Efficacy and Safety of Folic Acid on Acute Kidney Injury in Adults: A Feasibility Study

1. Background Information

Acute Kidney Injury (AKI) is a worldwide health issue affecting over 13 million people each year with a significant hospital mortality of 20-40%. It is characterized by an abrupt loss of kidney function and is associated with multiple long-term sequelae including chronic kidney disease (CKD) and reliance on renal replacement therapy (RRT). Patients with AKI place a substantial financial burden on healthcare resources. In England, the annual cost of AKI is estimated at £1 billion, consuming 1% of the National Health Service (NHS) budget; in the United States (US), inpatient AKI costs $5 to $24 billion per year. However, there are few therapies to moderate the risk and long-term sequelae of AKI. Timely, efficient treatment of AKI will benefit both patients and health care systems.

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report on hospital mortality primarily due to AKI judges that good clinical practice occurred in only 50% cases, 33% patients were under insufficient investigations, 29% patients received inadequate clinical management, and complications were badly handled in over 50% cases. Progression of the admission stage of AKI to a higher stage was reported to be associated with a 39% inpatient mortality compared with a 21% mortality in those who did not progress. If the AKI stage could be prevented to deteriorate to a higher stage, the mortality rate of AKI patients during hospital stay would drop almost half.

1.1 Epidemiology, Etiology and Pathophysiology of AKI AKI is a common problem in all countries of the world, and its prevalence has been reported to range from <1% to 66%. Apart from population differences, different classification systems used in epidemiological studies also conduced to the varied estimation of AKI incidence. Little epidemiological data is available for AKI in Hong Kong (HK). Szeto reported a crude hospital admission of AKI of 12% amongst 140,000 hospital admissions observed in a tertiary referral center of HK. The crude mortality rate of AKI in patients attending an emergency department (ED) in HK is 25%.

AKI is a multifactorial syndrome. The causes of AKI can be classified into three categories: prerenal, intrinsic renal and postrenal. Prerenal causes involve reduced renal perfusion due to medication, sepsis or volume depletion (e.g., diuretic overuse and diarrhea). Intrinsic renal causes typically result from infections, prolonged hypotension, nephrotoxic drugs or pre-existing renal impairment (e.g., glomerulonephritis and vasculitis). Postrenal AKI is due to obstruction of urinary flow, especially common in elderly men. Sepsis, infection and use of nephrotoxic drugs are common causes of AKI overall, leading to reduced renal blood flow. Sepsis is the most common contributor to AKI (25%). In intensive care unit (ICU) settings, AKI was found to occur in more than half of patients, and half of all patients with AKI in ICU have sepsis. Drug induced AKI occurs in 20% of hospital cases, and those drugs include non-steroidal anti-inflammatory drugs (NSAIDs), metformin, aminoglycosides, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARBs), diuretics and iodine containing X-ray contrast. In low-to-middle-income settings, environmental factors such as endemic infections (e.g., malaria and dengue fever) and contaminated water are also common factors to induce AKI.