Commentary

AKI Transition of Care: A Potential Opportunity to Detect and Prevent CKD

Stuart L. Goldstein, Bertrand L. Jaber, Sarah Faubel, Lakhmir S. Chawla and for the Acute Kidney Injury Advisory Group of the American Society of Nephrology
CJASN March 2013, 8 (3) 476-483; DOI: https://doi.org/10.2215/CJN.12101112

Summary

The incidence rate of AKI is increasing across the spectrum of hospitalized children and adults. Given the increased morbidity and mortality associated with AKI, significant research effort has been appropriately focused on standardizing AKI definitions, identifying risk factors, and discovering and validating novel, earlier structural biomarkers of kidney injury. In addition, a growing body of evidence demonstrates that AKI is a risk factor for the future development or accelerated progression of CKD. Unfortunately, prospective observational studies have not consistently followed survivors of episodes of AKI for longitudinal outcomes after hospital discharge, which could lead to ascertainment bias in terms of over- or underestimation of CKD development. Furthermore, data show that clinical follow-up of AKI survivors is low. This lack of systematic study and clinical follow-up represents a potential missed opportunity to prevent chronic disease after an acute illness and improve outcomes. Therefore, prospective study of transitions of care after episodes of AKI is needed to identify which patients are at risk for CKD development and to optimally target therapeutic interventions.

Introduction

The incidence rate of AKI has increased over the past decades in hospitalized adults and children (1,2). The development of standardized, multidimensional classification criteria for AKI, such as the RIFLE (Risk, Injury, Failure, Loss, and ESRD), Acute Kidney Injury Network, and pediatric RIFLE criteria, provides the means for consistent epidemiologic assessment of AKI incidence and severity (3–6). The application of these criteria in numerous hospital-based cohort studies has helped identify patients at high risk for development of AKI and demonstrated an indisputably strong association between development and severity of AKI and mortality (7,8). More precise AKI risk stratification, using a combination of demographic characteristics and clinical signs, also known as “renal angina,” has recently been proposed to guide more optimal AKI biomarker assessment and drive the design of prevention trials in AKI (9).

The focus on AKI prevention and mitigation is understandable because researchers hypothesize that prevention of AKI will lead to improved outcomes and decreased mortality. Unfortunately, prevention trials of AKI are especially difficult to conduct (10); improving outcomes in AKI will require attention to other important areas of AKI care. In particular, survivors of episodes of AKI who are at risk for the development or worsening of CKD need greater attention. The burden of CKD on the global health care system is well documented, so the importance of preventing or minimizing CKD progression in survivors of AKI episodes cannot be overstated. To this end, the recent Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline proposed a new conceptual model, called acute kidney disease, to highlight the need to follow survivors of AKI episodes in the near term and monitor development of signs and symptoms of CKD, with a focus on screening for markers of kidney damage (i.e., proteinuria) and/or reduced GFR (6).

Implementation of electronic health records enhances the opportunity to systematically identify patients with AKI (11,12). As a result, survivors of AKI episodes can become readily identifiable for longitudinal follow-up, especially in integrated health care delivery systems. Yet, as we will demonstrate in this review, published follow-up studies of survivors of AKI episodes reveal high attrition rates. We view this lack of systematic follow-up as a missed opportunity to identify and test strategies to prevent chronic disease after an acute illness.

The Potential Scope of the Problem

AKI complicates up to 20% of hospital admissions and currently has an estimated population incidence of 2147 per million people. The incidence of AKI is increasing, however, and is expected to double over the next decade (13,14). AKI is associated with numerous in-hospital and long-term complications, including an independent increased risk of death (15,16). Although the increased mortality from AKI is well documented, the effect of an episode of AKI on other outcomes has only recently been brought into focus, particularly with regard to the increased risk of CKD (17,18). There are three patterns by which patients with AKI who have normal baseline kidney function might progress to CKD (19). For some, the initial episode results in permanent kidney failure, and the patient remains dialysis dependent (AKI to ESRD). For others, the initial episode of AKI results in incomplete recovery of AKI compared with the baseline kidney function, resulting in CKD (AKI to CKD). In a third pattern, the kidney function initially returns close to baseline after an episode of AKI, and later the patient progresses to CKD (AKI to “subclinical CKD”). Although some patients may completely recover kidney function after an AKI episode, such patients may also be at increased risk of CKD (20).

Thirty percent of patients with AKI have preexisting CKD (21,22); thus, three similar patterns of outcome after AKI may apply to patients with preexisting CKD: (1) AKI to ESRD, (2) AKI to worsening CKD, and (3) AKI to initial recovery followed by worsening CKD. AKI to CKD is also an important issue in kidney transplant recipients; notably, a recent report demonstrated that 11% of kidney transplant recipients developed AKI within the first 3 years of transplantation, which, in turn, was associated with an increased subsequent risk of CKD and graft loss (23).

