The document outlines various kidney function tests, including assessments of glomerular filtration rate (GFR) and renal tubular function. It emphasizes the importance of understanding when to evaluate renal function based on patient history and health conditions, primarily utilizing biochemical tests like creatinine clearance, plasma urea, and urinalysis. It also discusses the implications of abnormal results and conditions such as nephrotic syndrome and proteinuria.

1. KIDNEY (RENAL) FUNCTIONS TESTS
RENAL CLEARENCE TESTS

2. When should you assess renal function?
 Older age
 Family history of Chronic Kidney disease (CKD)
 Decreased renal mass
 Low birth weight
 Diabetes Mellitus (DM)
 Hypertension (HTN)
 Autoimmune disease
 Systemic infections
 Urinary tract infections (UTI)
 Nephrolithiasis
 Obstruction to the lower urinary tract
 Drug toxicity

3. Biochemical Tests of Renal Function
 Measurement of GFR
 Clearance tests
 Plasma creatinine
 Urea, uric acid and β2-microglobulin
 Renal tubular function tests
 Osmolality measurements
 Specific proteinurea
 Glycosuria
 Aminoaciduria
 Urinalysis
 Appearance
 Specific gravity and osmolality
 pH
 osmolality
 Glucose
 Protein
 Urinary sediments

4. In acute and chronic renal failure, there is effectively a loss of function of
whole nephrons
 Filtration is essential to the formation of urine  tests of glomerular
function are almost always required in the investigation and
management of any patient with renal disease.
The most frequently used tests are those that assess either the GFR
or the integrity of the glomerular filtration barrier.
Biochemical Tests of renal function

5. 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.
TheVolume 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

6. Glomerular filtration rate

7. 1 to 2% of muscle creatine spontaneously converts to creatinine daily
and released into body fluids at a constant rate.
Endogenous creatinine produced is proportional to muscle mass, it is a
function of total muscle mass the production varies with age and sex
 Dietary fluctuations of creatinine intake cause only minor variation in
daily creatinine excretion of the same person.
 Creatinine released into body fluids at a constant rate and its plasma
levels maintained within narrow limits  Creatinine clearance may be
measured as an indicator of GFR.
Creatinine

8. 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 and clinical utility

9. The most frequently used clearance test is based on the measurement of
creatinine.
 Small quantity of creatinine is reabsorbed by the tubules and other
quantities are actively secreted by the renal tubules  So creatinine
clearance is approximately 7% greater than inulin clearance.
The difference is not significant when GFR is normal but when the GFR
is low (less 10 ml/min), tubular secretion makes the major contribution
to creatinine excretion and the creatinine clearance significantly
overestimates the GFR.
Creatinine clearance and clinical utility

10. 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

11.  Catabolism of proteins and nucleic acids results in formation of so
called nonprotein nitrogenous compounds.
 Urea , creatinine and uric acid
 In kidney dysfunction, the levels of these compounds are elevated in
plasma
Measurement of nonprotein nitrogen-containing compounds

12. Urea is the major nitrogen-containing metabolic product of protein catabolism in
humans,
 Its elimination in the urine represents the major route for nitrogen excretion.
 More than 90% of urea is excreted through the kidneys, with losses through the
GIT and skin
 Urea is filtered freely by the glomeruli
 Plasma urea concentration is often used as an index of renal glomerular function
 Urea production is increased by a high protein intake and it is decreased in
patients with a low protein intake or in patients with liver disease.
Plasma Urea

13. 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 15-39 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 15-39 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

14. 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

15.  2-microglobulin is a small peptide (molecular weight 11.8 kDa),
β
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 2-microglobulin is a good index of GFR in normal
β
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

16. Biochemical Tests of Renal Function
 Renal tubular function tests
Osmolality measurements
Specific proteinurea
Glycosuria
Aminoaciduria

