A study evaluating the use of proton pump inhibitors (PPIs) in 125,000 patients indicates that more than half of patients who develop chronic kidney damage while taking the drugs don't experience acute kidney problems beforehand.
Taking popular heartburn drugs for prolonged periods has been linked to serious kidney problems, including kidney failure. The sudden onset of kidney problems often serves as a red flag for doctors to discontinue their patients' use of so-called proton pump inhibitors (PPIs), which are sold under the brand names Prevacid, Prilosec, Nexium and Protonix, among others.
But a study evaluating the use of PPIs in 125,000 patients indicates that more than half of patients who develop chronic kidney damage while taking the drugs don't experience acute kidney problems beforehand, meaning patients may not be aware of a decline in kidney function, according to researchers at Washington University School of Medicine in St Louis and the Veterans Affairs St Louis Health Care System. Therefore, people who take PPIs, and their doctors, should be more vigilant in monitoring use of these medications.
The onset of acute kidney problems is not a reliable warning sign for clinicians to detect a decline in kidney function among patients taking proton pump inhibitors, said Dr Ziyad Al-Aly, the study's senior author and an assistant professor of medicine at Washington University School of Medicine. "Our results indicate kidney problems can develop silently and gradually over time, eroding kidney function and leading to long-term kidney damage or even renal failure. Patients should be cautioned to tell their doctors if they're taking PPIs and only use the drugs when necessary."
More than 15m Americans suffering from heartburn, ulcers and acid reflux have prescriptions for PPIs, which bring relief by reducing gastric acid. Many millions more purchase the drugs over-the-counter and take them without being under a doctor's care.
The researchers – including first author Yan Xie, a biostatistician at the St. Louis VA – analysed data from the Department of Veterans Affairs databases on 125,596 new users of PPIs and 18,436 new users of other heartburn drugs referred to as H2 blockers. The latter are much less likely to cause kidney problems but often aren't as effective.
Over five years of follow up, the researchers found that more than 80% of PPI users did not develop acute kidney problems, which often are reversible and are characterised by too little urine leaving the body, fatigue and swelling in the legs and ankles.
However, more than half of the cases of chronic kidney damage and end-stage renal disease associated with PPI use occurred in people without acute kidney problems.
In contrast, among new users of H2 blockers, 7.67% developed chronic kidney disease in the absence of acute kidney problems, and 1.27% developed end-stage renal disease. End-stage renal disease occurs when the kidneys can no longer effectively remove waste from the body. In such cases, dialysis or a kidney transplant is needed to keep patients alive.
"Doctors must pay careful attention to kidney function in their patients who use PPIs, even when there are no signs of problems," cautioned Al-Aly, who also is the VA's associate chief of staff for research and education and co-director of the VA's Clinical Epidemiology Centre. "In general, we always advise clinicians to evaluate whether PPI use is medically necessary in the first place because the drugs carry significant risks, including a deterioration of kidney function."
Abstract
Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m2 (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m2, incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy.
Authors
Yan Xie, Benjamin Bowe, Tingting Li, Hong Xian, Yan Yan, Ziyad Al-Aly
[link url="https://www.sciencedaily.com/releases/2017/02/170222082252.htm"]Washington University in St Louis material[/link]
[link url="http://www.kidney-international.theisn.org/article/S0085-2538(17)30005-4/abstract"]Kidney International abstract[/link]