Mentor Requirements:

Student Requirements:

Proton pump inhibitors (PPIs) are one of the most widely prescribed classes of medications in terms of monthly prescriptions and sales. ¹ PPIs have multiple indications for use such as acid-related gastrointestinal disorders, nonsteroidal anti-inflammatory drug associated gastrointestinal mucosal injury, and stress ulcer prophylaxis in critically ill patients. Reasons for their widespread use are their efficacy combined with a perceived lack of adverse effects. They are the most potent gastric acid suppressive therapy on the market and guidelines recommend PPIs as first line therapy in certain patient populations. PPIs also have very few adverse effects when used short-term. ² However, PPI use can become a problem when they are used for longer than the recommended duration or without an appropriate indication. The overuse of PPIs has been well documented and studies have estimated that 25-70% of patients lack an appropriate indication for therapy. ³ Although PPIs may be relatively safe for short-term therapy, studies have revealed several serious safety risks associated with their long-term use such as bone fracture, community-acquired pneumonia, Clostridium difficile infection, hypomagnesemia, and acute kidney injury (AKI). ^4,-8 Newer data is even showing an association between PPI use and dementia. ⁹ This article will focus on the association between PPIs and kidney disease.

Studies have shown that PPI use increases the risk of AKI, possibly caused by acute interstitial nephritis (AIN). AIN occurs when there is a renal lesion that results in a decrease in creatinine clearance, leading to inflammatory infiltrates and interstitial edema. ¹⁰ A population-based cohort study of adults aged 66 years and older evaluated the association of PPI use with kidney disease using ICD-9 codes for AKI as the primary outcome and AIN as a secondary outcome. The rates of AKI and AIN were higher in PPI users than with controls (HR 2.52; 95% CI, 2.27-2.79 and HR 3.00; 95% CI, 1.47-6.14, respectively.). ⁸ A nested case-control study published in BMC Nephrology demonstrated that AKI was positively associated with PPI use (OR 2.04: 95% CI 1.53-2.71)  and calculated a number needed to harm of 303. ¹¹ Even when both studies adjusted for potential confounders, the increased risk of AKI was still significant among PPI users.

There has been a rise in prevalence of chronic kidney disease (CKD) between 1988-1994 to 1999-2004 not explained by its most common causes. ^12,13 The fact that repeated AKI can result in permanent kidney damage has prompted the authors of two recent studies to investigate whether there is an association between PPI use and CKD. ^14,15 The first study published in JAMA Internal Medicine aimed to quantify the association between PPI use and CKD in the general population using two population-based cohorts. ¹⁶ The primary cohort came from the Atherosclerosis Risk in Communities (ARIC) study and consisted of patients aged 45-64 years from 4 different U.S. communities. It included 10,482 patients with an eGFR > 60 mL/min/1.73m

² who were followed for a median of 13.9 years. A replication cohort included 248,751 patients with an eGFR > 60 mL/min/1.73m ² that received care in the Geisinger Health System, a rural health system in Pennsylvania. Incident CKD was determined using hospitalization discharge codes in the ARIC cohort and outpatient eGFR measurements in the Geisinger replication cohort. Each cohort was divided into 3 groups: PPI users, H ₂ receptor antagonist users, and nonusers. Baseline characteristics were similar between the PPI users and the H ₂ receptor antagonist users. In the ARIC cohort, adjusted analysis found that the risk of incident kidney disease was significantly higher among PPI users than nonusers (HR 1.5; 95% CI, 1.14-1.96). The 10-year estimated absolute risk of CKD was 11.8% in the PPI users versus 8.5% in nonusers(absolute risk difference, 3.3%). Similar results were shown with the Geisinger replication cohort. In an a priori sensitivity analysis, PPI users had a greater risk of incident CKD than H ₂ receptor antagonist users in both cohorts (adjusted HR 1.39; 95% CI, 1.01-1.91 for the ARIC cohort.) Additionally, H ₂ receptor antagonist users were not associated with an increased risk of CKD compared to nonusers in both cohorts (adjusted HR 1.15; 95% CI, 0.98-1.36 in the ARIC cohort.)

      The second study published in the Journal of the American Society of Nephrology sought to determine the association between PPIs and the risk of renal events. ¹⁷ Using administrative data from the U.S. Department of Veteran Affairs, the cohort included 193,591 patients with an eGFR > 60 mL/min/1.73m ² . The cohort was divided into new PPI users and new H ₂ receptor antagonist users and followed for 5 years. Baseline characteristics were similar between both groups. The primary outcome was CKD as defined by two eGFR measurements <60 mL/min/1.73m ². Secondary outcomes included indices of kidney disease progression. A significantly increased risk of incident CKD was found in new PPI users compared to new H ₂ receptor antagonist users (adjusted HR 1.22; 95% CI, 1.18-1.26). Not only was PPI use associated with incident CKD, but also with a significantly increased risk for end-stage renal disease (ESRD) (adjusted HR 1.96; 95% CI, 1.21-3.8). Furthermore, there was a graded association between the duration of PPI use and risk for a decreased eGFR, CKD, and ESRD.

            Since PPIs are widely used, it is important that both healthcare providers and patients are aware of the evidence associating PPI use with an increased risk of kidney disease. Pharmacists can play a key role in ensuring safe and appropriate use of this class of medications. Educating prescribers and patients on the long-term risks associated with PPIs can help them assess whether the benefits PPI use outweigh the risks. Communication should happen with prescribers when a pharmacist identifies a patient in whom therapy can be appropriately discontinued. Alternatives to PPIs should also be considered, such as lifestyle changes or H ₂ receptor antagonists, which do not carry the increased risk of kidney disease.

VSHP Leadership Profile
Brian Baird 

What is your current leadership position in VSHP?

Historian.  Was VSHP President 2014-2015. 

 

What benefits do you see in being active in a professional association such as VSHP?  

Networking, advocacy

 

What initially motivated you to get involved in VSHP?

A colleague pointed out the benefits to me

 

Where did you go to pharmacy school?

Samford for my batchelor's, and VCU for my PharmD

 

Where have you trained or worked?  

University of Alabama Hospital, Henrico Doctors' Hospital, and VCU Medical Center.

 

Describe your current area of practice and practice setting:

I'm a Drug Information pharmacist with some extra emphasis on medication safety.

 

What advice would you give to student pharmacists?

Keep your options open and your debt as small as possible. Don't buy a big house or expensive car right after school - start small.

 

What pharmacy related issues keep you up at night?

Pretty much nothing keeps me up at night. However, I find the general deficiency of accurate medication histories to be a source of continuing frustration.

 

Do you have any special interests or hobbies outside of work?

Yes, and too many of them to name! My recent work with my neighborhood association has kept me busy. I'm also doing a bit better lately with my extracurricular reading.

 

What is your favorite place to vacation?

Generally that is somewhere I've never been before, but my wife's family has a place fairly far north in Michigan which is also lovely to visit. In the summer, not the winter.

 

What 3 adjectives would people use to best describe you?

I couldn't possibly imagine. I suppose it depends on who is doing the describing.