Hypertension is a clinical syndrome characterized by elevated systemic arterial pressure and its main complication is chronic kidney disease Hypertensive nephropathy is a common disease in nephrology and an important cause of end-stage renal disease (ESRD). The clinical manifestations of hypertensive nephropathy include increased nocturia, low specific gravity, mild to moderate proteinuria, progressive decline in glomerular filtration rate (GFR), and eventually ESRD. Currently commonly used antihypertensive drugs are mainly angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), diuretics, beta-blockers and so on. So, how to choose antihypertensive drugs for hypertensive nephropathy patients?
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proteinuria>1g/dfor hypertensive nephropathy non-dialysis patients, the blood pressure control target should be<130/80mmHg< /span>, non-dialysis patients with tolerable and stable renal function can further reduce systolic blood pressure to <120mmHg; urine protein ≤1g/d non-dialysis patients with hypertensive nephropathy, blood pressure control target<130/80mmHg. Hypertensive nephropathy non-dialysis patients with diabetes are recommended to control blood pressure<130/80mmHg, and those with proteinuria and well tolerated can further control systolic blood pressure levels <120mmHg. Age>65 years old with hypertensive nephropathy and non-dialysis patients, if the blood pressure can be tolerated, the blood pressure can be gradually lowered to <140/90mmHg< span>. The systolic blood pressure of hemodialysis patients should be controlled at 130-160mmHg.
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①The first choice of antihypertensive drugs for hypertensive nephropathyACEIandARB, but when the serum creatinine>3.0mg/dL will increase the incidence of adverse events (such as hyperkalemia, acute kidney injury), it is recommended to lower the dose and start using , and monitor blood biochemical indicators, and gradually titrate to the maximum effective tolerated dose. It is not recommended to combine ACEIARB.
②There is limited evidence for the use of direct renin inhibitors in hypertensive nephropathy, Combining ACEIor ARB can increase the risk of adverse events (eg, hyperkalemia, hypotension, increased creatinine) It is not recommended for patients with hypertensive nephropathy.
③Long time useACEI/ARB< /span>Aldosterone escape, a phenomenon in which serum aldosterone levels exceed baseline values, may occur. eGFR>30mL/（min 1.73 m2< span>) patients with hypertensive nephropathy using ACEI/ARBif the effect of controlling blood pressure and proteinuria is not satisfactory, especially when complicated with diabetes and cardiovascular and cerebrovascular diseases, it is recommended to contact Use a non-steroidal aldosterone receptor antagonist (MRA), but pay attention to the assessment of eGFR and renal function and monitoring of serum potassium.
④It is recommended that patients with hypertensive nephropathy with increased volume load should be combined with diuretics to control blood pressure.eGFR> 30mL/ (min·1.73 m2) can consider using thiazide eGFR<30mL/(min·1.73 m2< /span>) consider loop diuretics.
⑤single use is recommendedRASCombination use in patients with hypertensive nephropathy with poor inhibitory effectCCB, especially those on hemodialysis; with RASHypertensive nephropathy patients with contraindications to the use of inhibitors may be the first choiceCCB.
⑥The symptoms of tachycardia such as heart failure or sympathetic excitation are significantly higher In patients with hypertensive nephropathy, combined use of βreceptor blockers may be considered, rather than combined use of CCB. If there is no contraindication, the preferred recommended drug is carvedilol.
⑦Except for poor blood pressure control, it is not recommended for priority use< span>αreceptor blockers.
01
renin-angiotensin system Inhibitors
ACEI (such as enalapril, perindopril), ARBs (such as losartan, valsartan, irbesartan) can reduce blood pressure, and can also make kidney It has no adverse effect on glucose and lipid metabolism, and has a good preventive effect on cardiovascular end points.
It is contraindicated in patients with bilateral renal artery stenosis and hyperkalemia. ACEI/ARB can dilate the efferent arterioles and has the potential to reduce GFR. Therefore, regular monitoring of serum creatinine and eGFR is required during the medication process. 30% need to stop or reduce use.
