Raising awareness of acute kidney injury: a global perspective of a silent killer.

Worldwide, acute kidney injury (AKI) is associated with poor patient outcomes. Over the last few years, collaborative efforts, enabled by a common definition of AKI, have provided a description of the epidemiology, natural history, and outcomes of this disease and improved our understanding of the pathophysiology. There is increased recognition that AKI is encountered in multiple settings and in all age groups, and that its course and outcomes are influenced by the severity and duration of the event. The effect of AKI on an individual patient and the resulting societal burden that ensues from the long-term effects of the disease, including development of chronic kidney disease (CKD) and end-stage renal disease (ESRD), is attracting increasing scrutiny. There is evidence of marked variation in the management of AKI, which is, to a large extent, due to a lack of awareness and an absence of standards for prevention, early recognition, and intervention. These emerging data point to an urgent need for a global effort to highlight that AKI is preventable, its course is modifiable, and its treatment can improve outcomes. In this article, we provide a framework of reference and propose specific strategies to raise awareness of AKI globally, with the goal to ultimately improve outcomes from this devastating disease.

Introduction

AKI is now well established as a common, often under-recognized disorder, which is associated with a high risk for mortality, development of chronic kidney disease (CKD) and other organ dysfunction. This condition has both short and long-term effects on functional status, and leads to increased resource utilization (1–3). Several studies have confirmed that while the course of AKI is variable based on the setting where it occurs, the severity and duration of AKI determines outcomes, including dialysis requirement, renal functional recovery and survival (4, 5). There is increasing recognition both of the effect of AKI on the individual patient, and the resulting societal burden ensuing from its long term effects, including development of CKD and end stage renal disease (ESRD) requiring dialysis or transplantation(6).

Data derived from high-income countries (HI), using standardized definitions for diagnosis and staging of AKI, have facilitated comparisons of incidence and outcomes in different clinical settings (7). Conversely, a paucity of information on the prevalence, course and outcomes of AKI in low and middle income (LMI) countries contributes to a somewhat biased view of AKI as a disease of hospitalized patients. In LMI countries, while the majority of urban cases occur in the context of acute illness, usually in association with hypovolemia and sepsis, AKI occurring in the community (e.g. diarrheal states, malaria) is under-recognized(8, 9).

Despite emerging data and increasing interest in AKI as a major contributor to adverse outcomes, there is still considerable lack of understanding of the condition among physicians, allied personnel and the lay public. As a result, systematic efforts have been limited and few resources have been allocated to inform health care professionals and the public of the importance of AKI as a preventable and treatable disease. Recent publications have highlighted deficiencies and wide variation in the care of AKI patients worldwide (10, 11). These reports have demonstrated missed opportunities to prevent and detect AKI, and suboptimal management.

AKI is encountered in multiple settings and is commonly first encountered by nonspecialized health care providers, either in the community or the hospital setting. Since AKI is not associated with any specific symptoms and the diagnosis is largely based on measurement of lab parameters, it is essential that caregivers be educated on the risks for AKI and equipped with the knowledge for early recognition, timely intervention and effective follow up.

This article provides a rationale and a proposal for a calibrated approach to raise awareness of the incidence and consequences of AKI to all potential stakeholders, including patients. Our ultimate goal is to improve the recognition and timely management of this silent killer, and to emphasize the need for collaboration among all those involved in the care of these patients

Why do we need to raise awareness of the importance of acute kidney injury?

a. AKI is common worldwide and is encountered in multiple settings but remains poorly recognized

The incidence of AKI worldwide varies widely across different studies and is largely dependent on the setting (hospital (h-AKI) vs. community-acquired (c-AKI)) and the at-risk populations investigated. It affects between 7 and 18% of hospital inpatients (12–15) and ranges from 20–200 per million population in the community (Tables 1 and 2)(16). Hospital-acquired AKI (h-AKI) is more common in the elderly; patients presenting with community acquired AKI (c-AKI) are usually younger and healthier (17). In HI countries, while mild AKI developing in the general hospital ward has become less common, more severe forms in the intensive care unit (ICU) have become predominant. Among critically ill patients, the incidence of AKI varies between 30 and 70%; approximately 5% of ICU admissions require renal replacement therapy (RRT) (18). In LMI countries, clinical presentation of AKI is dependent on location: while in larger cities, ICU-acquired h-AKI predominates, in rural areas, c-AKI is more common.

