Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury

The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal. The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal. Acute kidney injury (AKI) is common and associated with poor renal outcomes,1Coca S.G. Singanamala S. Parikh C.R. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis.Kidney Int. 2012; 81: 442-448Abstract Full Text Full Text PDF PubMed Scopus (1369) Google Scholar but the clinical course is not well understood.2Coca S.G. Is it AKI or nonrecovery of renal function that is important for long-term outcomes?.Clin J Am Soc Nephrol. 2013; 8: 173-176Crossref PubMed Scopus (22) Google Scholar, 3Rifkin D.E. Coca S.G. Kalantar-Zadeh K. Does AKI truly lead to CKD?.J Am Soc Nephrol. 2012; 23: 979-984Crossref PubMed Scopus (153) Google Scholar, 4Hsu C. Yes, AKI truly leads to CKD.J Am Soc Nephrol. 2012; 23: 967-969Crossref PubMed Scopus (126) Google Scholar One reason for the increase in advanced chronic kidney disease (CKD) after AKI (vs. no AKI) is “nonrecovery,” that is, the occurrence of a step drop in estimated glomerular filtration rate (eGFR) during the AKI episode, which does not return to baseline once the episode has ended (Figure 1, pink dashed line). However, another path to advanced CKD after AKI may be a trajectory of subsequent renal decline after the episode has ended (Figure 1, red solid line). This distinction between subsequent progression and nonrecovery is crucial in clinical practice. At the time of a post-discharge clinical review, future subsequent renal decline is uncertain, whereas the extent of nonrecovery can already be observed. Moreover, because the trajectory of renal decline can vary from a gradual to a catastrophic loss of function,5O'Hare A.M. Batten A. Burrows N.R. et al.Trajectories of kidney function decline in the 2 years before initiation of long-term dialysis.Am J Kidney Dis. 2012; 59: 513-522Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar both hard outcomes (e.g., de novo long-term renal replacement therapy [RRT] or CKD stage 4) and intermediate outcomes (e.g., a 30% drop in kidney function)6Grams M.E. Sang Y. Coresh J. et al.Candidate surrogate end points for ESRD after AKI.J Am Soc Nephrol. 2016; 27: 2851-2859Crossref PubMed Scopus (36) Google Scholar are important for clinicians and their patients to understand when planning care. The Kidney Disease: Improving Global Outcomes AKI guidelines provide advice for post-AKI management based on expert opinion but without graded evidence.7Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work GroupKDIGO Clinical Practice Guideline for Acute Kidney Injury.Kidney Int Suppl. 2012; 2: 1-138Abstract Full Text Full Text PDF Scopus (1987) Google Scholar They state that people with AKI should be re-evaluated for resolution of kidney function and receive care based on CKD guidelines if they have developed CKD. However, this guidance does not apply to those who have had an episode of AKI and recovered to normal levels of kidney function after the episode. The relevance of post-episode recovery to baseline as a stratifying risk factor for AKI outcomes has been previously recognized in some studies but not in others.8Sawhney S. Mitchell M. Marks A. et al.Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.BMJ Open. 2015; 5: e006497Crossref Scopus (111) Google Scholar This is because previous studies have dichotomized recovery as being present or absent, with each using different cutoff values, but in reality, a spectrum of renal recovery exists.9Pannu N. James M. Hemmelgarn B. et al.Association between AKI, recovery of renal function, and long-term outcomes after hospital Discharge.Clin J Am Soc Nephrol. 2013; 8: 194-202Crossref PubMed Scopus (200) Google Scholar, 10Kellum J.A. How can we define recovery after acute kidney injury? Considerations from epidemiology and clinical trial design.Nephron Clin Pract. 2014; 127: 81-88Crossref PubMed Scopus (45) Google Scholar Moreover, even if patients could be adequately grouped by recovery status, the use of a pre-episode baseline for determining outcomes would not separate the initial progression caused by incomplete recovery (however slight) from the subsequent progression caused by ongoing decline. The solution in clinical practice is that a clinician will wait to see where a post-episode eGFR finally settles (which becomes the “new baseline”) before evaluating risk and planning care from that point on. Therefore this is the approach we adopted in our this study, we a AKI episode was associated with subsequent renal decline, after for a extent of initial renal recovery to baseline once