Renal Function Tests
Dr. Nazar Haddad
MBChB FIBMS FAACC Chemical Pathology
College of Medicine, University of Basrah
Department of Biochemistry
·
1/44
Learning Objectives
Knowledge Comprehensive Comprehensive Analysis Knowledge Comprehensive
Define basic Explain how Explain the Compare Identify tests Classify type
functions of renal function glomerular different tool for tubular of proteinuria
the kidney being function tests in assessment functions
impaired of glomerular
function
·
2/44
•kidneys are paired
retroperitoneal organs
•The functional unit of the
kidney is the Nephron
1 million nephrons,
Independent functional units
3/44
What Function the Kidney can do?
• Excretion of waste products (byproduct of Protein &
Nucleic Acid metabolism)
• Regulation of water, electrolyte and acid–base balance
they receive a rich blood supply, amounting to
about 25% of the cardiac output.
4/44
Kidney as Endocrine Gland
• Synthesize hormones
(Renin,Erythropoietin,
Calcitriol)
• Respond to action of
hormone (PTH,
Aldosterone)
• Inactivate Hormone
(insulin, glucagon)
5/44
Function of the kidney achieved by
•Glomerular filtration
•Tubular reabsorption
6/44
Tests of Glomerular Functions
GFR “ Glomerular Filtration Rate”
the volume of plasma from which a given substance is
completely cleared by glomerular filtration per unit
time
it estimates how much blood passes through
the glomeruli each minute.
9/44
Factor Affecting GFR
➢ Net pressure across the glomerular membrane,
➢ Physical nature of the membrane
➢ Surface area, which in turn reflects the number
of functioning glomeruli
10/44
How to Measure GFR
• Substance that is filtered at the glomerulus
• Neither reabsorbed nor secreted by the tubules
• Concentration in plasma needs to remain constant
throughout the period of urine collection
• Readily measured
11/44
Clearance = UV / P
• U is the concentration in urine
• V is the volume of urine produced per minute
• P is the concentration in plasma
mL/min/1.73 m 2
12/44
Inulin Clearance
• Inulin (a complex plant carbohydrate)
• Meet the Criteria Except
“it is not an endogenous compound but needs to be
administered by IV infusion. Tis makes it completely
impractical for routine clinical use”
• It is the Gold Standard Test
13/44
Serum Creatinine
• Creatine is synthesized in the liver and is transported to its
sites of usage, principally muscle and brain.
• 1–2% of the total muscle creatine pool is converted daily to
creatinine
• Creatinine is an end-product of nitrogen metabolism, and as
such undergoes no further metabolism, but is excreted in the
urine.
• Creatinine production reflects the body’s total muscle mass.
14/44
Creatinine & Glomerular Filtrate
• Completely Filtered
• Undergo Tubular Secretion
• Measurement subject to analytical overestimation
It can be used to determine the Creatinine
Clearance “130 m/min/1.73m2
15/44
• timed measurement of urine volume
• Urine Creatinine Concentration
Creatinine clearance measurements are therefore
cumbersome and potentially unreliable. They have
essentially been superseded by calculation of the
eGFR
16/44
Classification of Chronic Kidney Disease
Creatinine Clearance
• Stage 1 CrCl > 90
• Stage 2 CrCl 60-89
• Stage 3 CrCl 30-59
• Stage 4 CrCl 15-29
• Stage 5 CrCl <15
17
Plasma [Creatinine]
vs
Creatinine Clearance
18/44
Plasma [Creatinine]
• Endogenous production of creatinine remains constant,
• Inversely proportional to Creatinine Clearance
• Reference range
• 0.6 – 1.2 mg/dl
• 55 – 120 µmol/L
• Good indicator of impaired renal function
• Progressive rise in serial creatinine measurements, even
within the reference range, indicates declining renal
function
19/44
High Plasma [Creatinine]
Non renal cause of raised creatinine include
• High meat intake (temporary)
• Vigorous Exercise (Transient)
• Analytical overestimation “ Acetoacetate,
Cephalosporins Antibiotics”
• Drugs “ Salicylates, Cimetidine”
20/44
Low Plasma [Creatinine]
Pregnancy
Physiological Reduced muscle bulk (e.g.
Pathological starvation wasting diseases,
steroid therapy)
21/44
Estimated GFR [eGFR]
• poor inverse correlation between serum creatinine and GFR can be
improved by taking into account some of the confounding variables,
such as age, sex, ethnic origin and body weight.
Cockcroft and Gault
Creatinine clearance =
(140 - age) × wt × (0.85 if patient is female)
0.814 × serum[creatinine]
22/44
Modification of Diet in Renal Disease (MDRD)
Study are the most widely used of these
prediction equations
175 x SerumCr-1.154 x age-0.203 x 1.212 (if patient is black) x 0.742 (if
female)
23/44
CKD-EPI
• The CKD-EPI (Chronic Kidney Disease
Epidemiology Collaboration) equation was
developed in an effort to create a more
precise formula to estimate glomerular
filtrate rate (GFR) from serum creatinine
• GFR = 141 * min(Scr/κ,1)α * max(Scr/κ, 1)-1.209 *
0.993Age * 1.018 [if female] * 1.159 [if black]
*Use the Link for Practice
24/44
Plasma [Urea]
• Urea is formed in the liver from ammonia released by
deamination of amino acids.