Table 1

Reported incidence of AKI in high-income (HI) and low- and middle-income (LMI) countries. (Modified from (8)

	Community Acquired	Change In Incidence	Hospital Acquired	Change In Incidence
HI Countries	200 PMP	51 To 62%	60–288/100,000 Pop	6.8 Times Increase; 11%/Year Increase
LMI Countries	20 PMP	No Significant Change	5.4/100,000 Pop	1.06 Increase Over 5 Years

POP: population; PMP: per million population

Table 2

Incidence of hospital and community acquired AKI in the world (Modified from (8)

Reference	Location	Study features	Incidence	Change in incidence over time
Hospital acquired AKI in the developed world
Hou et al (1983)(99)	US	2,262 adult admissions	4.9% of admissions	N/A
Nash et al (2002)(12)	US	4,622 adult admissions	7.2% of admissions	N/A
Waikar et al (2006)(100)	US	Nationwide sample of 5,563,381 adults discharged 1988 to 2002	61–288 per 100,000 head of population	4.7 times increase
Waikar et al (2006)(100)	US	Nationwide sample of 5,563,381 adults who required dialysis discharged 1988 to 2002	4–27 per 100,000 head of population	6.8 times increase
Xue et al (2006)(19)	US	5,403,015 adults discharged between 1992–2001 from Medicare database	23.8 per 1,000 hospital discharges	11% per year increase
Uchino et al (2005)(18)	International	Multicenter study 1,738/29,269 ICU patients in 23 countries between 2000–2001	5–6% of ICU admissions; 80% received dialysis	N/A
Hospital acquired AKI in LMI countries
Abraham et al (1989)(101)	Kuwait (400,000 inhabitants)	77 adults admitted university hospital 1984–1986	5.4 per 100,000 head of population per year	N/A
Jha et al (1992)(23, 102)	North India	190 of 29,503 adults presenting to a referral center 1 year period	6.4 per 1,000 admissions per year	N/A
Noronha et al (1997)(23)	Sao Paulo, Brazil	Review of adult inpatients	7.9 per 1,000 admissions	N/A
Thomas et al (2000)(103)	Trinidad and Tobago	AKI post 205 cardiac surgeries 1993–1997	21 per 1,000 surgeries	N/A
Al-Homrany et al (2003)(104)	Saudi Arabia	26,000 adults 2 year period	3.7 per 1,000 admissions	N/A
Kohli et al (2007)(105)	Chandigarh, India	294/33,301 admissions large urban center 1 year period	2.1 per 1,000 admissions	N/A
Wang et al (2005 and 2007)(106, 107)	Peking, China	Retrospective review 225,000 inpatients university center 1994–2003	0.36 per 1,000 admissions	1.06 times increase over 5 years
Community acquired AKI in the developed world
Kaufman et al (1991)(108)	US	100 adults, increase SCr> 2 mg/dl or A/CKD	1% hospital admissions	N/A
Feest et al (1993)(109)	UK	125/444,971 adults, SCr>5.5 mg/dl.Requiring dialysis	172 PMP22 PMP	N/A
Chanard et al (1994)(110)	France	Adults who completed a questionnaire 1991	104 PMP	N/A
Liaño and Pascual (1996)(111)	Madrid, Spain	Multicenter; 665/4.2 million adults SCr>2 mg/dl or 50% increase in CKDAdults, 36% required dialysis	209 PMP75 PMP	N/A
Khan et al (1997)(84)	Scotland	311 adults, increased SCr or A/CKD52/311 severe AKI	620 PMP/year (50 PMP/yr. requiring dialysis)102 PMP	N/A
Stevens et al (2001)(30)	UK	288/593,000 adults	486 PMP/year	N/A
Metcalfe et al (2002)(112)	Scotland	Census assessment; 375 adults PMP dialyzed	203 PMP/year	N/A
Obialo et al (2000)(113)	US	Hospital discharges 1994–1996, 100 African-American; SCr>2.0 mg/dl; de novo AKI	Community acquired AKI 0.55%; hospital acquired 0.15%	N/A
Prescott et al (2007)(114)	Aberdeen, Scotland	Adults requiring dialysis 2002	282 PMP/year	N/A
Ali et al (2007)(115)	Scotland	523,390 adults in 2003; AKI and A/CKD RIFLE criteria	1,811 PMP AKI AND 336 PMP A/CKD	N/A
Hsu et al (2007)(16)	US	Kaiser Permanente California; 61,269 adults no dialysis AKI 1996–20033,885 adults dialysis AKI 1996–2003	Increase from 322.7 to 522.4 per 100,000 person-yearsIncrease from 19.5 to 29.5 per 100,000 person-years	62% increase51% increase
Community-acquired AKI in LMI countries
Abraham et al (1989)(101)	Kuwait	77 adults presenting to university hospital	4.1 per 100,000 head of population/year	N/A
Seedat and Nathoo (1993)(59)	Durban, South Africa	Adults, 1986–1988	20 PMP	No change 1980–1990
Anochie and Eke (2005)(116)	Nigeria	Children presenting referral center	11.7 per million children/year	N/A
Al-Homray (2003)(104)	Saudi Arabia	26,000 adults during 2 years observation	2.3 per 1,000 admissions	N/A
Vukusich et al (2004)(117)	Santiago, Chile	10 urban centers, 114 adults requiring dialysis 6-month period	0.31 per 1,000 discharges	N/A
Kohli et al (2007)(105)	Chandigarh, India	294 of 33,301 admissions large urban medical center 1 year period	6.6 of 1,000 admissions	N/A
Wang et al (2005/2007)(106, 107)	Peking, China	Retrospective review 225,000 patients university center 1994–2003	0.54 per 1,000 admissions	N/A

