2, reversible risk factors
Hypertension is the root cause of hypertensive kidney damage, and any factor that causes elevated blood pressure can be used as a risk factor for kidney damage, in addition, the characteristics of hypertension itself and coexisting clinical conditions are also closely related to kidney damage.
2.1 Hypertension risk factors
2.1.1 Adverse lifestyle
2.1.1.1 Dietary predilections Dietary structure has an important influence on hypertension. A high-sodium diet is a risk factor for hypertension. The prevalence and blood pressure levels of hypertension in different regions of the population are significantly correlated with the average intake of sodium and salt, and the higher the salt intake, the higher the prevalence and blood pressure levels, more significantly in salt-sensitive populations, and the mechanism is related to increased blood volume and sodium-water retention; in addition, a high-sodium diet can aggravate kidney damage, and this effect is related to both increased blood pressure and direct damage to glomerular foot cell repair function and oxidative stress by high salt This effect is closely related to the direct damage of glomerular foot cell repair function and the impact of oxidative stress.
In addition, dietary intake of potassium and protein is negatively correlated with blood pressure; inadequate calcium intake, as well as excessive intake of saturated fatty acids, or a reduced ratio of unsaturated to saturated fatty acids, can lead to increased blood pressure.
2.1.1.2 Smoking Smoking is a recognized risk factor for cardiovascular disease, which can lead to increased blood pressure and reduce the efficacy of antihypertensive drugs.
It can also reduce the efficacy of antihypertensive drugs. Nicotine and other harmful substances in tobacco can excite the central nervous system and sympathetic nerves and increase the release of catecholamines, causing increased heart rate and peripheral vasoconstriction. Long-term heavy smoking leads to sustained constriction of small arteries, degeneration of smooth muscle cells in the arterial wall, damage to the vascular endothelium, and thickening of the vascular wall, causing systemic small arteriosclerosis and accelerating the development of hypertension.
Smoking affects renal damage may be related to oxidative stress, vascular endothelial cell damage and aggravation of atherosclerosis.
2.1.1.3 Alcohol consumption Moderate or higher alcohol consumption both directly raises blood pressure and affects the efficacy of antihypertensive drugs. Epidemiological studies in China have confirmed that those who drink on average more than 50 ml of liquor per day (about 24 grams of alcohol, i.e., 2 standard glasses) have higher systolic and diastolic blood pressure than those who do not drink 3.0-4.0 mmHg and 1.0-2.0 mmHg, respectively, and the magnitude of the increase in blood pressure rises with the increase in the amount of alcohol consumed.
2.1.1.4 Lack of physical activity In normotensive people, sedentary and physically inactive individuals have a 20% to 50% increased risk of hypertension compared with active controls of the same age. Exercise helps to improve both the coexisting clinical conditions of hypertensive patients; it also lowers the blood pressure level of patients, and the mechanism may be related to factors such as relieving sympathetic tension, increasing the production of vasodilator substances, improving endothelial diastolic function, and affecting the body’s glucolipid metabolism.
2.1.2 Psychosocial factors
Psychosocial factors are closely related to the occurrence and progression of hypertension. Long-term mental tension, irritability, anger, noise and other malignant stimuli, as well as strain, sleep deprivation, anxiety, fear and depression and other adverse psychological can lead to the occurrence of hypertension. The mechanism is mainly stressful state, excitation of cerebral cortex, enhanced sympathetic nerve activity, and increased release of catecholamines, which cause vasoconstriction. In addition, long-term mental stress can lead to hyperplasia and hypertrophy of vascular smooth muscle cells, resulting in a sustained increase in blood pressure.
2.1.3 Obstructive sleep apnea syndrome (OSA)
OSA is a respiratory disorder, mainly manifested by frequent loud snoring during sleep, apnea, nocturnal hypoxemia, daytime sleepiness, etc. OSA can often cause a variety of cardiovascular system diseases, and numerous studies have shown that OSA is an important independent risk factor for hypertension, at least 30% of hypertensive patients have OSA, and 4%-48% of OSA patients have hypertension. Not only is the mean 24-hour blood pressure elevated, but the blood pressure rhythm is also affected.
