This document discusses biomarkers for the early diagnosis of acute kidney injury (AKI). It notes that current diagnostic criteria based on serum creatinine and urine output can lead to delayed diagnosis in intensive care unit patients. Emerging urine and plasma biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), cystatin C, and the combination of tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can provide earlier detection of AKI before functional changes occur. The combination of TIMP-
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Sudden impairment of kidney function occurring over a period of hours to days.
AKI is present in 7% of all hospitalized patients, and up to 30% of patients in ICU
The incidence is increasing at an alarming rate
That's why we need ideal biomarker to diagnose the AKI as early as possible and deliver better treatment to the patient.
Presentation on Alkaline Phosphatase Assay in serumra5398433
ALP is a laboratory test. Various diseases are diagnosed by determining the enzymatic activity of alkaline phosphatase enzyme. In this presentation you should completely learn about Alkaline phosphatase assay in serum.
Biochemical kidney function tests with their clinical applicationsrohini sane
An illustrative presentation on Biochemical kidney function tests with their clinical applications for medical ,dental, pharmacology and biotechnology student to facilitate easy-learning.
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Sudden impairment of kidney function occurring over a period of hours to days.
AKI is present in 7% of all hospitalized patients, and up to 30% of patients in ICU
The incidence is increasing at an alarming rate
That's why we need ideal biomarker to diagnose the AKI as early as possible and deliver better treatment to the patient.
Presentation on Alkaline Phosphatase Assay in serumra5398433
ALP is a laboratory test. Various diseases are diagnosed by determining the enzymatic activity of alkaline phosphatase enzyme. In this presentation you should completely learn about Alkaline phosphatase assay in serum.
Biochemical kidney function tests with their clinical applicationsrohini sane
An illustrative presentation on Biochemical kidney function tests with their clinical applications for medical ,dental, pharmacology and biotechnology student to facilitate easy-learning.
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Over the last decades, more than 35 different definitions have been used to describe acute kidney injury (AKI). Multiple definitions for AKI have obviously led to a great disparity in the reported incidence and mortality of AKI making it difficult or even impossible to compare the various published studies focusing on AKI. Therefore, it became crucial to establish a consensual and accurate definition of AKI that could desirably be used worldwide. Recent consensus criteria for AKI definition and classification [the Risk Injury Failure Loss of kidney function End-stage kidney disease (RIFLE) and the Acute Kidney Injury Network (AKIN) classifications] have led to more consistent estimates of its epidemiology. This review will present and critically discuss current literature about AKI diagnosis and epidemiology.
Creatinine clearance may be used as indicator for GFR because:
Creatinine is endogenously produced.
Creatinine is released into body fluid at constant rate.
Its plasma level maintained within narrow limits.
Its plasma level not affected by dietary factors
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
Basic Pharmacy Calculations and PharmacokinetesJoy Awoniyi
This was a lecture presented to the Davie campus of Florida A&M University College of Pharmacy P4 students. The lecture was presented during their final semester, at a course geared towards NAPLEX preparation. During the lecture, students wer asked to participate. We worked through each problem together and questions were encouraged.
This presentation quotes various pharmaceutical calculations with examples. The following aspects like percentage calculations, alcoholic dilutions, Alligation method, proof spirit calculations, isotonicity adjustment, posology, temperature measurements, dialysis clearance, Pharmacokinetics calculations were covered with examples.
Urine Neutrophil Gelatinase-Associated Lipocalin Moderately Predicts Acute Kidney Injury in Critically Ill Adults
Edward D. Siew*, Lorraine B. Ware, Tebeb Gebretsadik, Ayumi Shintani, Karel G. M. Moons, Nancy Wickersham, Frederick Bossert and T. Alp Ikizler
Procalcitonin is an excellent biomarker for antibiotic use in bacterial infections alone. POCT guided PCT levels can help decide whether to add antibiotics or not in opd settings for respiratory tract infection.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Couples presenting to the infertility clinic- Do they really have infertility...
Salon b 13 kasim 15.45 17.00 müge aydoğdu-ing
1. BIOMARKERS IN ACUTE
KIDNEY INJURY
Dr MÜGE AYDOĞDU
GAZİ UNIVERSITY MEDICAL FACULTY
PULMONARY DISEASES DEPARTMENT AND CRITICAL CARE UNIT
13.10.2014
2. Acute Kidney Injury (AKİ):
Epidemiology
• AKI occurs in 5% of hospitalised patients and in
30-50% of critical care patients * ;
• Incidence is increasing with extensive ICU
procedures!!!!
• Mortality among the ICU patients with AKI
requiring RRT is; > %50*.
