for complement abnormalities if TMA is confirmed 1
• Fundoscopic examination for hypertensive retinopathy or hemorrhages 1

Critical caveat: Malignant hypertension can cause secondary TMA, but aHUS can present as malignant hypertension—the distinction determines whether complement blockade (eculizumab) is needed. 1

Blood Pressure Management

Target Blood Pressure

Target BP <130/80 mmHg for this patient with stage 3-4 CKD (creatinine 3 mg/dL corresponds to eGFR approximately 20-30 mL/min/1.73m²). 2

• The 2017 ACC/AHA guidelines establish <130/80 mmHg as the goal for all CKD patients based on SPRINT trial data showing cardiovascular and mortality benefits 2
• Do not target systolic BP <120 mmHg as this provides no additional benefit and increases adverse events 3

Antihypertensive Medication Selection

Start with an ACE inhibitor (or ARB if ACE inhibitor not tolerated) as first-line therapy given the presence of significant proteinuria indicated by hypoalbuminemia and renal impairment. 2, 3, 4

• ACE inhibitors/ARBs reduce intraglomerular pressure and proteinuria independent of systemic BP reduction 2, 5
• These agents slow progression to end-stage renal disease in patients with CKD and proteinuria 3, 5

Expect and tolerate up to 30% increase in serum creatinine after initiating ACE inhibitor/ARB therapy—this reflects hemodynamic changes from reduced intraglomerular pressure, not progressive kidney damage. 2, 4

• Monitor creatinine and potassium within 7-14 days of starting therapy 3
• Discontinue or reduce dose only if creatinine rises >30% or hyperkalemia develops 2, 4
• Ensure patient is not volume depleted, as diuretic-induced hypovolemia is the most common cause of excessive creatinine elevation 2

Add a thiazide-like diuretic (chlorthalidone or indapamide preferred) as second-line agent if BP remains ≥130/80 mmHg on ACE inhibitor/ARB alone. 3, 6

• Chlorthalidone remains effective even in stage 4 CKD (eGFR 15-30 mL/min) based on the CLICK trial 6
• Loop diuretics may be needed if eGFR <30 mL/min and patient has volume overload 6

Add a long-acting dihydropyridine calcium channel blocker (amlodipine) as third-line therapy if BP control inadequate on ACE inhibitor/ARB plus diuretic. 3, 5, 6

• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) as they may worsen proteinuria 5

For resistant hypertension (BP uncontrolled on 3 drugs including diuretic), add low-dose spironolactone with careful potassium monitoring. 3, 6

• Monitor potassium closely as hyperkalemia risk is substantial with eGFR <30 mL/min 3, 6
• Chlorthalidone can mitigate hyperkalemia risk when used with spironolactone 6

Management of Anemia

Investigate cause of anemia before attributing to CKD alone:

• If hemolytic anemia confirmed (elevated LDH, low haptoglobin, schistocytes), urgent hematology consultation for possible plasma exchange is required 1
• If anemia of CKD (normocytic, normochromic without hemolysis), consider erythropoiesis-stimulating agents only if hemoglobin <10 g/dL and symptomatic 7

Do not target hemoglobin >11 g/dL with erythropoietin as this increases mortality, cardiovascular events, and stroke risk. 7

Management of Thrombocytopenia

Platelet count <150,000/μL in the setting of hemolytic anemia and renal failure mandates TMA evaluation as outlined above. 1

• If TMA confirmed, plasma exchange is first-line therapy and should be initiated urgently 1
• If aHUS diagnosed, eculizumab (complement C5 inhibitor) may be required for long-term management 1

Monitoring Strategy

Weekly monitoring initially:

• Serum creatinine and potassium within 7-14 days of starting/adjusting ACE inhibitor/ARB 3
• CBC to track hemoglobin and platelet trends 1
• BP measurements to assess control 3

Monthly monitoring once stable:

• Serum creatinine, eGFR, electrolytes 4
• Urine albumin-to-creatinine ratio to assess proteinuria response 3, 4

Nephrology Referral

Urgent nephrology consultation is mandatory for this patient given:

• eGFR <30 mL/min (creatinine 3 mg/dL) 4
• Possible TMA/aHUS requiring specialized management 1
• Rapidly progressive kidney disease suggested by thrombocytopenia and hemolytic anemia 4

Dietary Modifications

Restrict dietary protein to 0.8 g/kg/day for stage 3-4 CKD not on dialysis. 4

Restrict dietary sodium to <2 g/day to enhance antihypertensive medication effectiveness and reduce proteinuria. 2, 3