A comprehensive description of kidney disease progression after acute kidney injury from a prospective, parallel-group cohort study

Abstract

Acute kidney injury (AKI) is associated with adverse long-term outcomes, but many studies are retrospective, focused on specific patient groups or lack adequate comparators. The ARID (AKI Risk in Derby) Study was a five-year prospective parallel-group cohort study to examine this. Hospitalized cohorts with and without exposure to AKI were matched 1:1 for age, baseline kidney function, and diabetes. Estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (uACR) were measured at three-months, one-, three- and five-years. Outcomes included kidney disease progression, heart failure episodes and mortality. In 866 matched individuals, kidney disease progression at five years was found to be significantly increased in 30% of the exposed group versus 7% of those non-exposed (adjusted odds ratio 2.49 [95% confidence interval 1.43 to 4.36]). In the AKI group, this was largely characterized by incomplete recovery of kidney function by three months. Further episodes of AKI during follow-up were significantly more common in the exposed group (odds ratio 2.71 [1.94 to 3.77]) and had an additive effect on risk of kidney disease progression. Mortality and heart failure episodes were more frequent in the exposed group, but the association with AKI was no longer significant when models were adjusted for three-month eGFR and uACR. In a general hospitalized population, kidney disease progression after five years was common and strongly associated with AKI. Thus, the time course of changes and the attenuation of associations with adverse outcomes after adjustment for three-month eGFR and uACR suggest non-recovery of kidney function is an important assessment in post-AKI care and a potential future target for intervention.Study registrationISRCTN25405995 Acute kidney injury (AKI) is associated with adverse long-term outcomes, but many studies are retrospective, focused on specific patient groups or lack adequate comparators. The ARID (AKI Risk in Derby) Study was a five-year prospective parallel-group cohort study to examine this. Hospitalized cohorts with and without exposure to AKI were matched 1:1 for age, baseline kidney function, and diabetes. Estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (uACR) were measured at three-months, one-, three- and five-years. Outcomes included kidney disease progression, heart failure episodes and mortality. In 866 matched individuals, kidney disease progression at five years was found to be significantly increased in 30% of the exposed group versus 7% of those non-exposed (adjusted odds ratio 2.49 [95% confidence interval 1.43 to 4.36]). In the AKI group, this was largely characterized by incomplete recovery of kidney function by three months. Further episodes of AKI during follow-up were significantly more common in the exposed group (odds ratio 2.71 [1.94 to 3.77]) and had an additive effect on risk of kidney disease progression. Mortality and heart failure episodes were more frequent in the exposed group, but the association with AKI was no longer significant when models were adjusted for three-month eGFR and uACR. In a general hospitalized population, kidney disease progression after five years was common and strongly associated with AKI. Thus, the time course of changes and the attenuation of associations with adverse outcomes after adjustment for three-month eGFR and uACR suggest non-recovery of kidney function is an important assessment in post-AKI care and a potential future target for intervention. ISRCTN25405995 Lay SummaryAcute kidney injury (AKI) is a sudden decline in kidney function, which is a common problem in people admitted to hospital. AKI has been linked to serious long-term problems for patients, but there are few studies that identify a wide range of people shortly after AKI and closely monitor them thereafter. The Acute Kidney Injury Risk in Derby study recruited 2 groups of people who had recently been in hospital and monitored them for 5 years. One group had AKI, and the other did not. Comparing the 2 groups, we found that worsening kidney health, admission for heart failure, and death were all more common in the group who had AKI at the start of the study. Our results suggested that some people do not fully recover kidney health after AKI. This is important to guide assessment and care for people after AKI. Acute kidney injury (AKI) is a sudden decline in kidney function, which is a common problem in people admitted to hospital. AKI has been linked to serious long-term problems for patients, but there are few studies that identify