2.1.4 Inflammatory factors
Inflammation is involved in the development and progression of renal impairment in hypertension. Hypertension may be an underlying inflammatory state in which target organ damage is accompanied by an inflammatory response.
Resistin is a newly discovered cysteine-rich plasma protein belonging to a family of peptides. In humans, resistin is mainly derived from monocytes and macrophages in the blood, suggesting that the action of resistin in humans may be mainly related to inflammation. High resistin is a risk factor for kidney damage. Resistin is involved in the pathological process of atherosclerosis (AS), hypertension and its target organ damage.
2.2. Characteristics of hypertension itself
2.2.1 Duration and degree of hypertension
The duration and degree of hypertension is positively correlated with renal damage. According to Perera’s study, the duration of hypertension alone is 15 years, and renal damage occurs in about 42% of cases. It is presumed that the clinical symptoms of renal damage in essential hypertension usually appear in 10-15 years, but it actually varies because of the influence of other risk factors that patients have. The results of MRFIT show that the risk of ESRD is 2 times higher in patients with normal high blood pressure (135/85 mmHg) than in those with normal blood pressure (120/80 mmHg); and in patients with grade 3 hypertension, the risk increases to 12 times, so not only must blood pressure be strictly controlled in patients with severe hypertension, but also in patients with grade 1 to 2 mild hypertension. Patients with severe hypertension and even those with normal high blood pressure should also be actively intervened in order to effectively prevent and control the occurrence of renal damage.
2.2.2 Salt sensitivity of blood pressure
Salt-sensitive hypertension is defined according to the different responses of individual blood pressure to changes in salt intake, and there is no unified standardized measurement method or determination criteria. As a special type of primary hypertension, the most distinctive feature of salt-sensitive hypertension is the susceptibility to renal damage, which is characterized by the early appearance and severity of renal damage and is often accompanied by insulin resistance.
Currently, the synergistic effect between “salt-sensitive-oxidative stress-inflammation” and systemic and local renal RAS is of great interest. In addition, the increased insulin resistance and vascular endothelial dysfunction in salt-sensitive hypertensive patients are also correlated with their renal damage.
2. 2.3 Circadian rhythm of blood pressure
There is a circadian rhythm in normal blood pressure, i.e., a >10% decrease in blood pressure at night compared to daytime, called the arytenoid rhythm. The presence of the arytenoid rhythm depends on good tissue and organ perfusion. Organ ischemia, especially cerebral ischemia, may activate cardiovascular regulatory mechanisms that maintain organ blood flow, inhibiting the nocturnal blood pressure drop and changing the blood pressure rhythm to a non-arytenoidal pattern.
Blood pressure rhythm is a factor influencing hypertensive renal damage and its prognosis. Blood pressure in a non-arytenoidal rhythm is associated with higher cardiovascular events in ESRD patients, and blood pressure rhythm is an independent predictor of long-term cardiovascular events in hypertensive hemodialysis patients.
Non-arrythmic rhythm blood pressure suggests a prolonged cardiovascular system overload, aggravating vascular endothelial dysfunction, activation of the endogenous coagulation system, and eventually vasoconstriction-diastole imbalance, blood hypercoagulation, vascular remodeling, and myocardial hypertrophy, causing and aggravating target organ damage. Anti-hypertensive therapy should be effective in controlling blood pressure at night.
2. 2.4 Pulse pressure
There is a correlation between pulse pressure and hypertensive renal damage, and increased pulse pressure is an independent risk factor for hypertensive renal damage. The greater the pulse pressure, the more severe the renal damage, and the higher the incidence of hypertensive nephropathy, which is manifested early in the renal damage. Pulse pressure, which represents the compliance of large arteries, has a detrimental effect on renal function independent of systolic pressure, and the mechanism may be the reduced elasticity of renal arteries, reduced compliance, and increased arterial pulse wave conduction velocity, resulting in greater pressure waves in the middle and small renal arteries, and atherosclerotic stenosis of the vessel wall, which ultimately affects renal function.
