Chronic Kidney Disease and Risk for Gastrointestinal Bleeding in the Community: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background and objectives: Patients on dialysis are known to have higher risk for gastrointestinal (GI) bleeding. However, data on mild to moderate CKD, particularly elevated albuminuria, are limited.

Design, setting, participants, & measurements: Among 11,088 participants in the Atherosclerosis Risk in Communities (ARIC) Study, we investigated the association of eGFR and urinary albumin-to-creatinine ratio (ACR) with risk for hospitalization with GI bleeding. Kidney measures were assessed at visit four (1996-1998), and follow-up was continued through 2011.

Results: During a median follow-up of 13.9 years, 686 first incident hospitalizations with GI bleeding were observed (incidence rate, 4.9 per 1000 person-years [95% confidence interval (95% CI), 4.5 to 5.3]). Multivariable Cox proportional hazards models revealed that both lower eGFR and higher ACR were associated with higher risk for GI bleeding. With eGFR≥90 ml/min per 1.73 m² as a reference, risk for GI bleeding was significant in moderately decreased eGFR of 30-59 ml/min per 1.73 m² (hazard ratio [HR], 1.51; 95% CI, 1.13 to 2.02), and was highest in severely decreased eGFR<30 ml/min per 1.73 m² (HR, 7.06; 95% CI, 3.91 to 12.76). Compared with ACR<10 mg/g, risk for GI bleeding became significantly higher in mild albuminuria with ACR 10-29 mg/g (HR, 1.36; 95% CI, 1.08 to 1.69), and was nearly double in moderate and severe albuminuria (HR, 2.13; 95% CI, 1.66 to 2.71 for ACR 30-299 mg/g, and HR, 2.07; 95% CI, 1.33 to 3.22 for ACR≥300 mg/g). These results were largely consistent in demographic and clinical subgroups and independent of incident cardiovascular events or dialysis during follow-up.

Conclusions: Individuals with even mild to moderate CKD warrant clinical attention regarding the risk of hospitalization with GI bleeding.

Keywords: Albumins; Atherosclerosis; Attention; Follow-Up Studies; Humans; Incidence; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk; albuminuria; chronic kidney disease; chronic kidney failure; chronic renal failure; creatinine; gastrointestinal complications; glomerular filtration rate; hospitalization; kidney; proteinuria; renal dialysis.

Figure 1.

Incidence rate of GI bleeding was higher in lower eGFR and higher ACR. Incidence rate for GI bleeding overlaid with histogram according to (A) eGFR and (B) ACR. The solid line indicates the point estimate, and the shaded area indicates corresponding 95% confidence intervals. Bars in the background indicate the histogram for distribution of eGFR and ACR. The models were adjusted for age, sex, and race. ACR, albumin-to-creatinine ratio; GI, gastrointestinal.

Figure 2.

In subgroup analyses, no significant interaction was observed except for race in the analysis of ACR. Hazard ratios for GI bleeding according to (A) eGFR (< versus ≥60 ml/min per 1.73 m²) and (B) ACR (≥ versus <30 mg/g). Models were adjusted for age, sex, race, body mass index, alcohol consumption, smoking status, education level, aspirin, anticoagulant agents, nonsteroidal anti-inflammatory drugs, H² blocker, proton pomp inhibitor, hypertension, diabetes, abnormal liver function, cardiovascular disease, neoplasm, and gastroesophageal reflux disease/peptic ulcer. The circles represent the point estimate of relative hazard, and the horizontal lines indicate corresponding 95% confidence intervals. 95% CI, 95% confidence interval; ACR, albumin-to-creatinine ratio; GI, gastrointestinal; HR, hazard ratio.