1Radiometer Medical ApS, Åkandevej 21, DK-2700 Brønshøj, Tel: +45 38 27 38 27, www.radiometer.com

Physiology and clinical application

RTC, October 2006

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• Current clinical state for Radiometer • What is creatinine?• The kidneys• Assessment of kidney function• Creatinine in the hospital• Future clinical state for Radiometer• Read more

Agenda

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Current clinical state of ABL

Blood gas

ElectrolytesMetabolites

Full oximetry

ER

NICU

ORPICU

LAB

ICU

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Our customers want more....

Blood gas

ElectrolytesMetabolites

Full oximetry

Creatinine

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• Current clinical state for Radiometer • What is creatinine?

Metabolism Levels of creatinine

• The kidneys• Assessment of kidney function• Creatinine in the hospital• Future clinical state for Radiometer• Read more

Agenda

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Creatinine is ..

• A product of normal muscle metabolism • Produced from creatine in the muscles• Serves no metabolic purpose – a waste component• Removed from the blood by the kidneys• Diagnostic value: kidney functionality

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Levels of creatinine

• Relatively constant within each individual• Due to turnover of skeletal muscle it is higher in weightlifters,

lower in children and adults, especially elderly Changes in dietary intake causes only minor fluctuations

• Creatinine tends to decrease with age• Conflicting information about levels in neonates• African-American race higher muscle mass, higher Crea levels• NB! The levels are highly method specific

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Normal range of creatinine

µmol/L mg/dL

Male 80-133 0.9-1.5

Female 62-115 0.7-1.3

Neonate-0-1 week-1 week-1 month-1-6 months

53-9727-6218-35

0.6-1-10.3-0.70.2-0.4

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• Current clinical state for Radiometer • What is creatinine?• The kidneys

Anatomy and function Pathology of kidneys

• Assessment of kidney function• Creatinine in the hospital• Future clinical state for Radiometer• Read more

Agenda

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The kidneys

• Two kidneys

• Essentially a sophisticated blood filter

• 180 L blood are filtered daily and 1-1,5 L of urine is formed

• Important excretory and metabolic functions Excretion of waste products, e.g. Crea Regulation of fluid Regulation of electrolytes Regulation of acid-base balance Etc

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Anatomy of kidneys

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Functionality of kidneys

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Pathology of kidneys

• Most kidney diseases affect the nephrons Acute, as a result of critical illness, injury or poisoning Chronic, as a result of slow destruction by diabetes

and/or high blood pressure

• Loss of filtering capacity Impaired kidneys fail to separate albumin from the

urine Symptoms include protein, blood, glucose in the urine

• Decreased kidney function 50 % of normal: possible to live a normal life Less than 25 %: Serious health problems Less than 15 %: Need dialysis or transplantation to

survive

Blood and urine flow pattern

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Filtration system pathology

• Pre-renal Low blood volume being presented to the glomerulus for

filtration. Causes: hypovolemia due to shock, hemorrhage, burns,

salt and water depletion.

• Renal: Damage of filter Causes: inflammatory damage

• Post-renal: Blockage on distal side of the glomerulus opposing

filtration pressure. Causes: any cause of urine retention e.g. stone in the

ureter, tumor growth (prostatic carcinoma)

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• Current clinical state for Radiometer • What is creatinine?• The Kidneys• Assessment of kidney function

Creatinine, urea, blood gases, electrolytes Glomerular filtration rate, GFR Standardization of Crea and GFR

• Creatinine in the hospital• Future clinical state for Radiometer• Read more

Agenda

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Assessment of kidney function

• Glomerular Filtration Rate - GFR - is the best estimate of kidney function Requires creatinine measurement

• Creatinine is the most important marker of kidney damage – but not the only one Relation to urea/BUN important for more in depth diagnosis Calculation of GFR

• Urea/Crea ratio reported to give higher specificity in diagnosis Often no strict critical values for therapy

• Na and K are often included to provide a full picture of the patient status

• Crea with full blood gas picture relevant for ICU patients Risk of MOF, multi organ failure

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Glomerular Filtration Rate - GFR

• GFR calculation is more accurate for determining whether a person has reduced kidney function

• Calculation of the efficiency with which the kidneys filter waste from the blood

• Traditionally: Measurement of excretion and plasma level of a substance that is freely filtered by the kidneys

• New equation allows for calculation from cCrea and age Promoted by NKDEP, National Kidney Disease Education Program (USA) Implemented on ABL8x7 FLEX

GFR = k1(cCrea)k2(Age)k2

(0.741 if female)

(1.210 if African-American)

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The kidneys and GFR

• Inverse proportionality between cCrea and GFR

• A high GFR reflects a high filtration rate and therefore a low cCrea

• Different GFRs exist

• Renewed focus on GFR

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• Current clinical state for Radiometer • What is creatinine?• The kidneys• Assessment of kidney function• Creatinine in the hospital

Where, why, when, STAT and together with what? Acute renal failure Chronic renal failure

• Future clinical state for Radiometer• Read more

Agenda

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Current state – who wants creatinine?