The etiology of h-AKI in urban areas of both HI and LMI countries is similar, but treatment resources differ widely (18–20). Hospital-acquired AKI develops in the ICU, in the context of multiple organ failure, post-cardiovascular procedures or sepsis, or as a complication of nephrotoxic medications. Patients affected are generally elderly, obese and diabetic. Conversely, the etiology of c-AKI differs considerably between HI and LMI countries. In LMI countries, AKI is often a disease of the young, caused by specific infections or toxins resulting in diarrhea and hypovolemia. Etiology is dependent on geographical location and may be secondary to infectious agents such as malaria, leptospirosis, dengue, envenomation (snakes or arthropods), and be subject to seasonal variation. In those regions, HIV disease, obstetric complications (e.g. septic abortion), or intoxications (often caused by traditional herbs or household products) are prevalent (21–27).

A common factor across HI and LMI countries is that most cases of AKI are managed by non-nephrologists, who maybe unfamiliar with the risk factors and early manifestations of the disease. This contributes to delayed recognition and suboptimal management. For instance, fluid accumulation decreases of serum creatinine concentration by increasing total body water, thus contributing to delayed diagnosis and underestimation of the severity of AKI (28, 29).

The quality of care delivered to hospitalized patients with AKI has been recently reviewed in different studies and revealed large gaps in the care including delayed recognition, inadequate investigations, deficient monitoring, delayed and often flawed management and lack of follow up (30),(31). These findings were encountered even when nephrologists were available and illustrate the clear need for educating caregivers in all disciplines regarding this disorder.

In LMI countries, insufficient and late recognition is even more problematic both in the community and in the hospital setting. Late recognition leads to delayed management, by which time associated morbidity and mortality have worsened considerably. Late recognition may account for the apparently 10-fold lower incidence in LMI countries: it is likely that AKI cases are underreported due to several factors, including access to appropriate medical care, lack of knowledge, and non-availability of standard tests that are considered routine in the developed world (e.g. serum creatinine). As an example, a recent report describes an “epidemic” of kidney disease in Central America that is blamed for several deaths annually in impoverished sugar cane workers across Nicaragua, Costa Rica, El Salvador and Guatemala. It is believed that the condition results from repetitive episodes of AKI secondary to dehydration. Standard work-days of 12–14 hours, with double shifts during the summer planting season when temperatures top 40° C likely cause heat stroke, rhabdomyolysis and AKI. Alternative mechanisms including environmental toxins and pesticides are being evaluated (32). Survivors develop a disproportionate degree of CKD. Limited resources make chronic dialysis treatment unlikely, thus making the condition quite deadly.

b. AKI contributes to adverse outcomes including Chronic Kidney Disease and Mortality

