CKD and Risk of Renal Cell Carcinoma

Hofmann, Jonathan N.; Purdue, Mark P.

doi:10.1681/asn.2014040376

Cited by 11 publications

(11 citation statements)

References 14 publications

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“…Specifically, we found the upregulated pathway of RCC and the downregulated pathway of glutathione metabolism in HK-2 cells under hypoxic conditions. A previous study demonstrated that patients with CKD may have an increased risk of RCC (39), and another study showed that RCC may be associated with CKD in patients, although the mechanisms involved are unclear (40). In this study, our data suggest that hypoxia may be an important factor in promoting the development of RCC in patients with CKD.…”

Section: Discussionsupporting

confidence: 52%

Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing

Wang

et al. 2016

International Journal of Molecular Medicine

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Chronic hypoxia often occurs among patients with chronic kidney disease (CKD). Renal proximal tubular cells may be the primary target of a hypoxic insult. However, the underlying transcriptional mechanisms remain undefined. In this study, we revealed the global changes in gene expression in HK‑2 human renal proximal tubular cells under hypoxic and normoxic conditions. We analyzed the transcriptome of HK‑2 cells exposed to hypoxia for 24 h using RNA sequencing. A total of 279 differentially expressed genes was examined, as these genes could potentially explain the differences in HK‑2 cells between hypoxic and normoxic conditions. Moreover, 17 genes were validated by qPCR, and the results were highly concordant with the RNA seqencing results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to better understand the functions of these differentially expressed genes. The upregulated genes appeared to be significantly enriched in the pathyway of extracellular matrix (ECM)-receptor interaction, and in paticular, the pathway of renal cell carcinoma was upregulated under hypoxic conditions. The downregulated genes were enriched in the signaling pathway related to antigen processing and presentation; however, the pathway of glutathione metabolism was downregulated. Our analysis revealed numerous novel transcripts and alternative splicing events. Simultaneously, we also identified a large number of single nucleotide polymorphisms, which will be a rich resource for future marker development. On the whole, our data indicate that transcriptome analysis provides valuable information for a more in depth understanding of the molecular mechanisms in CKD and renal cell carcinoma.

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Section: Discussionsupporting

confidence: 52%

Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing

Wang

et al. 2016

International Journal of Molecular Medicine

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“…There is some epidemiological evidence of a link between poor kidney function as measured by eGFR and incident RCC 43 but it remains unclear whether this association reflects a causal relationship. 44 …”

Section: Discussionmentioning

confidence: 99%

OUP accepted manuscript

Alcala

Mariosa

Smith-Byrne

et al. 2022

International Journal of Epidemiology

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Background The relation between blood pressure and kidney cancer risk is well established but complex and different study designs have reported discrepant findings on the relative importance of diastolic blood pressure (DBP) and systolic blood pressure (SBP). In this study, we sought to describe the temporal relation between diastolic and SBP with renal cell carcinoma (RCC) risk in detail. Methods Our study involved two prospective cohorts: the European Prospective Investigation into Cancer and Nutrition study and UK Biobank, including >700 000 participants and 1692 incident RCC cases. Risk analyses were conducted using flexible parametric survival models for DBP and SBP both separately as well as with mutuality adjustment and then adjustment for extended risk factors. We also carried out univariable and multivariable Mendelian randomization (MR) analyses (DBP: n instruments = 251, SBP: n instruments = 213) to complement the analyses of measured DBP and SBP. Results In the univariable analysis, we observed clear positive associations with RCC risk for both diastolic and SBP when measured ≥5 years before diagnosis and suggestive evidence for a stronger risk association in the year leading up to diagnosis. In mutually adjusted analysis, the long-term risk association of DBP remained, with a hazard ratio (HR) per standard deviation increment 10 years before diagnosis (HR 10y ) of 1.20 (95% CI: 1.10–1.30), whereas the association of SBP was attenuated (HR 10y : 1.00, 95% CI: 0.91–1.10). In the complementary multivariable MR analysis, we observed an odds ratio for a 1-SD increment (OR sd ) of 1.34 (95% CI: 1.08–1.67) for genetically predicted DBP and 0.70 (95% CI: 0.56–0.88) for genetically predicted SBP. Conclusion The results of this observational and MR study are consistent with an important role of DBP in RCC aetiology. The relation between SBP and RCC risk was less clear but does not appear to be independent of DBP.

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“…Both pathologies share the main, non-hereditary risk factors, including age, high-blood pressure, obesity, diabetes and smoking. Kidney cancer is also a risk factor for renal insufficiency and vice-versa [ 11 ]. Renal physiology with its low pO 2 is susceptible to hypoxic damage, in particular from conditions that compromise blood supply to the kidneys such as vasoconstriction and vascular damage.…”

Section: Hypoxia Response and Renal Pathophysiologymentioning

confidence: 99%

“…This iatrogenic ischemia can also result in hypoxic damage to the kidney. There is a positive association between RCC diagnosis and CKD, however any underlying mechanisms connecting both pathologies are still largely unknown [ 11 ].…”

Section: Hypoxia Response and Renal Pathophysiologymentioning

confidence: 99%

Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort

et al. 2021

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Kidney cancer and chronic kidney disease are two renal pathologies with very different clinical management strategies and therapeutical options. Nonetheless, the cellular and molecular mechanisms underlying both conditions are closely related. Renal physiology is adapted to operate with a limited oxygen supply, making the kidney remarkably equipped to respond to hypoxia. This tightly regulated response mechanism is at the heart of kidney cancer, leading to the onset of malignant cellular phenotypes. Although elusive, the role of hypoxia in chronic kidney diseases is emerging as related to fibrosis, a pivotal factor in decaying renal function. The present review offers a perspective on the common biological traits shared between kidney cancer and chronic kidney disease and the available and prospective therapies for both conditions.

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CKD and Risk of Renal Cell Carcinoma

Cited by 11 publications

References 14 publications

Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing

Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing

OUP accepted manuscript

Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort

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