This is the first study to prospectively determine the incidence, aetiology, severity and outcomes of com-AKI in an unselected patient cohort in sub-Sahara Africa (SSA). AKI is common, serious and treatable in the developed world. Estimates of incidence based on developed world data suggest an undiagnosed epidemic in less developed countries, and reports of deficiencies in care raise the concept that young lives are being unnecessarily lost [
2]. However, particularly in SSA, data to corroborate these hypotheses are sparse. We therefore undertook this real-life, pragmatic study to understand the current epidemiology of AKI in Malawi.
Key results
We have demonstrated that com-AKI is both common and severe in medical admissions in Malawi. 17 · 2% of patients had established AKI on admission over the 3-month data collection period; 10 · 5% of general medical admissions had stage 3 AKI. Patients were young, from an economically viable section of the population, and HIV prevalence was high, particularly in patients with AKI.
The predominant aetiological category of AKI was Sepsis/hypoperfusion, encompassing conditions that are amenable to early identification and effective treatments routinely available across much of SSA. The most common infections were GE, acute TB, and falciparum malaria.
Hospital outcomes in patients with AKI were poor and these worsened with AKI stage. Hospital mortality was 44 · 4% in patients with AKI overall and almost half of patients with stage 3 AKI died. The majority of patients with AKI who survived left hospital with persistent and severe renal injury, particularly patients with stage 3 AKI.
Interpretation
AKI affects 1 in 5 inpatients in developed settings [
2], but the majority is mild and hospital-acquired [
10]. Com-AKI is less common, with incidence estimates of 4 · 3% in the UK [
11], whereas in SSA com-AKI predominates [
6,
7,
12].
Rates of com-AKI in this study were more than quadruple what is seen in developed settings (Additional file
2 Table S2). Moreover the kidney injury was predominantly severe (stage 3 in 60 · 5%) as opposed to the mild pattern of AKI seen in developed settings (stage 1 in 80%) [
2]. This burden and severity of AKI is likely multifactorial in nature. Delayed referral to hospital due to limited awareness of kidney injury and the resources to detect it in health centres and district hospitals [
13,
14], logistical and financial challenges transporting patients to hospital, an admission cohort primed for AKI in terms of co-morbidity (high HIV prevalence), community nephrotoxin use, and severe acute presenting illness all contribute.
Data from SSA with which to compare these incidence and severity estimates is limited [
7]. The rate of AKI in the two previous prospective studies in medical cohorts in SSA were similar to ours: 16% in 387 patients presenting with sepsis in urban Uganda and 15 · 2% in 151 medical inpatients in rural Ethiopia [
15,
16]. The majority of AKI was severe in both, with 46-48% of AKI stage 3.
The age of patients with AKI in our study is similar to findings from other studies from SSA, where mean ages of patients with AKI have ranged from 28 · 7–44 · 4 years [
7]. Patients are around 20 years younger than AKI cohorts in developed settings [
10].
The prevalence rate of HIV is approximately 10% in 15–49 year-olds in the general population in Malawi [
17]. Patients with HIV were disproportionately represented in the medical admission cohort as a whole, but particularly so if presenting with AKI. 58 · 8% of patients with AKI had HIV; similar rates have been recently reported in other SSA AKI cohorts [
15]. HIV may increase the risk of AKI through direct renal injury, through ART nephrotoxicity, and through susceptibility to acute infective illness. Routine measurement of renal function pre or post initiation of TDF ART (first-line in adults) is not recommended in Malawi despite the potential nephrotoxic effects of TDF [
18], which may delay diagnosis of AKI in this cohort. Importantly, AKI in Malawi is occurring in patients that are young with limited comorbidity outside HIV. Such patients are often responsible for the social and financial stability of extended families and thereby the impact of AKI extends beyond the individual.
Medical causes of AKI predominate in SSA and, similar to previous data, AKI in this study was largely due to infective illnesses [
6,
7]. Microbiological causes of GE were rarely identified, as faecal microbiology is not routinely undertaken. Typhoid and non-typhoid salmonella bacteraemia did, in some cases, present with diarrhoeal illness. Despite this study occurring outside malaria season, it remained a common cause of AKI. Acute decompensated heart failure was the commonest cause of renal hypoperfusion outside infective illness, and this was particularly prevalent in the non-HIV AKI group.
