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Published in: BMC Nephrology 1/2019

Open Access 01-12-2019 | Acute Kidney Injury | Research article

Statin use and the risk of acute kidney injury in older adults

Authors: Marcello Tonelli, Anita M. Lloyd, Aminu K. Bello, Matthew T. James, Scott W. Klarenbach, Finlay A. McAlister, Braden J. Manns, Ross T. Tsuyuki, Brenda R. Hemmelgarn, for the Alberta Kidney Disease Network

Published in: BMC Nephrology | Issue 1/2019

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Abstract

Background

As more patients at lower cardiovascular (CV) risk are treated with statins, the balance between cardiovascular benefits and the risk of adverse events becomes increasingly important.

Methods

We did a population-based cohort study (May 1, 2002 to March 30, 2013) using province-wide laboratory and administrative data in Alberta. We studied new statin users aged 66 years of age and older who were not receiving renal replacement therapy at baseline. We assessed statin use at 30-day intervals to allow time-varying assessment of statin exposure in Cox proportional hazards models that examined the relation between statin use and hospitalization with acute kidney injury (AKI).

Results

Of the 128,140 new statin users, 47 and 46% were prescribed high- and medium-intensity regimens at the index date. During median follow-up of 4.6 years (interquartile range 2.2, 7.4), 9118 individuals were hospitalized for AKI. Compared to non-use, the use of high- and medium-intensity statin regimens was associated with significant increases in the adjusted risks of hospitalization with AKI: hazard ratios 1.16 [95% confidence interval (CI) 1.10, 1.23] and 1.07 (95% CI 1.01, 1.13), respectively. Risks of AKI were higher among women than men, and among users of angiotensin converting enzyme inhibitors/angiotensin receptor blockers than non-users, and among diuretic users (p for interaction 0.002, 0.01, and 0.04 respectively).

