Biochemical markers in diagnosis: Kidney disease

(how do they work?)

Gary Oh

• National Institute of Health (NIH) 2001 defined a biomarker as "a characteristic that is objectively measured and evaluated as an indicator of normal biological, pathologic processes, or pharmacologic responses to a therapeutic intervention• As markers of renal function creatinine,

urea, uric acid and electrolytes are for routine analysis

• Creatinine (Cr)• Commonly used as measure of kidney function. • Muscle breakdown product: creatine phosphate. • Produced at a constant rate by the body depending on

muscle mass. • Cr clearance test is used to monitor renal disease

progression. Renal failure is suspected when serum Cr is greater than the upper limit of the “normal” interval.

• Normal Cr clearance test valve is 110-150ml/min in male and in female it is 100-130ml/min.

• The National Kidney Disease Education Program recommends calculating glomerular filtration rate from serum Cr concentration.

• In CRF and uremia, Cr excretion is reduced by both the glomeruli and the tubules.

• Cr values may vary as its generation influenced by muscle function, muscle composition, activity, diet and health status.

• Increased tubular secretion of Cr in some patients with kidney dysfunction could give false negative value.

• Elevated values are also seen in muscular dystrophy paralysis, anemia, leukemia and hyperthyroidism.

• Decreased values are noticed with glomerulonephritis, congestive heart failure, acute tubular necrosis, shock, polycystic kidney disease, and dehydration.

• Blood Urea Nitrogen (BUN)• Renal function• It is useful in differential diagnosis of ARF and pre renal condition

where blood urea nitrogen–creatinine ratio is increased. • Urea is major nitrogenous end product of protein/amino acid

catabolism• Urea cycle converts nitrogen from peripheral (muscle) and

enteral sources (protein ingestion) into urea that is water soluble and excreted.

• Filtered out of blood by glomerulli and partially reabsorbed with water.

• Two moles of nitrogen (one from ammonia and one from aspartate) are converted to urea in each cycle.

• Ammonia nitrogen derives from circulating amino acids, mostly glutamine and alanine.

• Aspartate is a substrate for argininosuccinic acid synthesis. 

• Urea clearance is a poor indicator of GFR as its overproduction rate depends on several non renal factors, including diet and urea cycle enzymes.

• Increased blood urea nitrogen (BUN) is seen associated with kidney disease or failure, blockage of the urinary tract by a kidney stone, congestive heart failure, dehydration, fever, shock and bleeding in the digestive tract.

• High BUN levels can sometimes occur during late pregnancy or result from eating large amounts of protein-rich foods.

• If BUN is higher than 100 mg/dL it points to severe kidney damage whereas decreased BUN is observed in fluid excess.

• Low levels are also seen in trauma, surgery, opioids, malnutrition, and anabolic steroid use

Creatine and creatinine metabolism.

1) l-arginine:glycine amidinotransferase (AGAT)

2)S-adenosyl-l-methionine:N-guanidinoacetate methyltransferase (GAMT)

3) creatine kinase (CK) 4) arginase (l-arginine

amidinohydrolase) 5) ornithine

carbamoyltransferase 6) argininosuccinate synthase7) argininosuccinate lyase8) l-ornithine:2-oxo-acid

aminotransferase (OAT)N) nonenzymatic reaction.  

• Inulin• Gold standard of exogenous filtration markers. • Inulins are naturally occurring polysaccharides produced by

many types of plants. (fructans)• Unique. At glomerulus it is completely filtered and neither

secreted, metabolized nor reabsorbed by the tubules. The clearance of inulin is a highly accurate measure of GFR

• The amount of inulin filtered at the glomerulus is equal to the amount excreted in the urine, which can be measured.

• Classic protocol requires a continuous intravenous infusion, multiple blood samples, and bladder catheterization

• Cons: Inulin is in short supply, expensive, and difficult to assay. Classic protocol is complex. Inulin is expensive and difficult to handle and there are other markers provide reasonable approximations of inulin clearance

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