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Do PPIs Pose a Danger to Kidneys?
Q) Is it true that PPI use can cause kidney disease?
Proton pump inhibitors (PPIs) have been available in the United States since 1990, with OTC options available since 2009. While these medications play a vital role in the treatment of gastrointestinal (GI) conditions, observational studies have linked PPI use to serious adverse events, including dementia, community-acquired pneumonia, hip fracture, and Clostridium difficile infection.1-4
Studies have also found an association between PPI use and kidney problems such as acute kidney injury (AKI), acute interstitial nephritis, and incident chronic kidney disease (CKD).5-7 One observational study used the Department of Veterans Affairs (VA) national databases to track the renal outcomes of 173,321 new PPI users and 20,270 new histamine H2 receptor antagonist (H2RA) users over the course of five years. Those who used PPIs demonstrated a significant risk for decreased renal function, lower estimated glomerular filtration rate (eGFR), doubled serum creatinine levels, and progression to end-stage renal disease (ESRD).8
Another study of 10,482 patients (322 PPI; 956 H2RA; 9,204 nonusers) and a replicate study of 248,751 patients (16,900 PPI; 6,640 H2RA; 225,211 nonusers) with an initial eGFR ≥ 60 mL/min/1.73m2 also found an association between PPI use and incident CKD, which persisted when compared to the other groups. Additionally, twice-daily PPI use was associated with a higher CKD risk than once-daily use.9
The pathophysiology of PPI use and kidney deterioration is poorly understood at this point. It is known that AKI can increase the risk for CKD, and AKI has been an assumed precursor to PPI-associated CKD. However, a study by Xie and colleagues reported an association between PPI use and increased risk for CKD, progression of CKD, and ESRD in the absence of preceding AKI. Using the VA databases, the researchers identified 144,032 new users of acid-suppressing medications (125,596 PPI; 18,436 H2RA) who had no history of kidney disease and followed them for five years. PPI users were found to be at increased risk for CKD, and a graded association was discovered between length of PPI use and risk for CKD.10
While these studies are observational and therefore do not prove causation, they do suggest a need for attentive monitoring of kidney function in patients using PPIs. Evaluating the need for PPIs and inquiring about OTC use of these medications is highly recommended, as research has found 25% to 70% of PPI prescriptions are not prescribed for an appropriate indication.11 Considerations regarding PPI use should include dosage, length of use, and whether alternate use of an H2RA is appropriate. —CAS
Cynthia A. Smith, DNP, CNN-NP, FNP-BC, APRN
Renal Consultants, PLLC, South Charleston, West Virginia
1. Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.
2. Lambert AA, Lam JO, Paik JJ, et al. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PloS One. 2015;10(6):e0128004.
3. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296(24):2947-2953.
4. Dial S, Alrasadi K, Manoukian C, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171(1):33-38.
5. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study. BMC Nephrol. 2013;14:150.
6. Blank ML, Parkin L, Paul C, et al. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86:837-844.
7. Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3(2):E166-171.
8. Xie Y, Bowe B, Li T, et al. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. 2016;27(10):3153-3163.
9. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.
10. Xie Y, Bowe B, Li T, et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int. 2017;91(6):1482-1494.
11. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336(7634):2-3.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National KidneyFoundation's Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month's responses were authored by Cynthia A. Smith, DNP, CNN-NP, FNP-BC, APRN, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, and Marlene Shaw-Gallagher, MS, PA-C, who is an Assistant Professor at University of Detroit Mercy in Michigan and practices in the Division of Nephrology at the University of Michigan in Ann Arbor.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National KidneyFoundation's Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month's responses were authored by Cynthia A. Smith, DNP, CNN-NP, FNP-BC, APRN, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, and Marlene Shaw-Gallagher, MS, PA-C, who is an Assistant Professor at University of Detroit Mercy in Michigan and practices in the Division of Nephrology at the University of Michigan in Ann Arbor.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National KidneyFoundation's Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month's responses were authored by Cynthia A. Smith, DNP, CNN-NP, FNP-BC, APRN, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, and Marlene Shaw-Gallagher, MS, PA-C, who is an Assistant Professor at University of Detroit Mercy in Michigan and practices in the Division of Nephrology at the University of Michigan in Ann Arbor.
Q) Is it true that PPI use can cause kidney disease?
