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Renal injury in the elderly: Diagnosis, biomarkers and prevention

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Acute kidney injury (AKI) in the elderly patient is a common iatrogenic complication of major surgery that impacts morbidity, mortality and resource use. Several renal functional and structural changes have been described, including a substantially decreased nephron mass. Loss of renal function defines AKI and is classified by the RIFLE (R: renal risk, I: injury, F: failure, L: Loss and E: End-stage renal disease) criteria; however, it frequently occurs many hours to several days after the injury to the kidney. Therefore, novel biomarkers indicating tubulo-interstitial damage are needed for early AKI diagnosis. The limitations of serum creatinine are much more pronounced in the elderly, including its dependence on muscle mass and the presence of multiple drug use and co-morbidities. Although it is conceivable that earlier AKI diagnosis and application of classical preventive measurements, including postponement of surgery or preference of medical treatment, optimisation of haemodynamics, euvolaemia, aggressive avoidance of nephrotoxic antibiotics or analgesics may translate into better patient outcomes, much more data are needed in this specific cohort.

Section snippets

Current definitions of AKI

AKI, previously referred to as acute renal failure (ARF), is defined as abrupt, persisting and theoretically reversible worsening or loss of renal function associated with a decline in diuresis and increase in serum creatinine and urea. Until recently, more than 35 different interpretations of the AKI definition were described in the literature. In response to the lack of a standard definition and classification system for AKI and to achieve comparability of study findings and to establish

AKI: a serious and epidemic postoperative complication

AKI is a major clinical issue affecting up to 30% of hospitalised patients,7, 8 with persistently high hospital re-admission and mortality rates of up to 60% when renal replacement therapy (RRT) is required.11, 12 It is increasingly acknowledged that AKI per se, within hours to a few days, may incite injurious changes in distant organs, such as the lungs, with alterations of vascular permeability and pulmonary oedema and the cerebrum with cell apoptosis.13, *14 Increasing severity and duration

Current understanding of perioperative renal injury particularly in the elderly

In older age, a reduction in serum-creatinine generation is observed due to an age-related decline in muscle mass. A reduction in the glomerular capillary plasma flow rate and the glomerular capillary ultrafiltration coefficient leads to a glomerular filtration rate (GFR) decrease. Functional changes further comprise increased glomerular capillary pressure,41 in addition to a reduced autoregulatory capacity and decreasing functional reserve.42 Ageing is associated with altered activity and

Diagnosis of preoperative renal-function impairment

In current clinical practice, the diagnosis of AKI is based on either an abrupt change in serum creatinine or a decrease in urine output. The concentration of serum creatinine is affected by factors that influence its generation (e.g., age, gender, muscle mass and diet), GFR (e.g., hypertension) and tubular secretion (e.g., CKD or AKI). The clinical usefulness of serum creatinine for timely diagnose and assessment of the severity of AKI is limited, as serum creatinine only rises 24–48 h after

Newer methods to detect tubular injury: neutrophil gelatinase-associated lipocalin (NGAL) and fatty acid-binding protein (FABP)

Markers of reduced renal function (creatinine and diuresis) increase 24–72 h after the injurious event to the kidney20, *64, 65 and do not indicate either the nature or the site of the kidney injury.66 Therefore, novel biomarkers for AKI are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) and fatty acid-binding proteins (FABPs) have shown promise for early AKI diagnosis and outcome prediction.20, *64, 65, 67

NGAL is one of the most intensively investigated novel renal

Methods to reduce perioperative renal injury

Despite growing insight in the pathophysiology of AKI, there is still no effective prevention which has been established in current clinical practice. Barriers to successful therapies or preventive measurements are multifactorial and include the complexity of AKI in humans, the influence of patients’ comorbidities, pathological interactions between the kidney and distant organs and the dose and, perhaps foremost, the timing of potentially nephroprotective intervention. Avoiding kidney-damaging

Research agenda

The relationship between AKI and older age is still not completely understood and requires future studies addressing the many risk factors of elderly patients compared with younger adults. A vast number of pharmacological interventions have been tested in animals and in clinical studies of AKI. Many substances have shown preventive abilities in ‘pilot’ animal studies; however, most of them did not reach the level of larger clinical trials, or if they did, they did not achieve convincing

Summary

Elderly patients with impaired renal function are at the highest risk of postoperative AKI.

Early diagnosis is especially difficult in these patients, given the known imperfections of the renal functional markers currently used. The association of AKI with ageing needs further scientific attention, as this group is overproportionally increasing. Specifically, improved mechanistic understanding and data from clinical studies investigating the predictive value of novel renal biomarkers and the

Conflict of interest statement

Michael Haase has received lecture fees from Abbott Diagnostics and Biosite/Alere Inc. Both companies are involved in the development of NGAL assays to be applied in clinical practice.

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