PRESENTED BY
ERIC ADRIAAN J. HOSTE

Presentation Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Eric Adriaan J. Hoste

Global epidemiology of acute kidney injury
Acute kidney injury (AKI) represents a syndrome associated with a wide variety of aetiologies and pathophysiological pathways, eventually leading to impaired kidney function. AKI induces a generalized inflammatory response affecting different organs. Uncertain recovery of kidney function leaves these patients at an increased risk of morbidity and death. Estimates of AKI prevalence are different, ranging from <1% to as high as 66%. In patients requiring intensive care, AKI occurs in one in five adults, and one in four pediatric patients. These variations can be explained by population differences and inconsistent use of standardized  Acute Kidney Injury Network (AKIN) criteria (1). For instance, in Finland, nearly 40% of patients with AKI fulfilled AKIN criteria, while according to AKI-EPI study data almost 60% of ICU patients fulfilled these criteria (2, 3). The need for renal replacement therapy (RRT) in these patients depends on several factors, such as age, presence of comorbidities (hypertension and diabetes), as well as the etiology of AKI. Furthermore, high-income countries show a lower incidence of AKI than low and middle-income countries. Namely, contaminated water and endemic diseases, such as malaria, contribute to a high burden of AKI in underdeveloped areas (Figure 1).

Figure 1. Global variation in the incidence of AKI (1)

AKI carries a high mortality burden
Hospital mortality in AKI patients is notably higher than in non-AKI patients, with reported incidence rates of 27%, compared to 7% (3). Even though this difference cannot be solely attributed to AKI since other factors, such as comorbidities, age, severity of illness, etc. must be taken into consideration, a high mortality rate is also observed in AKI stages 2 and 3.  Studies evaluating interventions to reduce mortality have examined different RRT modalities but showed no short-term improvement in outcomes. Suboptimal early recognition and care of patients with AKI impede their recovery and lead to severe complications, high mortality, and cost of treatment (1). Furthermore, patients with AKI treated with RRT and surviving to 90 days are at high risk of dying after 3.5 years, with an established mortality rate of 31.9% (4).
AKI survivors commonly develop cardiovascular disease (CVD). Early- and late-onset AKI within 30 days of elective cardiac surgery is associated with a similarly increased 5-year risk of myocardial infarction, heart failure, stroke, and increased all-cause mortality (5). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge (6-8).

AKI and proteinuria
AKI is a risk factor for an incident or worsening proteinuria, possibly linking it with ensuing chronic kidney disease (CKD). The type of proteinuria, its pathophysiology, and clinical significance warrant further studies as a potentially modifiable risk factor in the pathway from AKI to CKD (9). A three-year prospective matched parallel-group cohort study, in which renal function and proteinuria were measured at 3 months, 1 year, and 3 years concluded that albuminuria was more common in the AKI group, and increased with AKI severity. Factors independently associated with CKD development following AKI, were non-recovery at 90 days, male gender, diabetes, and recurrent AKI (10).

The complex relationship between AKI and CKD
There is a strong relationship between AKI and the risk of developing CKD. Almost half of the patients with AKI are discharged with impaired kidney function and remain at increased risk of new or progressive CKD, end-stage renal disease (ESRD), and death (3, 14, 18). A large Swedish study demonstrated a significant risk for CKD development following an episode of AKI, which increased with worsening AKI severity, as defined by the duration of injury and time to recovery (13). Another systematic review demonstrated that AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population (11). These findings establish the poor long-term outcomes of AKI and highlight the importance of injury severity, co-morbidities, and clinical setting in the estimation of risk. On the other hand, preexisting CKD may lower the threshold for developing AKI, and acute-on-chronic kidney disease is also associated with adverse outcomes (15). Recent studies imply that these two syndromes are not distinct entities but rather are closely interconnected — CKD is a risk factor for AKI, and AKI is a risk factor for the development of CKD, while both are risk factors for CVD (15).

AKI and CKD are interrelated and seem to have a common denominator. After an AKI episode, follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression of kidney disease (16). Full AKI recovery may be defined as the absence of AKI criteria, and partial recovery as a fall in the AKI stage. Risk factors for poor recovery from AKI are age, CKD, comorbidity, higher AKI severity, and acute disease scores.