17. 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

18. The glomerular basement membrane does not usually allow passage of albumin and
large proteins.A small amount of albumin, usually less than 25 mg/24 hours, is found
in urine.
Urinary protein excretion in the normal adult should be less than 150
mg/day.
When larger amounts, in excess of 250 mg/24 hours, are detected, significant
damage to the glomerular membrane has occurred.
Quantitative urine protein measurements should always be made on complete 24-
hour urine collections.
Albumin excretion in the range 25-300 mg/24 hours is termed microalbuminuria
Proteinuria

19.  TYPES OF PROTEINURIA
 Glomerular proteinuria
 Tubular proteinuria
 Overflow proteinuria
Proteinuria

20. Glomerular proteinuria
 Glomerular proteinuria — Glomerular proteinuria is due to
increased filtration of macromolecules (such as albumin) across
the glomerular capillary wall.The proteinuria associated with
diabetic nephropathy and other glomerular diseases, as well as
more benign causes such as orthostatic or exercise-induced
proteinuria fall into this category. Most patients with benign
causes of isolated proteinuria excrete less than 1 to 2 g/day

21. Tubular proteinuria
 Low molecular weight proteins — such as ß2-microglobulin,
immunoglobulin light chains, retinol-binding protein, and
amino acids — have a molecular weight that is generally under
25,000 in comparison to the 69,000 molecular weight of
albumin.These smaller proteins can be filtered across the
glomerulus and are then almost completely reabsorbed in the
proximal tubule. Interference with proximal tubular
reabsorption, due to a variety of tubulointerstitial diseases or
even some primary glomerular diseases, can lead to increased
excretion of these smaller proteins

22. Overflow proteinuria
 Increased excretion of low molecular weight proteins can occur
with marked overproduction of a particular protein, leading to
increased glomerular filtration and excretion.This is almost
always due to immunoglobulin light chains in multiple myeloma,
but may also be due to lysozyme (in acute myelomonocytic
leukemia), myoglobin (in rhabdomyolysis), or hemoglobin (in
intravascular hemolysis

23. Biochemical Tests of Renal Function
 Urinalysis
 Appearance
 Specific gravity and osmolality
 pH
 Glucose
 Protein
 Urinary sediments

24. Biochemical testing of urine involves the use of commercially available disposable strips When the
strip is manually immersed in the urine specimen, the reagents react with a specific component of urine
in such a way that to form color
 Colour change produced is proportional to the concentration of the component being tested for.
To test a urine sample:
fresh urine is collected into a clean dry container
the sample is not centrifuged
 the disposable strip is briefly immersed in the urine specimen;
The colour of the test areas are compared with those provided on a colour chart
Urinalysis using disposable strips

25. polyurea
Increased osmotic load, e.g due to glucose
Increased water ingestion
Diabetes insipidus: - Failure of ADH production results in
marked polyuria (diabetes insipidus), which stimulates thirst
and greatly increases water intake
Nephrogenic diabetes insipidus: The kidneys’ lack of
response to ADH has similar effect ( failure of the tubules to
respond to Vassopressin (ADH

26. Nephrotic syndrome
 The nephrotic syndrome is caused by renal diseases that increase the
permeability across the glomerular filtration barrier. It is classically
characterized by four clinical features, but the first two are used
diagnostically because the last two may not be seen in all patients:
 Nephrotic range proteinuria — Urinary protein excretion greater than 50
mg/kg per day
 Hypoalbuminemia — Serum albumin concentration less than 3 g/dL (30 g/L)
 Edema
 Hyperlipidemia

27. SODIUM 135 to 145 mEq/L
POTASSIUM 3.5 to 5.5 mEq/L
CHLORIDES 100 to 110 mEq/L
BICARBONATE 24 to 26 mEq/L
CALCIUM 8.6 to 10 mgs/dl
MAGNESIUM 1.6 to 2.4 mgs/dl
PHOSPHORUS 3.0 to 5.0 mgs/dl
URIC ACID 2.5 to 6.0 mgs/dl
pH 7.4
CREATININE 0.8 to 1.4 mgs/dl
Normal values of Internal Chemical
Environmentcontrolled by the Kidneys
:
15 to 20 mgs/dl
BUN (Blood Urea Nitrogen)