Factors associated with acute kidney injury recovery in a tertiary hospital in Ghana: a prospective study

Introduction Acute kidney injury (AKI) is a challenging problem in developing countries due to late presentation of its victims to health care facilities. Data on the pattern of AKI, its outcome and factors associated with its recovery is scanty in developing countries therefore impeding AKI management. Aim: to study AKI recovery rate and its associated factors. Methods An observational study conducted from September 2013 to June 2014 at Korle-Bu Teaching Hospital (KBTH). Participants were adults, admitted with AKI at KBTH. Kidney Disease: Improving Global Outcomes (KDIGO) criteria was used to diagnose and stage AKI. Results Mean age (SD) of the participants was 41.9 (± 19.2) years. About a third of the patients (34.6%) were less than 29 years with 30-39 years and 40-60 years constituting 23.0% and 23.6% respectively. Females were in the majority (56.0%). AKI stages I, II and III accounted for 11.0%, 6.8% and 70.7% respectively. Majority, 82.2% of the patients recovered their kidney function. Stage III AKI was significantly associated with decreasing odds of recovery [OR = 0.4, 95%CI = 0.4-2.6, p = 0.002]. In addition, normal blood sodium was associated with recovery from AKI [OR, 95%CI = 2.3, (1.1-5.3), p = 0.043]. Almost half (45.5%) presented with fever whereas 32.5% and 22.5% presented with peripheral oedema and pulmonary oedema respectively. Conclusion The study demonstrated high kidney function recovery following AKI. Dominant clinical features were fever, peripheral and pulmonary oedema. Advanced stage was associated with poor recovery whereas normal serum sodium level improves kidney function recovery.


Introduction
AKI is an important risk factor for chronic kidney disease (CKD), rapid progression to end-stage renal disease (ESRD), development of cardiovascular events (stroke, myocardial infarction), disability, diminished quality of life, high cost of treatment and death [1,2].
According to Hoste & Schurgers , 2-3 cases of AKI are estimated per 1000 persons [3]. Nash et al. estimated that 7% of hospitalized patients at intensive care unit [4] develop AKI, often as a part of multiple organ dysfunctions [5,6]. AKI patients have nine-time risk of CKD development and two-time risk of premature death than patients without AKI [2]. In developing countries, like Ghana, AKI affects young individuals who are previously well and thus predisposing them to high morbidity, mortality and high cost [7,8].
AKI is reversible and treatment inexpensive if detected early and the underlying cause managed aggressively [9]. However, at Korle-Bu Teaching Hospital (KBTH) in Ghana, cases of AKI are often referred very late from district hospitals as medical emergencies requiring urgent renal replacement therapy. Patients are often unable to give the exact clinical picture of their illness and this sometimes make it difficult to differentiate AKI from CKD/ESRD. Sonographic evaluation by looking at the cortico-medullary differentiation (CMD) of the kidneys does not help in this differentiation either since poor CMD can be a feature of both AKI and CKD or ESRD. In such late presentations and referrals, recovery from AKI becomes a problem [10].
The prognosis of AKI depends hugely on the underlying aetiology.
Knowledge of the factors associated with renal recovery are important. In-depth knowledge of the recovery rate and its associated factors will help to guide decisions concerning treatment and prognosis. The overall aim of this study was to gain insight into the demographics, pattern and outcome of patients with AKI admitted to a tertiary hospital in Ghana. We hope to create awareness on AKI by educating the general public on the demographics, clinical presentations, factors associated with recovery of kidney function and its outcome. More importantly, the findings from this study will enable policy makers; both governmental and non-governmental to make decisions concerning prevention and factors that significantly affect recovery from AKI.

Methods
Study design and setting: this was an observational prospective study carried out at Korle-Bu Teaching Hospital (KBTH). KBTH is a tertiary referral centre located in the capital of Ghana, Accra. The hospital has a 1,600 bed capacity and twelve different departments.
Being the largest hospital in Ghana, it receives referrals from all other hospitals in the country. This study was conducted from September 2013 to June 2014.
Study population and subject recruitment: any patient who met the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI was eligible for recruitment. In accordance with this guideline, patients were deemed to have AKI if their calculated baseline serum creatinine increase by 26umol/l within 48 hours, an increase in serum creatinine by > 1.5 times the baseline value within 7 days and/or a fall in urine output of <0.5ml/kg/hour for more than 6 hours. Patients with a previous history of chronic kidney disease, patients with ultrasonography evidence of chronic kidney disease (i.e. shrunken kidneys), patients already on chronic haemodialysis therapy and/or patients aged less than 14 years were all excluded from the study. In all, 230 patients were recruited but 39 were lost to follow-up and were therefore excluded from analysis. One hundred and ninety one patients were therefore included in the analysis. Patients were contacted at or after 3 months (ninety days) following diagnosis for a repeat serum creatinine. Patients who had abnormal serum creatinine levels were referred for follow up as chronic kidney disease at the Renal Unit.  Those with normal blood sodium are 2.3 times more likely to recover from AKI than those with abnormal blood sodium.