Several epidemiological studies have demonstrated the independent association of AKI with a higher risk of death. As severity increases so does mortality, which is highest among patients requiring renal replacement therapy (50–60%) (Figure 1) (8). Duration and severity of AKI predict progression to CKD and contribute to the unabated increase in the number of ESRD patients (4, 5). Older patients are at higher risk of AKI, as they have less renal functional reserve and are affected by multiple co-morbidities. After the acute episode, significant increase in cardiovascular risk associated with CKD creates new demand for follow-up and treatment (33–39). Although a direct causal relationship for AKI leading to CKD has not been clearly established(40), there is considerable evidence from both animal and human studies supporting a strong association of AKI with CKD (41). For instance, a fourfold increase in the incidence of AKI over the last 15 years, and the higher proportion of severe AKI requiring dialysis (which has nearly doubled), have been implicated as important determinants to the increase in the incidence of CKD (42–44). Figures 2a and b illustrate the burden of cases of AKI, deaths and progression to CKD in HI and LMI countries. In the latter, calculations were made assuming a similar incidence as in HI countries; actual data is, as discussed, currently unavailable.

Figure 1

The global burden of AKI (Modified from (13)

Figure 2

FIGURE 2A: HIGH INCOME COUNTRIES

FIGURE 2B: LOW AND MIDDLE INCOME COUNTRIES

Figures 2A and 2B illustrate the burden of cases of AKI, deaths and progression to CKD in HI and LMI countries. In the latter, calculations were made assuming a similar incidence as in HI countries; actual data is unavailable. (Figures modified from (118)

Most of the data on AKI outcomes are derived from studies in HI countries: in LMI countries, the long-term impact of AKI is almost completely unknown. The limited available evidence suggests that AKI may represent one of the main causes of CKD and ESRD in those countries, especially among children (45, 46), equally as important as the increasing incidence of obesity and diabetes. In El Salvador, end stage renal disease is the leading cause of hospital deaths in adults, the second cause of death in men and the fifth leading cause of death in adults of both sexes in the general population (32).

c. AKI is preventable, treatable and reversible

Although intuitively true, evidence that prevention is indeed associated with better outcomes is hindered for two main reasons. In HI countries, diversity of definitions and heterogeneous management hamper interpretation of whether prevention is associated with benefit. Preventive treatment has been demonstrated for only a few etiologies of AKI, including radio-contrast-induced and post-cardiac surgery, but there is persistent controversy on the best methods of prevention (47). When AKI develops in the context of multiple organ failure and sepsis, late diagnosis thwarts preventive treatment. Results of the ongoing Surviving Sepsis Campaign large randomized controlled trials may in the future clarify this point. Recent studies addressing the impact of early nephrology consultation (31, 48, 49) leading to simple preventive and management measures (e.g. providing proper volume assessment and adjusting medication regimens to prevent further hemodynamic or toxic kidney injury) have shown a decrease in the incidence and severity of h-AKI. Given the observational nature of those studies, residual confounding may explain the association with timely nephrology consultation. (31). Advances in electronic medical records and e-Alerts are emerging as potential approaches for identifying high-risk patients and modifying the use of nephrotoxic medications (15) (15, 50, 51).

In LMI countries c-AKI is often preventable by simple measures such as rehydration of volume-contracted patients with cholera, or use of bed netting to avert severe malaria (52–55). This area is nevertheless not free of contention, as recent evidence in Sub-Saharan Africa suggesting that vigorous volume expansion may be damaging in children primarily affected by malaria-induced AKI (56).

d. AKI causes a societal burden

The proportion of patients with renal failure who receive treatment is a reflection of each country’s economic status(8). There is a clear correlation between the number of nephrologists, dialysis facilities, number of patients on chronic dialysis and a country’s gross domestic product (GDP) (57). In LMI countries, hemodialysis is a rare and expensive resource. Peritoneal dialysis is often a better and less costly alternative but it is generally available for only a limited period of time, to support the patient through the acute phase. Concerns have been raised on the adequacy of peritoneal dialysis therapy for the treatment of hypercatabolic AKI (58–61), but recent studies (22, 62–66) have demonstrated good results. Patients who fail to recover kidney function are unlikely to receive long-term RRT(67). Lack of healthcare workers in LMI countries has been a major constraint in limiting progress in initiatives such as the HIV “3 by 5” and Millennium Development Goals. Lack of human and financial resources in LMI has hampered nephrology programs both in detection and prevention of CKD and the ability of doctors, nurses and other personnel to provide acute and chronic dialysis and transplantation(68). In HI countries outcomes post AKI may be dismal in the median- and long-term, with a large number of patients ending their lives in nursing homes or disabled (69, 70). Given the increasing burden of CKD, even HI countries will soon become unable to appropriately afford the increasing costs of a growing ESRD population.