a wide range of people shortly after AKI and closely monitor them thereafter. The Acute Kidney Injury Risk in Derby study recruited 2 groups of people who had recently been in hospital and monitored them for 5 years. One group had AKI, and the other did not. Comparing the 2 groups, we found that worsening kidney health, admission for heart failure, and death were all more common in the group who had AKI at the start of the study. Our results suggested that some people do not fully recover kidney health after AKI. This is important to guide assessment and care for people after AKI. Acute kidney injury (AKI) is common and increasing among hospitalized populations.1Hoste E.A.J. Kellum J.A. Selby N.M. et al.Global epidemiology and outcomes of acute kidney injury.Nat Rev Nephrol. 2018; 14: 607-625Crossref PubMed Scopus (601) Google Scholar In addition to poor short-term outcomes, studies have demonstrated that AKI is associated with longer-term adverse effects including increased mortality, development of chronic kidney disease (CKD), and cardiovascular events.2Noble R.A. Lucas B.J. Selby N.M. Long-term outcomes in patients with acute kidney injury.Clin J Am Soc Nephrol. 2020; 15: 423-429Crossref PubMed Scopus (51) Google Scholar However, previous work in this area is predominantly retrospective, leaving many studies susceptible to increased risk of confounding and ascertainment bias. In addition, lack of standardized timed follow-up assessments prevents clear descriptions of the patterns of changes in kidney function after AKI and the mechanisms by which these may occur.3Selby N.M. Taal M.W. Long-term outcomes after AKI—a major unmet clinical need.Kidney Int. 2019; 95: 21-23Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar More recently, the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study confirmed this increased risk of CKD after AKI in a large prospective US study.4Hsu C.-Y. Chinchilli V.M. Coca S. et al.Post–acute kidney injury proteinuria and subsequent kidney disease progression: the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study.JAMA Intern Med. 2020; 180: 402-410Crossref PubMed Scopus (85) Google Scholar The study population comprised patients from 4 cohorts, which included specific patient groups such as critical care and cardiothoracic surgery. Reported outcomes include associations between AKI and subsequent CKD and between 3-month albuminuria in AKI survivors and clinical outcomes.4Hsu C.-Y. Chinchilli V.M. Coca S. et al.Post–acute kidney injury proteinuria and subsequent kidney disease progression: the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study.JAMA Intern Med. 2020; 180: 402-410Crossref PubMed Scopus (85) Google Scholar,5Ikizler T.A. Parikh C.R. Himmelfarb J. et al.A prospective cohort study of acute kidney injury and kidney outcomes, cardiovascular events, and death.Kidney Int. 2021; 99: 456-465Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Performed at a similar time, the Acute Kidney Injury Risk in Derby (ARID) study is a UK-based prospective cohort study that was also designed to examine the long-term effects of AKI. Similarities exist between the ARID and Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury study designs, but key differences in the ARID study include its European population and a focus almost entirely on general hospital (ward-level) patients. Here, we report a comprehensive description of the 5-year outcomes from the ARID study, with specific focus on the natural history of CKD after AKI. The ARID study is a prospective matched cohort study designed to report long-term outcomes after AKI. Between May 2013 and May 2016, the study recruited 2 cohorts of people hospitalized at the Royal Derby Hospital, Derby, UK, who had survived at least 90 days after hospital admission. One cohort consisted of people who had developed AKI during hospital admission (exposed group), and the second cohort had not (non-exposed group). After recruitment, exposed and non-exposed participants were matched 1:1 for baseline estimated glomerular filtration rate (eGFR) stage (eGFR > 60 ml/min per 1.73 m2, eGFR stages 3A, 3B, or 4), age (±5 years), and diabetes. Approvals for the study were obtained from the Derbyshire Research Ethics Committee and the National Information Governance Board. All participants provided written informed consent. Participants were eligible if they were aged between 18 and 85 years, had at least 1 inpatient serum creatinine measurement, and baseline creatinine within the preceding 12 months. Potential participants were identified through automated screening of serum creatinine laboratory results, as previously described.6Selby N.M. Crowley L. Fluck R.J. et al.Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients.Clin J Am Soc Nephrol. 2012; 7: 533-540Crossref PubMed Scopus (204) Google Scholar,7Horne K.L. Packington R. Monaghan J. et al.The effects of acute kidney injury on long-term renal function and proteinuria in a general hospitalised population.Nephron Clin Pract. 2014; 128: 192-200Crossref PubMed Scopus (16) Google Scholar The presence of AKI was determined according to serum creatinine components of the Kidney Disease: Improving Global Outcomes criteria.8Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work GroupClinical Practice Guideline for Acute Kidney Injury.Kidney Int Suppl. 2012; 2: 1-141Abstract Full Text Full Text PDF Scopus (2295) Google Scholar The baseline creatinine value was taken as the most recent serum creatinine hospital admission. was not to AKI of its in a general hospitalized were or during CKD stage or All AKI episodes were by a of the to the presence of AKI, Kidney Disease: Improving Global Outcomes and of AKI was determined by of electronic patient The results of participants in the non-exposed group were also to that they had not AKI during hospital eGFR Kidney and albuminuria were measured at 1 years, and 5 years after the the exposed group, this was the of AKI and for the non-exposed group, this was the at admission. Participants were not to for at least 12 a and were to an were from clinical with and within in the hospital In addition to eGFR the eGFR per 1.73 per between was for hospital admission inpatient laboratory results, and were from the hospital electronic The clinical were between exposed and non-exposed kidney disease progression, mortality, and heart failure The follow-up for all outcomes was 5 years. Kidney disease progression was as a in eGFR of associated with a decline in eGFR Disease: Improving Global Outcomes (KDIGO) CKD Work clinical for the and of chronic kidney Int Suppl. Full Text Full Text PDF Scopus Google Packington R. et during recovery from AKI and of long-term in estimated J Kidney Full Text Full Text PDF PubMed Scopus Google Scholar This was in with CKD at baseline and in those with baseline eGFR > 60 ml/min per 1.73 kidney of of serum of kidney or eGFR ml/min per 1.73 was also who had a progression to the renal were also as kidney disease progression. was as ratio with the renal was to the of long-term Mortality and hospital including heart failure episodes were taken from the electronic were the and for are as or are as and were for for and were for for and and for and were to examine and heart failure was to identify of kidney disease progression. potential was to identify those with significant association that all important were included in the and with the most significant on the of R.A. Lucas B.J. Selby N.M. Long-term outcomes in patients with acute kidney injury.Clin J Am Soc Nephrol. 2020; 15: 423-429Crossref PubMed Scopus (51) Google Scholar and were the risk was the for reporting for risk Med. PubMed Scopus Google Scholar to the function, for the risk of death and significant The of the time in which kidney disease progression was when participants with to this of participants were of were for of 866 participants were with participants in the exposed and non-exposed and follow-up are in 5 years, the to follow-up rate was at participants from the exposed group and from the non-exposed group). The baseline of the 866 participants are in was with few differences between the exposed and non-exposed In the of participants with and CKD and who those were or were the between of participants in the exposed group were and at the time of hospital in the exposed and non-exposed (AKI) ml/min per 1.73 eGFR ml/min per 1.73 (17) heart acute kidney estimated glomerular filtration are as or in a AKI, acute kidney estimated glomerular filtration are as or for group are in The exposed group had a longer hospital and more frequent of admission to the care during the was the group). 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AKI was associated with kidney disease progression at 5 years in the confidence interval and in the adjusted associated with kidney disease progression at 5 acute kidney confidence estimated glomerular filtration odds in a AKI, acute kidney confidence estimated glomerular filtration odds to this with the after to the exposed and non-exposed groups, and AKI an of kidney disease progression with a similar adjusted the of the matched groups and results of are in and also to for the risk of death on the of kidney disease progression. 