Hypertension is very closely related to the kidney, and persistent hypertension can be the cause of direct kidney damage; while kidney disease itself can also lead to hypertension, exacerbating the deterioration of kidney function, forming a vicious circle. This kind of hypertension caused by various kidney diseases is called renal hypertension.
Classification
1, renal vascular hypertension.
Secondary hypertension mainly caused by narrowing of the main trunk or branches of one or both renal arteries and obstruction causing ischemia of the renal parenchyma, which activates the renin-angiotensin-aldosterone system (RAS). Common causes include aortitis, fibromuscular dysplasia and renal artery atherosclerosis.
2, renal parenchymal hypertension.
It is mainly caused by parenchymal lesions on one or both sides of the kidney such as: various acute and chronic glomerulonephritis, diabetic nephropathy, lupus nephritis, chronic pyelonephritis, polycystic kidney and other renal parenchymal diseases.
Pathogenesis
1. Volume-dependent mechanism.
Mainly by the kidney’s ability to excrete sodium and water, water and sodium retention occurs, resulting in increased blood volume and increased blood pressure.
2. Renin-dependent mechanism.
Renal ischemia caused by renal parenchymal lesions can stimulate glomerular parietal cells to secrete large amounts of renin, which causes vasoconstriction, water and sodium retention, and increased blood pressure through the renin-angiotensin-aldosterone system (RAS).
Treatment
1. Treatment of renal vascular hypertension.
The treatment of renal vascular hypertension is based on surgical procedures, including nephrectomy, renal revascularization, autologous kidney transplantation, and interventions such as percutaneous transluminal renal arterioplasty (PTRA) and renal artery stenting (metal endoprosthesis), which have progressed more rapidly in recent years.
Drug therapy is not the preferred method for renal vascular hypertension, and antihypertensive drugs are used only for those who are not suitable for or refuse to receive the above treatments. The drug of choice is calcium channel blockers, such as felodipine and nifedipine, which can effectively lower blood pressure and less likely to cause renal impairment. The next is beta receptor antagonists, such as betalactam.
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II (Ang II) receptor antagonists are prohibited in the treatment of renal vascular hypertension. This is because Ang II production is increased in renal artery stenosis and renal ischemia, which constrict the small glomerular outflow arteries and maintain glomerular filtration rate (GFR). When ACEI or Ang II receptor antagonists are used, the formation and action of Ang II is inhibited, leading to a decrease in GFR and aggravation of the condition.
2.Treatment of renal parenchymal hypertension
(1) Non-pharmacological treatment.
This includes promoting a healthy lifestyle and eliminating behaviors and habits that are detrimental to mental and physical health to achieve a reduction in the risk of hypertension and other cardiovascular diseases. Adjusting lifestyle habits, quitting smoking, moderating alcohol consumption, treating environmental stress properly, and maintaining a normal state of mind.
For patients with end-stage renal failure receiving dialysis, the first step is to adjust the intake of water and salt to achieve the ideal dry weight. Pay attention to low sodium and low fat. Low sodium can not only effectively control sodium and water retention, but also increase the antihypertensive effect of ACEI and calcium channel blockers (CCB).
(2) Drug therapy.
Blockade of the renin-angiotensin system (RAS) is the preferred method. There are two major classes of RAS-blocking drugs in clinical use: ACEI and Ang II receptor antagonists. Dosing should, in principle, avoid kidney-damaging drugs, start at low doses, and be combined.
Diuretics.
It is one of the most valuable antihypertensive drugs.
Potassium-depleting diuretics include high-efficiency tab diuretics represented by furosemide and medium-acting thiazide diuretics represented by hydrochlorothiazide, which are indicated for water and sodium retention in renal disease, but have a tendency to hypokalemia, hyperuricemia, and hyperglycemia.
The aldosterone receptor blockers, represented by Antiseptic, are potassium-preserving diuretics, which inhibit the action of aldosterone to diuretic and also lower blood pressure, and can reduce the damage of aldosterone to the cardiovascular system.
Indopamine, with diuretic and calcium antagonistic effect, is especially suitable for mild to moderate hypertension. It has a long-lasting effect, lowers blood pressure smoothly, and does not cause disorders of glucose, lipid and uric acid metabolism.
Calcium antagonists (CCB).
Mainly through the expansion of peripheral resistance vessels and lowering blood pressure, no dilating effect on the volume vessels at therapeutic doses. Including non-dihydropyridines and dihydropyridines two categories.
Dihydropyridines mainly include nifedipine, felodipine, amlodipine, etc. Currently, long-acting or slow-release preparations are recommended, and their short-acting preparations can cause large fluctuations in blood pressure as well as disorders of glucose and lipid metabolism and aggravation of proteinuria, and their use is no longer recommended.