• Over 75% of nonprotein nitrogen is excreted as urea,
mainly by the kidneys;
Urea measurements are widely available, and have
come to be accepted as giving a measure of renal
function
25/44
Reduced plasma [urea]
Causes of an abnormal plasma[urea]. Low protein diet, severe liver
disease, water retention
Increased plasma [urea]
Pre-renal causes High protein diet, GI
hemorrhage (‘meal’ of blood) Any cause
of increased protein catabolism (e.g.
trauma, surgery, extreme starvation)
Any cause of impaired renal perfusion
(e.g. ECF losses, cardiac failure,
hypoproteinemia)
Renal causes
Post-renal causes
26/44
plasma [urea] is inferior to
plasma [creatinine]
Why???
27/44
Plasma [Cystatin C]
• Endogenous substance
• 13-kda protein that is a member of the family of cystine
proteinase inhibitors
• Cystatin C is not secreted by the renal tubules and does not
return to the bloodstream after glomerular filtration
• ‘ideal’ endogenous marker for GFR
• Not routinely available
28/44
Tubular Functions
• Ability to concentrate urine
• Excrete an appropriately acidic urine,
• Reabsorption of amino acids, glucose,
phosphate,
29/44
Tubular Function Tests
• Urine osmolality and renal concentration tests
• Urine acidification tests
• Glycosuria
• Amino Acidurias
30/44
Urine osmolality and renal
concentration tests
• Urine osmolality varies widely in health, between
50 and 1250 mmol/kg, depending upon the
body’s requirement to produce a maximally dilute
or a maximally concentrated urine.
• The failing kidney loses its capacity to concentrate
urine at a relatively late stage.
31/44
Urine osmolality and renal
concentration tests
Urine osmolality
is directly proportional to the osmotic work done by the
kidney, and is a measure of concentrating power
Urine specific gravity
is usually directly proportional to osmolality, but gives
spuriously high results if there is significant glycosuria or
proteinuria
32/44
• In patients with polyuria, measurement of the osmolality of
early morning urine specimens should be made before
proceeding to formal concentration tests.
• If urinary osmolality greater than 800 mmol/kg,
concentrating ability will be normal and no need for further
tests
33/44
Urinary acidification tests
• Urine is normally acidic
• Urine pH over the range 5–9 (dipsticks)
• Measure urine pH on freshly voided urine specimens.
34/44
>
Impairment of Renal Function
Pre renal : decrease Renal Perfusion
✓ Hypovolemia
✓ Low Blood Pressure
Body Response:
➢ Vasoconstriction
➢ Stimulation of vasopressin secretion
➢ Stimulation of renin–angiotensin–aldosterone
system causes the excretion of small volumes of
concentrated urine with a low Na content
=>
7/44
• Renal causes may be due to acute kidney injury or
chronic kidney disease, with reduction in glomerular
filtration.
• Post-renal causes occur due to outflow obstruction,
which may occur at different levels (Stone, Cancer,
prostate)
8/44
Proteinuria
• Glomerular filtrate normally contains about 30 mg/L
protein
• Less than 200 mg of protein is normally excreted in
the urine each day
36/44
Mechanisms
of proteinuria
• Glomerular proteinuria
• Tubular proteinuria
• Overflow proteinuria
• Tamm–Horsfall proteinuria
37/44
Glomerular proteinuria
• Most often due to abnormally ‘leaky’ glomeruli
• The extent of this ‘leakiness’ varies enormously
• the ability of the body to replace the lost protein is
exceeded, and the protein concentration in the
patient’s blood falls
38/44
Nephrotic syndrome
• Large amounts of protein are lost in the urine
• Hypoproteinemia and edema (due to the low
(albumin)
• Protein losses in the urine are over 5 g/24 h
• Secondary hyperlipidemia
39/44
Tubular proteinuria
• Proteinuria is due to failure of the tubules to
reabsorb some of the plasma proteins filtered
by the normal glomerulus
• Possibly due to abnormal secretion of protein
into the urinary tract
40/44
Tubular proteinuria
• Mostly have a low molecular mass, for example
β2-microglobulin (11.8 kDa) and lysozyme (15 kDa)
• Urinary β2-microglobulin excretion is normally
very small (<0.4 mg/24 h).
• Its measurement has been used as a sensitive test
of renal tubular damage.
41/44
Overflow proteinuria
• Abnormal amounts of low molecular mass proteins
(<70 kDa) in plasma and in urine
• Multiple Myeloma.
malignant proliferation of a clone of plasma cells.
• Bence-Jones proteins are light chain fragments of the
immunoglobulin that can be detected in the urine.
42/44
Renal Stone
• 90 % is radiopaque
• Stone happen when solubility exceeded in presence of seed for its
formation “Debris or Bacteria”
44/44
Thank You
45