ACEI can cause cough, acute kidney injury, hyperkalemia, hypotension, and angioedema. ACEI was discontinued when serum potassium was >6.0 mmol/L or serum creatinine increased by >50% or >265 μmol/L.
ARB can cause hyperkalemia, renal insufficiency, hypotension, etc. Rarely, cough and angioedema may occur. It should be used with caution in patients with serum creatinine > 265 μmol/L.
The combined use of ACEI and ARB to control blood pressure is not recommended for CKD patients because it does not further increase renal benefit, but it can lead to more severe hyperkalemia and short-term GFR The risk of rapid decline in internal medicine and increased incidence of adverse events such as hypotension, syncope, and acute kidney injury (AKI).
02
Calcium channel blockers ( CCB)
CCB reduces blood pressure by dilating blood vessels, including dihydropyridine CCB (DHP-CCB, such as nifedipine sustained and controlled release preparations, amlodipine, felodipine, levothyroxine clodipine) and non-dihydropyridine CCB (NDHP-CCB, such as verapamil, diltiazem), have renal protection ability, of which DHP-CCB mainly acts on arteries, and has better selectivity to blood vessels, NDHP -CCB has poor vascular selectivity and has negative chronotropic, negative conduction and negative inotropic effects on the heart. DHP-CCB and NDHP-CCB can effectively reduce blood pressure when used in hypertensive nephropathy patients, and can also reduce cardiovascular events in high-risk groups. They have no adverse effects on metabolism, and their antihypertensive effects are not affected Effects of a high-salt diet, and combined CCB and ACEI therapy in patients with systolic hypertension can reduce cardiovascular events.
Currently commonly used antihypertensive drugs are mainly DHP-CCB, which is not affected by renal dysfunction and has anti-atherogenic properties. It can significantly reduce the risk of stroke in hypertensive patients. Long-acting preparations are not easy to be cleared by dialysis. They can be used as second-line antihypertensive drugs for hemodialysis patients, or for patients with RAS inhibitor contraindications or cardiac conduction defects. Hypertensive nephropathy first-line medication. Can stimulate renin release, cause RAAS activation and cause reflex sympathetic excitation (excessive vasodilator effect). Common ankle edema, gingival hypertrophy / gingival hyperplasia, reflex heart rate, flushing and so on. High fat-soluble statins such as simvastatin and lovastatin are mainly metabolized by CYP3A4. Amlodipine has a moderate inhibitory effect on CYP3A4. Therefore, when amlodipine is combined with simvastatin and lovastatin, the doses of the latter two should be the same. ≤20mg.
NDHP-CCB can reduce blood pressure, but due to its cardiac affinity and its negative inotropic and negative transmission effects on myocardial, sinoatrial node function, and atrioventricular conduction , more suitable for hypertension with angina pectoris, hypertension with supraventricular tachycardia and hypertension with carotid atherosclerosis. Verapamil and diltiazem are drugs (substrates)/inhibitors of CYP3A4 metabolism, and interact with other drugs such as statins, calcineurin inhibitors, etc. NDHP-CCB and β-receptor blockade Combination of drugs can cause atrioventricular conduction delay and complete heart block. NDHP-CCB is contraindicated in patients with second- to third-degree atrioventricular block, and is relatively contraindicated in patients with heart failure.
03
Diuretics
including loop diuretics ( Such as furosemide, torasemide), thiazide diuretics (such as hydrochlorothiazide, indapamide), aldosterone receptor antagonists (such as spironolactone, eplerenone), mainly through natriuretic diuresis, reducing systemic volume load and exert a hypotensive effect.
Loop diuretics and thiazide diuretics can be used in the treatment of hypertensive nephropathy. Diuretics can be used as a combination of antihypertensive drugs in patients with hypertensive nephropathy when the volume is overloaded. The combination of the two with ACEI/ARB can synergistically reduce blood pressure and reduce hyperkalemia. disease risk. It is recommended that patients with hypertensive nephropathy with increased volume load and poor blood pressure control can consider combined diuretic antihypertensive therapy. Thiazide diuretics can be used in patients with mild renal insufficiency in CKD1-3 stages, and loop diuretics should be used in patients with low eGFR (eGFR<30mL/(min·1.73m2)).
