Chronic Kidney Disease and Cancer: Inter-Relationships and Mechanisms

Abstract

Chronic kidney disease (CKD) has been recognized as an increasingly serious public health problem globally over the decades. Accumulating evidence has shown that the incidence rate of cancer was relatively higher in CKD patients than that in general population, which, mechanistically, may be related to chronic inflammation, accumulation of carcinogenic compounds, oxidative stress, impairment of DNA repair, excessive parathyroid hormone and changes in intestinal microbiota, etc. And in patients with cancer, regardless of tumor types or anticancer treatment, it has been indicated that the morbidity and incidence rate of concomitant CKD was also increased, suggesting a complex inter-relationship between CKD and cancer and arousing increasing attention from both nephrologists and oncologists. This narrative review focused on the correlation between CKD and cancer, and underlying molecular mechanisms, which might provide an overview of novel interdisciplinary research interests and the potential challenges related to the screening and treatment of CKD and cancer. A better understanding of this field might be of help for both nephrologists and oncologists in the clinical practice.

Breast cancer, alcohol, and phosphate toxicity

“…Although excess phosphate in breast tissue may not directly attract other toxins into the breast, excessive accumulation of Pi, considered a uremic toxin by some researchers, is associated with more than 153 other uremic toxins originating from impaired renal function (Falconi et al, 2021). Uremic patients were found to have persistently high serum levels of carcinogenic compounds, which is associated with an increased incidence of cancer in patients with chronic renal failure (Hu et al, 2022). Women with CKD have an increased risk of mortality from breast cancer related to the release of proinflammatory cytokines (Hill et al, 2020), which is stimulated by uremic toxins, primarily indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid (Brito et al, 2020).…”

The Onco-Nephrology Field: The Role of Personalized Chemotherapy to Prevent Kidney Damage

“…Regarding CKD, there seems to be a bidirectional relationship between CKD itself and cancer [ 19 ]. In fact, CKD patients have a higher incidence of cancer compared to the general population, and this phenomenon could be explained by the presence of (i) the low-grade chronic inflammation [ 20 , 21 , 22 , 23 ], (ii) the overload of the carcinogenic compounds, (iii) the alteration of DNA repair mechanisms, (iv) the oxidative stress [ 24 ] and (v) the gut microbiota dysbiosis [ 25 , 26 , 27 , 28 ].…”

Deep immune profiling of patients with renal impairment unveils distinct immunotypes associated with disease severity

“…The uremia-associated defects in the innate and adaptive immune systems have been demonstrated to be interrelated and imperative to recapitulate the prognosis of CKD and to influence its progression into end-stage renal disease (ESRD) [ 1 ]. As such, ESRD patients are highly vulnerable to microbial infections [ 2 ] and often bear unsatisfactory vaccination responses [ 3 ] and an increased susceptibility to malignancies [ 4 ], mainly due to accumulation of carcinogenic toxins, alteration in gut microbiota, and a state of acquired immunodeficiency and oxidative stress [ 5 , 6 ]. In addition, two common comorbidities in CKD, cardiovascular disease [ 7 ] and infections [ 2 ], both of which have been largely attributed to dysregulated immunity, together account for up to 70% of death in renal failure, implicating a detrimental role for this ominous disturbance of immune responses in CKD management.…”