the episode has subsequent renal decline by using post-episode eGFR as the reference for subsequent renal outcomes. that more patients with AKI (vs. no AKI) would ongoing renal decline 30% eGFR in more patients with AKI CKD stage patients with an hospital admission in patients were and not long-term after hospital admission (Figure This with AKI and without the study of de novo CKD stage 4, an patients who already had eGFR at study were patients were for the study of renal decline and for the study of de novo CKD stage The of the study up to years after the hospital and a of years of follow-up. a reference point of the eGFR after a hospital admission episode, sustained subsequent 30% eGFR decline developed in of patients for AKI, for no and sustained new CKD stage 4 in of patients for AKI, for no Overall, patients were more to than subsequent renal as 30% renal decline (37.5% 11.3%) or as new CKD stage 4 the of patients with and without AKI during the hospital with AKI (vs. no AKI) were and were more on an or to a care They had more episode baseline eGFR was higher among those with AKI, post-discharge eGFR was and a greater of patients had a 30% decline in eGFR from the episode to the episode AKI, no AKI) was common among patients with AKI and post-episode eGFR 60 The of patients with post-episode was higher among those with for patients with and without acute kidney of of in years of the of hospital care care of hospital in eGFR eGFR was the eGFR at a time point after from the hospital This was as the reference for determining subsequent renal in in eGFR was the between pre-episode baseline and post-episode eGFR can irrespective of the of was based on during or of the hospital AKI acute kidney estimated glomerular filtration not of the of eGFR was the eGFR at a time point after from the hospital This was as the reference for determining subsequent renal in eGFR was the between pre-episode baseline and post-episode eGFR can irrespective of the of was based on during or of the hospital in a new AKI, acute kidney estimated glomerular filtration not the of people after hospital who renal decline de novo CKD stage 4 and death before progression during the study years after AKI (vs. no was an excess of renal decline, or decline and death outcomes among those with post-episode eGFR 60 This excess was not present among those with a post-episode The of de novo CKD stage 4 was more common among those with AKI, but among those with post-episode eGFR 60 AKI, no AKI) and eGFR AKI, no with eGFR AKI, no outcomes at years after hospital with but with 4 the of subsequent renal decline and and de novo CKD stage 4 and by AKI and post-episode for the competing risk of Follow-up in after study Death without progression was more common than progression and in the of a post-episode eGFR 60 de novo CKD stage 4 was 2 the baseline of patients who or were without subsequent progression at the end of the with subsequent progression by were and had more baseline renal as were those who A greater of patients who progression had as with those who without whereas the was for the for each progression renal decline or sustained 30% renal before 30% renal CKD stage 4 or novo CKD stage before de novo CKD stage of of of of of of in years of the of hospital care care eGFR are patients in de novo CKD stage 4 because patients had at study acute kidney estimated glomerular filtration of the of in a new are patients in de novo CKD stage 4 because patients had at study AKI, acute kidney estimated glomerular filtration renal each progression with subsequent progression by had a greater with a post-episode AKI, AKI, and in eGFR a or during the admission episode. The with post-episode was higher in those with progression than in those who without The increased progression among those with AKI not vary by AKI for each progression renal decline or sustained 30% renal before 30% renal CKD stage 4 or novo CKD stage before de novo CKD stage of of of of of of eGFR was the eGFR at a time point after from the hospital This was as the reference for determining subsequent renal in in eGFR was the between pre-episode baseline and post-episode eGFR can irrespective of the of was based on during or of the hospital AKI are patients in de novo CKD stage 4 because patients had at study acute kidney estimated glomerular filtration eGFR was the eGFR at a time point after from the hospital This was as the reference for determining subsequent renal in eGFR was the between pre-episode baseline and post-episode eGFR can irrespective of the of was based on during or of the hospital in a new are patients in de novo CKD stage 4 because patients