The effect of these patterns of CKD after AKI regarding CKD development, progression to ESRD, and long-term mortality is substantial. Acute tubular necrosis is cited as the cause of ESRD for nearly 3% of patients with incident ESRD according to the U.S. Renal Data System annual report (24). In cohorts of patients with preexisting CKD, up to 15% of patients with an episode of AKI remain dialysis dependent after hospital discharge (25). Although the clinical distinction between AKI to CKD and AKI to “subclinical CKD” has not been clearly defined, these patterns of CKD progression after episodes of AKI probably represent the larger public health concern because they affect more of the population. Observational studies report that 20%–50% of survivors of AKI episodes progress to CKD (26,27). If the aforementioned estimated AKI population incidence (of 2147 per million people) is applied to the population of the developed world (about 1 billion living in the United States, Canada, Europe, and Australia/New Zealand), we would estimate more than 2 million cases of AKI annually (Figure 1). Of these, 10%–15% will die in the course of the associated acute illness, 3%–15% will develop permanent kidney failure (i.e., ESRD), and 20%–50% will progress to CKD. Even if the most conservative values are taken for each of these estimates, AKI will be associated in the developed world with death, ESRD, or CKD for approximately 600,000 patients annually.

View this table:
Table 1.

Follow-up studies of adults with AKI and progression to CKD

Figure 1.
Figure 1.

Estimates of AKI burden in developed countries and outcomes of survivors. Assumptions are based on an estimated population of about 1 billion in developed countries, which represent the United States, Canada, Europe, and Australia/New Zealand, and an AKI incidence of 2147 cases per million people. ESKD, end-stage kidney disease.

AKI to CKD in Adults

Major risk factors for CKD progression after AKI include advanced age, diabetes mellitus, hypertension, heart failure, increased Charlson comorbidity score during AKI episode, preexisting CKD (as defined by proteinuria or reduced GFR), and low levels of serum albumin, a dual marker of nutrition and inflammation (17,18,20,28) (Table 1). The presence of these risk factors should alert practitioners to be especially vigilant for CKD development after an episode of AKI. In addition, severity and frequency of AKI episodes have been shown to be independently associated with CKD progression (28–30). The findings linking both severity and frequency of AKI episodes to CKD progression support the premise that CKD progression after AKI is not just an epiphenomenon but is intrinsically linked to episodes of kidney injury; recent studies show that biomarkers of inflammation and tubular injury, at the time of clinical AKI, may play a role in predicting the degree of renal recovery after an episode of severe AKI (RIFLE F). Ongoing inflammation also appears to be a risk factor for CKD progression (31). These clinical findings are supported by preclinical data that mirror those risk factors identified in large observational studies (17,32–34).

The pathophysiology of CKD progression after AKI is a rapidly evolving field of investigation. Preclinical studies suggest that there may be a threshold for the development and progression of CKD compared with normal kidney repair and regeneration (32). The main mechanisms incriminated in CKD progression include inappropriate vascular, interstitial, and tubular regeneration after AKI (17). These maladaptive processes appear to be linked to impaired angiogenesis and reduced endothelial proliferation (35,36), cell cycle arrest (37), persistent fibrosis (38), epigenetic changes (33), increased expression in kidney tissue microRNAs associated with renal fibrosis (39), and ongoing inflammation (34). Further research to identify potential therapeutic targets to mitigate CKD progression after AKI in humans is urgently needed.

AKI to CKD in Children

Children provide an informative group for the study of AKI leading to CKD development and/or progression because they do not possess many of the comorbid conditions seen in adults. Furthermore, many of the first biomarker validation studies in AKI were performed in children, including cohorts of cardiac surgery, multiorgan failure, and primary kidney disease (e.g., hemolytic uremic syndrome) (40–42). The negative health outcomes of CKD are well established, and the association between childhood CKD (even at early stages) and cardiovascular disease (CVD) is evident. Children with CKD have subclinical atherosclerosis and multivessel calcification (43,44), endothelial dysfunction, hypertension, left ventricle hypertrophy, and increased risk of cardiovascular events, such as myocardial infarction (43–47). Microalbuminuria is an established risk factor for CVD-related morbidity and mortality (48,49). Because the pathogenesis of CVD begins early in children with CKD, prompt identification of risk factors for CKD and early CKD detection are paramount. AKI may be a significant risk factor for early childhood CKD development, incurring higher risk for negative health outcomes, including CVD. Recent reviews detail the high rates of CKD, hypertension, and microalbuminuria in children who survive an AKI episode (50 ) and reveal a very low rate of long-term follow-up. Children who develop AKI do, in fact, display long-term findings of CKD, as evidenced by the development of hypertension, microalbuminuria, and reduced GFR (Table 2) (37,51–56). The post-AKI rates of hypertension, microalbuminuria, and low GFR are remarkable, given the low prevalence of these kidney-related outcomes in the general pediatric population. Review of Table 2 demonstrates that children with cancer-associated AKI have routine kidney function assessment (100% follow-up rate) as part of national clinical research networks, yet long-term follow-up rates for children with non–cancer-associated AKI episodes range from 32% to 71%. Because these rates were ascertained in the context of clinical studies of patients who developed AKI, the actual risk of transitioning from AKI to CKD remains unknown. These studies are also limited by the small sample size, lack of control populations, and, for the most part, lack of gold standard GFR measurements.

View this table:
Table 2.

