Kidney Function Testing CHAPTER-IX

K.ANITA PRIYADHARSHINILECTURER DEPT.OF PHARMACEUTICAL CHEMISTRYSRM COLLEGE OF PHARMACY

An Introduction to the Urinary System

Produces urine

Transports urine towards bladder

Temporarily store urine

Conducts urine to exterior

The Function of Urinary System

Excretion & Elimination:removal of organic wastes products

from body fluids (urea, creatinine,uric acid)

Homeostatic regulation:Water -Salt BalanceAcid - base Balance

Enocrine function:Hormones

A)

B)

C)

excretion of excess electrolytes, nitrogenous wastes and organic acids

The maximal excretory rate is limited or established by their plasma

concentrations and the rate of their filtration through the glomeruli

The maximal amount of substance excreted in urine does not exceed the

amount transferred through the glomeruli by ultrafiltration except in the

case of those substances capable of being secreted by the tubular cells.

The excretory functionA)

Each kidney consists of one million functional units: Nephrone

A) GlomerulusB) Glomerular CapsuleC) Renal Tubule

proximal convoluted tubule • loop of Henle• distal convoluted tubule D) Collecting Duct

Nephron structure

Urine formation requiers :

Urine Formation

Glomerular FiltrationDue to differences in pressure water, small molecules move from the glomerulus capillaries into the glomerular capsule

Tubular reabsorption many molecules are reabsorbed from the nephron

into the capillary (diffusion, facilitated diffusion,osmosis, and active transport)i.e. Glucose is actively reabsorbed with transportcarriers.If the carriers are overwhelmed glucose appears inthe urine indicating diabetes

Tubular secretionSubstances are actively removed from blood andadded to tubular fluid (active transport)ie. H+, creatinine, and some drugs are moved byactive transport from the blood into the distalconvoluted tubule

a)

b)

c)

Measurement of GFRClearance testsPlasma creatinineUrea, uric acid and β2‐microglobulin

Renal tubular function testsOsmolality measurementsSpecific proteinureaGlycouriaAminoaciduria

UrinalysisAppearanceSpecific gravity and osmolalitypHosmolalityGlucoseProteinUrinary sediments

Biochemical Tests of Renal Function

Older ageFamily history of Chronic Kidney disease (CKD)Decreased renal massLow birth weightDiabetes Mellitus (DM)Hypertension (HTN)Autoimmune diseaseSystemic infectionsUrinary tract infections (UTI)NephrolithiasisObstruction to the lower urinary tractDrug toxicity

When should you assess renal function?

Measurement of GFRClearance testsPlasma creatinineUrea, uric acid and β2-microglobulin

Biochemical Tests of Renal Function

GFR can be estimated by measuring the urinary excretion of a substance that is completely filtered from the blood by the glomeruli and it is not secreted, reabsorbed or metabolized by the renal tubules.

Clearance is defined as the (hypothetical) quantity of blood or plasma completely cleared of a substance per unit of time.

Clearance of substances that are filtered exclusively or predominantly by the glomeruli but neither reabsorbed nor secreted by other regions of the nephron can be used to measure GFR.

Inulin

The Volume of blood from which inulin is cleared or completely removed in one minute is known as the inulin clearance and is equal to the GFR.

Measurement of inulin clearance requires the infusion of inulin into the blood and is not suitable for routine clinical use

GFR = (U V)P

inulin

inulin

×V is not urine volume, it is urine flow rate

Measurement of glomerular filtration

rate

The most frequently used clearance test is based on themeasurement of creatinine.

Small quantity of creatinine is reabsorbed by the tubules andother quantities are actively secreted by the renal tubules Socreatinine clearance is approximately 7% greater than inulinclearance.

The difference is not significant when GFR is normal but whenthe GFR is low (less 10 ml/min), tubular secretion makes themajor contribution to creatinine excretion and the creatinineclearance significantly overestimates the GFR.

Creatinine clearance and clinical

utility

An estimate of the GFR can be calculated from the creatinine content of a 24-hour urine collection, and the plasma concentration within this period.

The volume of urine is measured, urine flow rate is calculated (ml/min) and the assay for creatinine is performed on plasma and urine to obtain the concentration in mg per dl or per ml.

Creatinine clearance in adults is normally about of 120 ml/min, The accurate measurement of creatinine clearance is difficult, especially in outpatients, since it is necessary to obtain a complete and accurately timed sample of urine

Creatinine clearance clinical utility

The 'clearance' of creatinine from plasma is directly related to the GFR if:

The urine volume is collected accurately

There are no ketones or heavy proteinuria present to interfere with the creatinine determination.

It should be noted that the GFR decline with age (to a greater extent in males than in females) and this must be taken into account when interpreting results.

Creatinine clearance and clinical utility

Catabolism of proteins and nucleic acids results in formation of so called nonprotein nitrogenous compounds.

Protein

↓ Proteolysis, principally enzymatic

Amino acids

↓ Transamination and oxidative deamination

Ammonia

↓ Enzymatic synthesis in the “urea cycle”

Urea

Measurement of nonprotein nitrogen-

containing compounds

Many renal diseases with various glomerular, tubular, interstitial or vascular damage can cause an increase in plasma urea concentration.