• Among the ICU patients receiving RRT; CKD or
ESRD develops with in 3-5 years*
*Cole vd., 2000; Gursel ve Demir, 2006; Hoste vd., 2006; KDIGO, 2012;
Uschino vd., 2005
3. AKI-Why Early Diagnosis?
• AKI can be reversible when diagnosed earlier.
• With eary diagnosis;
• It will be possible to start treatment earlier
• Nephrotoxic procedures or medications can be avoided
5. AKI- Problems of Diagnosis in ICU
• Etiology of AKI is multifactorial (nephrotoxic
drug use, sepsis, ischemia etc)
RIFLE ve AKIN diagnostic criteria depend on
serum creatinin and urine output levels
These will lead to misdiagnosis or delayed
diagnosis in ICU
6.
7. AKI: Problems of Early Diagnosis
Serum Creatinin Caused Delayed Diagnosis
8. AKI: Problems of Early Diagnosis
Serum Creatinin Caused Delayed
Diagnosis
9. AKI: Problems of Early Diagnosis
Factors decreasing
creatinin levels:
Muscle mass and activity
Hepatic failure
Sepsis
Body weight
Age
Sex
Gender
Protein intake
Excess volume
Pregnancy
IADH
Blood transfusion
Factors increasing
creatinin levels :
Trauma, rhabdomyolisis
Excessive protein intake
Fever
Immobilisation
Drugs (TMP, Cimetidine,
Triamterene, Probenecide,
Spironolacton, Amiloride)
10. AKI: Problems of Early
Diagnosis
• BUN
• Low molecular weight,water soluble by-product of protein
metablolism
• Serum marker of uremic solute retansion and elimination.
• Not a sensitive marker of renal injury
• Increased BUN levels with extrarenal factors :
• High protein diet
• Critical illness (sepsis, burn, trauma)
• GI bleeding
• Glucocorticoid treatment and tetracycline use
• Decreased BUN levels with extrarenal factors
• Chronic hepatic disease
• Low protein intake
11. AKI: Problems of Early Diagnosis
Oliguria
• At least 6 hours are necessary for detection of oliguria
• In most of the patients excretory function of kidneys are
not disturbed during AKI
• Misdiagnosis can be made by just looking oliguria in acute
tubular injury
• Trend should be followed in ICU
• Has low sensitivity and specificity
14. AKI Biomarkers :Why Necessary?
• To make earlier diagnosis of structural abnormalities during
renal injury before funtional abnormalities take place
• To make differential diagnosis of reversible AKI and CKD
• Risk classification and triage
• To start treatment and to take preventive measure as soon as possible
• To define indications and criteria for future therapies.
• To identify prognosis (dialysis, death, ICU and hospital stay)
• Similar to Troponin and BNP
• Monitorization of treatment response
15. How Biomarkers Are Developed?
• Phase 1-Discovery Phase
• To find the candidate biomarkes and to evaluate the
biological competence by using scientific technologies
• Gene analysis (cDNA microarray ve NextGen
sequencing)
• Protein analysis (Proteomics)
• Phase 2-Translational Phase
• To define and develop the assay methods, tests for
candidate biomarkers.
• Phase 3-Validation Phase
• To evalute the prognostic value and clinical applicability
of the biomarker with large clinical trials.
Devarajan, Biomarkers Med 201; 4: 265-80
16. How can be the ideal biomarker?
1. Noninvasive
2. Easy, rapid result, cheap, can be studied in an already
present sample like urine
3. High sensitivity and specificity
4. Rapid and reliable rise secondary to renal injury
5. Correlated with the level of renal injury
6. Provide prognostic information and risk classification
7. Specific to kidneys
8. Can be applied to differen populations.
9. Can show possible causes of renal injury (Prerenal,
intrarenal, postrenal)
10. Stabile during time, at different temperatures and pHs
11. Not affected from other drugs
17.
18. AKI –Biomarker Studies
In recent years many studies have being performed for
AKI early diagnosis, both from urine and plasma
samples.
[ serum Cystatin C, urine IL-18 and neutrophil gelatinase
associated lipocalin (NGAL), urine KIM-1(kidney injury marker-1)
and urine L-FABP (liver fatty acid binding protein) ]
22. Neutrophil gelatinase associated
lipocalin-2 (NGAL)
• 25 kDa protein, covalenty bound to neutrophil
gelatinase
• Expressed at low levels in lungs, stomach, colon
and renal proximal tupular epithelial cellls
• It was found to be increasing so rapidly with in 2 hours
after an ischemic insult in (Mishra et al, 2003)
• In 2005, Mori et al identified that in AKI developing in
ICU patients, plasma NGAL levels increase 10 times,
and urine NGALlevels increase 100 times when
compared with non AKI controls.