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The as CKD if eGFR and albuminuria were was in the exposed group and in the non-exposed In the exposed group, participants had at least 1 of AKI during follow-up versus in the non-exposed group The follow-up in which AKI episodes is in associations with the development of AKI during the follow-up are in including all matched that AKI during follow-up was associated with kidney disease progression at 5 years after adjustment for baseline AKI during 3-month and eGFR at associations with AKI during the follow-up during or at at acute kidney confidence estimated glomerular filtration odds in a AKI, acute kidney confidence estimated glomerular filtration odds there was a effect of episodes of AKI, in that the with kidney disease progression at 5 years was the among those who had AKI during admission and during with kidney disease progression were similar between the exposed group without AKI during follow-up and the group of patients who did have AKI during with significantly in those who had AKI. are in In addition, the of time in which AKI during follow-up was an of 5-year kidney disease progression when adjusted for AKI during 3-month and (adjusted the 5-year follow-up was in the exposed group in the non-exposed group that time was in the exposed group days in the exposed group 18 days in the non-exposed The increased ratio in the exposed group when adjusted for age, baseline and diabetes. However, the association of AKI and was and no longer significant when adjusted for albuminuria and eGFR at for the effect of AKI on and heart failure for the effect of AKI on for the effect of AKI on heart failure episodes for age, and at for age, at and acute kidney confidence estimated glomerular filtration for AKI for 5-year and heart failure and adjusted in a AKI, acute kidney confidence estimated glomerular filtration for AKI for 5-year and heart failure and adjusted In the exposed group, 90 had at least 1 of heart failure with in the non-exposed group that time to heart failure was in the exposed group in the non-exposed group days in the exposed group days in the non-exposed an increased ratio in the exposed group was after for age, baseline and but was and no longer significant when adjusted for albuminuria and eGFR at or AKI patterns were with cardiovascular and have demonstrated increased of kidney disease progression, AKI, heart failure and after AKI to a group 5 years of prospective Kidney disease progression in almost a of those who had developed AKI, the who developed kidney failure was for albuminuria increased the with and to a in those who had been exposed to AKI. of kidney function and albuminuria at as as subsequent episodes of AKI to be important of subsequent heart failure and mortality. is that AKI is associated with long-term adverse patient outcomes, including and development of associations have been in many studies and R.A. Lucas B.J. Selby N.M. Long-term outcomes in patients with acute kidney injury.Clin J Am Soc Nephrol. 2020; 15: 423-429Crossref PubMed Scopus (51) Google S. Parikh C.R. kidney disease after acute kidney a and Int. 2012; Full Text Full Text PDF PubMed Scopus Google et risk of adverse outcomes after acute kidney a and of cohort studies of Int. 2019; 95: Full Text Full Text PDF PubMed Scopus Google Scholar However, a recent the of studies in this area are in of the included studies of the were from the care or and albuminuria in of N.M. Taal M.W. Long-term outcomes after AKI—a major unmet clinical need.Kidney Int. 2019; 95: 21-23Abstract Full Text Full Text PDF PubMed Scopus (17) Google et risk of adverse outcomes after acute kidney a and of cohort studies of Int. 2019; 95: Full Text Full Text PDF PubMed Scopus Google Scholar studies with a risk of confounding and with follow-up are to these but also to on the natural history of the long-term of AKI. Our results that kidney disease progression was strongly and associated with AKI, in those with kidney function and in those with The of this association was in and risk In addition, there was an additive effect of AKI episodes on the risk of kidney disease progression at 5 years, which the that AKI is to subsequent are with those from the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury which similar of increased adjusted of CKD and CKD progression after T.A. Parikh C.R. Himmelfarb J. et al.A prospective cohort study of acute kidney injury and kidney outcomes, cardiovascular events, and death.Kidney Int. 2021; 99: 456-465Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar and that 3-month albuminuria was an risk for subsequent kidney disease C.