e. AKI is poorly managed

Recent reports and anecdotal experience demonstrate that it is necessary to improve the recognition and response to patients developing AKI and to improve the management of the condition once it has occurred. The UK National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) Adding Insult to Injury AKI Study, reported in 2009 that only 50% of patients who died from a diagnosis of AKI received good care (71). There were deficiencies in the recognition and management of patients who developed AKI. A further NCEPOD report (72), confirmed that a significant proportion of patients over the age of 80 who died within 30 days of surgery, developed AKI. It was recommended that there should be improvements in general medical care and risk assessment of AKI in this patient group. Failure to recognize the condition results in a delay in treatment and appropriate referral. Aitken et al (73) showed in a cohort of over 1500 patients in a single hospital in Glasgow that AKI was unrecognized in 23.5% of patients, of which 2/3 were discharged without resolution of renal function. Significant weaknesses were found in the management including poorly kept fluid balance charts (48.2%), failure to adjust nephrotoxic drugs (38.2%) and failure to act on abnormal biochemistry results (41%). The recent outbreak of hemolytic uremic syndrome (HUS) associated with serotoxin E. Coli in Germany highlights the importance of having well-established AKI patient pathways to cope with significant outbreaks of AKI associated with food poisoning (74).

Cultural and political differences often impact on the incidence and management of AKI. Thus, policies on abortion and obstetric complications have a clear impact on the incidence of septic AKI or pre-eclamptic complications in pregnant women with poor prenatal care in both LMI and HI countries.(8, 75–77) In LMI countries, cultural barriers often impair seeking treatment of AKI, and patients prefer the help of traditional healers.(77, 78) Practical geographical and transportation barriers impair the early management of AKI and emphasize the need of early prevention measures. Gender, age and income discrimination impact the outcome of AKI(8). Thus, being a female child is a risk factor for worse AKI survival in Africa and India, and being poor and Black worsens the survival of disease in Africa and in America(8, 59, 79–83).

It must not be forgotten that although the majority of cases of AKI in HI countries result from sepsis and shock, a significant proportion of cases still develop AKI due to inappropriate medications or rarer causes such as vasculitis and obstruction that require prompt referral to nephrologists or urologists. Delays in recognizing AKI in these specific settings will potentially lead to irreversible injury. This reinforces the need to provide prompt and appropriate therapy to patients developing AKI wherever it is diagnosed. In many cases, radiology services for diagnostic ultrasound or interventional procedures are not guaranteed 24 hours, seven days a week. Hospitals need to consider how to provide such specialized services when not available on-site.

e. Healthcare workers are not well informed about the disease and its consequences

AKI is ubiquitous; given the myriad of factors contributing to its development, it is essential that healthcare workers and the public be aware of the risk factors for AKI and the key concepts in prevention and management. For instance, c-AKI may result from the use of non-steroidal drugs to control pain after a dental procedure in a patient with underlying CKD, if patient and prescriber are unaware of the risks. Similarly, although public awareness of CKD has improved considerably with concerted educational efforts across the world, emphasis has been on controlling hypertension and diabetes as potential causes, without much discussion on preventing AKI as a potential modifiable risk factor. Often, the earliest reversible phases of AKI may be missed because of lack of awareness.

Who is the target audience?

Given the relative paucity of nephrologists worldwide in relation to the prevalence of AKI (approximately 40,000 nephrologist worldwide for 7 billion population) only a fraction of patients who get AKI are seen by nephrologists, and in most instances a range of other healthcare professionals provide initial management. In the UK, only 22 to 31% of AKI patients were referred to nephrologists (71, 84), with a bias against referring older and more comorbid patients (84). Additionally, in LMI countries availability for specialty care may be further limited e.g. in India there are approximately 1200 nephrologists to care for a 1.2 billion population. As AKI will most commonly initially present to non-nephrologists, it is essential to identify other healthcare professionals who can make a significant difference to the prevention, detection and management of AKI. First and foremost, physicians in primary care and specialists are essential targets as they are already knowledgeable about kidney disease but may not be as familiar with the recent advances in AKI. Providing them with the evidence that small changes in renal function contribute to often severely adverse outcomes, and updating their knowledge for risk assessment, prevention, diagnosis and management, will be key. Professionals who directly care for patients (e.g. dentists, chiropractors) will similarly need to be engaged, as they are very likely to encounter patients and prescribe potentially nephrotoxic medications.

