Gross Anatomy of the Kidney

The kidneys are a paired organ; one kidney weighs 120–200 g. The normal
kidney measures 10–12 cm vertically, 5–7 cm transversely and 3 cm a.p. The
outer surface can be divided into anterior side, dorsal side, upper pole and
lower pole. The lateral surface is convex. The medial surface is concave,
deeply grooved (renal sinus) and forms the renal hilum. The ureter/renal
pelvis, renal artery, renal vein, lymphatic vessels and nerves enter or exit
through the renal hilum the kidney.

Fascias of the kidney

The kidneys have a tough organ capsule (Capsula fibrosa), which follows
medially the renal parenchyma and does not surround the renal hilum. The
kidneys are surrounded by a layer of perinephric fat (Capsula adiposa). The
perinephric fat is surrounded by a connective tissue sheath, Gerota's
fascia (Fascia renalis). Gerota's fascia surrounds the kidney, including
perinephric fat and the adrenal gland. Cranially and laterally, the Gerota's
fascia is closed by fusion of the anterior and posterior sheat. Medially and
inferiorly, there is no connection between the anterior and posterior sheat of
the Gerota's fascia: renal fluid collections can drain into the pelvis. The
anterior sheat of the Gerota's fascia lies immediately below the parietal

peritoneum [fig . renal and retroperitoneal fascias].

1
 fig. renal and retroperitoneal
fascias: fascia transversalis
(1), anterior sheat of the
Gerota's fascia (2), parietal
peritoneum (3), perinephric
fat (Capsula adiposa) (4),
paranephric fat (5), M.
quadratus lumborum (6), M.
erector spinae (7). Figure
from Gray's Anatomy, Lea
and Febinger 1918,
Philadelphia, USA.

Topographic Anatomy of the kidneys

The kidneys are located in the retroperitoneum, right and left of the spine and below
the diaphragm. Normal position:

 Left kidney: from the 11th rib to third lumbar vertebra.

 Right kidney: slightly lower position, 12th rib to the lower part of the third
lumbar vertebra.

Topographic Anatomy of the Right Kidney

 Dorsally: 12th rib, subcostal nerve, iliohypogastric nerve, ilioinguinal nerve,

quadratus lumborum muscle, diaphragm with pleura at the upper pole

2
 Cranially: adrenal gland.

 Medially: psoas major muscle, inferior vena cava, ovarian/testicular vein,

ureter.

 Ventrally: liver, duodenum, ascending colon.

Topographic Anatomy of the Left Kidney

 Dorsally: 11th and 12th rib, subcostal nerve, iliohypogastric nerve,

ilioinguinal nerve, quadratus lumborum muscle, diaphragm with pleura at
the upper pole

 Cranially: adrenal gland, spleen.

 Medially: psoas major muscle, aorta, ovarian/testicular vein, ureter.

 Ventrally: spleen, pancreas, stomach, descending colon.

Internal Anatomy of the Kidneys

The renal parenchyma has two distinct components: the renal cortex and the renal
medulla. Since the form of the renal medulla is of pyramid shape, it is also
called renal pyramids. In longitudinal section, the individual functional units of the
kidney can be seen [fig. internal anatomy of the kidney]. The kidney consists of 7–
9 renal lobes. Each lobe has a renal pyramid and is surrounding by cortex. Each
lobe drains with its collecting tubules to an own renal calix, the collecting tubules
indent the calix and form the renal papilla. Each kidney has 7–9 calices. The cortex-

3
like parenchyma in between the renal pyramids is called renal columns of
Bertin (Columnae renales).

The human kidney is principally a blend of about 14 single kidneys. In other

species, the morphological separation of the single kidneys is more clearly visible
(renculation). As a morphological variant, renculation is seen as Ren lobatus in
some men, too.

The urine drains from the calix via the renal pelvis into the ureter.

fig. internal anatomy of the

kidney: renal pyramids (renal
medulla) (1), renal cortex (2), minor
calices (3), renal papilla (4), major
calix (5), Sinus (6), Columns of
Bertin (7), neck of calix (8), renal
pelvis (9), ureter (10). Fig. from
Gray’s Anatomy, Lea and Febinger
1918, Philadelphia, USA.

4
Vascular Supply of the Kidney: Renal Artery, Vein and
Nerves

Renal Artery

The kidneys are supplied by parietal branches of the aorta (renal artery). The
vascular supply (A. renalis dexter et sinistra) is often subject to variations. The right
renal artery passes under the vena cava to the right kidney. Both renal arteries run
together with the renal veins.

Renal Vein

The renal veins drain into the vena cava inferior. The left renal vein is longer and
passes over the aorta below the superior mesenteric artery into the vena cava.

Lymphatic Vessels of the Kidney

The left kidney drains into the paraaortic lymph nodes. The right kidney drains into
the paracaval and interaortocaval lymph nodes. The cranial and caudal extent of the
renal lymph nodes along the vena cava and aorta ranges from the inferior mesenteric
artery to the diaphragm.