The reference interval for serum urea of healthy adults is 5-39 mg/dl. Plasma concentrations also tend to be slightly higher in males than females. High protein diet causes significant increases in plasma urea concentrations and urinary excretion.

Measurement of plasma creatinine provides a more accurate assessment than urea because there are many factors that affect urea level.

Nonrenal factors can affect the urea level (normal adults is level 5-39 mg/dl) like:

Mild dehydration,

high protein diet,

increased protein catabolism, muscle wasting as in starvation,

reabsorption of blood proteins after a GIT haemorrhage,

treatment with cortisol or its synthetic analogous

Plasma Urea

• States associated with elevated levels of urea in blood are referred to as uremia or azotemia.

• Causes of urea plasma elevations:Prerenal: renal hypoperfusionRenal: acute tubular necrosisPostrenal: obstruction of urinary flow

Clinical Significance

Renal handling of uric acid is complex and involves four sequential steps:

Glomerular filtration of virtually all the uric acid in capillary plasma entering the glomerulus.

Reabsorption in the proximal convoluted tubule of about 98 to 100% of filtered uric acid.

Subsequent secretion of uric acid into the lumen of the distal portion of the proximal tubule.

Further reabsorption in the distal tubule.

Hyperuricemia is defined by serum or plasma uric acid concentrations higher than 7.0 mg/dl (0.42mmol/L) in men or greater than 6.0 mg/dl (0.36mmol/L) in women

Uric acid

β2-microglobulin is a small peptide (molecular weight 11.8 kDa),

It is present on the surface of most cells and in low concentrations in the plasma.

It is completely filtered by the glomeruli and is reabsorbed and catabolized by proximal tubular cells.

The plasma concentration of β2-microglobulin is a good index of GFR in normal people, being unaffected by diet or muscle mass.

It is increased in certain malignancies and inflammatory diseases.

Since it is normally reabsorbed and catabolized in the tubules, measurement of β2-microglobulin excretion provides a sensitive method of assessing tubular integrity.

Plasma β2-microglobulin

Renal tubular function tests

• To ensure that important constituents such as water, sodium, glucose and a.a. are not lost from the body, tubular reabsorption must be equally efficient

• Compared with the GFR as an assessment of glomerualr function, there are no easily performed tests which measure tubular function in quantitative manner

• Investigation of tubular function:

1. Osmolality measurements in plasma and urine; normal urine: plasma osmolality ratio is usually between 1.0-3.0

2. Specific proteinuria

3. Glycosuria

4. Aminoaciduria

Proteinuria may be due to:

1. An abnormality of the glomerular basement membrane.

2. Decreased tubular reabsorption of normal amounts of filtered proteins.

3. Increased plasma concentrations of free filtered proteins.

4. Decreased reabsorption and entry of protein into the tubules consequent to tubular epithelial cell damage.

Measurement of individual proteins such as β2-microglobulin have been used in the early diagnosis of tubular integrity.

With severe glomerular damage, red blood cells are detectable in the urine (haematuria), the red cells often have an abnormal morphology in glomerular disease.

Haematuria can occur as a result of lesions anywhere in the urinary tract,

Assessment of glomerular integrity

Urinalysis is important in screening for disease is routine test for every patient, and not just for the investigation of renal diseases

Urinalysis comprises a range of analyses that are usually performed at the point of care rather than in a central laboratory.

Urinalysis is one of the commonest biochemical tests performed outside the laboratory.

Examination of a patient's urine should not be restricted to biochemical tests.

Urinalysis

– This is a semi-quantitative measure of concentration.

– A higher specific gravity indicates a more concentrated urine.

– Assessment of urinary specific gravity usually just confirms the impression gained by visually inspecting the colour of the urine. When urine concentration needs to be quantitated,

Urinalysis: Specific gravity

– Osmolality serves as general marker of tubular function. Because the ability to concentrate the urine is highly affected by renal diseases.

– This is conveniently done by determining the osmolality, and then comparing this to the plasma.

– If the urine osmolality is 600mosm/kg or more, tubular function is usually regarded as intact

– When the urine osmolality does not differ greatly from plasma (urine: plasma osmolality ratio=1), the renal tubules are not reabsorbing water

Urinalysis: Osmolality measurements in plasma and urine

pH- Urine is usually acidic - Measurement of urine pH is useful in suspected drug toxicity, abuse.., or where there is an unexplained metabolic acidosis (low serum bicarbonate or other causes…).

Urine sediments- Microscopic examination of sediment from freshly passed urine involves looking for cells, casts, fat droplets - Blood: haematuria is consistent with various possibilities ranging from malignancy through urinary tract infection to contamination from menstruation. - Red Cell casts could indicate glomerular disease- Crystals - Leucocytes in the urine suggests acute inflammation and the presence of a urinary tract infection.

Urinalysis

To maintain water homeostasis, the kidneys must produce urine in a volume precisely balances water intake and production to equal water loss through extra renal routes.

Minimum urine volume is determined by the solute load to be excreted whereas maximum urine volume is determined by the amount of excess water that must be excreted

Urine volume