Can Albuminuria Predict Cancer Risk?

Cancer is a significant public health problem and is one of the leading causes of morbidity and mortality in adults worldwide and the second cause of mortality in the United States. This year, the American Cancer Society estimated that there will be 2,001,140 new cancer cases and 611,720 cancer deaths in the United States (1). Delay in diagnosing and treating patients leads to an increase in advanced stage cancer and increased mortality. Thus, a crucial need arises to identify new cancer detection and prevention markers.

Albuminuria is a known marker of kidney damage, defined as a persistent albumin excretion of > 300 mg/day. A 24-hour urine collection is the gold standard for determining albuminuria (2). This is a marker of kidney injury but also of endothelial dysfunction and has been consistently associated with higher risk of chronic kidney disease progression (3), cardiovascular events (4), and cerebrovascular disease (5). However, the connection between albuminuria and cancer remains unclear.

Prior studies have demonstrated a potential association between albuminuria and cancer. An observational study by Ahn et al. (6) examined the association between proteinuria and cancer incidence among 9,714,387 participants, followed over a median duration of 4 years. Their findings revealed a statistically significant increase in the overall cancer risk among participants with proteinuria (adjusted hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.134–1.173). Similarly, another observational study by Tu et al. (7) investigated cancer incidence and mortality. The investigators followed 405,878 participants for an average of 8.7 years. They found that cancer incidence and mortality increased significantly with increasing severity of proteinuria. Risk increased with the severity of proteinuria: 12% (HR, 1.12; 95% CI, 1.04–1.21; p = 0.004) with trace proteinuria and 21% (HR, 1.21; 1.09–1.35; p < 0.001) with proteinuria defined as ≥+.

Recently published data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study (8) and the Stockholm Creatinine Measurements (SCREAM) project (9) support the association of albuminuria and increased cancer risk and cancer mortality, independent of estimated glomerular filtration rate (eGFR) (Figure 1).

View Full Size

Can albuminuria predict cancer risk?

Citation: Kidney News 16, 3

• Download Figure
• Download figure as PowerPoint slide

The PREVEND study (8) prospectively analyzed data from 8490 participants with a mean age of 49.8 ± 12.7 years, median baseline urinary albumin excretion (UAE) of 9.4 (interquartile range, 6.3–17.8) mg/24 hours, and mean baseline eGFR of 94.6 ± 17.3 mL/min/1.73 m². After a median follow-up of 17.7 years, the 10-year absolute risk for cancer was 8.1% (95% CI, 7.5%–8.6%). After multivariable adjustment, for every doubling of UAE, there was a 7% higher risk of overall cancer incidence, a 15% higher risk of urinary tract cancer and this association remained after adjustment for eGFR respectively. Concerning a cancer site, there was an increased risk of lung cancer (HR, 1.13; 95% CI, 1.04–1.22), and hematological cancer (HR, 1.12; 95% CI, 1.00–1.25). Additionally, the risk of cancer mortality was 9% higher per doubling of UAE after multivariable adjustment, including eGFR (HR, 1.09; 95% CI, 1.03–1.14).

The SCREAM project (9) analyzed data from two retrospective cohorts: one with 250,768 participants with at least one urine albumin-creatinine ratio (ACR) test and another with 433,850 participants with at least one dipstick albuminuria test. Patients in the ACR cohort had a mean age of 60.1 ± 15.8 years and a mean eGFR of 89.1 ± 21.8 mL/min/1.73 m². During a median follow-up of 4.3 years, 21,901 (8.7%) of these patients developed cancer, with a 10-year crude incidence of overall cancer of 16.2% (95% CI, 16.0%–16.5%). After multivariable adjustment including eGFR, participants had a 23% higher risk of cancer incidence with an ACR of 30–299 mg/g (HR, 1.23; 95% CI, 1.19–1.28) and a 40% higher risk with an ACR ≥300 mg/g (HR 1.40; 95% CI, 1.31–1.50) when compared with participants with an ACR <30 mg/g. This association was observed for urinary tract, gastrointestinal tract, lung, and hematological cancer (p < 0.05), and results were similar in the dipstick test cohort.

The definitive nature of this association, whether it signifies causation or mere coincidence, remains to be determined. Possible mechanisms include the role of chronic inflammation, endothelial dysfunction, and the activation of the renin-angiotensin system. These factors may collectively contribute to both albuminuria and tumor growth (9). Nonetheless, future studies are crucial to elucidate these mechanisms.

In summary, a distinct correlation between albuminuria and cancer risk, irrespective of the eGFR, has been established by Luo et al. (8, 9). Integrating routine albuminuria assessment in clinical practice is paramount, helping to identify patients with high risk of cancer. Further studies should also address whether reduction in albuminuria after initiation of intervention would be associated with improved prognoses.