In addition to infection, nephrotoxins (in particular NSAIDs) were the other main contributors to AKI. The crucial significance of these causes and contributors is that it suggests the majority of this AKI is preventable and treatable by relatively simple means such as early fluid resuscitation, treatment of the underlying condition, and avoidance of nephrotoxic drugs. These are universally achievable interventions that don’t require sophisticated diagnostic techniques or expensive treatments. Despite this, deficiencies in resources and skills to manage even these basic aspects of AKI across SSA persist [
13,
14].
The worldwide pooled mortality from AKI is 21% [
2] and this rises to 32% in studies undertaken in SSA [
7]. In-hospital mortality in this study was almost double worldwide estimates. Mortality increased with AKI stage, 49 · 5% in stage 3 AKI, a closer reflection of the worldwide mortality of 42% seen at this stage of disease. In part, the high overall mortality reflects the severity of AKI encountered in this setting but may also relate to lack of resources to manage underlying conditions, in particular severe sepsis.
Some form of renal recovery occurred in the majority of adult survivors although this recovery was largely incomplete. This may represent patients with resolving AKI, undiagnosed or
de novo CKD, and highlights the need for follow up and assessment of longer-term outcomes post AKI, especially in this part of the world. Recurrent, severe AKI in SSA may contribute to the growing burden of CKD in this setting [
19].
Taken together, the mortality and persistent renal injury seen in this study are concerning. Moreover, the outcomes in this study, whilst poor, were achieved in a clinical research environment in which all patients had immediate assessment of renal function, management by a nephrologist, and free access to renal replacement therapy (RRT). This is not the case during routine clinical practice across SSA. The poor outcomes therefore represent, in our view, a “best-case scenario” for SSA and highlight the urgency with which we as a global healthcare community must improve AKI detection and management in resource poor settings worldwide.
Strengths and limitations
Most studies investigating AKI in SSA are retrospective case series, often focusing on patients that present requiring RRT or on a single cause of AKI (Additional file
3 Table S3). There has been no previous prospective study in SSA that we are aware of in which an unselected medical admission cohort has been screened for com-AKI. This is important as laboratory assessment of renal function is not routine in SSA and therefore only through this approach can the frequency, severity and outcomes of com-AKI be accurately determined. Our study is the first to do this in SSA, screening 892 patients, and the 153 patients with com-AKI identified represents the largest prospective AKI cohort reported from this region of the world.
This was a single centre study conducted during a single season of the year in medical admissions only. This study focused on community acquired AKI and the development of AKI in hospital was not assessed. Lack of known baseline creatinines in almost all patients and practical challenges in collecting urine output data (e.g. lack of urine measuring jugs, lack of catheter bags with graduations to accurately measure urine volume) may have resulted in some patients with AKI being classified as AKD, underestimating the true incidence. Unresolvable technical problems with the creatinine analyser meant a second machine had to be used for part of the study and consequently no data is available to assess any assay variability between the different machines. It is unlikely this resulted in any significant misclassification of stage of AKI and whilst we recognise that this is a limitation of the study, the situation represents the real-life pragmatic challenges related to research conducted in this and similar settings. Resource restrictions meant supporting diagnostics were limited and causes of AKI were based largely on clinical assessment but this is reflective of standard clinical practice across much of SSA. Hospital outcome was captured in all patients, but longer follow up thereafter was not.
Our aim, and that of the International Society of Nephrology 0by25 Initiative, is to investigate AKI in low-income settings. Malawi ranks as one of the poorest countries in the world [
20] and therefore this study reflects AKI in a truly low-income setting. This study was undertaken in a centre which serves both urban and rural populations. Healthcare is provided free at the point of delivery and therefore the population represented in this study is not influenced by financial factors limiting access to care. We are sanguine about the fact that many other neighbouring healthcare systems levy a charge for even basic interventions including intravenous fluids and antibiotics. Thus, our study may not be generalisable to these settings, where outcomes from AKI may be even worse.