Machine Learning for Identifying Medication-Associated Acute Kidney Injury

One of the prominent problems in clinical medicine is medication-induced acute kidney injury (AKI). Avoiding this problem can prevent patient harm and reduce healthcare expenditures. Several researches have been conducted to identify AKI-associated medications using statistical, data mining, and machine learning techniques. However, these studies are limited to assessing the impact of known nephrotoxic medications and do not comprehensively explore the relationship between medication combinations and AKI. In this paper, we present a population-based retrospective cohort study that employs automated data analysis techniques to identify medications and medication combinations that are associated with a higher risk of AKI. By integrating multivariable logistic regression, frequent itemset mining, and stratified analysis, this study is designed to explore the complex relationships between medications and AKI in such a way that has never been attempted before. Through an analysis of prescription records of one million older patients stored in the healthcare administrative dataset at ICES (an independent, non-profit, world-leading research organization that uses population-based health and social data to produce knowledge on a broad range of healthcare issues), we identified 55 AKI-associated medications among 595 distinct medications and 78 AKI-associated medication combinations among 7748 frequent medication combinations. In addition, through a stratified analysis, we identified 37 cases where a particular medication was associated with increasing the risk of AKI when used with another medication. We have shown that our results are consistent with previous studies through consultation with a nephrologist and an electronic literature search. This research demonstrates how automated analysis techniques can be used to accomplish data-driven tasks using massive clinical datasets.

[1]  S. Dawlilng,et al.  The pharmacokinetics of nortriptyline in patients with chronic renal failure. , 1981, British journal of clinical pharmacology.

[2]  P. McCullagh,et al.  Generalized Linear Models , 1984 .

[3]  J. Kaufman,et al.  Community-acquired acute renal failure. , 1991, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[4]  S. Aamdal Can ondansetron hydrochloride (Zofran) enhance the nephrotoxic potential of other drugs? , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  Tomasz Imielinski,et al.  Database Mining: A Performance Perspective , 1993, IEEE Trans. Knowl. Data Eng..

[6]  J. Boccanfuso,et al.  The effects of megestrol acetate on nutritional parameters in a dialysis population. , 2000, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[7]  V. Jha,et al.  Treatment-related acute renal failure in the elderly: a hospital-based prospective study. , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  K. Lopau,et al.  Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury. , 2001, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  Y. Mori,et al.  Safety and availability of doxazosin in treating hypertensive patients with chronic renal failure. , 2001, Hypertension research : official journal of the Japanese Society of Hypertension.

[10]  V. Adhiyaman,et al.  Nephrotoxicity in the Elderly Due to Co-Prescription of Angiotensin Converting Enzyme Inhibitors and Nonsteroidal Anti-Inflammatory Drugs , 2001, Journal of the Royal Society of Medicine.

[11]  S. Hou,et al.  Hospital-acquired renal insufficiency. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[12]  A. Dupont Carvedilol and the kidney , 2004, The clinical investigator.

[13]  Jonathan Himmelfarb,et al.  Spectrum of acute renal failure in the intensive care unit: the PICARD experience. , 2004, Kidney international.

[14]  B. Vanderperren,et al.  Acute Liver Failure with Renal Impairment Related to the Abuse of Senna Anthraquinone Glycosides , 2005, The Annals of pharmacotherapy.

[15]  K. Loboz,et al.  Drug combinations and impaired renal function -- the 'triple whammy'. , 2005, British journal of clinical pharmacology.

[16]  John A Kellum,et al.  Acute renal failure in critically ill patients: a multinational, multicenter study. , 2005, JAMA.

[17]  Miet Schetz,et al.  Drug-induced acute kidney injury , 2005, Current opinion in critical care.

[18]  M. Rammohan,et al.  Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. , 2005, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[19]  Jonathan Himmelfarb,et al.  Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. , 2006, Journal of the American Society of Nephrology : JASN.

[20]  E. McCarthy,et al.  Declining mortality in patients with acute renal failure, 1988 to 2002. , 2006, Journal of the American Society of Nephrology : JASN.

[21]  D. Choudhury,et al.  Drug-associated renal dysfunction and injury , 2006, Nature Clinical Practice Nephrology.

[22]  Daryl A Jones,et al.  Diuretics in the management of acute kidney injury: a multinational survey. , 2007, Contributions to nephrology.

[23]  N. Pannu,et al.  An overview of drug-induced acute kidney injury , 2008, Critical care medicine.

[24]  P. Audia,et al.  Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction , 2008, Clinical toxicology.

[25]  Alice Miller,et al.  Gabapentin toxicity in renal failure: the importance of dose adjustment. , 2009, Pain medicine.

[26]  Eleni Georgaki-Angelaki,et al.  Olmesartan medoxomil-induced acute renal failure in a premature newborn following maternal exposure during pregnancy: a case report and review of the literature , 2009, NDT plus.

[27]  J. Kellum,et al.  Diuretics in acute kidney injury. , 2009, Minerva anestesiologica.

[28]  Sanjeev Kumar,et al.  Dexamethasone ameliorates renal ischemia-reperfusion injury. , 2009, Journal of the American Society of Nephrology : JASN.

