Abstract
Chronic kidney disease (CKD) is a worldwide health problem, and prevention of CKD is important for preservation of renal function after kidney surgery. There is evidence that transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) has a vital antioxidant and detoxifying role in protecting the kidneys against various diseases. Impaired activation of Nrf2 is associated with oxidative stress related to CKD, and Nrf2 is also a key player in the development of cancer. However, the clinical impact of Nrf2 has not been investigated in patients with renal cell carcinoma (RCC). A retrospective study was performed in 89 patients undergoing nephrectomy for RCC. The estimated glomerular filtration rate (eGFR) and serum uric acid (SUA) were investigated over time after surgery. We investigated Nrf2 protein expression in all tumors and single nucleotide polymorphisms (SNPs) of the Nrf2 gene in 7 tumors. In patients whose tumors showed higher Nrf2 expression, there was a more rapid decrease of eGFR and increase of SUA after nephrectomy. Multivariate analysis confirmed that increased Nrf2 expression was an independent poor prognostic factor related to shorter overall survival. Among the 7 tumor samples, an SNP on exon 5 of the Nrf2 gene in one tumor and three genotypes (C/C, C/A, and A/A) of rs6721961 at the promoter region of the Nrf2 gene were observed. Although the mechanisms underlying the influence of Nrf2 are still unclear, our findings suggested that elevated tumor expression of Nrf2 was associated with postoperative CKD and biologically aggressive RCC with an unfavorable prognosis.
Highlights
Chronic kidney disease (CKD) is an important health problem worldwide [1]
While estimated glomerular filtration rate (eGFR) decreased in both groups after surgery, it decreased more rapidly in the radical nephrectomy group compared to the partial nephrectomy group
The radical nephrectomy group was divided into two subgroups by the median level of nuclear factor erythroid 2–related factor 2 (Nrf2) expression in the primary tumor shown by western blotting, a radical A subgroup with lower expression and a radical B subgroup with higher expression
Summary
The glomerular filtration rate (GFR) is regarded as the best overall measure of renal function. Current clinical practice guidelines define chronic kidney disease as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1·73 m2, or by detection of markers of kidney damage (such as albuminuria or abnormal imaging studies) for at least 3 months [2]. Despite various advances in slowing the progression of CKD, the incidence of end-stage renal disease (ESRD) is still increasing around the world, with a severe impact on both patients and society [1]. It is well known that kidney function is affected by renal surgery [4, 5], and we have encountered RCC patients showing a decrease of eGFR and increase of serum uric acid (SUA) after nephrectomy who eventually developed CKD. Preservation of renal function after nephrectomy for prevention of CKD is an important issue, and better understanding of the mechanisms underlying postoperative occurrence of CKD in RCC patients is required
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