While decreased renal function is a well-known risk factor of kidney cancer (KC), association of proteinuria with KC is unclear. In this large cohort study, we evaluated the risk of KC according to glomerular filtration rate (GFR) and dipstick proteinuria, as well as the joint effects between the two.
A total of 9,809,366 participants who participated in the nationwide health screening program in 2009 and did not have history of any cancer were included. The impact of GFR, dipstick proteinuria, and interactive associations of the two factors on the development of KC were analyzed.
During the median follow-up of 7.3 years, 10,634 participants developed KC (overall incidence rate: 14.9 per 100,000 person-years). Subjects with low GFR (<60 mL/min/1.73 m2) had a higher incidence of KC (adjusted hazard ratio [aHR] 1.26, 95% CI 1.18-1.34) than those with a high GFR (≥ 60). When GFR of 60-90 was considered the reference group, KC risk was higher in low GFR groups: GFR <30 (aHR 1.21) and GFR 30-60 group (aHR 1.27), while there was no decreased risk in higher GFR groups (GFR >90 or ≥ 120). A clear dose-response relationship was also found with the degree of dipstick proteinuria; compared to the no proteinuria group, even the trace group had an elevated risk of KC (aHR 1.20) and the risk increased more than double in the 4+ proteinuria group (aHR 2.15). Analyses of joint effects of GFR and dipstick proteinuria showed that in the no proteinuria group, the increased incidence of KC was less evident with decreasing GFR, whereas in the proteinuria group, there was marked increase in KC incidence along with decreasing GFR. The association between smoking and KC was more evident in low GFR groups (GFR <30 and GFR 30-60) (P-interaction <0.001), while there were no interactions between smoking and proteinuria. Clinically significant association was not found between body mass index and GFR/proteinuria.
Low GFR and proteinuria were associated with future KC development, possibly in synergistic manner. Smoking had a more profound effect when GFR was lower. Further research is warranted to develop strategies to reduce cancer risk in the chronic kidney disease population.
The authors.
a creative research program grant from Samsung Medical Center.
All authors have declared no conflicts of interest.