5
Innervation of the kidney

The renal plexus is located around the renal artery and contains postganglionic
fibers from the sympathetic nervous system (Th10 to L2). The nerve fibers from the
plexus enter the kidney with the branches of the renal artery and regulate the
vascular tone and the secretion of renin.

The renal function is not dependent of the above mentioned innervation, as shown
with the renal function after renal transplantation (complete transsection of the
innervation). Most of the renal functions are regulated by hormones.

Benninghoff 1993 BENNINGHOFF, A.:

Makroskopische Anatomie, Embryologie und Histologie des Menschen.
15. Auflage.
München; Wien; Baltimore : Urban und Schwarzenberg, 1993

Glomerular Filtration Rate

In the glomerulus, the primary urine is filtered from the blood, which flows through
the capillaries of the glomerulus. With the exception of proteins over a molecular
mass of 10 kDa, all components of the plasma are filtered into the primary urine.
Subsequently, the active and passive reabsorption of important substances in the
renal tubules from the primary urine is of elementary importance (see tubular
reabsorption .

6
The renal blood flow is approximately 20% of the cardiac output at rest (1–1.2
l/min). About 10% of renal blood flow is filtered and make up the primary urine. The
filtration speed of the primary urine is called glomerular filtration rate (GFR) and is
approximately 120 ml/min. The following variables increase the GFR: increased
hydraulic pressure in the glomerular capillaries and the area (amount) of glomerular
capillaries. The following variables decrease the GFR: increased hydraulic pressure
in the Bowmann's capsule, increased colloid osmotic pressure in the glomerular
capillaries, decreased permeability of the glomerular capillaries.

Regulation of Glomerular Filtration Rate

The hydrostatic pressure in the glomerular capillaries is directly dependent on the

arterial blood pressure and is the decisive factor for the normal regulation of the
glomerular filtration rate (GFR). Several kidney mechanisms provide for a constant
GFR over wide ranges of physiological blood pressure variations.

Autonomic vasoreactive (myogenic) reflex:

Blood pressure fluctuations are compensated by vasoconstriction and vasodilation of
the afferent arteriole.

Tubuloglomerular feedback:
Increased hydrostatic pressure in the glomerulus leads to glomerular hyperfiltration
and increased fluid load on the tubule. This is registered at the macula densa of the

7
distal tubule and leads to vasoconstriction of the afferent arteriole using the
transmitters ATP and adenosine.

Renin-angiotensin system:
Low blood pressure and decreased kidney perfusion result in the release of renin
and activation of angiotensin II via intermediate steps [see Renin-Angiotensin-
System]. Angiotensin II leads to vasoconstriction of the efferent arteriole and
increases the filtration pressure in the glomerulus.

Renal Clearance

The glomerular filtration rate cannot be measured directly. For approximation, the
elimination of a substance is measured, which is

 completely filtered with the primary urine

 not reabsorbed in the renal tubules

 not secreted in the renal tubules

Definition of the Renal Clearance (Cl)

Renal clearance is the virtual plasma volume per minute, from which a substance is
completely eliminated. If a substance is chosen, which is not secreted or reabsorbed

8
in the renal tubules, the measured clearance corresponds to the glomerular filtration
rate (GFR).

Calculation of the creatinine clearance

The concentration of creatinine (UKrea in mg/dl) and the urine volume (Uvol in ml)
of a 24 hour urine collection is measured. In addition, the serum concentration of
creatinine (PKrea in mg/dl) is measured. The time span of the urine collection has to
calculated in minutes (usually 24 h = 1440 min). The creatinine clearance (ClKrea)
is calculated with the following formula:

Calculation of the creatinine clearance

An estimation of the creatinine clearance can be obtained using the formula of

Cockroft and Gault using the serum concentration of creatinine (SKrea in mg/dl),
gender (factor F=72 for men and F=85 for women), weight (kgKG in kg) and age
(Alter in years):

Estimation of the glomerular filtration rate

using the formula of Cockroft and Gault

9
Substances with exclusive glomerular filtration (without tubular secretion or
reabsorption) as creatinine have serum concentrations in direct dependence of the
glomerular filtration rate (GFR). A halving of GFR leads to a doubling of the serum
creatinine concentration. This means, that a reduction of the GFR by 75% leads to a
significant fourfold increase of the serum creatinine concentration. Further (only
slight) reductions in GFR lead to dramatic increases creatinine concentrations
[fig. creatinine concentration and GFR].

fig. creatinine
concentration in
dependence of the
glomerular filtration rate
(GFR). Only a pronounced
reduction of the GFR leads
to a significant rise of the
serum creatinine
concentration.

