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The Kidney: Physiology,

Function
and Assessment of Function
Felicity Stokes
Senior Clinical Biochemist
Department of Clinical Chemistry and Metabolic Medicine
Royal Liverpool and Broadgreen University Hospitals
Overview of talk
Review of kidney structure
Review of kidney function
Tests for assessment of kidney function
Gross anatomy of kidneys
Located in the retroperitoneal space
The right kidney is situated slightly lower than the left
Adult kidneys:
~ 12cm long weigh 135g in women and 150g in men
Adrenal glands located just above kidneys
Renal Blood Supply
Very important that the kidneys have a good
blood supply for their functions
Receives ~ 25% of cardiac output
Aorta
afferent arterioles
efferent arterioles
renal venules
renal veins
inferior vena cava
renal artery
A complex array of regulatory
mechanisms ensure that the blood
flow to the kidneys is maintained
across a range of blood pressures.
Microstructure of kidney
Outer zone = cortex
Inner zone = medulla
Functional unit = nephron
~ 1 million nephrons in each kidney
Urinary Tract
Filtered toxins and water leave each kidney
though the ureter
Each ureter drains into the urinary bladder
Urine is then excreted through the urethra
Kidney
Ureter
Bladder
Urethra
Excretion of waste products of protein metabolism

Water and electrolyte homeostasis

Acid base homeostasis
Main Function of Kidneys
Endocrine Functions
Production of renin
Activation of Vitamin D
Production of erythropoietin
Creatinine
Urea
Excretion of H
+
Regeneration of bicarbonate
Sodium
Potassium
Chloride
Carried out by filtering the blood and excreting what is not wanted in the
urine, while reabsorbing everything that is useful back into the body
Water
The nephron
Glomerulus
Proximal convoluted tubule
Loop of Henle descending limb
ascending limb
Distal convoluted tubule
Collecting duct

The glomerulus
Where the blood is filtered to maintain important
constituents like blood cells in the blood but
remove fluid, waste products and regulate H
+
, Na
+

and K
+
concentrations
Blood is separated from the lumen of the
nephron by 3 layers that filter it:

Capillary endothelial cells
Glomerular basement membrane
Podocytes of glomerular epithelium
Capillary vascular space
Glomerulus lumen
Basement membrane
Endothelial cells
Slit pores
Fenestrations
Na
+
Cl
-
K
+
K
+
K
+
Na
+
Cl
-
Cl
-
Na
+
Na
+
Low MW proteins and
electrolytes
Cells and large
MW proteins
Podocytes
with foot
processes
Glomerular Filtrate
An ultrafiltrate of the blood enters the lumen
of the glomerulus
Composition similar to plasma except blood
cells and molecules of protein > 50 kDa are
absent
Molecules around the size of albumin
(68kDa) and larger are prevented from
entering lumen
Proteins prevented according to charge as
well as size (more negatively charged
proteins retained in blood)
Proximal convoluted tubule
Carries out most of the reabsorption
of electrolytes from the filtrate back
into circulation
75% of sodium and chloride
Water (follows sodium and chloride
passively by osmolality)
Almost all bicarbonate, calcium,
potassium, glucose and amino
acids

Loop of Henle
Has a descending limb and ascending limb
Not all nephrons have a loop of Henle
Extends from the cortex down
into the medulla and back up
again

Thick ascending limb is
impermeable to water

It is responsible for creating a
hyperosmolar medulla

This is necessary for the
production of a concentrated urine
Counter-current system
Ascending loop of Henle reabsorbs 25% of sodium/chloride

These diffuse through the interstitial space and some diffuse
back into the descending limb. (flow back into ascending
limb)

No water follows them as it is impermeable to water
This alters the osmolality of the fluid in
the nephron and in the surrounding
interstitial space of the medulla

Causes a gradient of osmolality to be
created with the osmolality increasing
with deep down into the medulla

