International Journal of Clinical Case Reports, 2025, Vol.15, No.4, 171-181 http://medscipublisher.com/index.php/ijccr 172 2 The Pathogenesis and Classification of CKD 2.1 Main causes and pathological mechanisms of CKD Diabetes and hypertension are the main causes of CKD worldwide, accounting for the majority of cases in both high-income and low-income countries (Webster et al., 2017; Cockwell and Fisher, 2020). Other factors include glomerular diseases, congenital organ abnormalities and acute kidney injury, etc., which can accelerate the development of CKD (Yan et al., 2021). The pathogenesis of CKD is related to the complex interaction of factors such as chronic inflammation, oxidative stress, mitochondrial dysfunction and fibrosis, which can lead to irreversible reduction of nephron and impairment of renal function (Ruiz-Ortega et al., 2020; Irazabal et al., 2022). Systemic inflammation is usually caused by other diseases or acute kidney injury and is considered a key factor in the development of CKD and its complications (Tinti et al., 2021; Petreski et al., 2021; Speer et al., 2022). Recent research findings have highlighted the role of certain molecular and cellular processes, such as mitochondrial damage, abnormal immune responses, and epigenetic changes, all of which are associated with the occurrence and progression of CKD (Irazabal et al., 2022). Multi-omics techniques are now more commonly used to identify the individual characteristics of CKD patients, thereby clarifying which molecular subtypes of patients may be more suitable for targeted therapy. These advancements indicate that a deeper understanding of the pathogenic process of CKD is necessary to provide a basis for the development of more effective prevention and treatment methods (Eddy et al., 2020; Ruiz-Ortega et al., 2020). 2.2 CKD staging criteria and clinical classification The staging criteria for chronic kidney disease (CKD) are determined based on kidney damage or a continuous decline in glomerular filtration rate (GFR) for at least three months, regardless of the cause. The most commonly used staging system at present is the standard proposed by the KDIGO (Nephropathy: Improving Global Prognosis) guideline, which divides CKD into five stages based on the level of GFR and the degree of urinary protein. GFR is usually calculated using the serum creatinine formula, while urine protein is detected by the ratio of albumin to creatinine in urine (Webster et al., 2017; Cockwell and Fisher, 2020). This staging method is helpful in determining whether the condition will progress to end-stage renal disease and whether it will cause other complications. However, even according to the above-mentioned uniform staging method, patients at the same stage still vary greatly in terms of symptom manifestation, disease progression rate and treatment response. In order to better classify CKD, recent studies have attempted to combine multi-omics data and machine learning techniques to identify patient groups that can be distinguished by molecular characteristics, in order to more accurately reflect the internal mechanism of the disease and provide a basis for personalized diagnosis and treatment. This continuously improved classification system is expected to enhance the accuracy of diagnosis, the ability of risk prediction and the matching degree of treatment plans (Eddy et al., 2020). 2.3 The impact of decreased renal function on systemic metabolism With the decline of renal function, CKD has extensive effects on metabolism, disrupting energy balance, mineral metabolism and neuroendocrine signaling. Patients may experience dysbalance of calcium, phosphate and vitamin D in their bodies, leading to an increased risk of mineral and bone disorders (CKD-MBD), vascular calcification and cardiovascular diseases (Nakanishi et al., 2020; Yamada and Nakano, 2023). Anemia, metabolic acidosis and protein-energy depletion are also common, which further increase the morbidity and mortality rates (Webster et al., 2017; Zoccali et al., 2017; Tinti et al., 2021). Chronic kidney disease is now widely regarded as a systemic health problem. Diseased kidneys may disrupt the coordinated operation among multiple organ systems. Systemic inflammation, oxidative stress and intestinal flora imbalance play a core role in the formation of CKD-related complications (such as cardiovascular diseases, bone diseases and immune dysfunction) (Vaziri et al., 2016). These systemic effects highlight the necessity of adopting an integrated and multidisciplinary management approach to address the complex metabolic disorders in CKD (Zoccali et al., 2017; Tinti et al., 2021; Evenepoel et al., 2023).
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