It can cause electrolyte disturbances such as hypokalemia, glucose and lipid metabolism disorders, and hyperuricemia. Thiazide diuretics have adverse effects on glucose and lipid metabolism and electrolytes, and should be used with caution. Small doses have little effect on metabolism. Patients with hyperuricemia should be used with caution, and those with gout should be banned. The combined use of diuretics and beta-blockers may affect glucose and lipid metabolism or electrolytes, and combined use is not recommended.
aldosterone receptor antagonists/mineralocorticoid receptor antagonists (MRAs) such as spironolactone, eplerenone and feneridone can diuretic, reduce blood pressure, and can also resist Salt and antisodium, reduction of proteinuria levels, and adjuvant therapy for the prevention and treatment of renal and cardiovascular complications, which may bring renal benefit through blockade of RAAS. At present, MRA is recommended for the treatment of hypertension in advanced heart failure and myocardial infarction. Feneridone is used in patients with eGFR>30mL/(min·1.73m2) CKD, especially those with diabetes who may have better renal and cardiovascular conditions. benefit. The combination of MRA and ACEI/ARB can effectively control hypertension, significantly reduce urinary albumin or urinary protein excretion rate, and reduce the incidence of cardiovascular events to a certain extent.
spironolactone | eplerenone | non- Nellidone | |
generation | First GenerationMRA | Second GenerationMRA | third generationMRA< /span> |
Features< /span> | Binds to mineralocorticoid receptors, but also to androgen and progesterone receptors , has a relatively large effect on the gonads. | Highly selective aldosterone receptor antagonist, anti-aldosterone activity is spironolactone 2 times. | New highly selective non-steroidal span>MRA, with high selectivity for mineralocorticoid receptors, compared with the first and second generationMRA Has higher specificity and affinity for mineralocorticoid receptors, can selectively bind to mineralocorticoid receptors, and has lower affinity for androgen, glucocorticoid, progesterone and estrogen receptors, which can achieve the target While reducing the incidence of adverse events, it may be more advantageous for CKDcombined with high risk of cardiovascular disease complications, which can reduce< span>CKD Urine albumin. |
bad Response | can block testosterone synthesis and produce anti-androgenic effects, which can Impotence, loss of libido, gynecomastia, gynecomastia/hyperplasia of mammary glands or menstrual disorders in women, etc. | Its receptor blocking effect is weaker than that of aldosterone and does not antagonize androgen Hormone and progesterone receptors, and the adverse reactions related to sex hormones are significantly less than spironolactone. | Compared with spironolactone, it has a lower incidence of hyperkalemia and is associated with sex hormones. The associated adverse reactions were also significantly reduced, and the risk of worsening renal function was smaller. |
spironolactone, eplerenone It can cause hyperkalemia, so it is contraindicated in patients with hyperkalemia and severe renal insufficiency [eGFR<30ml/(min•1.73m2)]. The combination of MRA and ACEI/ARB may increase the risk of hyperkalemia, so special attention should be paid to the risk of hyperkalemia and significantly lower eGFR.
04
beta Body blockers
β-blockers can reduce blood pressure, inhibit overactive sympathetic nerve activity, inhibit myocardial contractility, slow down heart rate, and effectively prevent angina pectoris and coronary artery disease Generally hypertensive patients are not recommended as initial monotherapy with beta-blockers. It can be divided into non-selective β-blockers, selective β-blockers (such as metoprolol, bisoprolol) according to the selectivity of receptors , α1/β receptor blockers (such as arolol, carvedilol, labetalol, etc.), among which α1/β receptor blockers also have vasodilator effects, and play a cardio-renal protective effect, Can reduce renal vascular resistance, but does not reduce renal blood flow and glomerular filtration rate.
