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These studies suggest that kidney disease can be caused by genetic mutations, metabolic alterations, inflammation, hyperglycemia, nephrotoxicity, and infections.
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Kidney disease, encompassing both chronic kidney disease (CKD) and acute kidney injury (AKI), arises from a multitude of factors. These factors can be broadly categorized into genetic predispositions, metabolic disorders, infections, and exposure to nephrotoxic substances. This article delves into the primary causes of kidney disease, highlighting the complex interplay of these factors.
Genetic mutations play a significant role in early-onset CKD. Over 200 different monogenic genes have been identified as potential culprits, with conditions such as congenital anomalies of the kidneys and urinary tract, steroid-resistant nephrotic syndrome, and chronic glomerulonephritis being prevalent among children. Advances in high-throughput sequencing have facilitated the identification of these genetic mutations, providing insights into disease mechanisms and enabling personalized treatment approaches.
DKD, a major cause of CKD, is influenced by both genetic and environmental factors. Genetic susceptibility to DKD is supported by familial aggregation studies, although the specific genes and molecular mechanisms remain poorly understood. Recent research has identified new susceptibility loci associated with DKD, such as SNPs in the AFF3 and ERBB4 genes, which are implicated in renal tubule fibrosis and differential gene expression in type 2 diabetes, respectively.
Diabetes and hypertension are the leading causes of CKD globally. Hyperglycemia in diabetes leads to metabolic alterations, including changes in energy utilization and mitochondrial dysfunction, which are critical in the initiation and progression of DKD . Hypertension exacerbates kidney damage through mechanisms such as glomerular hyperfiltration and increased intraglomerular pressure, contributing to progressive renal scarring and fibrosis.
Obesity and cardiovascular disease are significant extrinsic factors contributing to kidney disease. These conditions can lead to nephron loss and increased susceptibility to CKD through mechanisms such as systemic and glomerular hypertension, dyslipidemia, and proteinuria .
Infections can cause kidney injury either directly through microbial invasion or indirectly via immune-mediated mechanisms. Conditions such as post-infectious glomerulonephritis and infection-related glomerulonephritis are examples of immune-mediated kidney injuries. The prevalence and severity of infection-induced kidney diseases are influenced by factors such as poverty, high population density, and inadequate access to healthcare.
Exposure to nephrotoxic substances, including certain drugs, environmental pollutants, and natural toxins, can induce kidney damage. Nephrotoxic drugs include cancer therapeutics, antibiotics, and radiocontrast agents, while environmental pollutants such as cadmium, mercury, and arsenic are known to target the kidneys. The mechanisms of nephrotoxicity often overlap with those of other causes of renal failure, emphasizing the need for integrated approaches to diagnosis and treatment.
Kidney disease is a multifactorial condition with genetic, metabolic, infectious, and toxicological underpinnings. Understanding these diverse causes is crucial for developing effective prevention and treatment strategies. Advances in genetic research, improved infection control practices, and careful management of metabolic disorders and nephrotoxic exposures are essential steps toward mitigating the burden of kidney disease.
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