Conclusions

We found a graded, independent association between the intensity of statin use and the risk of hospitalization with AKI, although the absolute magnitude of the excess risk was small.
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Literature
1.
go back to reference Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R, de Lemos J, Braunwald E, Blazing M, Murphy S, Downs JR, Gotto A, Clearfield M, Holdaas H, Gordon D, Davis B, Koren M, Dahlof B, Poulter N, Sever P, Knopp RH, Fellstrom B, Holdaas H, Jardine A, Schmieder R, Zannad F, Goldbourt U, Kaplinsky E, Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Fuller J, Neil A, Wanner C, Krane V, Sacks F, Moye L, Pfeffer M, Hawkins CM, Braunwald E, Barter P, Keech A, Tavazzi L, Maggioni A, Marchioli R, Tognoni G, Franzosi MG, Maggioni A, Bloomfield H, Robins S, Collins R, Armitage J, Keech A, Parish S, Peto R, Sleight P, Pedersen TR, Ridker PM, Holman R, Meade T, Simes J, Keech A, MacMahon S, Marschner I, Tonkin A, Shaw J, Serruys PW, Nakamura H, Knatterud G, Furberg C, Byington R, Macfarlane P, Cobbe S, Ford I, Murphy M, Blauw GJ, Packard C, Shepherd J, Kjekshus J, Pedersen T, Wilhelmsen L, Braunwald E, Cannon C, Murphy S, Collins R, Armitage J, Bowman L, Parish S, Peto R, Sleight P, Baigent C, Baxter A, Collins R, Landray M, La Rosa J, Rossouw J, Probstfield J, Shepherd J, Cobbe S, Macfarlane P, Ford I, Flather M, Kastelein J, Newman C, Shear C, Tobert J, Varigos J, White H, Yusuf S, Mellies M, McGovern M, Barclay J, Belder R, Mitchel MY, Musliner T, Ansquer JC, Llewellyn BM, Bortolini M, Brandrup-Wognsen G, Bryzinski B, Olsson G, Pears J, DeMicco D, Baxter A, Baigent C, Barnes EH, Bhala N, Blackwell L, Buck G, Collins R, Emberson J, Herrington WG, Holland LE, Kearney PM, Keech A, Kirby A, Lewis DA, Marschner I, Pollicino C, Reith C, Simes J, Sourjina T. Efficacy and safety of more intensive lowering of ldl cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.CrossRef Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R, de Lemos J, Braunwald E, Blazing M, Murphy S, Downs JR, Gotto A, Clearfield M, Holdaas H, Gordon D, Davis B, Koren M, Dahlof B, Poulter N, Sever P, Knopp RH, Fellstrom B, Holdaas H, Jardine A, Schmieder R, Zannad F, Goldbourt U, Kaplinsky E, Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Fuller J, Neil A, Wanner C, Krane V, Sacks F, Moye L, Pfeffer M, Hawkins CM, Braunwald E, Barter P, Keech A, Tavazzi L, Maggioni A, Marchioli R, Tognoni G, Franzosi MG, Maggioni A, Bloomfield H, Robins S, Collins R, Armitage J, Keech A, Parish S, Peto R, Sleight P, Pedersen TR, Ridker PM, Holman R, Meade T, Simes J, Keech A, MacMahon S, Marschner I, Tonkin A, Shaw J, Serruys PW, Nakamura H, Knatterud G, Furberg C, Byington R, Macfarlane P, Cobbe S, Ford I, Murphy M, Blauw GJ, Packard C, Shepherd J, Kjekshus J, Pedersen T, Wilhelmsen L, Braunwald E, Cannon C, Murphy S, Collins R, Armitage J, Bowman L, Parish S, Peto R, Sleight P, Baigent C, Baxter A, Collins R, Landray M, La Rosa J, Rossouw J, Probstfield J, Shepherd J, Cobbe S, Macfarlane P, Ford I, Flather M, Kastelein J, Newman C, Shear C, Tobert J, Varigos J, White H, Yusuf S, Mellies M, McGovern M, Barclay J, Belder R, Mitchel MY, Musliner T, Ansquer JC, Llewellyn BM, Bortolini M, Brandrup-Wognsen G, Bryzinski B, Olsson G, Pears J, DeMicco D, Baxter A, Baigent C, Barnes EH, Bhala N, Blackwell L, Buck G, Collins R, Emberson J, Herrington WG, Holland LE, Kearney PM, Keech A, Kirby A, Lewis DA, Marschner I, Pollicino C, Reith C, Simes J, Sourjina T. Efficacy and safety of more intensive lowering of ldl cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.CrossRef
2.
go back to reference Thompson PD. What to believe and do about statin-associated adverse effects. Jama. 2016;316:1969–70.CrossRef Thompson PD. What to believe and do about statin-associated adverse effects. Jama. 2016;316:1969–70.CrossRef
3.
go back to reference Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67:2395–410.CrossRef Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67:2395–410.CrossRef
4.
go back to reference Hennessy DA, Tanuseputro P, Tuna M, Bennett C, Perez R, Shields M, Ko DT, Tu J, Manuel DG. Population health impact of statin treatment in Canada. Health Rep. 2016;27:20–8.PubMed Hennessy DA, Tanuseputro P, Tuna M, Bennett C, Perez R, Shields M, Ko DT, Tu J, Manuel DG. Population health impact of statin treatment in Canada. Health Rep. 2016;27:20–8.PubMed