Follow-up studies of children with AKI and progression to CKD

Clinical and Research Recommendations for Transitions of Care after Episodes of AKI

The data presented in this review demonstrate that AKI is clearly associated with CKD development. Whether AKI is an independent causal factor for CKD development or simply represents an association with CKD by virtue of shared risk factors has been the subject of recent editorial commentaries (57,58 ) and is beyond the aim of our review. We argue neither for nor against a unidirectional causal AKI-to-CKD relationship at this point but rather suggest that proof of causality is not necessary at this point because AKI may be a “canary in the coal mine” to uncover unrecognized CKD. Although no conclusive data exist to demonstrate whether less severe AKI leads to CKD, we are reminded that before the development of the RIFLE or Acute Kidney Injury Network classification systems, few would have thought that “mild” degrees of AKI, such as a 50% or 0.3-mg/dl increase in serum creatinine, would be independently associated with death. Indeed, in a recent study demonstrating that an episode of AKI nearly doubled the risk of CKD development, 70.6% of the AKI cohort had AKI stage I, suggesting that even “mild” AKI is a risk factor for subsequent CKD (20). Thus, it may be prudent to withhold judgment on which patients to exclude for follow-up of AKI to CKD. Until we can reliably predict which AKI survivors will develop CKD, we urge that adults and children who survive episodes of AKI be followed regularly to assess for early evidence of CKD (i.e., development of hypertension, proteinuria, or reduced GFR), to allow for low-technology, low-cost, well established interventions to slow progression of diagnosed CKD to ESRD. Currently, only approximately one third of patients with dialysis-requiring AKI (the equivalent of KDIGO AKI stage III) are seen by a nephrologist within 30 days of hospital discharge. This rate increases to 48.6% within 1 year of hospital discharge, which is probably the result of reduced GFR (59).

Because AKI survivors have not been followed systematically, we cannot provide evidence-based guidance on which AKI survivors or what AKI severity stage should prompt follow-up. A reasonable approach may be to follow all patients who received renal replacement therapy or who developed KDIGO AKI stage II or III. However, because recent adult and pediatric studies reveal that fluid overload can mask AKI by dilution of serum creatinine (60,61), we cannot confidently state that patients with AKI stage I should not be followed. Simple interventions, such as the avoidance of nephrotoxins (e.g., nonsteroidal antiinflammatory drugs), use of blockers of the renin-angiotensin-aldosterone system, and BP control may prove to be critical interventions to mitigate CKD progression in these at-risk patients (62). At this time, however, we cannot be sure that such measures will be effective in mitigating the potential progression of AKI-associated CKD; such information can be developed only through systematic follow-up and prospective study. To ensure better recognition and follow-up, we recommend that an “episode of AKI” be documented in the medical history portion of the electronic health record; furthermore, a past episode of AKI should be ascertained as part of the routine evaluation of all patients with CKD. Hospital discharge risk scores can also be deployed to identify patients in whom CKD progression is more likely (28). As noted at the beginning of this review, AKI survivors provide a potentially captive longitudinal patient population for the study of CKD development and progression. Although some evidence suggests that AKI severity, including acute temporary dialysis requirement, and repeated episodes of AKI may portend an increased risk of CKD in adults and children, these hypotheses need to be examined systematically. Currently, the Translational Research Investigating Biomarker Endpoints for AKI Study consortium (TRIBE-AKI, www.yale.edu/tribeaki) and the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI) consortium will examine long-term kidney outcomes in several cohorts, including children who have survived cardiopulmonary bypass–associated AKI from at least three pediatric centers (63). As we await the results of these important studies, we propose that pilot and feasibility studies should be conducted to help mitigate the development and progression of CKD after episodes of AKI.

Disclosures

None.

Acknowledgments

The authors would also like to acknowledge Rachel Shaffer of the ASN for the organizational and logistical support for the AKI advisory group.

All the authors are members of the Acute Kidney Injury Advisory Group of the American Society of Nephrology (ASN). The opinions expressed in this manuscript are the opinions of the authors and not necessarily the opinions of their institutions or all the members of the ASN.

Acute Kidney Injury Advisory Group to the ASN 2012 Members: Jorge Cerda (Albany Medical College, Albany, NY), Lakhmir S. Chawla (George Washington University, Washington, DC), Sarah Faubel (University of Colorado and Denver Veterans Affairs Medical Center, Denver, CO), Dinna N. Cruz (University of California, San Diego, CA), Zheng Dong (Medical College of Georgia, Augusta, GA), Stuart L. Goldstein (Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Benjamin D. Humphreys (Harvard Medical School, Boston, MA), Jay L. Koyner (University of Chicago, Chicago, IL), Bertrand L. Jaber (Tufts University School of Medicine, Boston, MA), Kathleen D. Liu (University of California, San Francisco, CA), Thomas D. Nolin (University of Pittsburgh, Pittsburgh, PA), Krishna R. Polu (Affymax, Palo Alto, CA), Didier Portilla (University of Arkansas College of Medicine, Little Rock, AR), Krystyna E. Rys-Sikora (National Institutes of Health, Bethesda, MD), Mark D. Okusa (University of Virginia School of Medicine, Charlottesville, VA), Rachel N. Shaffer (American Society of Nephrology, Washington, DC).