[29]  Shiliang Liu,et al.  Temporal trends and regional variations in severe maternal morbidity in Canada, 2003 to 2007. , 2010, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[30]  K. Ho,et al.  Benefits and risks of furosemide in acute kidney injury , 2010, Anaesthesia.

[31]  M. Dixit,et al.  Significant Acute Kidney Injury Due to Non-steroidal Anti-inflammatory Drugs: Inpatient Setting , 2010, Pharmaceuticals.

[32]  Allison B McCoy,et al.  A computerized provider order entry intervention for medication safety during acute kidney injury: a quality improvement report. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[33]  E. Lipson,et al.  Lenalidomide-induced acute interstitial nephritis. , 2010, The oncologist.

[34]  S. Goldstein,et al.  Acute kidney injury and increasing nephrotoxic-medication exposure in noncritically-ill children. , 2011, Clinical journal of the American Society of Nephrology : CJASN.

[35]  N. Kolhe,et al.  Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[36]  P. Tao,et al.  A population-based study on the association between acute renal failure (ARF) and the duration of polypharmacy , 2012, BMC Nephrology.

[37]  Heather Thiessen Philbrook,et al.  Secular trends in acute dialysis after elective major surgery — 1995 to 2009 , 2012, Canadian Medical Association Journal.

[38]  F. Steinhäuslin,et al.  Renal Effects of Nimesulide in Furosemide-Treated Subjects , 2012, Drugs.

[39]  Ognjen Gajic,et al.  Risk Factors for Development of Acute Kidney Injury in Critically Ill Patients: A Systematic Review and Meta-Analysis of Observational Studies , 2012, Critical care research and practice.

[40]  Anuj Gupta,et al.  Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state. , 2012, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[41]  J. Fournier,et al.  Laboratory Monitoring of Patients Treated with Antihypertensive Drugs and Newly Exposed to Non Steroidal Anti-Inflammatory Drugs: A Cohort Study , 2012, PloS one.

[42]  Susana B. Martins,et al.  Quality of Care for Patients with Multiple Chronic Conditions: The Role of Comorbidity Interrelatedness , 2014, Journal of General Internal Medicine.

[43]  L. Peres,et al.  Acute nephrotoxicity of cisplatin: molecular mechanisms. , 2013, Jornal brasileiro de nefrologia : 'orgao oficial de Sociedades Brasileira e Latino-Americana de Nefrologia.

[44]  M. Etminan,et al.  Risk of acute kidney injury associated with the use of fluoroquinolones , 2013, Canadian Medical Association Journal.

[45]  P. Jha,et al.  Sunitinib induced nephrotic syndrome and thrombotic microangiopathy , 2013, Indian journal of nephrology.

[46]  A. Garg,et al.  Atypical Antipsychotic Drugs and the Risk for Acute Kidney Injury and Other Adverse Outcomes in Older Adults , 2014, Annals of Internal Medicine.

[47]  M. Devonald,et al.  A real-time electronic alert to improve detection of acute kidney injury in a large teaching hospital. , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[48]  R. Watanabe,et al.  A case of acute kidney injury associated with the use of oseltamivir and clarithromycin that was treated by hemodialysis , 2014 .

[49]  Arsh K Jain,et al.  Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study , 2014, BMC Nephrology.

[50]  N. Chen,et al.  Diuretics associated acute kidney injury: clinical and pathological analysis , 2014, Renal failure.

[51]  J. Fournier,et al.  Drug interactions between antihypertensive drugs and non‐steroidal anti‐inflammatory agents: a descriptive study using the French Pharmacovigilance database , 2014, Fundamental & clinical pharmacology.

[52]  Eric McArthur,et al.  Kidney function and population-based outcomes of initiating oral atenolol versus metoprolol tartrate in older adults. , 2014, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[53]  Shiliang Liu,et al.  Hypertensive disorders of pregnancy and the recent increase in obstetric acute renal failure in Canada: population based retrospective cohort study , 2014, BMJ : British Medical Journal.

[54]  Alicia Mackowski,et al.  Successful management of chronic high-output ileostomy with high dose loperamide , 2015, BMJ Case Reports.

[55]  D. Zink,et al.  Prediction of drug-induced nephrotoxicity and injury mechanisms with human induced pluripotent stem cell-derived cells and machine learning methods , 2015, Scientific Reports.

[56]  N. Puri,et al.  Dipyridamole attenuates ischemia reperfusion induced acute kidney injury through adenosinergic A1 and A2A receptor agonism in rats , 2016, Naunyn-Schmiedeberg's Archives of Pharmacology.

[57]  M. Perazella,et al.  The urine sediment as a biomarker of kidney disease. , 2015, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[58]  S. Allison Acute kidney injury: Effect of perioperative aspirin and clonidine on AKI , 2015, Nature Reviews Nephrology.

[59]  Javier A. Neyra,et al.  Rhabdomyolysis-induced acute kidney injury in a cancer patient exposed to denosumab and abiraterone: a case report , 2015, BMC Nephrology.

[60]  F. Assadi,et al.  Drug-induced renal disorders , 2015, Journal of renal injury prevention.

