الفهرس 
Chapter (1): Acute Kidney InjuryOnly 14 pages are availabe for public view
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Abstract
AKI is a major clinical problem in hospitalized patients. Effective treatment and early diagnosis of this syndrome are not currently available. NGAL is one of the most intensively investigated novel renal biomarkers with promising data from animal experiments and clinical studies comprising the populations at risk for AKI. Within minutes to a few hours after a renal insult, NGAL is induced in and released from the injured distal nephron. So, it appears to fulfill many characteristics of an appropriate ’real-time’ biomarker for AKI detection.
Studies of large adult cohorts have revealed that contrast-induced AKI is the third most common cause of hospital-acquired AKI, accounting for approximately 11% of cases.
Approximately half of these cases are in subjects undergoing cardiac catheterization and angiography, and approximately a third follow computed tomography.
A variety of definitions of CIN are present in the literature. They most commonly consist of either a relative (25–100%) or absolute (0.3–1.0 mg/dL) increase in serum creatinine above baseline levels. It has been suggested that a change of 0.3 mg/dL is not statistically significant in many laboratories. The most commonly used definition of CIN, therefore, is either a relative increase in serum creatinine from baseline value of 25% or an absolute increase of 0.5 mg/dL within 48 to 72 hours after contrast exposure. Additionally, the creatinine elevation must not be attributable to other causes and must persist for 2 to 5 days. Treatment of CIN begins with identification of the injury and is similar for other causes of acute renal failure. Patients should be monitored by a nephrologist in an inpatient setting. Management typically involves careful monitoring of electrolytes, adjusting nutrition, and strict monitoring of body weight and fluid balance. Metabolic disturbances such as hyperphosphatemia can be managed with phosphate binders (calcium carbonate); hyperkalemia with dietary restriction of potassium, potassium binding resins, or insulin and dextrose infusion; and metabolic acidosis may require oral sodium bicarbonate. In rare cases, patients may require temporary or permanent dialysis.
The early diagnosis of AKI currently depends on detection of reduced kidney function by the rise in serum creatinine concentration, which is a delayed and unreliable measure in the acute setting. In general, there are several non-renal factors influencing the serum creatinine concentration such as body weight, muscle mass, race, age, gender, total body volume, drugs, muscle metabolism and protein intake. In the face of AKI, serum creatinine is an even poorer reflection of kidney function, because the subjects are not in steady state and serum creatinine therefore lags far behind renal injury by 24-48 hours. Furthermore, significant chronic kidney disease can exist with minimal or no change in creatinine because of renal reserve and enhanced tubular secretion of creatinine.
Several investigators have examined the role of NGAL as a predictive biomarker of nephrotoxicity following contrast administration.
Neutrophil gelatinase-associated lipocalin (NGAL), small inflammatory cytokine, is a 25-kDa protein belonging to the lipocalin super family .It was initially found in activated neutrophils, however, many other cells, like kidney tubular cells, may produce NGAL in response to various insults. In subsequent studies, urine NGAL has been found to be an early predictor for acute kidney injury (AKI). Newer devices for early bedside detection of NGAL are now available. Since serum creatinine is known to be an inadequate and late marker of acute kidney injury (AKI), NGAL might soon emerge as an early marker for AKI. Recent evidence also suggests its role as a biomarker in a variety of other renal and non-renal conditions.
Recent studies have demonstrated the utility of early NGAL measurements for predicting clinical outcomes of AKI.
The 2-h urine NGAL levels were highly correlated with duration and severity of AKI, length of hospital stay, dialysis requirement and death.
This increase in NGAL preceded the increase in serum creatinine by 24–48 h. Similar increases in NGAL levels were observed in other clinical settings, including contrast-induced AKI, sepsis-associated AKI and AKI following kidney transplantation.
Our study aims to evaluate urinary NGAL as an early marker of contrast induced acute kidney injury after cardiac catheterization and as a predictor of clinical outcomes.
Our study was conducted on 40 patients with different relating diseases were selected from Ain-Shams University Hospitals compared with 40 control individuals. Informed consent will be obtained from all participants. The study subjects are arranged in two groups as follows:
A) Group 1: includes 40 patients with symptoms suggestive of coronary heart disease undergoing diagnostic cardiac catheterization.
B) Group 2: includes 40 healthy control individuals. They are matched with the group 1 patients for age and gender.
And the patients will be excluded if they had any of the following:
1- Preexisting renal insufficiency
2-Administration of the following drugs within 48 hours prior to or after contrast: Aminoglycosides - Amphotericin B – Nephrotoxic chemotherapeutic agents (platinum-based agents, methotrexate,ifosfamide)-Non-steroidal anti-inflammatory drugs (NSAIDs)-ACE inhibitors.
3-A documented episode of hypotension (MAP<60) within 48 hours prior to or after contrast administration
4-Sepsis
5-After renal transplantation
6-Peripheral vascular disease
7- Elderly >65 years
All the Individuals included in the study were subjected to:
I) Full medical history and examination
II) Laboratory Measurements:
i) CBC
ii) BUN, Na+, K+, calcium, base line phosphate.
iii) Urine analysis, protein creatinine ratio.
iv) Serum creatinine: immediately before and daily for 3 successive days after the procedure.
v) NGAL will be measured in the urine (immediately before, 2 hours and 4 hours after the contrast administration) using the ELISA commercially available kit, according to the manufacturer’s instructions. Its levels will be expressed as ng/ml.
III) Estimated creatinine clearance: by Cockcroft-Gault formula immediately before and daily for 3 successive days after the procedure.
IV) ECG , Echocardiography and Pelvi-abdominal ultrasound.
V) Results were statistically analyzed for correlation between the study parameters in the different groups.
Our study included forty patients diagnosed with with different relating diseases and compared them with forty normal individuals.
Our study showed that of 40 patients had coronary catheterization 9 patients developed AKI and 31 patients didn’t develop AKI.
All the 9 patients who developed AKI had elevated u-NGAL after 2 hours with more elevations after 4 hours, This elevation was detectable at an earlier time (after 2 hours) with respect to serum creatinine (measured after day 1 post cardiac catheter).
Also there is statistically significant difference between u-NGAL after 2 hours between the patients who developed AKI and the patients who didn’t develop AKI (P = 0.000).
Our study showed statistically significant correlation between u-NGAL after 2 hours and both Hb level and MAP.
Our study showed statistically significant difference between AKI patients and non-AKI patients regarding age, MAP.
Our study showed significant correlation between u-NGAL and Ejection fraction in AKI patients.
Our study showed that there is no correlation between u-NGAL after 2 hours and the amount of the intravenous contrast.
Our study showed that the cut off value of serum creatinine after 1 day post catherterization was ≥ 1.15 mg/dl while that of u-NGAL after 4 hours was ≥ 203.5 ng/ml, also shows that the sensitivity and specificity of s.creatinine was 66.7% and 74.2% respectively with a positive predictive value 42.9% and a negative predictive value 88.5% while both sensitivity and specificity of u-NGAL was 100% and both PPV and NPV 100%.