Kidney Damage to Kidney Cancer

Abstract

Epidemiologic studies have demonstrated a strong relationship between acute or chronic renal injury and kidney cancer. However, it is not obvious if or how these relationships are caused by one another. We have proposed a novel pathophysiological theory with urgent implications for the management of patients with kidney disease and kidney tumors as the matter is currently being clarified by the accumulation of data from basic and clinical research. The main premise of this review is that kidney injury and repair processes, which are active during acute kidney injury as well as persistent injuries in chronic renal disease, work as DNA damage triggers, promoting the formation of pre-malignant cell clones. Renal progenitors have been found in various investigations to be the cell of origin for a variety of benign cancers.

Introduction 

A complex process called cancerogenesis involves somatic and/or germline mutations that cause mutant cells to grow out of control. This frequently happens in a sequence of phases when different mutational combinations slowly pass the cutoff for unrestrained cell expansion.  For two reasons, tissue damage is a known catalyst for the development of cancer: I the potential for DNA damage and somatic alterations to be caused, particularly in tissue-resident long-lived stem cells; and (ii) its ability to encourage the growth of these altered cells during the course of tissue repair. For instance, these 2 systems play a role in colorectal cancer associated with inflammatory bowel illness, lung cancer associated with exposure to carcinogenic smoke and dust, as well as stomach cancer associated with atrophic gastritis and hepatocellular carcinoma associated with cirrhosis. Numerous epidemiologic studies have documented the link between kidney cancer and Chronic Kidney Disease (CKD). It is yet unknown whether or how these correlations are connected by causation, despite the fact that both occur ideally in the second half of life. For instance, the higher risk of acute kidney injury (AKI) and Chronic Kidney Disease (CKD) associated with tumor therapy, including surgery, antiangiogenic drugs, Mechanistic Target of Rapamycin (mTOR), and immune checkpoint inhibitors, suggests that causation may be one way. Similar to kidney damage, it is unclear if kidney injury leads to kidney cancer, while some studies indicate that kidney cancer may appear after an incident of AKI or after years of CKD to the point of renal failure.

Risk Factors for Renal Illness also Include Risk for Kidney Cancer 

Epidemiologic research finds connections, but as causality is not always established, these associations can lead to incorrect interpretations. For instance, epidemiologic studies found various "risk factors" for kidney cancer, although a clear causal relationship to cancer genesis was not always evident. Obesity, diabetes, high blood pressure, smoking, nephrotoxic medications, and heavy metals all increase the risk of kidney injury, including AKI and CKD, and may indirectly affect kidney cancer incidence rates. Indeed, heavy metals and nephrotoxic medications cause toxic AKI episodes linked to necroinflammation and oxidative stress. Obesity, diabetes, and smoking are known to increase the risk of glomerular hyperfiltration and glomerulosclerosis-related CKD. As a result, nephrons are lost and the remaining nephrons undergo significant adaptive cellular changes to meet the demands of the metabolic process. Last but not least, hypertension is typically a complication of renal disease and a sensitive sign of early CKD, rather than a cause. Increasing amounts of data point to putative renal progenitors as a critical link between a number of kidney cancer types, AKI, and CKD. Immature epithelial cell precursors called renal progenitors are found in the collecting duct, glomerulus, and all nephron segments. Renal progenitors are mostly quiescent and exhibit a limited capacity for spontaneous proliferation to replace physiological losses of podocytes and tubular epithelial cells, in contrast to the highly proliferative phenotype of tissue-resident progenitors in high turnover organs, such as the skin or gut. According to the conventional theory of kidney repair, the majority of tubular epithelial cells have the capacity to proliferate and undergo dedifferentiation in response to injury.

Conclusion

Prospective research indicates that CKD directly contributes to kidney cancer, especially the clear cell RCC (ccRCC) histotype, which accounts for 70%–80% of kidney malignancies. Moderate CKD at baseline was found to increase the incidence of kidney cancer in a follow-up analysis of 33,346 participants, aged 26 to 61 at the start with a median follow-up of 28 years. Diabetes and obesity, which encourage CKD, also fuel the growth of RCC. The metabolic stress of the proximal tubule cells in remnant nephrons suffering dramatically elevated single-nephron hyperfiltration serves as a link between these 2 states (and tubular hyperreabsorption).

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