Risk of acute kidney injury in patients with HIV receiving proton pump inhibitors
Publication: Journal of Comparative Effectiveness Research
Abstract
Aims/patients & methods: To evaluate the risk of acute kidney injury (AKI) in patients with HIV receiving proton pump inhibitors (PPI) a cohort study was conducted utilizing the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database. Patients were followed from the index date until the earliest date of AKI, 120 days or end of study period, or death. Statistical analyses utilized a Cox proportional hazards model. Results: A total of 21,643 patients (6000 PPI and 15,643 non-PPI) met all study criteria. The PPI cohort had twice the risk of AKI compared with controls (2.12, hazard ratio: 1.46–3.1). Conclusion: A nationwide cohort study supported the relationship of an increased risk of AKI in patients receiving PPIs.
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References
Papers of special note have been highlighted as: • of interest
1.
Moss JA. HIV/AIDS review. Radiol. Technol. 84(3), 247–267 (2013).
2.
Report MW. HIV surveillance – United States, 1981–2008. MMWR Morb. Mortal. Wkly Rep. 60(21), 689–693 (2011).
3.
Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord1, Lewden C, Bouteloup V et al. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. Int. J. Epidemiol. 41(2), 433–445 (2012).
4.
Kalim S, Szczech LA, Wyatt CM. Acute kidney injury in HIV-infected patients. Semin. Nephrol. 28(6), 556–562 (2008).
• Acute kidney injury (AKI) is common in HIV-infected patients and has been associated with increased morbidity and mortality. Prior to the introduction of effective antiretroviral therapy, AKI in HIV-positive patients was most commonly the result of volume depletion, septicemia or nephrotoxic medications. AKI remains a significant problem in the antiretroviral era and is still commonly attributed to infection or nephrotoxic medications.
5.
Wyatt CM, Arons RR, Klotman PE, Klotman ME. Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality. AIDS 20(4), 561–565 (2006).
6.
Seedat F, Martinson N, Motlhaoleng K et al. Acute kidney injury, risk factors, and prognosis in hospitalized HIV-infected adults in South Africa, compared by tenofovir exposure. AIDS Res. Hum. Retroviruses 33(1), 33–40 (2017).
7.
Choi AI, Li Y, Parikh C, Volberding PA, Shlipak MG. Long-term clinical consequences of acute kidney injury in the HIV-infected. Kidney Int. 78(5), 478–485 (2010).
• A national sample of HIV-infected persons demonstrated the clinical repercussions of AKI and document that they appear to extend beyond the hospital setting. The paper highlights that AKI can contribute to excess cardiovascular risks, end-stage renal disease and mortality.
8.
Newsome BB, Warnock DG, McClellan WM et al. Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch. Intern. Med. 168(6), 609–616 (2008).
9.
Wald R, Quinn RR, Luo J et al. Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. J. Am. Med. Assoc. 302(11), 1179–1185 (2009).
10.
Scheel PJ, Liu M, Rabb H. Uremic lung: new insights into a forgotten condition. Kidney Int. 74(7), 849–851 (2008).
11.
Klein CL, Hoke TS, Fang W-F, Altmann CJ, Douglas IS, Faubel S. Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int. 74(7), 901–909 (2008).
12.
Grigoryev DN, Liu M, Hassoun HT, Cheadle C, Barnes KC, Rabb H. The local and systemic inflammatory transcriptome after acute kidney injury. J. Am. Soc. Nephrol. 19(3), 547–558 (2008).
13.
Liu M, Liang Y, Chigurupati S et al. Acute kidney injury leads to inflammation and functional changes in the brain. J. Am. Soc. Nephrol. 19(7), 1360–1370 (2008).
14.
Murugan R, Karajala-Subramanyam V, Lee M et al. Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. Kidney Int. 77(6), 527–535 (2010).
15.
Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir. Chem. Chemother. 12(3), 133–150 (2001).
16.
Hunt PW, Martin JN, Sinclair E et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J. Infect. Dis. 187(10), 1534–1543 (2003).
17.
Kuller LH, Tracy R, Belloso W et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 5(10), 1496–1508 (2008).
18.
Hunt PW, Brenchley J, Sinclair E et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J. Infect. Dis. 197(1), 126–133 (2008).
19.
Hsue PY, Hunt PW, Sinclair E et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses. AIDS 20(18), 2275–2283 (2006).
20.
