More than 15 Million Americans at Risk of Significant Kidney Damage

By John Henry Dreyfuss, MDalert.com staff.

Save to PDF Primary CarePerformance-Based MedicineGastroenterologyNephrology By
  • Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide.
  • H2 blockers are equally effective for acid control and pose significantly less risk.
  • Long-term PPI exposure is linked to significantly increased risk of chronic kidney disease (CKD), CKD progression, and end-stage renal disease.
  • The risk of developing these diseases correlated directly with the duration of therapy.
  • PPI use was associated with CKD in all analyses, including a time-varying new-user design.
  • Twice-daily PPI dosing was associated with a higher risk than once-daily dosing.

Long-term use of proton pump inhibitors (PPIs) can damage the kidneys according to a recent report in the Journal of the American Society of Nephrology (JASN). The results suggest that PPI exposure is linked to increased risk of chronic kidney disease (CKD), CKD progression, and end-stage renal disease (ESRD).

In 2013, an estimated 15 million Americans were prescribed PPIs. The authors of a report in JAMA Internal Medicine suggested that this number is likely an underestimate because the medications are also available over-the-counter.

 

Proton pump inhibitors (PPIs) are among
the most commonly used drugs worldwide.

H2 blockers are equally effective for acid control
and pose significantly less risk.

 

The JASN study revealed a duration-dependent risk between PPI use and kidney damage. To assess the safety of PPIs, the researchers analyzed information from the Department of Veterans Affairs national databases. They identified new users of PPIs (n=173,321) and new users of histamine H2 receptor blockers (20,270) and followed both groups for 5 years. Patients taking PPIs were more likely to experience kidney function decline than those taking H2-receptor blockers (Figure 2) during the followup period.

PPI users also had a 28% increased risk of developing chronic kidney disease and a 96% increased risk of developing kidney failure (Figures 1 and 2). The researchers also reported a graded association between duration of PPI use and risk of kidney problems. Patients who took PPIs for a longer period were significantly more likely to develop kidney damage. The JASN study was conducted at the Clinical Epidemiology Center at the VA Saint Louis Health Care System and Washington University in St. Louis.

 

Figure 1. End-stage renal disease.

 

Figure 2. Polycystic kidney disease.

The JAMA Internal Medicine trial included 10,482 participants in the Atherosclerosis Risk in Communities study and compared these with results with a replicated in an administrative cohort of 248,751 patients with an estimated glomerular filtration rate (EGFR) of at least 60 mL/min/1.73 m2 from the Geisinger Health System. The patients were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data were analyzed from May 2015 to October 2015. (Figure 3.)

 

 

Figure 3. The diagnostic criteria for acute renal failure.
The Analyses

 

The authors of the JASN study used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI and new users of histamine H2-receptor antagonists. In adjusted Cox survival models, the PPI group, compared with the H2-blockers group, had an increased risk of incident EGFR<60 mL/min/1.73m2and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively).

“Patients treated with PPIs also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of EGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2 blockers versus patients taking PPIs and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD,” the authors explained. PPIs and H2 blockers are prescribed for gastric acid control (Figure 4.)

 


Figure 4. Gastric acid secretion in the presence of various drugs cropped

 

The authors of the JAMA Internal Medicine examined participants in the Atherosclerosis Risk in Communities study. The mean (SD) age was 63.0 (5.6) years, and 43.9% of participants were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication, the authors noted.

PPI use was associated with CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% CI, 1.11-1.90). The analysis was also adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96). The data were also analyzed with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55), the researchers explained.

“The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score-matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21),” they concluded.

“Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD,” they added.


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