Potential Risk of Chronic Kidney Disease in Long Term Use of Acid Reducing Medications

Chronic kidney disease (CKD) is a condition that involves a progressive loss of kidney function. There are several possible causes of CKD, including exposure to toxins, obesity, type 2 diabetes, cardiovascular diseases, and birth defects in the nephron.

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It is estimated that 1 in 7 adults in the United States have CKD. According to the CDC, age can also be a contributing factor to CKD, making it more common in elderly patients aged 65 years or older than in younger adults aged 45 to 64 years or aged 18 to 44 years.¹

The kidneys' main function is to remove waste and excess fluid from the blood by releasing it into the urine. Gradual loss of kidney function may lead to the accumulation of harmful toxins and waste in the blood. Cardiovascular diseases such as coronary artery disease, heart failure, and heart attack can also be major consequences of CKD.¹

CKD is typically diagnosed using laboratory studies to determine the presence of proteinuria, elevated protein in the urine, or hematuria, blood in the urine. An estimated glomerular filtration rate (eGFR) can also be used to determine kidney function by measuring the amount of cleansed blood filtered out per minute per body surface area.

The eGFR typically declines in elderly patients due to a loss in muscle mass. However, patients with CKD will have a progressive decline in eGFR even at a younger age.² There are 5 different stages of eGFR that classify the kidney’s functional status: Stage 1 (eGFR of ≥ 90) indicates mild kidney damage and is still classified as functional; Stage 2 (eFGR of 60 - 89) indicates a functional kidney with higher damage than stage 1; Stage 3 (eGFR 30 - 59) indicates lower kidney function with possible symptoms including fatigue, darker urine, kidney pain, and fluid retention; Stage 4 (eGFR 15 - 30) indicates poor kidney function with moderate to severe damage; and Stage 5 (eGFR ≤ 15) indicates kidney failure and a need for dialysis.^2,3

Proton pump inhibitors (PPIs) are one of the most common agents prescribed for the short-term treatment of gastroesophageal reflux disease (GERD). PPIs include omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole.

These agents function to decrease stomach acid by blocking the H+/K+ ATPase enzyme and inhibiting gastric acid secretion by the parietal cell.⁴ Prolonged use of PPIs has been associated with malabsorption of certain medications or vitamins, risk of bone fractures, infections, and renal damage.⁵

According to an observational study on Atherosclerosis Risk in Communities (ARIC) trial, there was 1.45 times (95% CI, 1.11 - 1.9; P=0.006) higher risk of incident CKD and 1.72 times (95% CI, 1.28 - 2.30; p<0.001) increased risk of acute kidney injury compared to non-users. The study suggests that there was a 20% to 50% higher risk of CKD incidence among PPI users.⁶

A retrospective cohort study on a large Health Maintenance Organization (HMO) population consisting of 14,514 individuals in the CKD cohorts were exposed to a PPI showed that the association of CKD in PPI group compared to non-users were 34.3 compared to 8.75 per 1000 individuals per years (OR 1.49; 95% CI 1.39 - 1.60; p<0.0001). The incidence rate of CKD was higher among PPI users at 34.0 compared to 8.32 per 1000 person-years (p<0.0001).⁷

These studies confirm that there are statistically significant associations between CKD and PPI use. However, these studies did not confirm if different PPI agents have a variable association with causing CKD.

With the widespread use of acid-reducing medications especially PPIs, it is important to understand that unnecessary use of these medications can greatly impact a patient's health. Pharmacists can use their clinical knowledge and professional judgment to educate patients about when it is appropriate to take these medications and when to avoid them.

References

1. Chronic kidney disease in the United States, 2021. Centers for Disease Control and Prevention. July 12, 2022. Accessed May 28, 2023. https://www.cdc.gov/kidneydisease/publications-resources/ckd-national-facts.html
2. Chen TK, Knicely DH, Grams ME. Chronic kidney disease diagnosis and management: a review. JAMA. 2019;322(13):1294-1304. doi:10.1001/jama.2019.14745
3. Hashmi MF, Benjamin O, Lappin SL. End-stage renal disease. StatPearls. Treasure Island (FL): StatPearls Publishing; February 19, 2023.
4. Ahmed A, Clarke JO. Proton pump inhibitors (PPI). StatPearls.Updated July 25, 2022. Accessed May 28, 2023. https://www.ncbi.nlm.nih.gov/books/NBK557385/
5. Castellana C, Pecere S, Furnari M, Telese A, et al. Side effects of long-term use of proton pump inhibitors: practical considerations. Pol Arch Intern Med. 2021;131(6):541-549. doi:10.20452/pamw.15997
6. Lazarus B, Chen Y, Wilson FP, Sang Y, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246. doi:10.1001/jamainternmed.2015.7193
7. Hart E, Dunn TE, Feuerstein S, Jacobs DM. Proton pump inhibitors and risk of acute and chronic kidney disease: a retrospective cohort study. Pharmacotherapy. 2019;39(4):443-453. doi:10.1002/phar.2235