Lopes JA, Fernandes J, Jorge S, Neves J, Antunes F, Prata MM. An assessment of the RIFLE criteria for acute renal failure in critically ill HIV-infected patients. Crit. Care 11, 121 (2007).
21.
Nadkarni GN, Patel AA, Yacoub R et al. The burden of dialysis-requiring acute kidney injury among hospitalized adults with HIV infection: a nationwide inpatient sample analysis. AIDS 29(9), 1061–1066 (2015).
22.
Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of renal disease among people living with HIV: a systematic review and meta-analysis. BMC Public Health 12, 234 (2012).
• Patients with HIV are at increased risk of renal disease, with greater risk at later stages of infection and at older ages. Antiretrovirals prolong survival and decreases the risk of renal disease. However, less reduction in renal disease risk occurs for tenofovir-containing antiretrovirals than for other regimens.
23.
Franceschini N, Napravnik S, Eron Jr JJ, Szczech LA, Finn WF. Incidence and etiology of acute renal failure among ambulatory HIV-infected patients. Kidney Int. 67(4), 1526–1531 (2005).
• AKI is common in ambulatory HIV patients and immunosuppression, infection and hepatitis C are important conditions associated with AKI in the postantiretroviral era.
24.
Roe J, Campbell LJ, Ibrahim F, Hendry BM, Post F. HIV care and the incidence of acute renal failure. Clin. Infect. Dis. 47(2), 242–249 (2008).
25.
Perazella MA, Luciano RL. Review of select causes of drug-induced AKI. Expert Rev. Clin. Pharmacol. 8(4), 367–371 (2015).
26.
Schooley RT, Ruane P, Myers RA et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 16(9), 1257–1263 (2002).
27.
Schaaf B, Aries SP, Kramme E, Steinhoff J, Dalhoff K. Acute renal failure associated with tenofovir treatment in a patient with acquired immunodeficiency syndrome. Clin. Infect. Dis. 37(3), e41–e43 (2003).
28.
Woodward CLN, Hall AM, Williams IG et al. Tenofovir-associated renal and bone toxicity. HIV Med. 10(8), 482–487 (2009).
29.
Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin. Infect. Dis. 51(5), 496–505 (2010).
• Although tenofovir disoproxil fumarate use was associated with a statistically significant loss of renal function, the clinical magnitude of this effect was modest. Our findings do not support the need to restrict tenofovir disoproxil fumarate use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical.
30.
Nelson MR, Katlama C, Montaner JS et al. The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS 21(10), 1273–1281 (2007).
31.
Young B, Buchacz K, Baker RK et al. Renal function in tenofovir-exposed and tenofovir-unexposed patients receiving highly active antiretroviral therapy in the HIV outpatient study. J. Int. Assoc. Physicians AIDS Care 6(3), 178–187 (2007).
32.
Fernandez-Fernandez B, Montoya-Ferrer A, Sanz AB et al. Tenofovir nephrotoxicity: 2011 update. AIDS Res. Treat. 2011, (2011) (Epub ahead of print).
33.
Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am. J. Kidney Dis. 57(5), 773–780 (2011).
34.
Horberg M, Tang B, Towner W et al. Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients. J. Acquir. Immune Defic. Syndr. 53(1), 62–69 (2010).
35.
Nkuize M, De Wit S, Muls V, Arvanitakis M, Buset M. Upper gastrointestinal endoscopic findings in the era of highly active antiretroviral therapy. HIV Med. 11(6), 412–417 (2010).
36.
Gawron AJ, Pandolfino JE, Miskevics S, Lavela SL. Proton pump inhibitor prescriptions and subsequent use in US veterans diagnosed with gastroesophageal reflux disease. J. Gen. Intern. Med. 28(7), 930–937 (2013).
• Many veterans receive high total daily dose proton pump inhibitor (PPI) prescriptions as initial therapy for a gastroesophageal reflux disease (GERD) diagnosis, and few patients have evidence for cessation or reduction of therapy. These results provide detailed data on prescribing and use of PPIs to help guide efforts for optimal PPI use in US veterans.
37.
Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig. Dis. Sci. 56(4), 931–950 (2011).
38.
Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern. Med. 176(2), 172–174 (2016).