Allied health professionals delivering patient care are a second major group that needs to be involved, in the community as well as in the hospital. Nursing plays a key role as an integral part of the patient care team. In this sense, care may be quite different based on available local resources. In HI countries, nurses play a central role in the care of hospitalized patients where standards of care are well established. Credentialing is required and ongoing educational programs are mandated to maintain nursing competence. In contrast, in LMI countries there is wider variation in the level of nursing care. Care is often provided in small private clinics where standards for nursing care may be highly variable and educational activities may not be as well defined.

In LMI countries, the role of allied health personnel in rural environments cannot be overemphasized. In those regions, where physicians are generally unavailable, most of the initial preventive strategies can and should be implemented by nurses and allied health professionals under nursing supervision. Many of those initiatives have to do with basic sanitation and the application of well-defined treatment algorithms (use of bed nets, rehydration in cholera), which will need to be applied by well-trained primary health care providers with basic levels of education, such as members of the community, students, and housewives. Educators and teachers have a crucial role, and such collaboration is frequently the most effective way to break down cultural and religious barriers to effective prevention and treatment of AKI(8).

Laboratory personnel, clinical biochemists, pharmacists, and dieticians will also play important roles. Clinical biochemists will be essential in developing potential electronic alert systems for patients who are identified as having rising serum creatinine and also for the future implementation of new biomarkers (85–87). Thorough monitoring of drug prescriptions, whether paper-based or electronically delivered, and close pharmacist involvement will be crucial. Given the high prevalence of medication-induced AKI, pharmacists have a central role in reviewing medications and advising on dosing for patients with CKD. Similarly, nutritional management is also extremely important in patients with AKI, for whom it is necessary to identify appropriate nutritional support.

Professional societies and organizations able to disseminate information effectively to their membership are a key component of AKI awareness initiatives. In this sense, the involvement of professional organizations such as the International Society of Nephrology (ISN) and the American Society of Nephrology (ASN), fostering AKI research and education agendas, plays a critical role. The advisory commissions of each organization on AKI are already generating documents and initiatives to address the problem in joint fashion. Networks such as the Acute Kidney Injury Network (AKIN), the Acute Dialysis Quality Initiative (ADQI) and Kidney Disease: Improving Global Outcomes (KDIGO) can be used to engage other societies and expand the reach to other specialists. The National Kidney Foundation (NKF) and the International Federation of Kidney Foundations (IFKF) will be important grass-roots organizations to promote these initiatives. Reaching out and collaborating with nursing and pharmacy professionals will allow widespread development and implementation of these activities.

Funding agencies are an important target: resources are required to create education tool kits and to support ongoing and future research endeavors.

Current models of increased awareness and intervention in underserved areas, joining the efforts of international private foundations and local resources, have demonstrated excellent results (88). Similar models must be developed to deal with AKI in LMI regions of the world, where the management of large problems (such as malaria) will necessarily have a strong impact on its renal complications.

Industry can play an important role in these initiatives by leveraging their distribution networks and sales force to disseminate information. New drugs to prevent and treat AKI and newer technologies for renal replacement therapy can be developed via collaborative multidisciplinary efforts. Newer diagnostic tools will permit earlier diagnosis of AKI, at stages where early intervention permits better patient outcomes.

If we are to make a significant and long-lasting difference to the care of patients at risk of or who develop AKI, there must be engagement with those who hold “the purse strings”. This will include hospital managers at the local level; health administrators and politicians at the national level; and members of international organizations such as the WHO and the United Nations (UN). To achieve this goal, it will be crucial to accrue more data on the epidemiology of AKI and its outcomes, not only in HI countries but also in LMI countries. Health administrators and politicians are perennially plagued by conflicting priorities and budget constraints; therefore, raising the awareness of the problem and achieving data on the quantitative impact of AKI is crucial to achieve these goals.

Fundamental to leveraging support across all these organizations will be patients and their families. The patients’ voice must be heard and their stories relayed, as this is what makes the problem real and tangible. Politicians will respond to the problem only if they think it is sufficiently important, or if there is a groundswell of support for its solution and convergence of goals. Patient-supported initiatives can be implemented via regional or international societies such as the National Kidney Foundation, or the International Federation of Kidney Foundations.