Proton pump inhibitors (PPIs) have been available in the United States since 1990, with OTC options available since 2009. While these medications play a vital role in the treatment of gastrointestinal (GI) conditions, observational studies have linked PPI use to serious adverse events, including dementia, community-acquired pneumonia, hip fracture, and Clostridium difficile infection.1-4
Studies have also found an association between PPI use and kidney problems such as acute kidney injury (AKI), acute interstitial nephritis, and incident chronic kidney disease (CKD).5-7 One observational study used the Department of Veterans Affairs (VA) national databases to track the renal outcomes of 173,321 new PPI users and 20,270 new histamine H2 receptor antagonist (H2RA) users over the course of five years. Those who used PPIs demonstrated a significant risk for decreased renal function, lower estimated glomerular filtration rate (eGFR), doubled serum creatinine levels, and progression to end-stage renal disease (ESRD).8
Another study of 10,482 patients (322 PPI; 956 H2RA; 9,204 nonusers) and a replicate study of 248,751 patients (16,900 PPI; 6,640 H2RA; 225,211 nonusers) with an initial eGFR ≥ 60 mL/min/1.73m2 also found an association between PPI use and incident CKD, which persisted when compared to the other groups. Additionally, twice-daily PPI use was associated with a higher CKD risk than once-daily use.9
The pathophysiology of PPI use and kidney deterioration is poorly understood at this point. It is known that AKI can increase the risk for CKD, and AKI has been an assumed precursor to PPI-associated CKD. However, a study by Xie and colleagues reported an association between PPI use and increased risk for CKD, progression of CKD, and ESRD in the absence of preceding AKI. Using the VA databases, the researchers identified 144,032 new users of acid-suppressing medications (125,596 PPI; 18,436 H2RA) who had no history of kidney disease and followed them for five years. PPI users were found to be at increased risk for CKD, and a graded association was discovered between length of PPI use and risk for CKD.10
While these studies are observational and therefore do not prove causation, they do suggest a need for attentive monitoring of kidney function in patients using PPIs. Evaluating the need for PPIs and inquiring about OTC use of these medications is highly recommended, as research has found 25% to 70% of PPI prescriptions are not prescribed for an appropriate indication.11 Considerations regarding PPI use should include dosage, length of use, and whether alternate use of an H2RA is appropriate. —CAS
Cynthia A. Smith, DNP, CNN-NP, FNP-BC, APRN
Renal Consultants, PLLC, South Charleston, West Virginia
Q) Is it true that PPI use can cause kidney disease?
Proton pump inhibitors (PPIs) have been available in the United States since 1990, with OTC options available since 2009. While these medications play a vital role in the treatment of gastrointestinal (GI) conditions, observational studies have linked PPI use to serious adverse events, including dementia, community-acquired pneumonia, hip fracture, and Clostridium difficile infection.1-4
Studies have also found an association between PPI use and kidney problems such as acute kidney injury (AKI), acute interstitial nephritis, and incident chronic kidney disease (CKD).5-7 One observational study used the Department of Veterans Affairs (VA) national databases to track the renal outcomes of 173,321 new PPI users and 20,270 new histamine H2 receptor antagonist (H2RA) users over the course of five years. Those who used PPIs demonstrated a significant risk for decreased renal function, lower estimated glomerular filtration rate (eGFR), doubled serum creatinine levels, and progression to end-stage renal disease (ESRD).8
Another study of 10,482 patients (322 PPI; 956 H2RA; 9,204 nonusers) and a replicate study of 248,751 patients (16,900 PPI; 6,640 H2RA; 225,211 nonusers) with an initial eGFR ≥ 60 mL/min/1.73m2 also found an association between PPI use and incident CKD, which persisted when compared to the other groups. Additionally, twice-daily PPI use was associated with a higher CKD risk than once-daily use.9
The pathophysiology of PPI use and kidney deterioration is poorly understood at this point. It is known that AKI can increase the risk for CKD, and AKI has been an assumed precursor to PPI-associated CKD. However, a study by Xie and colleagues reported an association between PPI use and increased risk for CKD, progression of CKD, and ESRD in the absence of preceding AKI. Using the VA databases, the researchers identified 144,032 new users of acid-suppressing medications (125,596 PPI; 18,436 H2RA) who had no history of kidney disease and followed them for five years. PPI users were found to be at increased risk for CKD, and a graded association was discovered between length of PPI use and risk for CKD.10
While these studies are observational and therefore do not prove causation, they do suggest a need for attentive monitoring of kidney function in patients using PPIs. Evaluating the need for PPIs and inquiring about OTC use of these medications is highly recommended, as research has found 25% to 70% of PPI prescriptions are not prescribed for an appropriate indication.11 Considerations regarding PPI use should include dosage, length of use, and whether alternate use of an H2RA is appropriate. —CAS
Cynthia A. Smith, DNP, CNN-NP, FNP-BC, APRN
Renal Consultants, PLLC, South Charleston, West Virginia
1. Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.
2. Lambert AA, Lam JO, Paik JJ, et al. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PloS One. 2015;10(6):e0128004.
3. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296(24):2947-2953.
4. Dial S, Alrasadi K, Manoukian C, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171(1):33-38.
5. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study. BMC Nephrol. 2013;14:150.
6. Blank ML, Parkin L, Paul C, et al. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86:837-844.
7. Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3(2):E166-171.
8. Xie Y, Bowe B, Li T, et al. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. 2016;27(10):3153-3163.
9. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.
10. Xie Y, Bowe B, Li T, et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int. 2017;91(6):1482-1494.
11. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336(7634):2-3.
1. Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.
2. Lambert AA, Lam JO, Paik JJ, et al. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PloS One. 2015;10(6):e0128004.
3. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296(24):2947-2953.
4. Dial S, Alrasadi K, Manoukian C, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171(1):33-38.
5. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study. BMC Nephrol. 2013;14:150.
6. Blank ML, Parkin L, Paul C, et al. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86:837-844.
7. Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3(2):E166-171.
8. Xie Y, Bowe B, Li T, et al. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. 2016;27(10):3153-3163.
9. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.
10. Xie Y, Bowe B, Li T, et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int. 2017;91(6):1482-1494.
11. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336(7634):2-3.