Footnotes

  • Published online ahead of print. Publication date available at www.cjasn.org.

References

  1. ↵
    1. Vachvanichsanong P,
    2. Dissaneewate P,
    3. Lim A,
    4. McNeil E
    : Childhood acute renal failure: 22-year experience in a university hospital in southern Thailand. Pediatrics 118: e786–e791, 2006pmid:16894011
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. American Society of Nephrology Renal Research Report
    American Society of NephrologyAmerican Society of Nephrology Renal Research Report. J Am Soc Nephrol 16: 1886–1903, 2005pmid:15888557
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Bellomo R,
    2. Ronco C,
    3. Kellum JA,
    4. Mehta RL,
    5. Palevsky P,
    6. Acute Dialysis Quality Initiative workgroup
    : Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8: R204–R212, 2004pmid:15312219
    OpenUrlCrossRefPubMed
    1. Mehta RL,
    2. Kellum JA,
    3. Shah SV,
    4. Molitoris BA,
    5. Ronco C,
    6. Warnock DG,
    7. Levin A,
    8. Acute Kidney Injury Network
    : Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 11: R31, 2007pmid:17331245
    OpenUrlCrossRefPubMed
    1. Akcan-Arikan A,
    2. Zappitelli M,
    3. Loftis LL,
    4. Washburn KK,
    5. Jefferson LS,
    6. Goldstein SL
    : Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71: 1028–1035, 2007pmid:17396113
    OpenUrlCrossRefPubMed
  6. ↵
    Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2: 1–138, 2012
  7. ↵
    1. Srisawat N,
    2. Hoste EE,
    3. Kellum JA
    : Modern classification of acute kidney injury. Blood Purif 29: 300–307, 2010pmid:20130395
    OpenUrlCrossRefPubMed
  8. ↵
    1. Slater MB,
    2. Anand V,
    3. Uleryk EM,
    4. Parshuram CS
    : A systematic review of RIFLE criteria in children, and its application and association with measures of mortality and morbidity. Kidney Int 81: 791–798, 2012pmid:22258324
    OpenUrlCrossRefPubMed
  9. ↵
    1. Goldstein SL,
    2. Chawla LS
    : Renal angina. Clin J Am Soc Nephrol 5: 943–949, 2010pmid:20299370
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Faubel S,
    2. Chawla LS,
    3. Chertow GM,
    4. Goldstein SL,
    5. Jaber BL,
    6. Liu KD,
    7. Acute Kidney Injury Advisory Group of the American Society of Nephrology
    : Ongoing clinical trials in AKI. Clin J Am Soc Nephrol 7: 861–873, 2012pmid:22442183
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Classen DC,
    2. Resar R,
    3. Griffin F,
    4. Federico F,
    5. Frankel T,
    6. Kimmel N,
    7. Whittington JC,
    8. Frankel A,
    9. Seger A,
    10. James BC
    : ‘Global trigger tool’ shows that adverse events in hospitals may be ten times greater than previously measured. Health Aff (Millwood) 30: 581–589, 2011pmid:21471476
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Matheny ME,
    2. Miller RA,
    3. Ikizler TA,
    4. Waitman LR,
    5. Denny JC,
    6. Schildcrout JS,
    7. Dittus RS,
    8. Peterson JF
    : Development of inpatient risk stratification models of acute kidney injury for use in electronic health records. Med Decis Making 30: 639–650, 2010pmid:20354229
    OpenUrlCrossRefPubMed
  13. ↵
    1. Ali T,
    2. Khan I,
    3. Simpson W,
    4. Prescott G,
    5. Townend J,
    6. Smith W,
    7. Macleod A
    : Incidence and outcomes in acute kidney injury: A comprehensive population-based study. J Am Soc Nephrol 18: 1292–1298, 2007pmid:17314324
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Chertow GM,
    2. Burdick E,
    3. Honour M,
    4. Bonventre JV,
    5. Bates DW
    : Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16: 3365–3370, 2005pmid:16177006
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Uchino S,
    2. Kellum JA,
    3. Bellomo R,
    4. Doig GS,
    5. Morimatsu H,
    6. Morgera S,
    7. Schetz M,
    8. Tan I,
    9. Bouman C,
    10. Macedo E,
    11. Gibney N,
    12. Tolwani A,
    13. Ronco C,
    14. Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators
    : Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 294: 813–818, 2005pmid:16106006
    OpenUrlCrossRefPubMed
  16. ↵
    1. Chertow GM,
    2. Levy EM,
    3. Hammermeister KE,
    4. Grover F,
    5. Daley J
    : Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104: 343–348, 1998pmid:9576407
    OpenUrlCrossRefPubMed
  17. ↵
    1. Chawla LS,
    2. Kimmel PL