26. Extrarenal Factors for NGAL Rise:
Systemic stress
CKD
Acute bacterial infection, sepsis
Gastric malignity
Pancreas carcinoma
Endometrial hyperplasia
Down Syndrome
Pelvic inflamatory disease, inflam. Bowel disease
Glioma
Esential thrombocytemia, policytemia vera
CML with molecular remission
ST segment elevation MI, as a prognostic indicator
Acute vs stabile coronary arterial disease
27. NGAL
Valuable for detecting subclinical AKI
Does sublinical AKI affects long term prognosis????
Not an ideal biomarker due to low specificity
28.
29. Serum Cystatin C
• Cystatin C; low molecular weight endogenous systein
proteinase inhibitor.
• Cystatin C; can be synthesized and released to plasma at a
stabile rate from all nucleated cells in the body
• Not affected from the age, gender, muscle mass and diet
protperties of the patients .
• Superior to serum creatinine in predicting GFR and in follow
up of renal functions. *
*Dhamidharka VR et al. Am J Kidney Disease 2002; 40: 221-6
*Coll E et al. Am J Kidney Disease 2000; 36: 29-34
30. Serum Cystatin C
• Has better performance in predicting GFR in some
special patient groups;
• Elderly
• Children
• Renal transplant patients
• Cirhosis
• Malnutrition
• Serum Cystatin C, when compared with creatinin more
sensitive to mild and earlier renal dysfunction
31. Serum Cystatin C
• In a small cohort study of critically ill patiens; rise in
Cystatin C levels can be identified 1-2 days before the rise
in serum creatinine (> 50% of the v-baseline) in AKI
patients.
• Due to developing standart immunonephelometric assays
serum Cystatin C is being used more commonly in our
daily practice and gives rapid results.
*Herget-Rosenthal S. et al. Kidney Int 2004; 66: 115-1122
32. Serum Cystatin C
• Among a large cross sectional study with 8058 patients some
other factors were found to be associated with increased
serum Cystatin C levels*;
• Old age,
• Male gender,
• Being tall and overweight,
• Active smoking,
• Increased CRP levels
• Cystatin C affected at the same time from**;
• Thyroid functional abnormalities
• Immunosuppressive treatment
• Systemic inflammation
*Knight EL et al. Kidney Int 2004; 66: 1115-22
**Manetti L et al. Clim Chim Acta 2005; 356:227-228
Manetti L et al. J Endocr Invest 2005; 28:346-349
33. Urine Cystatin C
• Cystatin C; also identified in urine of AKI patients. This
can be used for evaluating the severity of tubular injury..
• In a small prospective study among the critically ill
patients, increased urine Cystatin C levels were identified
to be more successfull in predicting the need for RRT
than other urinary biomarkers*
* Herget Rosenthal S et al. Clin Chem 2004; 50:552-558
48. AKI Biomarkers
• TIMP-2;
• Matrix metalloproteinase inhibitor
• Inhibits endothelial cell proliferation directly .
• IGFBP7:
• Stimulates cell adhesion, plays a role in cell cycle arrest
49. AKI Biomarkers
TIMP2 ve IGFBP7
•IGFBP7 (Insulin Like Growth Factor
Binding Protein-7) & TIMP-2 (Tissue
Inhibitor of Metalloproteinase-2);G1 cell
cycle arrest markers showing early
cellular injury
•After injury renal tubular cells enter a
short period of G1 cell cycle arrest
•G1 cell cycle arrest is a kind of
protective mechanismi preventing the
division and multiplication of injured
DNA
•IGFBP7 & TIMP-2 at the same time
plays a role of “alarm” released by
otocrine and paracrine ways from the
site of injury Kashani et al. Critical Care 2013, 17:R25
50. If no new injury occurs
and if sepsis treated
properly cyclin/CDK4
complex will allow cell
cycle to continue into
G1/S, and will lead to renal
In the earlier period of
sepsis , p53 ve p21
proteins will stop cell
cycle, and together with
released IGFBP-7 ve TIMP-2
cause the G1 cell cycle
cellular regeneration
arrest.
51. AKI Biomarkers
Urine IGFBP-7 ve TIMP-2 first studied in;
Early diagnosis of urinary system malignancies
Animal studies
Sapphire Study of Kashani K et al. in identifying AKI in early
period of AKI in septic ICU patients
*Are g g e r F, Ue hling e r DE, Wito ws ki J, Brunisho lz RA, Hunz ike r P, Fre y FJ, Jö rre s A. 2 0 1 3 .