Discussion
Incidence of AKI is on the rise in developing countries including  This high recovery rate correlates with the fact that most of the patients were young with identifiable and treatable causes (Table 1).
Furthermore, patients with more than 3months duration of illness or a previous history of chronic kidney disease or ultrasound evidence of shrunken kidneys were all excluded from the current study. If these patients had been included, the recovery rate might have gone down.
Our study found that most of the study participants were in the age ranges 30-39 and 40-60 years ( Moreover, in a systematic review, fifteen studies indicated that there was a significant association between young age and the occurrence of AKI [22]. This reiterates the observation that young patients are reported to be a predominant proportion of those presenting with AKI in developing countries and elderly patients reported to be more common in developed countries [22]. In this study, females dominated the AKI participants ( In assessing factors associated with recovery from acute kidney injury, the results showed that normal serum sodium concentration significantly increased the likelihood of kidney function recovery (  [28,29]. In this study however we did not find any significant association between leucocyte count and recovery from AKI (Table 3). Leucocyte count have been shown to vary significantly from one geographical location to another and therefore might have contributed to the inconsistencies between leucocyte count and AKI recovery. Fever, peripheral oedema and pulmonary oedema were the most common clinical features of the studied AKI patients ( Table 2).
These findings add to a growing literature regarding the importance of venous congestion manifested as peripheral oedema on renal outcomes [30]. Among a cohort of 12778 critically ill patients in the United States, the presence of AKI on admission was associated with a peripheral oedema [31].

Similar clinical presentations albeit slight variations were reported in a retrospective study conducted among AKI patients in a University
Hospital of Kinshasa, Congo in which fever accounted for 80.3% followed closely by jaundice (73.2%) [32]. Unsurprisingly, anaemia was recorded in more than one-fifth of the studied participants in this study (Table 1). In addition, pre-hypertension and hypertension were found in 45.0% and 24.7% among the participants in this study (Table 1). The relationship between AKI and BP elevation is unclear [33]. However, Survivors of AKI were more likely than those without AKI to have elevated BP defined as documented BP>140/90 mmHg in a retrospective cohort study done in Northern California [34]. Blood pressure is considered essential for organ perfusion in that maintaining the optimal blood pressure is an important aspect of preventing acute kidney injury (AKI), especially for vasopressor-dependent patients [34]. Non-availability of chemical analyzers in most hospitals meant that cases of AKI were only picked at peripheral hospital in advanced stage when fluid overload has set in. Patients are therefore likely to be referred to KBTH in advanced stage AKI (i.e. AKI stage III). Whereas some potential factors associated with AKI recovery have been adequately delineated in this study, we could not address partial recovery in participant who may have improved in AKI stage. Moreover, participants who apparently recovered completely from AKI may be prone to developing long-term complications of AKI and a longer follow-up is warranted in future studies.

Conclusion
The study demonstrates a considerably high recovery rate among the studied AKI participants. This was found to be due to the relatively young nature of AKI diseased patients. Most of the participants were in Stage III AKI. Significant factors found to be associated with recovery from AKI were serum sodium levels and Stage III AKI; whereas normal sodium levels increase odds of recovery, stage III AKI suggests a lesser chance of recovery. Dominant clinical features found in the participants were fever, peripheral and pulmonary oedema. In addition, anaemia and hypertension were important comorbidities found among the studied participants. Further studies which employ robust study design involving longer follow-ups with recruitment from peripheral health centres are warranted to fully understand the mechanism behind these associations.
What is known about this topic  Incidence of acute kidney injury is considerably high in Ghana and other under-resourced countries;  Acute Kidney Injury is a major risk factor of chronic kidney disease, morbidity and mortality;  Acute Kidney Injury is presented at later stages in Ghana which potentially affects recovery.

What this study adds
 The study reports high recovery rate among acute kidney injury patients at Korle-bu Teaching Hospital due probably to the young nature of such patients;  Normal blood sodium levels and stage III acute kidney injury affects recovery;  Fever, peripheral oedema and pulmonary oedema are major clinical features associated with acute kidney injury.

Competing interests
The authors declare no competing interest.  Table 1: socio-demographic, haematologic and biochemical characteristics of study participants