• Mounting evidence demonstrates that PPIs are associated with a number of adverse effects and are overprescribed. Most of the evidence supporting the adverse effects of PPIs is observational. Thus, it is possible that PPI users are sicker than nonusers, or that adverse effects are caused by other drugs or conditions associated with PPI use. However, some adverse effects have been documented by multiple high-quality observational studies and are likely causal.
39.
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. C Open 3(2), E166–E171 (2015).
40.
Avinash A, Patil N, Kunder SK et al. A retrospective study to assess the effect of proton pump inhibitors on renal profile in a south Indian hospital. J. Clin. Diagnostic Res. 11(4), FC09–FC12 (2017).
41.
Leonard CE, Freeman CP, Newcomb CW et al. Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury. Pharmacoepidemiol. Drug Saf. 21(11), 1155–1172 (2012).
42.
Lee J, Mark RG, Celi LA, Danziger J. Proton pump inhibitors are not associated with acute kidney injury in critical illness. J. Clin. Pharmacol. 1, 1–30 (2016).
43.
Waikar SS, Wald R, Chertow GM et al. Validity of International Classification of Diseases, Ninth Revision, clinical modification codes for acute renal failure. J. Am. Soc. Nephrol. 17(6), 1688–1694 (2006).
44.
Lazarus B, Chen Y, Wilson FP et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern. Med. 21205(2), 238 (2016).
45.
Quan H, Sundararajan V, Halfon P et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med. Care 43(11), 1130–1139 (2005).
46.
Braithwaite RS, Kozal MJ, Chang CCH et al. Adherence, virological and immunological outcomes for HIV-infected veterans starting combination antiretroviral therapies. AIDS 21(12), 1579–1589 (2007).
47.
Viswanathan S, Justice AC, Caleb Alexander G et al. Adherence and HIV RNA suppression in the current era of highly active antiretroviral therapy (HAART). J. Acquir. Immune Defic. Syndr. 69(4), 493–498 (2015).
48.
Therneau TM. A package for survival analysis in S. Survival (Lond). (2015). http://cran.r-project.org/package=survival
49.
Rwegerera GM, Molefe-Baikai OJ, Masaka A et al. Prevalence of chronic kidney disease using estimated glomerular filtration rate among diaetes patients attending a tertiary clinic in Botswana. Hosp. Pract. (1995) 46(4), 214–220 (2018).
50.
Ruffenach SJ, Siskind MS, Lien YHH. Acute interstitial nephritis due to omeprazole. Am. J. Med. 93(4), 472–473 (1992).
51.
Myers RP, McLaughlin K, Hollomby DJ. Acute interstitial nephritis due to omeprazole. Am. J. Gastroenterol. 96(12), 3428–3431 (2001).
52.
Blank M-L, Parkin L, Paul C, Herbison P. A nationwide nested case–control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 86(4), 837–844 (2014).
53.
Torpey N, Barker T, Ross C. Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit. Nephrol. Dial. Transplant. 19(6), 1441–1446 (2004).
54.
Yepuri G, Sukhovershin R, Nazari-Shafti TZ, Petrascheck M, Ghebre YT, Cooke JP. Proton pump inhibitors accelerate endothelial senescence. Circ. Res. 118(12), e36–e42 (2016).
55.
Ghebremariam YT, LePendu P, Lee JC et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation 128(8), 845–853 (2013).
56.
Sutton SS, Magagnoli J, Cummings T, Hardin JW. The association between the use of proton pump inhibitors and the risk of hypomagnesemia in a national cohort of HIV Veteran patients. J. Int. Assoc. Provid. AIDS Care 18, 2325958218821652 (2019).
57.
Sutton SS, Magagnoli J, Cummings TH, Hardin JW, Edun B, Beaubrun A. Chronic kidney disease, cardiovascular disease, and osteoporotic fractures in patients with and without HIV in the US Veteran’s Affairs Administration System. Curr. Med. Res. Opin. 31, 1–9 (2018).
58.
Sutton SS, Magagnoli J, Hardin JW. Impact of pill burden on adherence, risk of hospitalization, and viral suppression in HIV/AIDS patients receiving antiretroviral therapy. Pharmacotherapy 36(4), 385–401 (2016).
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Pages: 781 - 790
PubMed: 31167563
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© 2019 Future Medicine Ltd.
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Received: 23 January 2019
Accepted: 2 May 2019
Published online: 6 June 2019
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Risk of acute kidney injury in patients with HIV receiving proton pump inhibitors. (2019) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2019-0017
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