2.3 Coexisting clinical conditions of hypertension
2.3.1 Overweight or obesity
Weight and blood pressure are highly correlated, and overweight and obesity are not only independent risk factors for hypertension, but also closely related to renal damage.
Obesity refers to a body mass index (BMI) greater than 30 kg/m2 and is an important predictor of the occurrence of microalbuminuria and proteinuria, which increases the risk of renal damage. The main causes of obesity leading to proteinuria and glomerulosclerosis are as follows: (1) Glomerular hyperfiltration. (2) Hyperlipidemia. (3) Low plasma lipocalin levels. (4) The role of leptin (Leptin). Obesity mostly coexists with clinical conditions such as IR, hypertension and hyperlipidemia, which together exacerbate the development of renal damage.
2. 3.2 Insulin resistence (IR) or metabolic syndrome (MS)
Hypertension is often combined with metabolic abnormalities, such as abdominal obesity, hyperlipidemia, hyperglycemia and IR, among which IR is the core of MS. Several studies in the literature have shown that IR or MS is a risk factor for subclinical cardiovascular events and exacerbation of renal damage in hypertensive patients.
IR can cause constriction of the small efferent arteries and increased transmembrane pressure, and the persistent hyperperfusion and hyperfiltration state can lead to glomerulosclerosis and renal unit destruction; hyperinsulinemia itself can also activate the renin-angiotensin-aldosterone system (RAAS), leading to vascular endothelial damage, causing blood hypercoagulation and promoting thrombosis; in addition, disorders of glucolipid metabolism, increased end products of advanced glycosylation and concurrent multiple pathological changes, such as vascular inflammatory response, all act together to aggravate renal damage.
2. 3.3 Hyperglycemia
The kidney plays an important role in the dynamic balance of blood glucose, and abnormal blood glucose is closely related to the progression of renal disease and is a risk factor for aggravating hypertensive kidney damage.
Renal damage due to hyperglycemia is associated with increased production of glycosylation end products, abnormal hemodynamics, inflammatory mediators and oxidative stress.
2.3.4 Dyslipidemia
The 2007 European guidelines for the prevention and treatment of hypertension state that dyslipidemia includes both elevated total cholesterol (TC >6.5 mmol/L) and elevated LDL cholesterol (LDL-C >4.0 mmol/L) or reduced HDL cholesterol (HDL-C: <1.0 mmol/L in men and <1.2 mmol/L in women), pointing to the The close relationship between dyslipidemia and hypertension and the importance of regulating dyslipidemia in hypertensive patients is emphasized. Dyslipidemia is also is an important participant in kidney damage, and the co-existence of dyslipidemia and hypertension together accelerates the progression of kidney damage.
2. 3.5 Hyperuricemia
Hyperuricemia is closely related to hypertension and is both an independent marker and risk factor for renal damage in hypertension Hypertension and hyperuricemia interact with each other and work together to exacerbate the progression of renal damage.
In addition, hyperuricemia exacerbates renal damage and is associated with uric acid-mediated vascular smooth muscle cell proliferation and inflammatory responses. Uric acid deposition in the kidney leads to vascular smooth muscle cell proliferation through the cyclooxygenase-2 (COX-2) pathway, which damages the intima of arteries and aggravates atherosclerosis; it also activates RAAS, which exacerbates renal ischemia; it activates platelets, 5-hydroxytryptamine and other vasoactive substances. Weaken acetylcholine-mediated vasodilation, resulting in increased peripheral vascular resistance, which can further promote the development of hypertension, both of which form a vicious circle.
2.3.6 Homocysteine (Hcy)
A large number of studies have shown that Hcy can promote atherosclerosis and thrombotic disease, affect the systemic vasculature, lead to hypertension and other diseases, and is considered to be one of the new independent risk factors for cardiovascular disease. In patients with hypertension with cerebral infarction, Hcy was positively correlated with carotid intima-media thickness.