How do we raise the awareness of acute kidney injury?

The multiple and very diverse stakeholders on the management of AKI can be likened to the story of The Elephant in the Village of the Blind of the Indian subcontinent tradition, which illustrates the need for communication and respect for different perspectives when overall knowledge is difficult to achieve all at once. Thus, it is necessary to design a common framework that is anchored on evidence, and that builds on a rapidly expanding wealth of knowledge. The current conceptual framework for AKI recognizes that the disease is a process that evolves from early injury through severe damage, resulting in kidney failure and the need for renal replacement therapy. The natural course can vary from complete renal recovery to dialysis dependency or death. Individuals transition from one state to another during the course of the disease (Fig 3). This conceptual framework also recognizes that AKI can occur in individuals who have normal kidney function or have pre-existing kidney damage, thus allowing risk assessment. Based on this conceptual framework, we propose a strategy for raising awareness that emphasizes 5 areas of focus; Risk assessment, Recognition, Response, Renal support and Rehabilitation (Table 3). Each of these areas has specific components that can be adapted to develop an educational strategy and to target specific stakeholders, with an appropriate emphasis in each particular domain. While physicians and nursing personnel would need to be aware of the overall concept, risk assessment and early recognition could be emphasized for allied health professionals.

Fig 3

Conceptual framework and targeted approach for raising awareness of AKI (modified from ref (119)

Table 3

5R’s strategy for educating care givers on AKI adapted from NHS

Category	Component	Areas of Focus
Risk assessment
	Susceptibility	Genetic, Clinical risk scores
	Surveillance	E-Alerts, Drug dosing modifications
	Primary prevention	High risk patients and situations e.g. contrast exposure
Recognition
	Diagnosis	Functional changes (urine output), biomarkers
	Staging	AKIN, KDIGO, Duration of AKI
Response
	Reversible factors	Hydration, Hemodynamics, Relieve obstruction remove nephrotoxic medications
	Avoid nephrotoxins	Drug dose adjustments
	Referral	Nephrology consultation in high risk patients and at recognition
	Therapy	Emerging molecules targeting different pathways
Renal support
	Dialytic modalities,	Dosing, duration, timing of initiation and withdrawal
Rehabilitation
	Follow–Up	Team approach (primary care, specialist, nursing, social worker, patient family)
	Recovery	Targeted interventions e.g. hypertension management
	Functional assessment	Quality of Life

Based on the principles described above, we recommend a multipronged strategy (Table 4).

Table 4

A global agenda to raise awareness and improve patient care

Category	Components
Education - The five R’s
	Risk assessment
	Recognition
	Response
	Renal Support
	Rehabilitation
Research Agenda
	Epidemiological studies (outcomes, comparative effectiveness)
	Prevention studies
	Treatment studies
	Audits and Quality improvement
Funding strategy
	Governmental
	Non-Government organization
	International organizations- Leverage of ongoing worldwide strategies
Development of a tool kit for AKI
	Essential toolkit for recognition and management of AKI
	Emphasis on early recognition and management
	Utilize KDIGO guidelines on diagnosis and management
	Identify knowledge gaps and educate
	Appropriate to each region
	Community vs. hospital acquired AKI
	Culturally sensitive
	Avoidance of the problems of discrimination by income, gender, religion
	Appropriate for the resources available

First, it is essential to improve education on AKI at both undergraduate and postgraduate levels for all healthcare professionals, and to emphasize the importance of identifying patients at risk of AKI. The Academy of Royal Medical Colleges has published a core competency for AKI (89). This document provides a pragmatic approach relevant to each specific healthcare professional. It defines the knowledge, skills and behaviors required for safe and effective patient care along the Chain of Response as described by National Institute of Health and Clinical Excellence (NICE) (90). The Chain of Response reflects escalating levels of intervention in the care of an acute patient with input from staff with a variety of different backgrounds and skills. The health care team must have the competencies to record patient information and vital signs recognize abnormal values and Institute intervention at level appropriate to the patient’s clinical condition. Five levels of competency are recognized which are: Recorder, Recognizer, and Primary, Secondary and Tertiary Responder. It is hoped that the implementation of the AKI Core Competencies framework will assist in improving the care that patients with AKI receive.