WHERE WHY

ER For selected critical patients

ICU Renal function, ARF, hydration status

NICU/PICU Renal function, ARF, hydration status

OR Renal function, hydration status

Dialysis Renal function, monitor therapy

General wards Renal function, hydration status

CT scan To control possible kidney damage

• Creatinine is a marker of kidney function• Patient groups found at both critical and general wards

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Creatinine – Where, when, STAT and with what?

WHERE? WHEN? STAT? With WHAT?

ER As needed Yes Some always order creatinine and urea/BUN together, some don’t.

Other creatinine partners:Na, K, Cl, HCO3

-, tHb, iCa

ICU 1-2/days Sometimes

OR Before surgery

Sometimes

NICU/PICU 1-2/days Sometimes

Dialysis 1/week to 1/month

No

General wards 1/day No

CT scan Before a scan Yes Typically only creatinine

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At the Hospital – Acute

• Acute renal failure - ARF Many patients in the ICU develop ARF (20-50%) Very often surgery or shock patients It is “sudden” - develops over 1-3 days

• Characterized by Rapid increase of both creatinine and urea, with

creatinine as the most important marker Also changes in other parameters e.g. electrolytes

parameters

• Therapy Dialysis

• Outcome Some are reversible ARF mortality rate is 40-60 %

WHERE ?

ER

ICU

NICU/PICU

OR

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At the Hospital – Chronic

• Chronic kidney disease - CKD Progressive and irreversible destruction of kidney

tissue May develop over several years

• Cornerstone in diagnosis: GFR• Therapy

Change in diet Special care for diabetics etc Dialysis

• Focus area of NKDEP

WHERE

All departments

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Treatment of renal patients

• Dialysis or kidney transplantation• Life saving therapy for people with acute or chronic kidney failure• Dialysis is a method of removing toxic substances (impurities or

wastes) from the blood when the kidneys are unable to do so

• Each treatment has advantages and disadvantages• The patient needs to make some changes in his life, including

cutting down on calories and salt in the diet

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Treatment – kidney transplantation

• Kidney transplantation surgically places a healthy kidney from another person into the patient’s body

• The artery and vein of the new kidney is connected to the patient’s artery and vein so the blood flows through the donated kidney

• The new kidney may start working right away or may take up to a few weeks to make urine

• Unless the “old” kidneys are causing infection or high blood pressure, they are left in place

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Treatment - hemodialysis

• Blood is diverted from the venous access via dialysis catheters to a dialysis machine

• Filtration through special filters along with toxin-removing solutions (dialysate)

• The chemical imbalances and impurities of the blood are corrected and the blood is returned to the body

• Most patients undergo hemodialysis for three sessions of three to four hours every week

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Two challenges for us

• The lack of urea/BUN Will be added to the ABL later

• Some do not perceive creatinine as s STAT parameter Is true for the majority of the creatinine measurements in the hospital Some are STAT – therefore requested by some customers Very strong synergy to the other ABL parameters

Electrolytes

Blood gas

Metabolites

Full oximetry

Creatinine

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Future state - creatinine

• Creatinine on a BG analyzer makes perfect sense Increased therapeutic value of each measurement Evaluated together with the other parameters on the BG analyzer, including the

recommended GFR Critically ill patients carry a high risk of acute renal failure

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Read more

• http://www.kidneyatlas.org/• http://nkdep.nih.gov/labprofessionals/index.htm• http://dspace.dial.pipex.com/town/plaza/jc75/inf_2.htm• http://classes.kumc.edu/son/nurs320/module5.htm• http://www.nlm.nih.gov/medlineplus/ency/article/000501.htm#visualContent

• Lawson N, Lang T, Broughton A, Prinsloo P, Turner C, Marenah C. Creatinine assays: time for action? Ann Clin Biochem 39, 599-602. 1-1-2002.

• Miller W, Myers G, Ashwood E, Killeen A, Wang E, Thienpont L, et al. Creatinine measurement: state of the art in accuracy and interlaboratory harmonization. Arch Pathol Lab Med 2005; 129 (3): 297-04.

• Myers GL, Miller WG, Coresh J et al. Recommendations for improving serum creatinine measurement: a report from the laboratory working group of the national kidney disease education program. Clin Chem 2005; 52, 1: 5-18.

• Rowe D, Omar H, Barratt S, Biggs P. An evaluation of blood creatinine measurement by creatinase on the NOVA M7 blood gas analyzer. Clinica Chimica Acta 307, 23-26. 1-5-2001.

• Papadea C, Foster J, Grant S, Ballard S, Cate J, Southgate W, et al. Evaluation of the i-STAT Portable Clinical Analyzer for point-of-care blood testing in the intensive care units of a university children's hospital. Ann Clin Lab Sci 2002;32(3):231-43.

30Radiometer Medical ApS, Åkandevej 21, DK-2700 Brønshøj, Tel: +45 38 27 38 27, www.radiometer.com

RTC, October 2006RTC, October 2006