    : Acute kidney injury and chronic kidney disease: An integrated clinical syndrome. Kidney Int 82: 516–524, 2012pmid:22673882
    OpenUrlCrossRefPubMed
  18. ↵
    1. Coca SG,
    2. Singanamala S,
    3. Parikh CR
    : Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int 81: 442–448, 2012pmid:22113526
    OpenUrlCrossRefPubMed
  19. ↵
    1. Okusa MD,
    2. Chertow GM,
    3. Portilla D,
    4. Acute Kidney Injury Advisory Group of the American Society of Nephrology
    : The nexus of acute kidney injury, chronic kidney disease, and World Kidney Day 2009. Clin J Am Soc Nephrol 4: 520–522, 2009pmid:19225036
    OpenUrlFREE Full Text
  20. ↵
    1. Bucaloiu ID,
    2. Kirchner HL,
    3. Norfolk ER,
    4. Hartle JE 2nd.,
    5. Perkins RM
    : Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 81: 477–485, 2012pmid:22157656
    OpenUrlCrossRefPubMed
  21. ↵
    1. Khosla N,
    2. Soroko SB,
    3. Chertow GM,
    4. Himmelfarb J,
    5. Ikizler TA,
    6. Paganini E,
    7. Mehta RL,
    8. Program to Improve Care in Acute Renal Disease (PICARD)
    : Preexisting chronic kidney disease: A potential for improved outcomes from acute kidney injury. Clin J Am Soc Nephrol 4: 1914–1919, 2009pmid:19965524
    OpenUrlAbstract/FREE Full Text
  22. ↵
    1. Liangos O,
    2. Wald R,
    3. O’Bell JW,
    4. Price L,
    5. Pereira BJ,
    6. Jaber BL
    : Epidemiology and outcomes of acute renal failure in hospitalized patients: A national survey. Clin J Am Soc Nephrol 1: 43–51, 2006pmid:17699189
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Mehrotra A,
    2. Rose C,
    3. Pannu N,
    4. Gill J,
    5. Tonelli M,
    6. Gill JS
    : Incidence and consequences of acute kidney injury in kidney transplant recipients. Am J Kidney Dis 59: 558–565, 2012pmid:22226565
    OpenUrlCrossRefPubMed
  24. ↵
    U.S. Renal Data System, USRDS 2012 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, Table A.7, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2012
  25. ↵
    1. Lo LJ,
    2. Go AS,
    3. Chertow GM,
    4. McCulloch CE,
    5. Fan D,
    6. Ordoñez JD,
    7. Hsu CY
    : Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int 76: 893–899, 2009pmid:19641480
    OpenUrlCrossRefPubMed
  26. ↵
    1. Amdur RL,
    2. Chawla LS,
    3. Amodeo S,
    4. Kimmel PL,
    5. Palant CE
    : Outcomes following diagnosis of acute renal failure in U.S. veterans: Focus on acute tubular necrosis. Kidney Int 76: 1089–1097, 2009pmid:19741590
    OpenUrlCrossRefPubMed
  27. ↵
    1. Ponte B,
    2. Felipe C,
    3. Muriel A,
    4. Tenorio MT,,
    5. Liano F
    : Long-term functional evolution after an acute kidney injury: A 10-year study. Nephrol Dial Transplant 23: 3859–3866, 2008
  28. ↵
    1. Chawla LS,
    2. Amdur RL,
    3. Amodeo S,
    4. Kimmel PL,
    5. Palant CE
    : The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 79: 1361–1369, 2011pmid:21430640
    OpenUrlCrossRefPubMed
    1. Ishani A,
    2. Nelson D,
    3. Clothier B,
    4. Schult T,
    5. Nugent S,
    6. Greer N,
    7. Slinin Y,
    8. Ensrud KE
    : The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med 171: 226–233, 2011pmid:21325112
    OpenUrlCrossRefPubMed
  30. ↵
    1. Thakar CV,
    2. Christianson A,
    3. Himmelfarb J,
    4. Leonard AC
    : Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus. Clin J Am Soc Nephrol 6: 2567–2572, 2011pmid:21903988
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Srisawat N,
    2. Murugan R,
    3. Lee M,
    4. Kong L,
    5. Carter M,
    6. Angus DC,
    7. Kellum JA,
    8. Genetic and Inflammatory Markers of Sepsis (GenIMS) Study Investigators
    : Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia. Kidney Int 80: 545–552, 2011pmid:21677634
    OpenUrlCrossRefPubMed
  32. ↵
    Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV: Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nature Med 16: 535–543, 2010
  33. ↵
    1. Bechtel W,
    2. McGoohan S,
    3. Zeisberg EM,
    4. Müller GA,
    5. Kalbacher H,
    6. Salant DJ,
    7. Müller CA,
    8. Kalluri R,
    9. Zeisberg M
    : Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med 16: 544–550, 2010pmid:20418885
    OpenUrlCrossRefPubMed
  34. ↵
    1. Ko GJ,
    2. Grigoryev DN,
    3. Linfert D,
    4. Jang HR,
    5. Watkins T,
    6. Cheadle C,
    7. Racusen L,
    8. Rabb H
    : Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol 298: F1472–F1483, 2010pmid:20181666
    OpenUrlCrossRefPubMed
  35. ↵
    1. Basile DP,
    2. Zeng P,
    3. Friedrich JL,
    4. Leonard EC,
    5. Yoder MC
    : Low proliferative potential and impaired angiogenesis of cultured rat kidney endothelial cells. Microcirculation 19: 598–609, 2012pmid:22612333
    OpenUrlCrossRefPubMed
  36. ↵
    1. Basile DP,
    2. Friedrich JL,
    3. Spahic J,
    4. Knipe N,
    5. Mang H,
    6. Leonard EC,
    7. Changizi-Ashtiyani S,
    8. Bacallao RL,
    9. Molitoris BA,
    10. Sutton TA
    : Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury. Am J Physiol Renal Physiol 300: F721–F733, 2011pmid:21123492
    OpenUrlCrossRefPubMed
  37. ↵
    1. Askenazi DJ,
    2. Feig DI,
    3. Graham NM,
    4. Hui-Stickle S,
    5. Goldstein SL
    : 3-5 year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int 69: 184–189, 2006pmid:16374442
    OpenUrlCrossRefPubMed
  38. ↵
    1. Wynn TA
    : Fibrosis under arrest. Nat Med 16: 523–525, 2010pmid:20448575
    OpenUrlCrossRefPubMed
  39. ↵
    Chau BN, Xin C, Hartner J, Ren S, Castano AP, Linn G, Li J, Tran PT, Kaimal V, Huang X, Chang AN, Li S, Kalra A, Grafals M, Portilla D, MacKenna DA, Orkin SH, Duffield JS: MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med 4: 121ra18, 2012
  40. ↵
    1. Mishra J,
    2. Dent C,
    3. Tarabishi R,
    4. Mitsnefes MM,
    5. Ma Q,
    6. Kelly C,
    7. Ruff SM,
    8. Zahedi K,
    9. Shao M,
    10. Bean J,
    11. Mori K,
    12. Barasch J,
    13. Devarajan P
    : Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365: 1231–1238, 2005pmid:15811456
    OpenUrlCrossRefPubMed
    1. Zappitelli M,
    2. Washburn KK,
    3. Arikan AA,
    4. Loftis L,
    5. Ma Q,
    6. Devarajan P,
    7. Parikh CR,
    8. Goldstein SL
    : Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: A prospective cohort study. Crit Care 11: R84, 2007pmid:17678545
    OpenUrlCrossRefPubMed
  42. ↵
    1. Trachtman H,
    2. Christen E,
    3. Cnaan A,
    4. Patrick J,
    5. Mai V,
    6. Mishra J,
    7. Jain A,
    8. Bullington N,
    9. Devarajan P,
    10. Investigators of the HUS-SYNSORB Pk Multicenter Clinical Trial
    : Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: A novel marker of renal injury. Pediatr Nephrol 21: 989–994, 2006pmid:16773412
    OpenUrlCrossRefPubMed
  43. ↵
    1. Mitsnefes MM
    : Cardiovascular morbidity and mortality in children with chronic kidney disease in North America: lessons from the USRDS and NAPRTCS databases. Perit Dial Int 25[Suppl 3]: S120–S122, 2005pmid:16048275
    OpenUrlAbstract/FREE Full Text
  44. ↵
    1. Dennis VW
    : Coronary heart disease in patients with chronic kidney disease. J Am Soc Nephrol 16[Suppl 2]: S103–S106, 2005pmid:16251244
    OpenUrlFREE Full Text
    1. National Kidney Foundation
    : K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 39[Suppl 1]: S1–S266, 2002pmid:11904577
    OpenUrlCrossRefPubMed
    1. Kavey RE,
    2. Allada V,
    3. Daniels SR,
    4. Hayman LL,
    5. McCrindle BW,
    6. Newburger JW,
    7. Parekh RS,
    8. Steinberger J,
    9. American Heart Association Expert Panel on Population and Prevention Science,
    10. American Heart Association Council on Cardiovascular Disease in the Young,
    11. American Heart Association Council on Epidemiology and Prevention,
    12. American Heart Association Council on Nutrition, Physical Activity and Metabolism,
    13. American Heart Association Council on High Blood Pressure Research,
    14. American Heart Association Council on Cardiovascular Nursing,
    15. American Heart Association Council on the Kidney in Heart Disease,
    16. Interdisciplinary Working Group on Quality of Care and Outcomes Research
    : Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics. Circulation 114: 2710–2738, 2006pmid:17130340
    OpenUrlAbstract/FREE Full Text
  47. ↵
    1. Berenson GS,
    2. Srinivasan SR,
    3. Bao W,
    4. Newman WP 3rd.,
    5. Tracy RE,
    6. Wattigney WA
    : Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338: 1650–1656, 1998pmid:9614255
    OpenUrlCrossRefPubMed
  48. ↵
    1. Deckert T,
    2. Feldt-Rasmussen B,
    3. Borch-Johnsen K,
    4. Jensen T,
    5. Kofoed-Enevoldsen A
    : Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32: 219–226, 1989pmid:2668076