Second, physicians should be provided specific guidance for evaluating and managing patients with AKI based on the 5R approach. The recently published AKI Clinical Practice Guidelines in 2012 from Kidney Disease: Improving Global Outcomes (KDIGO) has provided a strong platform for this purpose (91). This international guideline has harmonized the definitions previously proposed by the by the Acute Dialysis Quality Initiative (RIFLE) and the Acute Kidney Injury Network (92–94) and provides guidelines for prevention, assessment and management of AKI that are designed to be applicable globally. These guidelines provide an opportunity to raise the awareness of AKI around a clearly characterized disease condition that has previously in poorly defined. We propose utilizing these guidelines as a common component to educate stakeholders in raising awareness of AKI.

Third, hospital administrators and quality control personnel should be made aware of the evidence for including AKI as a core measure of general medical care and as a key factor determining outcomes. Hospitals should be encouraged to adopt audit measures around the care of patients that develop AKI as proposed by NCEPOD and other guideline bodies (71). Episodes of avoidable AKI should be used as a benchmark for the care of acutely ill patients. This will provide an incentive to improve patient safety and reduce the number of episodes of AKI that are potentially avoidable. Specific AKI guidelines should be developed for community-based healthcare professionals and systems put in place to help detect patients developing AKI at an earlier stage in the disease process. The utilization of e-alerts in electronic medical records should be encouraged to provide real time feedback to care givers for recognizing high risk patients, early diagnosis and timely intervention including referral and follow up.

Fourthly, an AKI toolkit should be developed to be used globally including a checklist of simple measures that can be instituted to reduce the risk of AKI and how to manage it if it occurs. These checklists may be specific to individual groups of patients in a variety of different settings to take into account contrasting causes of AKI that occur in the developed and the developing world. For certain groups of healthcare professionals it will be essential to provide clear referral criteria. Patient education needs to be improved with the provision of information on websites. Patients who have suffered an episode of AKI should be provided with information regarding the causes of the episode and the need for long-term follow-up.

Finally, there are opportunities to raise the awareness of AKI as a complication of other disease processes in the developing world and mobilize local resources to manage it at an early phase. The World Health Organization (WHO)/United Nations UNDP Millennium Project and the Campaign to Eradicate Malaria deal with the main root causes of community disease in developing countries (95–97). The Millennium Project attempts to eradicate extreme poverty and hunger, achieve universal primary education, promote gender equality and empower women, improve maternal health and reduce child mortality, combat HIV/AIDS, malaria and other diseases, ensure environmental sustainability and promote a global partnership for development. All these issues are intimately related to AKI in developing countries. Malaria is a main cause of AKI in Sub-Saharan Africa and South-East Asia, obstetrical complications constitute a large cause of fatal AKI, and hemolytic uremic syndrome causes AKI frequently resulting in ESRD in children(8, 98). Furthermore, it is important to recognize that in many cases, gender and social/economical discrimination is at the cause root of the problem. International and regional initiatives must make all efforts to address that important aspect of the problem. The recognition and management of AKI in developing countries should be leveraged on such international initiatives, with the development of databases to demonstrate the scale of the problem.

Conclusions

Acute kidney injury is a common worldwide problem, which imposes a so far unrecognized global burden. It is necessary to raise awareness of AKI and to equip caregivers and patients with knowledge and tools to identify and adequately manage patients at risk. Efforts to address the problem are hindered by a fractured and sometimes ineffective approach. To a large extent, this is due to late recognition, inappropriate application of new knowledge, and lack of coordination among caregivers and institutions. In many cases, implementation of simple, actionable measures may go a long way to decrease incidence, severity, and death. Positive change will be dependent on progress at all levels, from the health care worker in the African village to the prominent politician making public health policy. Such an agenda must contain specific recommendations and be adaptable to different contexts:

At the practical level, we propose to develop a toolkit containing simple, immediately applicable measures to ensure early detection and fast action whenever AKI develops.

At the policy level, we propose a series of efforts destined to implement coordinated actions among government and non-government agencies, societies and institutions. Such initiatives should ensure continuity and coordination of such efforts, in the context of larger programs for the management of closely related conditions. For example, there is urgent need to address AKI in the context of ongoing programs combating increasingly prevalent, severe malaria in LMI regions of the world. Raising the awareness of this silent killer will be achieved only by coordinated efforts, involving the global nephrology community and the multiple components of the healthcare system in each region of the world.