Incidence of proteinuria following gemcitabine administration is a likely sign of poor outcome for cancer patients

Objective: It is well known that gemcitabine (GEM) rarely causes thrombotic microangiopathy. However, the prevalence and clinical significance of incident proteinuria among cancer patients after GEM administration are not fully understood. Methods: This longitudinal cohort study aimed to confirm the prevalence of incident proteinuria after GEM administration and investigate its association with mortality in cancer patients: 53 with pancreatic, six with biliary, and one with gallbladder cancer. Proteinuria was defined as a urine dipstick test result ≥1+ in at least two consecutive examinations within 6 months after GEM administration. To determine the factors related to incident proteinuria, we compared patient characteristics by the presence or absence of incident proteinuria. The cumulative mortality rate was estimated using the Kaplan–Meier method, with stratification into two groups by the presence or absence of incident proteinuria. Furthermore, a multivariate Cox proportional hazards regression model was used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for all-cause mortality after adjustment for age, sex, and clinical cancer stage. Results: The mean follow-up period was 1.03 ± 0.5 years, and the prevalence of incident proteinuria was 23.4%. The proportion of patients with a performance status score ≥2 was higher among those with incident proteinuria (4.4% vs. 50.0%: p = 0.0002), as were the C-reactive protein level (0.9 ± 1.3 vs. 1.7 ± 0.8 mg/dL; p = 0.0024) and cumulative GEM dose (8,140 mg/m2 vs. 11,604 mg/m2 ; p = 0.0189). Cumulative mortality was significantly higher in patients with incident proteinuria than in those without it (41.3% vs. 85.7%; p = 0.0002). On multivariate Cox proportional hazards regression, incident proteinuria was significantly associated with mortality (HR, 3.52; 95% CI, 1.58–7.51; p = 0.0028). Conclusions: Incident proteinuria may be a marker of poor prognosis in pancreatic, biliary, and gallbladder cancer patients who received GEM.