The impact of RRT on AKI outcomes
AKI treated with RRT is associated with adverse outcomes, such as increased length of stay, mortality, and ESRD. The rate of dialysis dependence may range between 24.6% at 60 days and 5.6% at 90 days follow-up (14, 18, 24).

There has been much debate about the possible impact of RRT modality on either renal recovery or the development of ESRD following AKI. A systematic review by Schneider et al, comparing the rate of prevailing dialysis dependence among severe AKI survivors according to the choice of initial RRT modality showed that initial treatment with intermittent RRT might be associated with higher rates of dialysis dependence than continuous RRT (19). However, this finding largely relies on data from observational trials, and is potentially subject to allocation bias, thus stipulating further investigations.

Initiative for improving quality of care in AKI patients
High-quality care for patients with AKI or those at risk of AKI starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. The quality of care provided to these patients decreases the cost of care and improves outcomes. Identification of factors that predict and promote kidney recovery and mitigate CKD development and appropriate implementation of such interventions would also improve the quality of care after AKI. To achieve a framework for improvement in AKI care, the 22nd Acute Disease Quality Initiative (ADQI) conference was convened to define the spectrum of AKI care (Figure 2) (20).

Figure 2. AKI quality of care continuity (19)

Improving the care of AKI survivors depends on identifying individuals at risk of CKD and interventions to prevent its progression and related complications. One quality of care indicator for patients with CKD after an AKI episode is the rate of nephrology referral. In a study by Siew et al. analyzing outpatient nephrology referral rates after AKI, the incidence of nephrology referral before dying, initiating dialysis, or experiencing an improvement in kidney function was 8.5% (21). A study by De Corte et al. demonstrated an association between increasing age, severity of illness, and continuous RRT with long-term mortality among hospital survivors with corresponding creatinine levels (14). Still, there seems to be a disparity between the attitudes of nephrologists and actual processes of care of patients with severe AKI following hospitalization (22). Kidney dysfunction is frequent in hospitalized patients but is usually not notified, suggesting that it is not considered important to disclose to primary-care physicians. This lack of information may decrease physicians’ awareness, and affect the continuity of care in patients with renal impairment (23).

References

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2. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study [published correction appears in Intensive Care Med. 2013;39(4):798]. Intensive Care Med. 2013;39(3):420-428. doi:10.1007/s00134-012-2796-5

3. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423. doi:10.1007/s00134-015-3934-7

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13. Rimes-Stigare C, Frumento P, Bottai M, et al. Evolution of chronic renal impairment and long-term mortality after de novo acute kidney injury in the critically ill; a Swedish multi-centre cohort study. Crit Care. 2015;19(1):221. doi:10.1186/s13054-015-0920-y

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18. RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627-1638. doi:10.1056/NEJMoa0902413

19. Schneider AG, Bellomo R, Bagshaw SM, et al. Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis. Intensive Care Med. 2013;39(6):987-997. doi:10.1007/s00134-013-2864-5

20. Kashani K, Rosner MH, Haase M, et al. Quality Improvement Goals for Acute Kidney Injury. Clin J Am Soc Nephrol. 2019;14(6):941-953. doi:10.2215/CJN.01250119

21. Siew ED, Peterson JF, Eden SK, et al. Outpatient nephrology referral rates after acute kidney injury. J Am Soc Nephrol. 2012;23(2):305-312. doi:10.1681/ASN.2011030315

22. Karsanji DJ, Pannu N, Manns BJ, et al. Disparity between Nephrologists’ Opinions and Contemporary Practices for Community Follow-Up after AKI Hospitalization. Clin J Am Soc Nephrol. 2017;12(11):1753-1761. doi:10.2215/CJN.01450217

23. Sautenet B, Caille A, Giraudeau B, et al. Deficits in information transfer between hospital-based and primary-care physicians, the case of kidney disease: a cross-sectional study. J Nephrol. 2015;28(5):563-570. doi:10.1007/s40620-015-0175-3

24. Wald R, McArthur E, Adhikari NK, Bagshaw SM, Burns KE, Garg AX, Harel Z, Kitchlu A, Mazer CD, Nash DM, Scales DC, Silver SA, Ray JG, Friedrich JO. Changing incidence and outcomes following dialysis-requiring acute kidney injury among critically ill adults: a population-based cohort study. Am J Kidney Dis. 2015 Jun;65(6):870-7. doi: 10.1053/j.ajkd.2014.10.017. PMID: 25533599.

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