5.
go back to reference James MT, Pannu N. Can acute kidney injury be considered a clinical quality measure. Nephron. 2015;131:237–41.CrossRef James MT, Pannu N. Can acute kidney injury be considered a clinical quality measure. Nephron. 2015;131:237–41.CrossRef
6.
go back to reference James MT. Tonelli M, Alberta kidney disease N. Financial aspects of renal replacement therapy in acute kidney injury. Semin Dial. 2011;24:215–9.CrossRef James MT. Tonelli M, Alberta kidney disease N. Financial aspects of renal replacement therapy in acute kidney injury. Semin Dial. 2011;24:215–9.CrossRef
7.
go back to reference Waikar SS, Liu KD, Chertow GM. The incidence and prognostic significance of acute kidney injury. Curr Opin Nephrol Hypertens. 2007;16:227–36.CrossRef Waikar SS, Liu KD, Chertow GM. The incidence and prognostic significance of acute kidney injury. Curr Opin Nephrol Hypertens. 2007;16:227–36.CrossRef
8.
go back to reference Molnar AO, Jain AK, Kitchlu A, Siddiqui N, Garg AX, Coca SG, Parikh CR, Devereaux PJ, Walsh M, Luo J, Michael Paterson J, Wald R. Statin use associates with a lower incidence of acute kidney injury after major elective surgery. J Am Soc Nephrol. 2011;22:939–46.CrossRef Molnar AO, Jain AK, Kitchlu A, Siddiqui N, Garg AX, Coca SG, Parikh CR, Devereaux PJ, Walsh M, Luo J, Michael Paterson J, Wald R. Statin use associates with a lower incidence of acute kidney injury after major elective surgery. J Am Soc Nephrol. 2011;22:939–46.CrossRef
9.
go back to reference Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, Lafrance J-P, Levy A, Garg AX, Ernst P, Canadian Network for Observational Drug Effect S, Suissa S, Henry D, Paterson M, Colin D, Hemmelgarn B, Teare G, Martens P, Caetano P, Ernst P, LeLorier J, Platt R, Levy A. Use of high potency statins and rates of admission for acute kidney injury: Multicenter, retrospective observational analysis of administrative databases. Bmj. 2013;346:f880.CrossRef Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, Lafrance J-P, Levy A, Garg AX, Ernst P, Canadian Network for Observational Drug Effect S, Suissa S, Henry D, Paterson M, Colin D, Hemmelgarn B, Teare G, Martens P, Caetano P, Ernst P, LeLorier J, Platt R, Levy A. Use of high potency statins and rates of admission for acute kidney injury: Multicenter, retrospective observational analysis of administrative databases. Bmj. 2013;346:f880.CrossRef
10.
go back to reference Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and wales: population based cohort study using the qresearch database. Bmj. 2010;340:c2197.CrossRef Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and wales: population based cohort study using the qresearch database. Bmj. 2010;340:c2197.CrossRef
11.
go back to reference Hemmelgarn BR, Clement F, Manns BJ, Klarenbach S, James MT, Ravani P, Pannu N, Ahmed SB, MacRae J, Scott-Douglas N, Jindal K, Quinn R, Culleton BF, Wiebe N, Krause R, Thorlacius L, Tonelli M. Overview of the Alberta kidney disease network. BMC Nephrol. 2009;10:30.CrossRef Hemmelgarn BR, Clement F, Manns BJ, Klarenbach S, James MT, Ravani P, Pannu N, Ahmed SB, MacRae J, Scott-Douglas N, Jindal K, Quinn R, Culleton BF, Wiebe N, Krause R, Thorlacius L, Tonelli M. Overview of the Alberta kidney disease network. BMC Nephrol. 2009;10:30.CrossRef
12.
go back to reference National Institute for Health and Clinical Excellence. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. 2014. National Institute for Health and Clinical Excellence. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. 2014.
13.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRef Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRef
14.
go back to reference Tonelli M, Wiebe N, Fortin M, Guthrie B, Hemmelgarn BR, James MT, Klarenbach SW, Lewanczuk R, Manns BJ, Ronksley P, Sargious P, Straus S, Quan H, Alberta Kidney Disease N. Methods for identifying 30 chronic conditions: Application to administrative data. BMC Med Inform Decis Mak. 2015;15:31.CrossRef Tonelli M, Wiebe N, Fortin M, Guthrie B, Hemmelgarn BR, James MT, Klarenbach SW, Lewanczuk R, Manns BJ, Ronksley P, Sargious P, Straus S, Quan H, Alberta Kidney Disease N. Methods for identifying 30 chronic conditions: Application to administrative data. BMC Med Inform Decis Mak. 2015;15:31.CrossRef