Causes water to diffuse out of the
descending limb into the hyperosmotic
medulla
Counter-current system (2)
The vasa recta capillary plays an
important role in this process by quickly
removing any water that is reabsorbed
from the descending limb

This maintains the high osmolality
The result is a fluid that is hypotonic
compared to the plasma going in to the
distal convoluted tubule

The dilute fluid enters the distal
convoluted tubule and collecting duct,
where water can be reabsorbed by
passive diffusion down the
concentration gradient by the medullary
hyperosmolality that has been created
Distal Convoluted Tubule
Carrries out the fine-tuning of
electrolyte reabsorption or excretion
Specifically Na
+
, K
+
, H
+

Affected by concentration of these in
plasma to carry out homeostasis
Under hormonal control (Aldosterone)
Distal Convoluted Tubule
Na
+
K
+
or H
+
Lumen
Tubular
cell
Aldosterone
Collecting duct
Carries out the reabsorption of water
Naturally impermeable to water
Passive diffusion under the control of osmolar difference
between tubular cells and lumen (created by counter-current
system of Loop of Henle)
ADH
If there is a need to
conserve water:
ADH is stimulated

Causes aquaporins
water transporters
to move to the
impermeable
membrane to allow
water to pass
through
Summary of nephron
Glomerulus filters blood
Proximal tubule bulk reabsorption
Loop of Henle production of osmostic
gradient for control of water
reabsorption
Distal tuble fine tuning of reabsorption
Collecting duct water reabsorption (or
excretion)
Assessment of renal function
Main function of kidneys is to clear waste
products from the plasma
This is used to assess and monitor renal
function
Creatinine produced at a constant rate by
skeletal muscle cells
Not really affected by other factors very
little reabsorption or secretion in renal
tubules
Can measure its clearance from plasma or
excretion in urine
Glomerular Filtration Rate (GFR)

Kidneys usually filter ~170L of water each day
(120 mL/min)

Affected by:
Number of nephrons
Blood supply to the nephron
Integrity of the glomerulus
These can be altered in disease and affect the GFR
The volume of plasma that is filtered by the kidneys
and from which a substance is completely cleared
per unit of time
Assessment of Renal Function
Serum Creatinine
1 blood sample convenient, cheap, quick
BUT - not sensitive
Serum creatinine only
starts to increase above
normal when the kidney
ia at about half function
with a GFR of
~60mL/min
A small person with a
low muscle mass will
has a much lower
serum creatinine
A body
builder will
have a much
higher serum
creatinine
AND affected by muscle mass
Assessment of Renal Function
Creatinine Clearance
Used to calculate Glomerular Filtration Rate
More sensitive at picking up small changes in renal
function
BUT 24 hr urine collection plus serum required
Inconvenient, lots of measurements and calculation =
lots of room for error!
Clearance = U x V
P
[Urine Creatinine (umol/L)] x Urine Volume (mL) = mL/min
[Plasma Creatinine (umol/L)] x Collection period (min)
U = Urine concentration
V = Volume
P = Plasma concentration
Assessment of Renal Function
eGFR (estimated GFR)
Uses serum creatinine to estimate GFR

More sensitive than creatinine
Uses only serum creatinine measurement and a
calculation, therefore only 1 blood sample
required more convenient

BUT not to be used in certain situations such as
acute illness, pregnancy, young and elderly
As it uses serum creatinine in its formula, still
affects by variations in muscle mass
eGFR
Various equations exist
Based on large scale studies that measured GFR or Cr Cl by
gold standard methods and serum creatinine and worked out
a formula to calculate these
Built in several other factors that affect serum creatinine
measurement age, sex, ethnicity, weight
Cockcroft-Gault
MDRD widely accepted and used as the best formula for estimating GFR
GFR (mL/min/1.72m
2
) = 175 x [serum creatinine (umol/L) x 0.011312]
-1.154
x (age)
-0.203


