What is the relationship between secondary hypertension and chronic kidney disease (CKD)?

From the Guidelines

Secondary hypertension in chronic kidney disease (CKD) requires aggressive management with a target blood pressure below 130/80 mmHg, as recommended by the 2020 International Society of Hypertension global hypertension practice guidelines 1. The management of secondary hypertension in CKD involves a multifaceted approach, including lifestyle modifications and pharmacological interventions.

Key Considerations

• First-line treatment typically includes an angiotensin-converting enzyme (ACE) inhibitor like lisinopril (10-40 mg daily) or an angiotensin receptor blocker (ARB) such as losartan (50-100 mg daily), which provide renoprotective effects beyond blood pressure control 1.
• Most patients will require multiple medications; adding a thiazide diuretic like chlorthalidone (12.5-25 mg daily) for mild-moderate CKD or a loop diuretic such as furosemide (20-80 mg twice daily) for advanced CKD is often necessary.
• Calcium channel blockers like amlodipine (5-10 mg daily) make excellent third-line agents.
• Dietary sodium restriction to less than 2 grams daily is crucial, as is limiting alcohol consumption and maintaining physical activity.

Monitoring and Follow-up

• Regular monitoring of kidney function, electrolytes, and proteinuria is essential, especially after medication adjustments.
• The effects of BP lowering on renal function (and albuminuria) are dissociated from cardiovascular benefit, highlighting the importance of close monitoring 1.

Pathophysiology

• The pathophysiology involves volume overload, increased renin-angiotensin-aldosterone system activity, sympathetic nervous system activation, and endothelial dysfunction, all contributing to persistent hypertension that accelerates kidney damage in a vicious cycle if left untreated 1.

Key Recommendations

• BP should be lowered if ≥140/90 mm Hg and treated to a target <130/80 mm Hg (<140/80 in elderly patients) 1.
• RAS-inhibitors are first-line drugs because they reduce albuminuria in addition to BP control.
• eGFR, microalbuminuria, and blood electrolytes should be monitored regularly.

From the FDA Drug Label

The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3. 0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]). Treatment with losartan resulted in a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease (ESRD), or death. The mean baseline blood pressures were 152/82 mmHg for losartan plus conventional antihypertensive therapy and 153/82 mmHg for placebo plus conventional antihypertensive therapy At the end of the study, the mean blood pressures were 143/76 mmHg for the group treated with losartan and 146/77 mmHg for the group treated with placebo.

Losartan is effective in reducing the risk of doubling of serum creatinine, end-stage renal disease (ESRD), and death in patients with type 2 diabetes and nephropathy.

• The study showed a 16% risk reduction in the primary endpoint.
• Losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29%.
• The effects of losartan were seen in patients also taking other anti-hypertensive medications.
• Losartan significantly reduced proteinuria by an average of 34%.
• The study suggests that losartan can be used to treat secondary hypertension due to chronic kidney disease in patients with type 2 diabetes and nephropathy 2.

From the Research

Secondary Hypertension due to Chronic Kidney Disease

• Secondary hypertension due to chronic kidney disease (CKD) is a significant comorbidity that increases the risk of end-stage renal disease (ESRD) and cardiovascular disease (CVD) 3.
• The pathophysiology of hypertension in CKD is complex and involves factors such as sodium retention, volume expansion, sympathetic nervous system activity, and endothelial dysfunction 4, 5.
• Treatment of hypertension in CKD is crucial to prevent disease progression and cardiovascular events, with a recommended blood pressure goal of <130 mmHg systolic and <80 mmHg diastolic 6.

Management of Hypertension in CKD

• The Japanese Society of Nephrology recommends angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) as first-line therapy for hypertensive patients with CKD and proteinuria 7.
• However, the actual use of these agents in clinical practice is unclear, with a study showing that only 28% of hypertensive patients with CKD and proteinuria were prescribed ARBs/ACEIs 7.
• Other treatment options include sodium-glucose cotransporter (SGLT) 2 inhibitors, mineralocorticoid receptor blockers, and renal denervation, which may have cardiorenal protective properties 3.

Importance of Blood Pressure Control

• Poorly controlled hypertension can accelerate the progression to end-stage kidney disease, highlighting the importance of close monitoring and adjustment of treatment 6, 4.
• Achieving optimal blood pressure control can provide long-term kidney protection and reduce the risk of cardiovascular events 6, 5.
• BP variability in the CKD population is significant, requiring close monitoring for appropriate management 5.