Chronic kidney disease (CKD) is defined as the presence of structural and functional renal dysfunction for at least 3 months and characterized by reduced glomerular filtration rate, albuminuria, renal morphological changes, tubular dysfunction, or a history of kidney transplantation (1). As a significant and growing global public health problem, CKD affects 800 million people worldwide (2), and causes millions of death every year (3), which ranked 16th leading cause of death worldwide (4) Liyanage et al. conducted a study on end-stage kidney disease (ESKD) renal replacement therapy in 123 countries. The findings revealed that in 2010, 2.618 million individuals underwent renal replacement therapy, out of which 2.05 million received dialysis. The prevalence of ESKD treatment exhibited significant regional variation, with 80 cases per million people in Africa and 1840 cases per million people in North America (5). The pathophysiology of CKD manifests as progressive renal damage, which may leads to the progression of renal dysfunction and may eventually progress to end-stage renal disease (ESRD) (6). The economic burden caused by CKD is increasing due to the aging population and prevalence of comorbid diseases (7).

In recent years, the role of inflammation in the pathogenesis of CKD has received extensive attention. One of the key features underlying the progression of CKD is the persistent and systemic inflammation observed in these patients (8, 9). Inflammation plays a crucial role in the initiation and progression of CKD and contributes to the development of various complications, such as cardiovascular diseases (10), malnutrition (11), anemia (12), and renal osteopathy (13). Microinflammatory state is an important risk factor for mortality in chronic kidney disease (14). Therefore, certain inflammatory biomarkers have been reported to be used as possible predictors and therapeutic targets for CKD (15).

Despite the rapidly growth of published literatures on the relationship of inflammation and CKD, there has been limited effort to systematically analyze and map the research landscape in the field. A comprehensive understanding of the current state of research, key players, and emerging trends is essential for guiding future research directions and identifying knowledge gaps.

Bibliometric analysis is a powerful tool for analyzing scientific literatures and visualizing research landscapes. It provides insights into influential countries, institutions, authors, and journals. It also helps to identify research hotspots and emerging trends (16). For instance, a bibliometric analysis reported the worldwide research patterns and focal points concerning autophagy and kidney disease between 2000 and 2022 (17), while another bibliometric analysis has been conducted on the topic of schizophrenia and inflammation studies (18). Nevertheless, as of now, no bibliometric analysis has been published regarding the subject of inflammation and CKD. In order to fill this research gap, we conducted this bibliometric analysis study to explore the field of inflammation-related research in CKD.

This article aims to explore the relationship between inflammation and chronic kidney disease through bibliometric analysis, as well as to identify current hotspots and trends in research development. The number of publications in this field has been steadily increasing since 2007, with a sharp rise in 2013 and reaching its peak in 2022, indicating a growing interest in this area of research. The top three authors in terms of publication output are Stenvinkel, Peter (87, 0.936%), Lindholm, Bengt (59, 0.635%), Ortiz, Alberto (59, 0.635%), highlighting their significant contributions to this field. Co-citation network analysis reveals that an article titled “Chronic Kidney Disease” in The Lancet journal (IF = 168.9) has the highest citation frequency, indicating its significant impact and influence in this field.This article highlights the significant role of inflammatory factors in the development of numerous chronic kidney diseases (22). The common pathological manifestations of CKD include renal fibrosis, characterized by glomerulosclerosis, tubular atrophy, and interstitial fibrosis (23). Glomerulosclerosis is primarily caused by endothelial injury, dysfunction, proliferation of smooth muscle cells and mesangial cells, and podocyte damage within the glomerular basement membrane. However, the initial process is initiated by inflammation of the glomerulus due to the activation of endothelial cells, where inflammatory cells (including macrophages and foam cells) activate mesangial cell proliferation (24). Transforming growth factor β1 and other growth factors (including platelet-derived growth factor, fibroblast growth factor, tumor necrosis factor, and interferon-γ) stimulate mesangial cells to revert to mesangial progenitor cells (immature mesangial cells). These mesangial progenitor cells can produce excessive extracellular matrix, leading to mesangial expansion, early signs of glomerular fibrosis, and ultimately stretching of podocytes. This stretching exposes the area of the glomerular basement membrane to Bowman’s capsule, causing adhesion and resulting in glomerulosclerosis. Moreover, tubular atrophy is also associated with inflammatory products (25). The close relationship between tubular atrophy, interstitial fibrosis, scar formation, glomerular filtration rate, and proteinuria is well established. The abnormal filtration of urinary proteins, including complement, cytokines, and albumin, stimulates tubular epithelial cells, resulting in the synthesis of inflammatory products such as reactive oxygen species and chemokines. These inflammatory products are transported to the renal interstitium through mediators and interact with interstitial myofibroblasts, ultimately leading to tubular atrophy. Furthermore, mounting evidence suggests that inflammation, oxidative stress, uremia, and hyperhomocysteinemia may induce epigenetic changes that mediate fibrosis and play a significant role in the progression of chronic kidney disease (26).

