2. Maintenance of homeostasis:
The kidneys are responsible for the regulation
of water, electrolyte & acid-base balance in
Excretion of metabolic waste products:
The end products of protein & nucleic acid
metabolism are eliminated from the body.
These include urea, creatinine, creatine, uric
acid, sulfate & phosphate.
3. Retention of substances vital to body:
The kidneys reabsorb & retain several
substances of biochemical importance in the
body e.g. glucose, amino acids etc.
The kidneys also function as endocrine
organs by producing hormones.
A peptide hormone, stimulates hemoglobin
synthesis and formation of erythrocytes.
The active form of vitamin D is finally
produced in the kidney.
It regulates calcium absorption from the gut.
A proteolytic enzyme liberated by kidney,
stimulates the formation of angiotensin II
which, in turn, leads to aldosterone
Angiotensin II & aldosterone are the
hormones involved in the regulation of
6. Nephron is the functional unit of kidney.
Each kidney is composed of approximately
one million nephrons.
Nephron, consists of a Bowman's capsule
(with blood capillaries), proximal convoluted
tubule (PCT), loop of Henle, distal convoluted
tubule (DCT) & collecting tubule.
7. The blood supply to kidneys is relatively
About 1200 ml of blood (650 ml plasma) passes
through the kidneys, every minute.
About 120-125 ml is filtered per minute by the
kidneys & this is referred to as glomerular
filtration rate (GFR).
8. With a normal GFR (120-125 ml/min), the
glomerular filtrate formed in an adult is
about 175-180 litres/day, out of which only 1.5
litres is excreted as urine.
More than 99% of the glomerular filtrate is
reabsorbed by the kidneys.
Urine formation basically involves two steps-
glomerular filtration & tubular reabsorption.
9. Glomerular filtration:
This is a passive process that results in the
formation of ultrafiltrate of blood.
All the (unbound) constituents of plasma,
with a molecular weight < 70,000, are passed
into the filtrate.
The glomerular filtrate is almost similar in
composition to plasma
10. Tubular reabsorption:
The renal tubules (PCT, DCT & collecting
tubules) retain water & most of the soluble
constituents of the glomerular filtrate by
This may occur either by passive or active
11. There are certain substances in the blood
whose excretion in urine is dependent on their
Such substances are referred to as renal
At the normal concentration in the blood, they
are completely reabsorbed by the kidneys.
12. The renal threshold of a substance is defined
as its concentration in blood (or plasma)
beyond which it is excreted into urine.
The renal threshold for glucose is 180 mg/dl;
ketone bodies 3 mg/dl; calcium 10 mg/dl
bicarbonate 30 mEq/l.
Tubular maximum (Tm):
The maximum capacity of the kidneys to
absorb a particular substance.
Tubular maximum for glucose is 350 mg/min.
13. Kidney function tests may be divided into 4
Glomerular function tests:
All the clearance tests (inulin, creatinine,
urea) are included in this group.
Tubular function tests:
Urine concentration or dilution test, urine
14. Analysis of blood/serum:
Estimation of blood urea, serum creatinine,
protein & electrolyte are useful to assess renal
Routine examination of urine - volume, pH,
specific gravity, osmolality & presence of
certain abnormal constituents (proteins, blood,
ketone bodies, glucose etc).
15. Clearance is defined as the volume of plasma
that would be completely cleared of a
substance per minute.
In other words, clearance of a substance
refers to the milliliters of plasma which
contains the amount of that substance
excreted by kidney per minute.
16. U = Concentration of the substance in urine.
V = Volume of urine in ml excreted per
P = Concentration of the substance in plasma.
U x V
17. The maximum rate at which the plasma can be
cleared of any substance is equal to the GFR.
This can be calculated by measuring the clearance of
a plasma compound which is freely filtered by the
glomerulus & is neither absorbed nor secreted in the
Inulin (a plant carbohydrate, composed of fructose
units) and 51Cr-EDTA satisfy this criteria.
Inulin is intravenously administered to measure GFR.
18. Creatinine is an excretory product derived
from creatine phosphate.
The excretion of creatinine is rather
constant & is not influenced by body
metabolism or dietary factors.
Creatinine is filtered by the glomeruli & only
marginally secreted by the tubules.
19. Creatinine clearance may be defined as the
volume (ml) of plasma that would be
completely cleared of creatinine per minute.
In the traditional method, creatinine content
of a 24 hr urine collection & the plasma
concentration in this period are estimated.
20. The creatinine clearance (C) can be calculated
U = Urine concentration of creatinine.
V = Urine output in ml/min (24 hr urine
volume divided by 24 x 60)
P = Concentration of creatinine.
U x V
21. Modified procedure:
Instead of a 24 hr urine collection, the
procedure is modified to collect urine for 1 hr,
after giving water.
The volume of urine is recorded.
Creatinine contents in plasma & urine are
The creatinine clearance can be calculated by
using the formula.
22. Reference values:
The normal range of creatinine clearance is
around 120-145 ml/min.
These values are slightly lower in women.
Serum creatinine normal range:
Adult male: 0.7-1.4 mg/dl
Adult female: 0.6-1.3 mg/dl
Children: 0.5-1.2 mg/dl
23. State Grade GFR ml/mt/1.73m2
Minima damage with normal GFR 1 >90
Mild damage with slightly low GFR 2 60-89
Moderately low GFR 3 30-59
Severely low GFR 4 15-29
Kidney failure 5 <15
24. Diagnostic importance:
A decrease in creatinine clearance value (<75
% normal) serves as sensitive indicator of a
decreased GFR, due to renal damage.