“Id e ntific a tio n o f IGFBP-7 by urina ry p ro te o m ic s a s a no ve l p ro g no s tic m a rke r in e a rly a c ute
kidne y injury ”. Kid ne y Inte rna tio na l; 8 5 : 9 0 9 -9 1 9
**Biho ra c A, Chawla L, Shaw AD, AL-Kha fa ji A, Da vis o n DL, De Muth GE, e t a l. 2 0 1 4. “Va lid a tio n o f
c e ll c y c le a rre s t bio m a rke rs fo r a c ute kidne y injury us ing c linic a l a d jud ic a tio n”. Am J o f Re s p ira to ry
a nd Critic a l Ca re Me d ic ine ; 1 8 9 (8 ): 9 3 2 -9 3 9 .
***Ka sha ni K, Kha fa ji AA, Ard ile s T, Artig a s A, Ba g shaw SM, Be ll M, e t a l. 2 0 1 3 . “Dis c o ve ry a nd
va lid a tio n o f c e ll c y c le a rre s t bio m a rke rs in hum a n a c ute kidne y injury ”. Crit Ca re ; 1 7 : R2 5
52. AKI Biomarkers
• Kashani K et al., evaluated the predictive value of
TIMP2.IGFBP-7 in AKI development with in 12 hours of
admission among the urine samples obtained in first 24
hours of admission to ICU.
• An additive affect was identified when urine TIMP2 and
IGFBP7 were evaluated together; AUC was 0.80
(This was 0.76 ve 0.79 when these parameters
were evaluated by themselves)).
Kashani et al. Critical Care 2013, 17:R25
53. AKI Biomarkers
Urine NGAL (ng/mL) [TIMP-2]•[IGFBP7] ((ng/mL)2 /
1000)
Kashani et al. Critical Care 2013, 17:R25
54. AKI Biomarkers
Urine KIM-1 (ng/mL) [TIMP-2]•[IGFBP7] ((ng/mL)2 / 1000)
Kashani et al. Critical Care 2013, 17:R25
55. AKI Biomarkers
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Risk for AKI (KDIGO Stage 2 -3)
A
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.01 0.1 1 10 100
Risk for MAKE30
[TIMP-2]•[IGFBP7] ((ng/mL)²/1000)
B
KDIGO 2-3 in
12h
MAKE30 (30 days) MAKE30
Death
RRT
Persistently elevated sCr
(2x over baseline)
Kashani et al. Critical Care 2013, 17:R25
56. AKI Biomarkers
• With the combination of two tests TIMP2-
IGFBP7 (NEPHROCHECK® Test) early
dignostic tool was developed and a
threshold level was searched for the early
diagnosis of AKİ;
• <0.3 (ng/ml)2/1000 low risk for (KDIGO 2-3) AKİ
• 0.3-2 (ng/ml)2/1000 high risk,
• > 2 (ng/ml)2/1000 highest risk
• < 0.3 (ng/ml)2/1000 cutt of level has a
sensitivity of 0.88 and a negative predictive
value of 0.94 for the exclusion of KDIGO 2-
3 AKI development with in first 12 hours.
Kashani et al. Critical Care 2013, 17:R25
57. AKI Biomarkers
IGFBP-7 in normal, sepsis ve
septic AKİ groups
TIMP-2 in normal, sepsis and ve
septic AKI groups
Normal Sepsis Sepsis+AKI
25
20
15
10
5
0
IGFBP-7 2,4 5,8 23,1
IGFBP - 7 ng/ml
Normal Sepsis Sepsis+AKI
700,00
600,00
500,00
400,00
300,00
200,00
100,00
0,00
TIMP-2 593,00 478,00 527,00
TIMP - 2 pg/ml
Aydogdu M ve ark. Septik Akut Böbrek Yetmezliği Erken Tanısında İdrar Hücre Siklusu Duraklama
Belirteçleri:TIMP-2 ve IGFBP-7'nin Yeri. 11.DCYB Kongresi Sözlü Sunum(SS001)
58. Figure 3- ROC curve for the
prediction of AKI with urine
IGFBP-7 (AUC: 0.83)
IGFBP-7; for 3.5ng/ml cut off level;
sensitivity %80, specificty %76
Area Under the Curve
Test Result Variable(s): ýgfbp7
Area Std. Errora
Asymptotic
Asymptotic 95% Confidence
Interval
Sig.b Lower Bound Upper Bound
,830 ,046 ,000 ,741 ,920
The test result variable(s): ýgfbp7 has at least one tie between the
positive actual state group and the negative actual state group. Statistics
may be biased.