[61]  Chia-Yi Wu,et al.  Cumulative Cardiovascular Polypharmacy Is Associated With the Risk of Acute Kidney Injury in Elderly Patients , 2015, Medicine.

[62]  D. Leaf,et al.  Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery. , 2015, Journal of the American Society of Nephrology : JASN.

[63]  L. Juncos,et al.  Mineralocorticoid Receptor Antagonism in AKI: A New Hope? , 2016, Journal of the American Society of Nephrology : JASN.

[64]  D. Leaf,et al.  Catalytic iron and acute kidney injury. , 2016, American journal of physiology. Renal physiology.

[65]  N. Kolhe,et al.  The epidemiology of hospitalised acute kidney injury not requiring dialysis in England from 1998 to 2013: retrospective analysis of hospital episode statistics , 2016, International journal of clinical practice.

[66]  Christine E Shulenberger,et al.  Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance , 2016, Pharmacotherapy.

[67]  P. H. Gois,et al.  Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection. , 2016, Free radical biology & medicine.

[68]  S. Morgan,et al.  Frequency and cost of potentially inappropriate prescribing for older adults: a cross-sectional study. , 2016, CMAJ open.

[69]  Deepak K Nandikanti,et al.  Acute Kidney Injury Associated with Linagliptin , 2016, Case reports in endocrinology.

[70]  Svetlana K. Eden,et al.  Predictors of Recurrent AKI. , 2016, Journal of the American Society of Nephrology : JASN.

[71]  John A Kellum,et al.  Drug Class Combination–Associated Acute Kidney Injury , 2016, The Annals of pharmacotherapy.

[72]  Bonnie Berger,et al.  Compact Integration of Multi-Network Topology for Functional Analysis of Genes. , 2016, Cell systems.

[73]  Joëlle Micallef,et al.  The drugs that mostly frequently induce acute kidney injury: a case − noncase study of a pharmacovigilance database , 2017, British journal of clinical pharmacology.

[74]  D. Collister,et al.  Health Care Costs Associated with AKI. , 2017, Clinical journal of the American Society of Nephrology : CJASN.

[75]  E. Mishima,et al.  Acute Kidney Injury from Excessive Potentiation of Calcium-channel Blocker via Synergistic CYP3A4 Inhibition by Clarithromycin Plus Voriconazole , 2017, Internal medicine.

[76]  Eric McArthur,et al.  Antihypertensive medications and the risk of kidney stones in older adults: a retrospective cohort study , 2017, Hypertension Research.

[77]  Z. Erbayraktar,et al.  Effects of donepezil on liver and kidney functions for the treatment of Alzheimer's disease. , 2017, Journal of integrative neuroscience.

[78]  A. Alirezaei,et al.  An update on allopurinol and kidney failure; new trend for an old drug , 2017 .

[79]  P. Donnan,et al.  Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis , 2017, BMC Nephrology.

[80]  Fernando Perez-Ruiz,et al.  Treatment with Allopurinol is Associated with Lower Risk of Acute Kidney Injury in Patients with Gout: A Retrospective Analysis of a Nested Cohort , 2017, Rheumatology and Therapy.

[81]  Yawen Jiang,et al.  A Retrospective Cohort Study of Acute Kidney Injury Risk Associated with Antipsychotics , 2017, CNS Drugs.

[82]  S. Bagshaw,et al.  Intermittent furosemide administration in patients with or at risk for acute kidney injury: Meta-analysis of randomized trials , 2018, PloS one.

[83]  Jianying Hu,et al.  Predicting adverse drug reactions through interpretable deep learning framework , 2018, BMC Bioinformatics.

[84]  Alok Sharma,et al.  An integrative machine learning approach for prediction of toxicity-related drug safety , 2018, Life Science Alliance.

[85]  H. Yamada,et al.  Quetiapine-related Acute Kidney Injury Requiring Transient Continuous Hemodiafiltration , 2018, Internal medicine.

[86]  A. Go,et al.  Risk Factors for Recurrent Acute Kidney Injury in a Large Population-Based Cohort. , 2019, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[87]  Krishan Kumar,et al.  Innovation in Pharmacovigilance: Use of Artificial Intelligence in Adverse Event Case Processing , 2018, Clinical pharmacology and therapeutics.

[88]  Bataclan Rp Metolazone and Furosemide Combination in Cardiorenal Syndrome: Short-Term Safety and Efficacy Among Admitted Patients in a Tertiary Hospital , 2019, JOJ Urology & Nephrology.

[89]  Bin Li,et al.  Applications of machine learning in drug discovery and development , 2019, Nature Reviews Drug Discovery.

[90]  A. Sari Nephrotoxic Effects of Drugs , 2019, Poisoning in the Modern World - New Tricks for an Old Dog?.

[91]  Jin Liu,et al.  Early β-blockers administration might be associated with a reduced risk of contrast-induced acute kidney injury in patients with acute myocardial infarction. , 2019, Journal of thoracic disease.

[92]  Sheikh S. Abdullah,et al.  Multiple Regression Analysis and Frequent Itemset Mining of Electronic Medical Records: A Visual Analytics Approach Using VISA_M3R3 , 2020, Data.