The mechanism of renal damage caused by hypertension has not been elucidated, including hemodynamic and non-hemodynamic mechanisms. The involvement of immune inflammatory response in the pathogenesis of hypertensive renal damage has gradually become a hot research topic in recent years [23]. The main purpose of this study was to investigate the effect of FAR, an inflammatory marker, on early renal damage in patients with hypertension. Samples consisted of patients with essential hypertension, grouped according to the FAR tertiles and the presence or absence of early renal impairment. The levels of early renal impairment indexes and inflammatory markers were compared among different groups. The results showed that the serum CysC and β2-MG levels of patients in the M-FAR group and H-FAR group were higher than those in the L-FAR group. The levels of fibrin and FAR in the renal impairment group were significantly higher than those in the normal renal function group. The serum albumin level was significantly lower than that in the normal renal function group. The FAR level had a positive correlation with β2-MG and serum CysC. The results of multiple linear regression analysis showed that: FAR level is a factor affecting blood β2-MG and serum CysC, suggesting that for patients with hypertension and increased levels of inflammatory factors, the early renal damage was more significant. FAR level is related to the changes of blood β2-MG and serum CysC.
Hypertension is a low-grade inflammatory state disease, and inflammation plays an important role in the occurrence, development and complications of hypertension [24]. Persistent inflammation is also a key feature of CKD, which can lead to progressive renal fibrosis, endothelial dysfunction and other aggravating renal damage [25]. Fibrinogen, a precursor of fibrin, is produced by the liver and has a serum concentration of 2.0–4.0 g/L, which plays an important role in thrombosis and inflammatory reaction [26]. A large number of studies have found that serum fibrinogen levels are related to cardiovascular risk factors or cardiovascular events [27], and fibrinogen has also been found to be significantly associated with renal impairment. For example, Lin et al. [28] in a cross-sectional study of 732 T2DM men found that serum fibrinogen was associated with decreased glomerular filtration rate, and another study reported [14] that elevated serum fibrinogen levels in T2DM patients were associated with end-stage renal disease. Fibrinogen has been identified as an independent risk factor for death and cardiovascular events in patients with chronic renal disease Stage 3 and 4 [29]. Celik et al. [30] found that serum fibrinogen levels were independently associated with the risk of contrast-induced acute kidney injury in patients with acute coronary syndrome receiving coronary intervention (OR 1.006,95% CI 1.003–1.009,p < 0.001). In summary, chronic inflammatory conditions, reflected in elevated serum fibrinogen levels, may have exacerbated renal impairment. This study found a significant increase in plasma fibrinogen levels in patients with early renal impairment compared to patients with normal renal function, demonstrating that mean concentrations in patients with renal impairment were significantly higher than in patients with normal renal function.
Serum albumin is a synthetic protein of the liver that maintains the plasma colloid osmotic pressure, transports lipids, and participates in the processes of acute and chronic inflammation [15, 31]. Serum albumin concentration is related to the increase of inflammatory load in vivo, and inflammation is related to the decrease of albumin synthesis and increase of catabolism [16]. Studies have shown that serum albumin level is a useful and reliable prognostic indicator for acute kidney injury [32]. An independent predictor of acute kidney injury in patients after PCI for acute coronary syndrome when serum albumin reduction at admission was identified [33]. The mechanism of kidney injury caused by low serum albumin is considered to be multi-factorial, including inhibition of platelet aggregation, increase of blood viscosity, reduction of antioxidant capacity, inflammatory response and destruction of endothelial function [16, 17, 34]. This study found that serum albumin levels decreased with the increase in inflammatory index levels, and serum albumin levels in patients with renal impairment were lower than those in the normal renal function group, which was consistent with the results of the above study.
It has been recently found that FAR is a novel inflammatory indicator that combines fibrinogen and albumin, and can more sensitively reflect the inflammatory state. Many studies have revealed the relationship between FAR and many diseases, including cardiovascular diseases. For example, that study by Mahmut et al. [35] indicate that FAR is a powerful predictor of early morning blood pressure increase in newly diagnosed and treated patients with primary hypertension and may be a bet predictor than single fibrinogen and albumin. In addition, FAR is significantly associated with the severity and short-term prognosis of coronary artery stenosis in patients with st-segment elevation myocardial infarction [36, 37]. Notably, a recent study found that FAR was independently associated with the occurrence of PC-Aki (post-contrast acute kidney disease) [38]. Jing JuanYang et al. [32] revealed that preoperative serum fibrinogen was associated with the risk of acute kidney injury after heart valve replacement (OR = 1.212, 95% CI 1.1089–1.347, P = 0.003).
At present, the markers used for evaluating renal impairment mainly include Scr, BUN, CysC, β2 -MG, etc. Among them, CysC, which is used to reflect glomerular function, is an effective indicator for the assessment of glomerular filtration rate at present. With high sensitivity and strong specificity, it is less affected by factors such as gender, age, and muscle content, and is one of the ideal indicators for the assessment of early renal injury [39]. Ozer et al. [40] found that compared with traditional renal injury markers Scr and BUN, CysC is the best indicator for predicting renal function in primary hypertension patients with mild decreased GFR. β2 -MG, a small molecular protein, has a low but constant content in the body, which is a sensitive indicator for assessing renal tubular function. In the early stage of decreased glomerular filtration function, serum β2 -MG level can be increased, and increases with the aggravation of renal impairment. It is a sensitive indicator reflecting early lesions of hypertensive renal injury [41]. In this study, the relationship between the new inflammatory marker FAR and early renal impairment was explored for the first time. The results showed that as the level of FAR increased, the levels of β2 -MG and CysC also increased, and there was a significant positive correlation between them. FAR level was a factor affecting blood β2-MG and serum CysC. With the increase of the value of FAR, the levels of β2 -MG and CysC increased by 6.362 and 1.991 respectively. It indicated that inflammation was a risk factor for early renal injury in patients with hypertension, and monitoring of FAR could well assess early renal impairment.
Limitations
Of course, the study has some limitations. First, our study results are based on a retrospective study design, and selection bias is inevitable. Second, this study was conducted in Chinese patients with hypertension, and no normal subjects were recruited as the control group. The results need to be verified in a healthy population and other ethnic groups. Third, the majority of the subjects included in the study with hypertension were in Grade 3 hypertension, and the proportion of other subjects was small, which limited the intensity of the results and conclusions of this study. Finally, we only measured albumin, fibrinogen, and FAR levels at admission; we did not perform continuous measurements of these parameters.
Conclusion& future perspective
This study has shown that elevated FAR levels are an independent risk factor for early renal damage in hypertensive patients and baseline FAR can provide a useful indicator of early renal damage in hypertensive patients and is superior to established inflammatory markers. Therefore, for patients with hypertension, in order to prevent target organ damage, we should pay attention to the treatment of inflammation while strictly controlling the blood pressure to reach the standard, in order to delay the occurrence of renal damage and reduce the risk of cardiovascular and cerebrovascular complications.