Under the nonparametric a. assumption
b. Null hypothesis: true area = 0.5
Aydogdu M ve ark. Septik Akut Böbrek
Yetmezliği Erken Tanısında İdrar Hücre Siklusu
Duraklama Belirteçleri:TIMP-2 ve IGFBP-7'nin
Yeri. 11.DCYB Kongresi Sözlü Sunum(SS001)
59.
60. TAKE HOME MESSAGES…
• Early diagnosis of AKI is so important inorder to prevent
morbidity and mortality.
• There are many biomarkers being studied, but no ideal
biomarker has yet been defined.
• New cell cycle arrest markers are promising but the
studies are not enough
• Whatever biomarker is preferred, it should be evaluated
together with the clinic of the patient…
Yoğun bakım ünitelerinde serum kreatinin düzeyi böbrek fonksiyonları dışında pek çok faktörden daha etkilenmekte, özellikle malnütrisyonu olan, kaşektik hastalarda böbrek yetmezliği gelişmesine rağmen kreatinin yükselmesi olmamaktadır. Aynı zamanda serum kreatinin glomerül filtrasyon hızını (GFR), tübüler hasarın derecesini doğru yansıtmazlar. İdrar çıkış miktarında da benzer durum söz konusudur; volüm durumundan, uygulanan diüretiklerden etkilenir ve tanıyı güçleştirir.
Renal hasar gerçekleştikten 48-72 saat sonra düzeyi artar (erken tanı mümkün değil)
Böbrek fonksiyonunun yaklaşık %50’si kaybolana kadar SCr değerleri artış göstermez
Kreatinin karaciğerde kreatin’in enzimatik olmayan dehidratasyonu ile oluşur ve kreatin’in %98 i kaslarda bulunur.
Yoğun bakım hastalarında çoğunlukla karaciğer fonksiyonları bozuk olduğu ve kas kitlesi çok azaldığı için Cr metabolizması belirgin olarak değişir
Cystatin C’nin ana katabolik bölgesi böbreklerdir
&gt;%99’u glomerüllerden filtre edilir; sekrete ve reabzorbe edilmez; hemen hemen tamamı proksimal renal tübüler hücrelerden metabolize edilir.
Dolayısıyla idrarda çok az veya hiç Cystatin C tespit edilir
GFR azalmasıyla serum Cystatin C artışı korrelasyon gösterir; ama gerçek Cystatin C klerensi tespit edilemez
Serum Cystatin C konsantrasyonlarının radyonüklid kullanımı ile ölçülen GFR değeri ile iyi bir ters korrelasyon gösterdiği bildirilmiştir.
Both markers may be involved in G1 cell cycle arrest and may signal that the renal epithelium has been stressed and has shut down function but may still be able to recover without permanent injury to the organ.
Importantly, TIMP-2 and IGFBP7 appear to be able to signal in autocrine and paracrine fashions, thus spreading the “alarm” from the site of injury.
TIMP-2 and IGFBP7 are known to be involed in the response to a wide variety of insults.
FIGURE 5 in publication
Bu durum DNA’daki hasar düzelene kadar hasarlı DNA’nın bölünerek, hasarın kalıcı hale gelmesini engelleyen koruyucu bir mekanizmadır.
Önemli olan sepsisin bu erken döneminde böbrek hücrelerinin kendilerini korumak için hücre siklusunu duraklattıkları dönemde TIMP.2 ve IGFBP7 ile olayı tespit edebilmek, böbreğe daha fazla ajanın zarar vermesini engelleyebilmektir
TIMP2; matriks metalloproteinaz inhibitörüdür. Direk olarak endotelial hücre proliferasyonunu baskılar.
IGFBP7 ise hücre adezyonunu stimüle eder, hücre siklusu duraklamasında rol oynar
FIGURE 3 from publication
In terms of discrimination between AKI of different severities and various non-AKI conditions including chronic kidney disease, [TIMP-2]•[IGFBP7] showed clear separation between AKI and non-AKI conditions.
FIGURE 3 from publication
In terms of discrimination between AKI of different severities and various non-AKI conditions including chronic kidney disease, [TIMP-2]•[IGFBP7] showed clear separation between AKI and non-AKI conditions.
FIGURE 4 in publication
Risk of AKI (KDIGO stage 2-3 within 12 hours) and MAKE30 elevated sharply for [TIMP-2]•[IGFBP7] above 0.3 and almost quintupled and doubled, respectively, for [TIMP-2]•[IGFBP7] above 2.0.
İdrar IGFBP-7 ile ABH tanısı için AUC 0.83 (p&lt;0.0001) olup, idrarda 3.5 ng/ml eşik değeri için duyarlılık :%80, özgüllük : %76 olarak bulundu