It is useful for early detection of impairment
in kidney function.
25. Creatinine coefficient:
It is the urinary creatinine expressed in
mg/kg body weight.
The value is elevated in muscular dystrophy.
Normal range is 20–28 mg/kg for males & 15–
21 mg/kg for females.
26. Urea is the end product of protein
After filtered by the glomeruli, it is partially
reabsorbed by the renal tubules.
Urea clearance is less than the GFR & it is
influenced by the protein content of the diet.
Urea clearance is not as sensitive as
27. Urea clearance is defined as the volume (ml)
of plasma that would be completely cleared
of urea per minute.
It is calculated by the formula:
Cm=Maximum urea clearance.
U = Urea concentration in urine (mg/dl).
V = Urine excreted per minute in ml.
P = Urea concentration in plasma.
U x V
28. If the output of urine is more than 2 ml per minute.
This is referred to as maximum urea clearance & the
normal value is around 75 ml/min.
Standard urea clearance:
The urea clearance drastically changes when the
volume of urine is less than 2 ml/min.
This is known as standard urea clearance (C) & the
normal value is around 54 ml/min.
29. Standard urea clearance is calculated by a
U x √V
30. Diagnostic importance:
A urea clearance value below 75 % of the
normal is serious, since it is an indicator of
Blood urea level is found to increase only
when the clearance falls below 50% normal.
Normal level of blood urea: 20-40 mg/dl
32. Post-renal causes:
Stones in the urinary tract
Tumors of bladder
33. Decreased Blood Urea:
Urea concentration in serum may be low in
late pregnancy, in starvation, in diet grossly
deficient in proteins and in hepatic failure.
Increase in the blood levels of NPN (creatinine,
urea, uric acid) is referred to as azotemia & is
the hallmark of kidney failure.
34. It is the terminal manifestation of renal failure.
A group of toxins contribute to this situation.
Increased urea lead to carbamoylation of
Increased uric acid causes uremic pericarditis.
Excess polyols is the basis of peripheral
β -2 microglobulin is reason for renal
35. This is a test to assess the renal tubular
It is a simple test & involves the accurate
measurement of specific gravity which
depends on the concentration of solutes in
A specific gravity of 1.020 in the early morning
urine sample is considered to be normal.
36. The osmolality of urine is variable.
In normal individuals, it may range from 500-
The plasma osmolality is around 300
The normal ratio of the osmolality between
urine & plasma is around 2-4.
37. It is found that the urine (without any protein
or high molecular weight substance) with an
osmolality of 800 mosm/kg has a specific
gravity of 1.020.
Therefore, measurement of urine osmolality
will also help to assess tubular function.
38. Estimation of serum creatinine & blood urea
These tests are less sensitive than the
Serum creatinine is a better indicator than
39. Urine examination:
The volume of urine excreted, its pH, specific
gravity, osmolality, the concentration of
abnormal constituents (such as proteins,
ketone bodies, glucose & blood) may help to
have some preliminary knowledge of
40. Glomerular proteinuria:
The glomeruli of kidney are not permeable
to substances with molecular weight more
than 69,000 & plasma proteins are absent in
When glomeruli are damaged or diseased,
they become more permeable & plasma
proteins may appear in urine.
41. The smaller molecules of albumin pass
through damaged glomeruli more readily.
Albuminuria is always pathological.
Large quantities of albumin are lost in urine
Small quantities are seen in urine in acute
nephritis, strenuous exercise & pregnancy.
42. It is also called minimal albuminuria or
It is identified, when small quantity of
albumin (30-300 mg/day) is seen in urine.
The test is not indicated in patients with overt
proteinuria (+ve dipstick).
Early morning midstream sample is
43. Micro albuminuria is an early indication of
nephropathy in patients with diabetes mellitus
All diabetics & hypertensive should be
screened for microalbuminuria.
It is an early indicator of onset of nephropathy.
The test should be done at least once in an
44. It is expressed as albumin-creatinine ratio.
Normal ratio being
Males < 23 mg/gm of creatinine
Females < 32 mg/gm of creatinine
45. When small molecular weight proteins are
increased in blood, they overflow into urine.
E.g, hemoglobin having a molecular weight
of 67,000 can pass through normal glomeruli &
if it exists in free form (as in hemolytic
conditions), hemoglobin can appear in urine
46. This occurs when functional nephrons are
reduced, GFR is decreased & remaining
nephrons are over-working.
The tubular reabsorption mechanism is
impaired, so low molecular weight proteins
appear in urine.
They are Retinol binding protein (RBP) & α-1
47. In CKD, there is a decrease in the number of
The compensatory rise in glomerular
filtration by other nephrons increases the
filtered load of proteins.
Even if there are no glomerular permeability
changes, tubular proteinuria is seen.
48. This is due to inflammation of lower urinary
tract, when proteins are secreted into the
Accumulation of proteins in tubular lumen
can trigger inflammatory reaction.
49. Text book of Biochemistry – DM Vasudevan
Text book of Biochemistry – U Satyanarayana
Text book of Biochemistry – MN Chatterjea