Abstract
Although upper tract urothelial carcinomas (UUC) is curable through nephrectomy or nephroureterectomy, progression of chronic kidney disease (CKD) and CKD-related mortality have been highlighted as clinical challenges in recent years owing to the loss of a large number of nephrons. While CKD can promote the development of UUC, other risk factors such as hypertension, diabetes mellitus, advanced age, and anemia can facilitate the progression of CKD. Conversely, CKD is especially prevalent in UUC patients. However, the relationship between CKD and UUC, mechanisms for CKD causing UUC, and gender disparity of UUC of CKD patients have so far not been well-reviewed. As UUC gradually grows, the cancer can be a physical obstacle in the urinary tract. It will cause an increased tract pressure, subsequently resulting in the dysfunction of both nephrons and kidney. At the molecular level, reduced level of oxidative stress was observed in female UUC patients. Furthermore, radical nephrectomy therapy for UUC patients accelerates the progress of chronic kidney dysfunction. Incidentally, the remedies for CKD containing aristolochic acid (AA) are carcinogenic. Our present review offers a comprehensive look at the relationship between CKD and UUC from multiple perspectives. Early and precise identification of progression of CKD and UUC will benefit the patients at high-risk of CKD or UUC, which will also be instructive in directing timely and effective therapeutic interventions whenever necessary. It may also shed light on unveiling the underlying mechanisms of carcinogenesis of UUC, preventing CKD progression, and prolonging the patients' overall survival.
Highlights
Different pathogenic factors can cause a variety of types of tumors, for instance, mesenchymal tumours in uraemic patients and epithelial and lymphoproliferative cancers in transplant recipients [1]
These research findings imply that chronic kidney disease (CKD) or end-stage renal disease (ESRD) as risk factors might promote the development of urothelial carcinomas especially in the upper urinary tract [9, 13]
While CKD may play a critical role in the development of urothelial carcinoma the upper urinary tract carcinoma, other risk factors such as hypertension, diabetes mellitus, advanced age, and anemia can facilitate the progression of CKD (Figure 1) [21, 22]
Summary
Different pathogenic factors can cause a variety of types of tumors, for instance, mesenchymal tumours in uraemic patients and epithelial and lymphoproliferative cancers in transplant recipients [1]. UUC including both ureters and kidneys are rare in the Western countries (only about 10% of all renal tumors and 5% of all UUC), whereas in Taiwan a high incidence of UUC was found among urothelial carcinomas cases (up to 20% to 31% of all UUC) [2, 3]. In patients with CKD or end-stage renal disease (ESRD) an especially higher percentage of high-grade UUC (60%) were observed [4, 9, 10].
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