Patients with chronic kidney disease (CKD) are at significantly increased risk of peptic ulcers, according to investigators in Taiwan.

Over a 10-year period (1998-2008), researchers found an incidence of peptic ulcer disease (PUD) that was approximately 10-12 times higher among CKD patients than among individuals without CKD.

Chih-Chia Liang, MD, of the China Medical University in Taichung, Taiwan, and colleagues conducted a nationwide, population-based study of data from Taiwan’s National Health Insurance Research (NHIR) database. The researchers compared 16,322 patients with newly diagnosed PUD with 32,644 controls without PUD.

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From 1998 to 2008, the incidence of PUD increased from 13.2 to 19.8 per 1,000 persons per year in CKD patients compared with 1.1 to 2.0 per 1,000 persons per year in individuals without CKD. CKD patients aged 65 years and older experienced a rapid increase in PUD incidence after 2004, whereas CKD patients younger than 65 years experienced a slight decline in PUD incidence during the study period, the investigators reported.

Compared with non-CKD individuals (the reference group), CKD patients not on hemodialysis (HD) and those on HD had a 3.8 and 9.7 times increased risk of PUD after adjusting for confounders, the investigators reported in PLoS One (2014;9:e87952). Maintenance HD patients were twice as likely to experience gastric rather than duodenal ulcers. Non-HD CKD patients had a similar risk for ulcers at both locations.

“Overall, we suggest that CKD itself is a strong independent risk factor for PUD, and the incidence of PUD among elderly CKD patients is substantially increasing,” the authors wrote.

CKD patients receiving a non-steroidal anti-inflammatory drug (NSAID) or clopidogrel were at increased risk for PUD compared with CKD patients not receiving these medications. Among subjects taking an NSAID or clopidogrel, non-HD CKD patients had a 4.6 times and 3.1 times increased risk of PUD, respectively, compared with non-CKD patients in adjusted analyses.

“Unexpectedly, the peptic ulcer risk in CKD patients on aspirin was quite distinct from that in CKD patients on [an] NSAID,” the authors wrote. “The use of aspirin did not increase the risk for PUD, which seems contradictory to the well-documented increase in peptic ulcer risk.”

Dr. Liang’s group pointed out that the strengths of their study included use of a national population database, which minimizes selection bias and provides sufficient statistical power. In addition, they looked at inpatients and outpatients as well as PUD with and without bleeding, which allows for generalization to clinical practice for general CKD patients, they noted. The study also examined the risk for PUD, not upper gastrointestinal bleeding (UGIB). “UGIB consists of many diseases, which presents challenges in conducting appropriate and meaningful analyses.”

The investigators acknowledged study limitations, noting, for example, that the NHIR database does not provide relevant laboratory values and data on lifestyle risk factors such as smoking and alcohol consumption. The researchers also stated that they did not have information available on the location of gastric ulcers (for example, cardia or pylorus).