-Y. Chinchilli V.M. Coca S. et al.Post–acute kidney injury proteinuria and subsequent kidney disease progression: the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study.JAMA Intern Med. 2020; 180: 402-410Crossref PubMed Scopus (85) Google Scholar Our results also that 3-month albuminuria and eGFR were associated with kidney disease progression at 5 years, with and the ARID study AKI in a general in which of had AKI stage results the of AKI care in which eGFR and urinary at important on future However, the of are not in of large of patients and of and follow-up all clinical to risk on the of clinical eGFR and and may potential Packington R. et during recovery from AKI and of long-term in estimated J Kidney Full Text Full Text PDF PubMed Scopus Google et of are for long-term after PubMed Scopus Google et and clinical after from the and ARID J Kidney Full Text Full Text PDF PubMed Scopus Google Scholar The of kidney disease progression we have that from at the time of AKI is more important CKD progression. The follow-up that kidney disease progression was characterized by recovery at in the of in the AKI This is by a previous study including patients without kidney disease that by in the who developed CKD between AKI and et risk of death and chronic kidney disease acute kidney Int. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar are also with models of AKI that mechanisms that to chronic including and and after the AKI of AKI to CKD Nephrol. 2020; Full Text Full Text PDF PubMed Scopus Google Scholar This is as that the focus for long-term outcomes be on the post-AKI the time course of changes between the time of AKI and a of in cohort developed CKD or kidney failure during the 5-year follow-up and the time to this was almost 2 years. are be with but the of CKD of who had baseline eGFR ml/min per 1.73 an of AKI of who were in the exposed to be and with previous Himmelfarb J. et kidney injury risk of among Am Soc Nephrol. PubMed Scopus Google Scholar More results suggest that in this kidney failure is a that the of AKI on population health in a general is or progression of CKD and with cardiovascular associations of AKI with and heart failure the 5-year follow-up However, the critical of of kidney function after AKI was in the association between these and AKI when for of eGFR and similar was in the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury T.A. Parikh C.R. Himmelfarb J. et al.A prospective cohort study of acute kidney injury and kidney outcomes, cardiovascular events, and death.Kidney Int. 2021; 99: 456-465Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar is to the risk of and heart failure after AKI the development of CKD and its on cardiovascular or those with of AKI are also those who were more by the AKI or those who had risk the this the of recovery of kidney function after an of AKI as a and target for future The of study are that is with a large The 2 cohorts were and few were to creatinine was in all and all AKI episodes were by a of the study include that albuminuria results were not may of results, but the cohort description for its In addition, the is by the of which that outcomes at 4 time In kidney disease progression after 5 years was common and strongly associated with AKI in a general hospitalized population with predominantly AKI stage The of kidney disease progression and associations with and heart failure suggest that the effect of AKI on long-term outcomes is predominantly determined within the and that of renal function is an important in this. AKI is common in AKI survivors and is also associated with poor to outcomes include renal recovery from AKI and to that a of patients, as a a 3-month of eGFR and This work was by a from Kidney Research has from the National for and Research and Kidney Research and for from and All the other no to are on to the with function the time to cardiovascular exposed and non-exposed associations with kidney disease progression at 5 years in the of the groups matched associations with kidney disease progression at 5 years after of estimated glomerular filtration rate (eGFR) as a for the effect of acute kidney injury (AKI) on subsequent of the renal and those kidney of in the exposed and non-exposed groups who had at least 1 acute kidney injury (AKI) during the follow-up associations with cardiovascular association of acute kidney injury (AKI) with 5-year In This et the progression of acute kidney injury (AKI) to chronic kidney disease by hospitalized who had AKI or had of AKI. patients were matched for age, kidney function, and diabetes. After 5 years, kidney disease progression in 30% of the AKI group with 7% of the group (adjusted odds After an of AKI, future episodes were more with an odds ratio of and to the risk of kidney function PDF

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