Because calcium antagonists can reduce glomerular capillary pressure, reduce the deposition of macromolecules in the glomerular thylakoid area, inhibit the proliferation of thylakoid cells and stroma to reduce the development of glomerulosclerosis, thus having a nephroprotective effect.
Receptor blockers.
Beta-blockers can block sympathetic nerve boosting effect, representative drugs are atenolol, metoprolol, but need to pay attention to the side effects of bradycardia, conduction block, bronchial asthma patients use with caution.
a1 receptor blockers can selectively block the a 1 receptor in the postsynaptic membrane of vascular smooth muscle, causing vasodilatation, resulting in a decrease in peripheral vascular resistance and a decrease in the amount of blood returned to the heart, thus lowering blood pressure. Representative drugs include prazosin, terazosin and uradil.
Alpha and beta receptor blockers are new antihypertensive drugs that promote the release of nitric oxide from glomerular capillary endothelial cells, resulting in intracellular ATP efflux, thereby relaxing and dilating glomerular microvessels and improving microcirculation. For example, Arotinolol and Carvedilol, combined with calcium antagonists, not only showed effective antihypertensive effects, but also effectively alleviated further decompensation of renal function and cardiovascular complications.
In addition, most α- and β-blockers have high protein binding rates, and dialysis patients do not need to adjust the dose or mode of administration. However, because carvedilol blocks β1 and β2 receptors non-selectively. Side effects related to glucose metabolism and respiratory disease should be noted.
ACEI:
ACEI can block the production of angiotensin II, reduce aldosterone synthesis, and lower systemic blood pressure in terms of reducing vascular resistance and blood volume; in addition, ACEI can also act on the local RAS of renal tissue, dilate the small glomerular arteries, and the effect of dilating the small glomerular arteries is stronger than that of the small glomerular arteries, improve the phenomenon of high transmembrane pressure, hyperfiltration and hyperperfusion in the glomerulus, and slow down the process of renal damage. It also improves the permeability of the glomerular filtration membrane to albumin and reduces urinary protein; it reduces the accumulation of extracellular matrix in the glomerulus and reduces glomerulosclerosis.
At present, ACEI is considered to have the most positive effect on kidney protection among antihypertensive drugs. The commonly used ACEI drugs include captopril, enalapril, benazepril, ramipril, fosinopril, etc. When using ACEI, start with small doses and gradually increase the amount to control blood pressure in a satisfactory range. If the increase of Scr does not exceed 50% and can be recovered within 2 weeks without medication, it is a normal reaction; if the increase of Scr exceeds 50% or the absolute value exceeds L33μmol/L and no decrease is seen after 2 weeks of medication, it is an abnormal reaction and should be discontinued.
Benazepril is highly permeable to renal tissues, and the metabolites are partially excreted by bile, so the dose should be reduced only when the creatinine clearance (Ccr) is <30 ml/min; while fosinopril has the largest proportion of excretion from bile among all ACE1 drugs, so there is no need to adjust the dose even if the renal function is reduced. Elderly patients may have renal artery atherosclerosis and will be particularly sensitive to ACEI for lowering blood pressure.
The use of ACEI in patients with bilateral renal artery stenosis or isolated renal artery stenosis may lead to acute renal failure and should be contraindicated. The use of ACEI in patients with end-stage renal disease (ESRD) has many side effects, such as hyperkalemia, neutropenia, allergic reactions, chronic cough, renal impairment, etc. The use of ACEI with EPO may affect the efficacy of EPO, and it is recommended to increase the dose of EPO.
Angiotensin II receptor antagonists (ARB) class.
It has a highly selective effect of blocking ATl and increasing AT2, and the representative drugs are Cloxacin and Valsartan. Unlike ACEI, ARB class has low incidence of hyperkalemia and cough, does not reduce renal blood flow, and its efficacy is not affected by ACE gene polymorphism; it can inhibit various effects of Ang II catalyzed by non-ACE, and some can also reduce blood uric acid (e.g., coxsartan). ARB class is indicated and prohibited for the same subjects as ACEI.
Combinations.
Antihypertensive drugs are usually started at low doses and if the blood pressure does not reach the target, the dose of the drug should be increased according to the patient’s tolerance. If the first drug is not effective, a reasonable combination should be used, usually with a second antihypertensive drug at a lower dose rather than a higher dose of the first drug.
Combination drug combinations are.
ACEI + diuretic;
diuretics + beta-blockers;
beta-blocker + calcium channel blocker;
ACEI+calcium channel blocker;
ACEI + ARB can synergistically lower blood pressure and reduce the occurrence of side effects.