    OpenUrlCrossRefPubMed
  49. ↵
    1. Arnlöv J,
    2. Evans JC,
    3. Meigs JB,
    4. Wang TJ,
    5. Fox CS,
    6. Levy D,
    7. Benjamin EJ,
    8. D’Agostino RB,
    9. Vasan RS
    : Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: The Framingham Heart Study. Circulation 112: 969–975, 2005pmid:16087792
    OpenUrlAbstract/FREE Full Text
  50. ↵
    1. Goldstein SL,
    2. Devarajan P
    : Acute kidney injury in childhood: Should we be worried about progression to CKD? Pediatr Nephrol 26: 509–522, 2011pmid:20936523
    OpenUrlCrossRefPubMed
  51. ↵
    1. Hingorani S,
    2. Guthrie KA,
    3. Schoch G,
    4. Weiss NS,
    5. McDonald GB
    : Chronic kidney disease in long-term survivors of hematopoietic cell transplant. Bone Marrow Transplant 39: 223–229, 2007pmid:17290279
    OpenUrlCrossRefPubMed
    1. Kist-van Holthe JE,
    2. Bresters D,
    3. Ahmed-Ousenkova YM,
    4. Goedvolk CA,
    5. Abbink FC,
    6. Wolterbeek R,
    7. Bredius RG,
    8. Pauwels EK,
    9. van der Heijden AJ
    : Long-term renal function after hemopoietic stem cell transplantation in children. Bone Marrow Transplant 36: 605–610, 2005pmid:16044134
    OpenUrlCrossRefPubMed
    1. Kist-van Holthe JE,
    2. Goedvolk CA,
    3. Brand R,
    4. van Weel MH,
    5. Bredius RG,
    6. van Oostayen JA,
    7. Vossen JM,
    8. van der Heijden BJ
    : Prospective study of renal insufficiency after bone marrow transplantation. Pediatr Nephrol 17: 1032–1037, 2002pmid:12478353
    OpenUrlCrossRefPubMed
    1. Sinha R,
    2. Nandi M,
    3. Tullus K,
    4. Marks SD,
    5. Taraphder A
    : Ten-year follow-up of children after acute renal failure from a developing country. Nephrol Dial Transplant 24: 829–833, 2009pmid:18852189
    OpenUrlCrossRefPubMed
    1. Slack R,
    2. Hawkins KC,
    3. Gilhooley L,
    4. Addison GM,
    5. Lewis MA,
    6. Webb NJ
    : Long-term outcome of meningococcal sepsis-associated acute renal failure. Pediatr Crit Care Med 6: 477–479, 2005pmid:15982443
    OpenUrlCrossRefPubMed
  56. ↵
    1. Mammen C,
    2. Al Abbas A,
    3. Skippen P,
    4. Nadel H,
    5. Levine D,
    6. Collet JP,
    7. Matsell DG
    : Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study. Am J Kidney Dis 59: 523–530, 2012pmid:22206744
    OpenUrlCrossRefPubMed
  57. ↵
    1. Rifkin DE,
    2. Coca SG,
    3. Kalantar-Zadeh K
    : Does AKI truly lead to CKD? J Am Soc Nephrol 23: 979–984, 2012pmid:22460531
    OpenUrlAbstract/FREE Full Text
  58. ↵
    1. Hsu CY
    : Yes, AKI truly leads to CKD. J Am Soc Nephrol 23: 967–969, 2012pmid:22499588
    OpenUrlFREE Full Text
  59. ↵
    U.S. Renal Data System. USRDS Annual Report 2007. NIH publication no 07–3176. Bethesda, Maryland, Department of Health and Human Services, National Institute of Diabetes and Digestive and Kidney Disease, 2007, 240–241
  60. ↵
    1. Liu KD,
    2. Thompson BT,
    3. Ancukiewicz M,
    4. Steingrub JS,
    5. Douglas IS,
    6. Matthay MA,
    7. Wright P,
    8. Peterson MW,
    9. Rock P,
    10. Hyzy RC,
    11. Anzueto A,
    12. Truwit JD,
    13. National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network
    : Acute kidney injury in patients with acute lung injury: impact of fluid accumulation on classification of acute kidney injury and associated outcomes. Crit Care Med 39: 2665–2671, 2011pmid:21785346
    OpenUrlCrossRefPubMed
  61. ↵
    1. Basu RK,
    2. Andrews A,
    3. Krawczeski CD,
    4. Manning PB,
    5. Wheeler DS,
    6. Goldstein SL
    : Acute kidney injury based on corrected serum creatinine is associated with increased morbidity in children following the arterial switch operation. Pediatr Crit Care Med 2013, in presspmid:21057358
    OpenUrlCrossRefPubMed
  62. ↵
    1. Williams AW,
    2. Dwyer AC,
    3. Eddy AA,
    4. Fink JC,
    5. Jaber BL,
    6. Linas SL,
    7. Michael B,
    8. O’Hare AM,
    9. Schaefer HM,
    10. Shaffer RN,
    11. Trachtman H,
    12. Weiner DE,
    13. Falk AR,
    14. American Society of Nephrology Quality, and Patient Safety Task Force
    : Critical and honest conversations: The evidence behind the “Choosing Wisely” campaign recommendations by the American Society of Nephrology. Clin J Am Soc Nephrol 7: 1664–1672, 2012pmid:22977214
    OpenUrlAbstract/FREE Full Text
  63. ↵
    1. Go AS,
    2. Parikh CR,
    3. Ikizler TA,
