The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation.

BACKGROUND: Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption. OBJECTIVES: To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy. DATA SOURCES: We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report. REVIEW METHODS: The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis. RESULTS: The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck® (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care. LIMITATIONS: The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing. CONCLUSIONS: Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value. STUDY REGISTRATION: The systematic review within this study is registered as PROSPERO CRD42014013919. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The cardiac surgery-associated neutrophil gelatinase-associated lipocalin (CSA-NGAL) score: A potential tool to monitor acute tubular damage.

Acute kidney injury (AKI), defined as a rise in serum creatinine (functional AKI), is a frequent complication after cardiac surgery. The expression pattern of acute tubular damage biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) has been shown to precede functional AKI and, therefore, may be useful to identify very early tubular damage. The term subclinical AKI represents acute tubular damage in the absence of functional AKI (biomarker positivity without a rise in serum creatinine) and affects hard outcome measures. This potentiates an tubular-damage-based identification of renal injury, which may guide clinical management, allowing for very early preventive-protective strategies. The aim of this paper was to review the current available evidence on NGAL applicability in adult cardiac surgery patients and combine this knowledge with the expert consensus of the authors to generate an NGAL based tubular damage score: The cardiac surgery-associated NGAL Score (CSA-NGAL score). The CSA-NGAL score might be the tool needed to improve awareness and enable interventions to possibly modify these detrimental outcomes. In boldly doing so, it is intended to introduce a different approach in study designs, which will undoubtedly expand our knowledge and will hopefully move the AKI biomarker field forward.

Acute Kidney Injury in Low-Resource Settings: Barriers to Diagnosis, Awareness, and Treatment and Strategies to Overcome These Barriers.

Acute kidney injury (AKI) is increasingly recognized as a major health problem worldwide, responsible for an estimated 1.4 million deaths per year. The occurrence of and approach to AKI in low-resource settings (LRS) present special challenges due to often limited health care resources, including insufficient numbers of trained personnel, diagnostic tools, and treatment options. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in LRS presents major challenges not only because of the lack of resources, but also because of the lack of awareness of the impact of AKI on patient outcomes, factors that are complicated by the challenge of cognitively dissociating the care of patients with AKI from the care of patients with chronic kidney failure. To better understand how to increase the awareness of AKI and develop strategies to improve the identification and treatment of patients with AKI in LRS, we administered an 18-item web-based questionnaire to physicians actively engaged in providing nephrology care in LRS. A checklist was then developed of meaningful and targeted approaches for implementation, with focus on engaging local and regional stakeholders, developing education programs and appropriate guidelines, enhancing training of health care workers, expanding health care resources, linking with other regional health care projects, and broadening research opportunities.

Relationship between patients' outcomes and the changes in serum creatinine and urine output and RIFLE classification in a large critical care cohort database.

We report the stepwise application of the RIFLE classification in 155,624 admissions in the UK Intensive Care National Audit & Research Centre Case Mix Programme database. The assumptions required to define RIFLE and their relationship with renal replacement therapy (RRT) and ICU mortality were assessed. Previous reports had not explored the method of estimating baseline creatinine, the position of class boundaries, or interactions between urine volume (AKI-U) and the peak/estimated baseline creatinine (AKI-Cr) within 24 h of ICU admission. The risk of developing AKI strongly depended on the assumed GFR increasing from 36 to 58% across the recommended range. AKI-U was often seen without AKI-Cr, and moderate oliguria (under 850 ml/24 h) was a stronger predictor of mortality than any degree of AKI-Cr partly because mortality fell when peak/estimated baseline creatinine ratios exceed fourfold. Mild oliguria (850-1500 ml/24 h) was common (38,928 admissions, 26%) and had a similar association with mortality (relative risk 1.6, 95% CI: 1.5-1.6) as did AKI-Cr defined Failure (risk ratio 1.5, 95% CI: 1.5-1.6). However, AKI-Cr was a strong predictor for RRT, which was used in 17,802 (11%) of admissions. Nearly half (48%) of the Failure patients never received RRT; nonetheless, most (66%) survived critical care. Thus, although the RIFLE classification may be attempted in large population cohorts, there is significant heterogeneity of both renal and, in particular, vital outcomes within each class.

A survey on the methodological processes and policies of renal guideline groups as a first step to harmonize renal guidelines.

BACKGROUND: Worldwide, several bodies produce renal guidelines, potentially leading to duplication of effort while other topics may remain uncovered. A collaborative work plan could improve efficiency and impact, but requires a common approved methodology. The aim of this study was to identify organizational and methodological similarities and differences among seven major renal guideline bodies to identify methodological barriers to a collaborative effort. METHODS: An electronic 62-item survey with questions based on the Institute of Medicine standards for guidelines was completed by representatives of seven major organizations producing renal guidelines: the Canadian Society of Nephrology (CSN), European Renal Best Practice (ERBP), Kidney Disease Improving Global Outcome (KDIGO), Kidney Health Australia-Caring for Australians with Renal Insufficiency (KHA-CARI), Kidney Disease Outcome Quality Initiative (KDOQI), Sociedad Latino-Americano de Nefrologia e Hipertension (SLANH) and United Kingdom Renal Association (UK-RA). RESULTS: Five of the seven groups conduct systematic searches for evidence, two include detailed critical appraisal and all use the GRADE framework. Five have public review of the guideline draft. Guidelines are updated as new evidence comes up in all, and/or after a specified time frame has passed (N = 3). Commentaries or position statements on guidelines published by other groups are produced by five, with the ADAPTE framework (N = 1) and the AGREEII (N = 2) used by some. Funding is from their parent organizations (N = 5) or directly from industry (N = 2). None allow funders to influence topic selection or guideline content. The budgets to develop a full guideline vary from $2000 to $500 000. Guideline development groups vary in size from <5 (N = 1) to 13-20 persons (N = 3). Three explicitly seek patient perspectives, for example, by involving patients in the scoping process, and four incorporate health economic considerations. All provide training in methodology for guideline development groups and six make their methods public. All try to avoid overlapping topics already planned or published by others. There is no common conflict of interest policy. CONCLUSIONS: Overall, there is considerable commonality in methods and approaches in renal guideline development by the different organizations, although some procedural differences remain. As the financial and human resource costs of guideline production are high, a collaborative approach is required to maximize impact and develop a sustainable work plan. Coming to consensus on methods and procedures is the first step and appears feasible.