x 0.742 if female
x 1.210 if African American
4 variables serum creatinine, age,
sex, ethnicity
Cr Cl (mL/min) = [(140 age) x weight/0.814 x serum creatinine (umol/L)]
x 0.85 if female
Limitations of eGFR
Serum Creatinine = 40 umol/L Serum Creatinine = 180 umol/L Serum Creatinine = 110 umol/L
Calculated eGFR =
>90 mL/min/1.73m
2
Calculated eGFR =
66 mL/min/1.73m
2
Calculated eGFR =
37 mL/min/1.73m
2
Actual GFR = 45
mL/min/1.73m
2
Actual GFR = 66
mL/min/1.73m
2
Actual GFR = >90
mL/min/1.73m
2
Specialist tests for GFR
In some situations, a very accurate GFR may be needed
Or in children, where MDRD equation is not validated

Exogenous markers
Inulin clearance = Gold standard measure of GFR
Infusion of inulin and urinary clearance
Collect blood and urine samples
Gold Standard measure of GFR
51
Cr-EDTA = standard clinical measure of GFR
Injection bolus of 51Cr-EDTA
Collect blood samples
Calculate eGFR from known amount injected and the decrease
in activity over time

Endogenous markers
Cystatin C
Protein produced by all nucleated cells
More specific than creatinine
But assay = expensive
Other tests for assessment of
kidney function
U&Es
CAPR


Urine analysis
Urine dipsticks
Urine proteins
Protein - proteinuria
Blood - haematuria
Proteinuria (1)
> half is Tamm-Horsfall protein, a protein
secreted by renal tubules
Others:
Albumin (because of its abundance in plasma)
Smaller proteins freely filtered by the glomerulus
In health ~ 150 mg/day of protein in urine
Large proteins are prevented from entering the nephron
lumen by the glomerulus
Small proteins are freely filtered by the glomerulus, but
most are digested into amino acids in the renal tubules
and reabsorbed
Proteinuria (2)
In kidney disease, these can go wrong and
increased levels of protein are seen in urine

Damaged to glomerulus can cause large proteins
or blood cells to leak through

Damage to the tubules can cause proteins (and
other things such as K
+
not be reabsorbed)


Proteinuria assessed by:
Urine dipsticks
ACR Albumin:creatinine ratio
PCR Protein:creatinine ratio
Total protein/ 24 hrs
Proteinuria (3)
ACR = Albumin Creatinine Ratio
Random urine sample
Differences in concentration are corrected
for by measuring Creatinine
PCR = Protein Creatinine Ratio

ACR more sensitive as measuring albumin which is
only JUST excluded by glomerulus
Also more standardised as a specific method
Measured in ALL diabetics on an annual basis to
screen for early signs of kidney disease
ACR = Urine Albumin
Urine Creatinine
PCR = Urine Total protein
Urine Creatinine
Summary Physiology & Function
Kidneys filter the blood to excrete toxins such as urea
and creatinine while altering reabsorption and excretion
of sodium, potassium, water to regulate their balance

They also play a role in acid-base homeostasis
Kidneys also:
Activate vitamin D (by 1-hydroxylase)]
Synthesize and secrete renin
Synthesize and secrete erythropoietin
The kidneys contain ~1 millions functional units called
nephrons

These have a glomerulus, proximal convoluted tubule,
loop of Henle, distal convoluted tubule and collecting
duct
Summary - Assessment
Excretion of creatinine:
Creatinine clearance
eGFR
Urea and Electrolytes:
Raised K
+
Raised Urea and Creatinine
Proteinuria
Dipsticks
PCR, ACR
24 hr urine protein
References
Clinical Biochemistry An illustrated
colour text by Allan Gaw

Clinical Chemistry by Marshall & Bangert
Little Marshall

ACB Publication: Kidney Diseasae and
Laboratory Medicine by Edmund Lamb &
Michael Delaney
Any Questions?