Objective
Understand what adjustments need to be made to antihypertensive drugs in renal insufficiency
Especially why ACEI + ARB are recommended in the early stage but used cautiously in the later stage
Overview of Antihypertensive Drugs
Antihypertensive drugs mainly fall into five categories:
A: Angiotensin converting enzyme inhibitors (ACEI, XX-pril) + Angiotensin receptor blockers (ARB, XX-sartan) — collectively called lisa (pril + sartan)
B: β-Blockers (beta blocker, XX-lol)
C: Calcium channel blockers (Ca channel blocker, CCB, XX-dipine)
D: Diuretics (diuretic)
In addition, there are less commonly used α-blockers
Antihypertensive Regimen for Patients with Renal Insufficiency
For renal insufficiency:
- CCB and β-blockers are basically unrestricted (the pharmacological mechanisms basically do not affect the kidney, further details will not be covered here)
- ACEI + ARB can be used in early chronic kidney disease (CKD) and may even help protect renal function; use cautiously in late stages (see details below)
- Diuretics are ineffective in late-stage CKD (kidney function is too poor, diuresis is ineffective no matter what)
- α-blockers are rarely used clinically nowadays and will be omitted
Why can ACEI + ARB protect renal function in early CKD but should be avoided in late CKD?
First, review the pharmacological mechanisms of ACEI + ARB, which requires reviewing the Renin-Angiotensin-Aldosterone System (RAAS)
Normal RAAS
When blood volume decreases, the juxtaglomerular cells in the kidney sense changes in glomerular sodium concentration and secrete renin. Renin enters the bloodstream and converts angiotensinogen into angiotensin I (Angiotensin Ⅰ, AⅠ). AⅠ is then converted by angiotensin converting enzyme (ACE) into angiotensin II (Angiotensin Ⅱ, AⅡ).
- AⅡ acts on arteries causing systemic vasoconstriction (mainly of small vessels). In the kidney’s arteries, both afferent and efferent arterioles constrict, especially the efferent arteriole.
- AⅡ also stimulates the adrenal cortex to release aldosterone, which promotes potassium excretion and sodium and water retention.
Of course, this is only an overview focusing on content related to this text; the full process is more complex.
Abnormal RAAS
When RAAS is excessively activated, prolonged action of AⅡ on kidney arteries causes sustained constriction of afferent and efferent arterioles, especially the efferent arteriole. This results in a chronically increased glomerular pressure difference, accelerating glomerulosclerosis and damage to the filtration barrier, eventually leading to renal function impairment (proteinuria, increased serum creatinine, etc.)
How ACEI + ARB Modulate RAAS to Protect Early CKD
By using ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARB), the concentration of AⅡ is reduced, avoiding the sustained elevated glomerular pressure difference caused by prolonged AⅡ action on renal arteries, thus preventing renal function decline
Why Use ACEI + ARB with Caution in Late CKD
The kidney is the main organ for potassium excretion, and hyperkalemia is a common complication in late-stage CKD.
ACEI + ARB inhibit angiotensin production and thereby suppress aldosterone secretion, and aldosterone is a crucial hormone for regulating renal potassium excretion. Therefore, ACEI + ARB can ultimately cause hyperkalemia, which in severe cases can lead to cardiac arrest!
Thus, ACEI + ARB should be used cautiously in late-stage CKD
References
Acknowledgments
Teacher Xiaowen
Teacher Xiacao
Student duodolll