had at study AKI, acute kidney estimated glomerular filtration 4 the between AKI and renal decline by post-episode eGFR The with a reference with no AKI and eGFR 60 AKI no AKI at each of post-episode The risk of renal decline for AKI (vs. no AKI) was greater in those with normal function than in those with post-episode hazard AKI no AKI) 2.29 1.50 and 0.95 for post-episode eGFR and respectively. a between AKI and de novo CKD stage 4, but the of the with post-episode eGFR was risk of subsequent sustained 30% renal decline after acute kidney episode or no renal renal of death without renal of death without renal AKI no no no no with between AKI and baseline are with reference to no AKI and eGFR 60 and for AKI no AKI each eGFR using the The for admission each separate and renal as in the acute kidney estimated glomerular filtration rate hazard in a new risk of de novo CKD stage 4 after acute kidney episode or no new CKD new CKD of death without renal of death without renal AKI no no no with between AKI and baseline are with reference to no AKI and eGFR 60 and for AKI no AKI each eGFR using the The for admission each separate and renal as in the acute kidney estimated glomerular filtration rate hazard in a new with between AKI and baseline are with reference to no AKI and eGFR 60 and for AKI no AKI each eGFR using the The for admission each separate and renal as in the AKI, acute kidney estimated glomerular filtration rate hazard with between AKI and baseline are with reference to no AKI and eGFR 60 and for AKI no AKI each eGFR using the The for admission each separate and renal as in the AKI, acute kidney estimated glomerular filtration rate hazard 2 the in for the renal decline The role of AKI (vs. no AKI) was by with greater risk in the than in the but in both was not by or A time was present and in a we at years after in the for AKI up to years among those at was greater than the for AKI up to years for those and at risk years after in we the for AKI no AKI those with post-episode with the those who had a eGFR for post-episode and the were for acute hospital and with the use of a and competing This of hospital survivors after AKI the risk of long-term subsequent progression of kidney disease from progression that has already because of an initial step drop in kidney function (incomplete this approach was AKI during a hospital admission was associated with increased subsequent renal progression irrespective of progression was irrespective of or AKI severity, and even if post-episode kidney function was normal. of the of renal progression study, the excess risk after AKI over time but persisted the years of the studies have an between AKI and long-term S.G. Singanamala S. Parikh C.R. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis.Kidney Int. 2012; 81: 442-448Abstract Full Text Full Text PDF PubMed Scopus (1369) Google Scholar, S.G. Is it AKI or nonrecovery of renal function that is important for long-term outcomes?.Clin J Am Soc Nephrol. 2013; 8: 173-176Crossref PubMed Scopus (22) Google Scholar, 3Rifkin D.E. Coca S.G. Kalantar-Zadeh K. Does AKI truly lead to CKD?.J Am Soc Nephrol. 2012; 23: 979-984Crossref PubMed Scopus (153) Google Scholar, 4Hsu C. Yes, AKI truly leads to CKD.J Am Soc Nephrol. 2012; 23: 967-969Crossref PubMed Scopus (126) Google Scholar but our the by greater and to the of our no previous studies of AKI prognosis have renal progression both in of an intermediate renal and a hard novo CKD stage 4 or long-term This that no renal progression is AKI is associated with long-term we that de novo CKD stage 4 was common among those with AKI who already had a previous have an as a risk factor for study in S. Mitchell M. Marks A. et al.Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.BMJ Open. 2015; 5: e006497Crossref Scopus (111) Google Scholar, N. James M. Hemmelgarn B. et al.Association between AKI, recovery of renal function, and long-term outcomes after hospital Discharge.Clin J Am Soc Nephrol. 2013; 8: 194-202Crossref PubMed Scopus (200) Google Scholar However, patients in this does not separate the initial renal decline nonrecovery to baseline that is already after the from subsequent renal decline of what does it for in eGFR that can irrespective of S.G. Is it AKI or nonrecovery of renal function that is important for long-term outcomes?.Clin J Am Soc Nephrol. 2013; 8: 173-176Crossref PubMed Scopus (22) Google Scholar the important whereas 25.7% of people with AKI a 30% decline between their pre-episode and post-discharge eGFR from the post-discharge eGFR of people with AKI subsequent renal decline. 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