Because beta-blockers can benefit patients with heart failure and acute myocardial infarction with reduced ejection fraction, CKD patients often coexist with heart failure, and CKD patients are prone to Sympathetic nerves are excited, especially those with ESRD, so beta-blockers are the first-line drugs for heart failure patients with reduced ejection fraction. Bisoprolol, carvedilol or metoprolol succinate are recommended, and beta-blockers are recommended. Blockers are preferred over CCB as the recommended drug for hypertensive nephropathy patients with chronic heart failure. β-blocker combined with ACEI can be the first choice for heart failure patients with reduced ejection fraction.
Categories | Drug | Solubility | cardiac selectivity (β1 span>selective) | peripheral vessels Dilation (α1selective) | Intrinsic sympathomimetic activity (ISA) |
selectiveβ1 span>Blockers | bisoprolol | Bi-solubility p> | + | – | none |
Metoprolol < /p> | lipid soluble | + | – < p> |
| |
Ati Lor | water soluble | + | – | none | |
hemodialysis patients, atenolol reduces blood pressure It appears to be superior to lisinopril and may reduce the incidence of cardiovascular events in hemodialysis patients. | |||||
α1/βblockers | < p>Carvedilol | lipid-soluble | – | + | none |
Arolol< /p> | Bi-solubility | – | + | none < /td> | |
Labelol
| lipid soluble | – | + | Yes | |
Carvedilol and othersbeta Compared with receptor blockers, it does not increase insulin resistance, the risk of hyperkalemia is relatively low, and there is no accumulation in patients with renal failure, and the dialysis clearance rate is almost zero, so it is suitable for patients with hypertensive nephropathy. It can be considered as the first-choice βreceptor blocker, and atenolol or bisoprolol can be considered as others. | |||||
Note:①lipid-solubleβreceptor blocker tissue penetration Strong, easy to enter the central nervous system, may be one of the causes of central adverse reactions (such as dreaminess, insomnia, dizziness, hallucinations, depression, etc.). ②intrinsic sympathomimetic activity (ISA) means that some betareceptor blockers have weak beta span>receptor agonism, this weak agonism is ISA, with ISA activity The effects of βreceptor blockers on cardiac depression and asthma induction were weak. | |||||
Can cause hyper/hypoglycemia, fatigue , headache, sleep disturbance, somnolence, depression, insomnia, increased airway resistance, exacerbation of asthma, hypotension, dizziness, slow heart rate (<55 beats/min), severe bradycardia, atrioventricular block , worsening of heart failure, extremity circulatory disorder, etc. Sudden withdrawal of β-blockers can easily induce angina pectoris, resulting in hypertension, tachyarrhythmia, aggravation of angina pectoris, and even myocardial infarction. Therefore, the drug should be stopped slowly, and the whole process will take at least 2 weeks. Patients with peripheral vascular disease (especially diabetic nephropathy with peripheral arterial stenosis and occlusion) should be used with caution.
05
Other drugs
alpha Body blockers: can reduce blood pressure, such as prazosin, terazosin, doxazosin, but are prone to orthostatic hypotension, which often occurs in the latter due to dialysis Hypotension, especially in people close to dry body weight, can cause serious falls and fractures if used. Therefore, it is not recommended to be preferred except for poor blood pressure control.
Angiotensin Receptor Enkephalinase Inhibitor (ARNI):For example, sacubitril and valsartan is a new type of antihypertensive drug, which can effectively, rapidly, steadily and lastingly lower blood pressure, protect target organs (heart, kidney, blood vessels, etc.), improve metabolic disorders, and excrete natriuresis and diuresis. It can reduce the risk of cardiovascular death and heart failure hospitalization in patients with chronic heart failure, and is suitable for patients with CKD1-3 stages. Can cause hyperkalemia, hypotension, renal damage, angioedema and so on. Use with caution in patients with severe renal impairment and renal artery stenosis.
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Disclaimer: This article is original content, author Redputao, for learning onlycommunication, < /span>The copyright belongs to the original author.
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