After analyzing the literature, it is evident that the research trends and hotspots in this field primarily focus on the following aspects: (1) Inflammatory biomarkers related to chronic kidney disease and their roles. Research results indicate that persistent low-grade inflammation is one of the harmful pathways leading to increased cardiovascular morbidity and mortality in end-stage renal disease patients. Studies also suggest that inflammation is a risk factor for chronic kidney disease. Therefore, detecting the levels of inflammatory factors in CKD patients can provide a direct understanding of the extent of renal inflammation. Currently, commonly used biomarkers for microinflammation status in domestic and foreign research include CRP, hs-CRP, IL, TNF-α, etc. CRP is an acute-phase reactant protein produced by the liver under the stimulation of IL-6, IL-1β, TNF-α, etc., which can reflect the activity of inflammation in the body (27). The level of CRP in CKD patients is significantly elevated, and the baseline level of CRP is closely related to the risk of developing end-stage renal disease or death in patients (28). IL is a type of cytokine widely distributed in various cells, which can activate and regulate the immune system and mediate the body’s inflammatory response. However, in CKD patients, the imbalance of Th1/Th2 balance leads to abnormal expression of cytokines (IL-1, IL-4, IL-6, IL-10, etc.), which has a certain impact on the progression and prognosis of the disease. Studies have found that the elevation of IL-4 and IL-10 levels in CKD patients is closely related to the loss of renal function. IL-6 can mediate the apoptosis of renal tubular epithelial cells through signaling pathways and is an independent risk factor for poor prognosis in CKD patients. Elevated levels of interleukin-1 (IL-1), interleukin-6 (IL-IL6), and other inflammatory markers in patients with CKD activate the inflammatory cascade, exacerbating renal damage and promoting renal fibrosis (29–31). This suggests that monitoring the trend of these indicators in clinical practice can aid in evaluating the renal function of CKD patients. Additionally, studies have demonstrated that the interaction between soluble CD14 levels (a pattern recognition receptor that can stimulate pro-inflammatory signaling in response to endotoxins) and circulating IL-6 can increase the risk of mortality in uremic patients undergoing hemodialysis (32). Based on these research findings, preventive measures can effectively reduce inflammation, infection, and endotoxemia. Tumor necrosis factor-alpha (TNF-α) is a well-established classical inflammatory marker that plays a crucial role in the body’s inflammatory and immune responses (33). In CKD, studies have shown that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP, TNF-α, and IL-6 are positively correlated and change in the same direction, reflecting the degree of inflammation in the body and the renal function status during the disease process, and are associated with poor prognosis. In recent years, there has been a growing interest in novel inflammatory markers in the field of nephrology research (34). These markers include the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen-to-albumin ratio (FAR). Among these markers, FAR is calculated as the ratio of plasma fibrinogen to serum albumin, and it has gained increasing attention as a novel inflammatory marker. Studies have demonstrated that elevated FAR levels are an independent risk factor for the progression of kidney damage in patients with CKD. Compared to more commonly studied clinical markers of microinflammation, FAR has shown superior predictive value for disease progression (35). (2) Treatment of chronic kidney disease guided by inflammatory markers (36). Due to the significant role of inflammation in the development of chronic kidney disease, inflammatory markers have become the primary targets of novel treatments, including specific anti-inflammatory and antioxidant therapies to regulate inflammation. Specific anti-inflammatory therapies include cholecalciferol supplementation, which has been shown to decrease levels of CRP, IL-6, IL-8, and TNF (37). Additionally, the immunomodulatory effect of ARB is mainly related to the inhibition of pro-inflammatory cytokine secretion, the reduction of adhesion molecule expression, and the normalization of CRP concentration in plasma (38). Furthermore, allopurinol treatment in patients with chronic kidney disease can not only reduce CRP levels but also lower cardiovascular risk and delay the progression of kidney disease (39). Antioxidant therapy can modulate inflammation (40). Research has demonstrated that supplementation with γ-tocopherol and docosahexaenoic acid can reduce levels of IL-6 (41). Additionally, a randomized controlled trial has shown that short-term oral administration of N-acetylcysteine (NAC) can also reduce IL-6 levels (42). Methyl bardoxolone is a current research focus, which primarily inhibits pro-inflammatory transcription factors (such as NF-kB and STAT3) by activating the transcription factor Nrf2. Studies have indicated that it can not only prevent the progression of kidney disease but also treat uremic protein-energy wasting and cardiovascular disease (43).

In conclusion, the discovery of inflammatory markers in chronic kidney disease and the development of treatment methods for inflammation and oxidative stress have been regarded as research hotspots. Intervening in inflammatory factors, developing new prevention strategies, and treatment methods to reduce the incidence and mortality of chronic kidney disease remain the direction of future research.