    4. Coca S,
    5. Siew ED,
    6. Chinchilli VM,
    7. Hsu CY,
    8. Garg AX,
    9. Zappitelli M,
    10. Liu KD,
    11. Reeves WB,
    12. Ghahramani N,
    13. Devarajan P,
    14. Faulkner GB,
    15. Tan TC,
    16. Kimmel PL,
    17. Eggers P,
    18. Stokes JB,
    19. Assessment Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury Study Investigators
    : The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: Design and methods. BMC Nephrol 11: 22, 2010pmid:20799966
    OpenUrlCrossRefPubMed
    1. Hsu CY,
    2. Chertow GM,
    3. McCulloch CE,
    4. Fan D,
    5. Ordoñez JD,
    6. Go AS
    : Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol 4: 891–898, 2009pmid:19406959
    OpenUrlAbstract/FREE Full Text
    1. Choi AI,
    2. Li Y,
    3. Parikh C,
    4. Volberding PA,
    5. Shlipak MG
    : Long-term clinical consequences of acute kidney injury in the HIV-infected. Kidney Int 78: 478–485, 2010pmid:20520594
    OpenUrlCrossRefPubMed
    1. Weiss AS,
    2. Sandmaier BM,
    3. Storer B,
    4. Storb R,
    5. McSweeney PA,
    6. Parikh CR
    : Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant 6: 89–94, 2006
    1. Newsome BB,
    2. Warnock DG,
    3. McClellan WM,
    4. Herzog CA,
    5. Kiefe CI,
    6. Eggers PW,
    7. Allison JJ
    : Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch Intern Med 168: 609–616, 2008pmid:18362253
    OpenUrlCrossRefPubMed
    1. James MT,
    2. Ghali WA,
    3. Knudtson ML,
    4. Ravani P,
    5. Tonelli M,
    6. Faris P,
    7. Pannu N,
    8. Manns BJ,
    9. Klarenbach SW,
    10. Hemmelgarn BR,
    11. Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) Investigators
    : Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation 123: 409–416, 2011pmid:21242477
    OpenUrlAbstract/FREE Full Text
    1. James MT,
    2. Hemmelgarn BR,
    3. Wiebe N,
    4. Pannu N,
    5. Manns BJ,
    6. Klarenbach SW,
    7. Tonelli M,
    8. Alberta Kidney Disease Network
    : Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet 376: 2096–2103, 2010pmid:21094997
    OpenUrlCrossRefPubMed
    1. Wald R,
    2. Quinn RR,
    3. Luo J,
    4. Li P,
    5. Scales DC,
    6. Mamdani MM,
    7. Ray JG,
    8. University of Toronto Acute Kidney Injury Research Group
    : Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA 302: 1179–1185, 2009pmid:19755696
    OpenUrlCrossRefPubMed
    1. LaFrance JP,
    2. Djurdjev O,,
    3. Levin A
    : Incidence and outcomes of acute kidney injury in a referred chronic kidney disease cohort. Nephrol Dial Transplant 25: 2203–2209, 2010
    1. Ishani A,
    2. Xue JL,
    3. Himmelfarb J,
    4. Eggers PW,
    5. Kimmel PL,
    6. Molitoris BA,
    7. Collins AJ
    : Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 20: 223–228, 2009pmid:19020007
    OpenUrlAbstract/FREE Full Text
    1. Buysse CM,
    2. Raat H,
    3. Hazelzet JA,
    4. Hulst JM,
    5. Cransberg K,
    6. Hop WC,
    7. Vermunt LC,
    8. Utens EM,
    9. Maliepaard M,
    10. Joosten KF
    : Long-term health status in childhood survivors of meningococcal septic shock. Arch Pediatr Adolesc Med 162: 1036–1041, 2008pmid:18981351
    OpenUrlCrossRefPubMed
    1. Skinner R,
    2. Parry A,
    3. Price L,
    4. Cole M,
    5. Craft AW,
    6. Pearson AD
    : Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: Relevance of age and dose as risk factors. Eur J Cancer 45: 3213–3219, 2009pmid:19850470
    OpenUrlCrossRefPubMed
    1. Hazar V,
    2. Gungor O,
    3. Guven AG,
    4. Aydin F,
    5. Akbas H,
    6. Gungor F,
    7. Tezcan G,
    8. Akman S,
    9. Yesilipek A
    : Renal function after hematopoietic stem cell transplantation in children. Pediatr Blood Cancer 53: 197–202, 2009pmid:19353620
    OpenUrlCrossRefPubMed
Back to top

In this issue

View Selected Citations (0)
Print
Download PDF
Email Article
Citation Tools
Request Permissions
AKI Transition of Care: A Potential Opportunity to Detect and Prevent CKD
Stuart L. Goldstein, Bertrand L. Jaber, Sarah Faubel, Lakhmir S. Chawla, for the Acute Kidney Injury Advisory Group of the American Society of Nephrology
CJASN Mar 2013, 8 (3) 476-483; DOI: 10.2215/CJN.12101112
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo

Jump to section

More in this TOC Section

Cited By...

Similar Articles

Related Articles

  • No related articles found.