15.
go back to reference Waikar SS, Wald R, Chertow GM, Curhan GC, Winkelmayer WC, Liangos O, Sosa M-A, Jaber BL. Validity of international classification of diseases, ninth revision, clinical modification codes for acute renal failure. J Am Soc Nephrol. 2006;17:1688–94.CrossRef Waikar SS, Wald R, Chertow GM, Curhan GC, Winkelmayer WC, Liangos O, Sosa M-A, Jaber BL. Validity of international classification of diseases, ninth revision, clinical modification codes for acute renal failure. J Am Soc Nephrol. 2006;17:1688–94.CrossRef
16.
go back to reference Andrade SE, Kahler KH, Frech F, Chan KA. Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf. 2006;15:565–74 discussion 575-567.CrossRef Andrade SE, Kahler KH, Frech F, Chan KA. Methods for evaluation of medication adherence and persistence using automated databases. Pharmacoepidemiol Drug Saf. 2006;15:565–74 discussion 575-567.CrossRef
17.
go back to reference Austin PC. Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat-Simul C. 2009;38:1228–34.CrossRef Austin PC. Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat-Simul C. 2009;38:1228–34.CrossRef
18.
go back to reference Layton JB, Brookhart MA, Jonsson Funk M, Simpson RJ Jr, Pate V, Sturmer T, Kshirsagar AV. Acute kidney injury in statin initiators. Pharmacoepidemiol Drug Saf. 2013;22:1061–70.PubMed Layton JB, Brookhart MA, Jonsson Funk M, Simpson RJ Jr, Pate V, Sturmer T, Kshirsagar AV. Acute kidney injury in statin initiators. Pharmacoepidemiol Drug Saf. 2013;22:1061–70.PubMed
19.
go back to reference Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R, on behalf of the SHARP Investigators. The effects of lowering ldl cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (study of heart and renal protection): A randomised placebo-controlled trial. Lancet. 2011;377:2181–92.CrossRef Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R, on behalf of the SHARP Investigators. The effects of lowering ldl cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (study of heart and renal protection): A randomised placebo-controlled trial. Lancet. 2011;377:2181–92.CrossRef
20.
go back to reference Roberts MD. Crestor (rosuvastatin calcium) nda 21-366 jupiter. Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2009. Roberts MD. Crestor (rosuvastatin calcium) nda 21-366 jupiter. Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2009.
21.
go back to reference Sarma A, Cannon CP, de Lemos J, Rouleau JL, Lewis EF, Guo J, Mega JL, Sabatine MS, O'Donoghue ML. The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome. J Am Heart Assoc. 2014;3:e000784.CrossRef Sarma A, Cannon CP, de Lemos J, Rouleau JL, Lewis EF, Guo J, Mega JL, Sabatine MS, O'Donoghue ML. The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome. J Am Heart Assoc. 2014;3:e000784.CrossRef
22.
go back to reference Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. Jama. 2016;315:877–88.CrossRef Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial. Jama. 2016;315:877–88.CrossRef
23.
go back to reference Cholesterol Treatment Trialists C, Reith C, Blackwell L, Emberson J, Mihaylova B, Armitage J, Fulcher J, Keech A, Simes J, Baigent C, Collins R. Protocol for analyses of adverse event data from randomized controlled trials of statin therapy. Am Heart J. 2016;176:63–9.CrossRef Cholesterol Treatment Trialists C, Reith C, Blackwell L, Emberson J, Mihaylova B, Armitage J, Fulcher J, Keech A, Simes J, Baigent C, Collins R. Protocol for analyses of adverse event data from randomized controlled trials of statin therapy. Am Heart J. 2016;176:63–9.CrossRef
24.
go back to reference Garcia MJ, Reinoso RF, Sanchez Navarro A, Prous JR. Clinical pharmacokinetics of statins. Methods Find Exp Clin Pharmacol. 2003;25:457–81.CrossRef Garcia MJ, Reinoso RF, Sanchez Navarro A, Prous JR. Clinical pharmacokinetics of statins. Methods Find Exp Clin Pharmacol. 2003;25:457–81.CrossRef
Metadata
Title
Statin use and the risk of acute kidney injury in older adults
Authors
Marcello Tonelli
Anita M. Lloyd
Aminu K. Bello
Matthew T. James
Scott W. Klarenbach
Finlay A. McAlister
Braden J. Manns
Ross T. Tsuyuki
Brenda R. Hemmelgarn
for the Alberta Kidney Disease Network
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-019-1280-7

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