Tubular Reabsorption of Sodium, Chloride and Fluids

99% of the glomerular filtrate volume (primary urine, 120 ml/min), 99% of the
filtrated sodium and 99% of the filtered Chloride are reabsorbed in the renal tubules
of the nephron. The reabsorption is energy consuming process; the needed energy

10
rises linearly with the NaCl-Reabsorption. The most common drive for the
reabsorption is the basolateral located Na-K-ATPase (sodium-potassium pump),
which transports three sodium atoms out of the cell and two potassium atoms into
the cell, the energy derives from the hydrolysis of one ATP molecule.

Proximal Tubule and Descending Part of the Henle Loop

In the proximal tubule, two thirds of the primary urine volume with electrolytes are
reabsorbed. Electrolyte reabsorption leads to the water reabsorption with help of the
leaky intercellular spaces of the proximal tubule epithelium. The solvent dragenables
the paracellular absorption of water and chloride due to electrolyte concentrations
between the tubule lumen and the renal interstitium.

The drive of the sodium transport is accomplished through the basolateral sodium-
potassium-pump. On the luminal side of the proximal tubule epithelium, sodium
enters the cell via symporter membrane proteins (Co-transport with glucose,
galactose, phosphate, sulfate or amino acids) or antiporter membrane proteins (Co-
transport with protons). The reabsorption of HCO3− is linked to the sodium
reabsorption and proton secretion with help of a luminal and intracellular carbonic
anhydrase.

The chloride reabsorption is not so clearly identified. Beside the solvent drag, there
are additional minor transcellular transport pathways for chloride in the luminal and
basolateral membrane.

11
Ascending part of Henle Loop

The thick ascending loop (TAL) of Henle is impermeable to water and transports
electrolytes into the interstitium of the kidney, producing a high osmotic pressure of
the interstitium. 30% of the filtered sodium is reabsorbed using a luminal Na-K-2Cl-
cotransport mechanism. The energy for the natrium reabsorption derives from the
basolateral sodium-potassium pump. The effective prevention of a passive water
flow with watertight tight junctions leads to a high osmotic pressure in the renal
medulla. The urine at the end of the TAL is hypotonic. Furosemide inhibits the Na-
K-2Cl cotransporter and leads to a massive natriuresis and loss of potassium,
calcium and magnesium.

Distal tubule

Active sodium transport via thiazide-sensitive Na-Cl-co-transporter; about 10% of

the filtered sodium is reabsorbed in the distal tubule. Thiazides inhibit the sodium
reabsorption in the distal tubule and lead to a mild diuresis without loss of calcium
(calcium-sparing diuretic).

Collecting Ducts

The permeability of the collecting ducts for water lead to a concentration of the
urine up to the fivefold osmolarity of the plasma. The permeability of the collecting
ducts is regulated with ADH (antidiuretic hormone, Vasopressin). ADH causes the
incorporation of additional water channels (aquaporins) into the luminal membrane.

12
The high osmotic pressure of the renal medulla is the responsible force for the urine
concentration. ADH can control 10% of the primary urine volume, thus can regulate
the diuresis between 1–20 l/d.

In the absence of ADH, the permeability of the collecting ducts for water is low, the
urine will not be concentrated. A deficiency of ADH secretion leads to diabetes
insibitus, a disorder with massive diuresis and excessive thirst.

Additional sodium reabsorption takes place in the collecting ducts via luminal
sodium channels. The energy for the sodium reabsorption derives from the
basolateral sodium-potassium pump. Aldosterone regulates the sodium and water
reabsorption and potassium secretion via expression of the sodium channels and the
basolateral sodium-potassium pump. The luminal sodium channels can be inhibited
by amiloride, a potassium-sparing diuretic.

Potassium reabsorption of the kidney

60–70% of the filtered potassium (K+) is reabsorbed in the proximal tubule. There
are no specific K-transporter, reabsorption is managed with the absorption of water
(solvent drag). 25–35% of the filtered potassium is reabsorbed in the loop of Henle
with the Na-K-2Cl-cotransport mechanism. 5–15% of the filtered potassium reaches
the distal nephron. Depending on the metabolism there are now possibilities of
potassium reabsorption or excretion (controlled by aldosterone).

13
Renal Calcium Reabsorption

60% of the filtered calcium is reabsorbed in the proximal tubule with the
paracellular absorption of water (solvent drag). Additionally, there are active
transport mechanisms.

Renal Phosphate Reabsorption

Phosphate is completely filtered, 80–90% of the phosphate are reabsorbed in the

proximal tubule. With high phosphate concentrations in serum, a saturation of the
phosphate reabsorption is reached and phosphate is excreted till the normalization of
the phosphate concentration. An increased phosphate concentration is the stimulus
for the parathyroid hormone release and leads to phosphate excretion, calcium
phosphate deposition into the bone and lowers the serum calcium.

Proton Excretion and Acid-Base Homeostasis

The renal excretion of protons is a major factor in the acid-base homeostasis;

mechanisms are the phosphate excretion, ammonia excretion and reabsorption of
bicarbonate.

14
Phosphate Excretion:

Phosphate dissociates in the blood to 80% in HPO42-. In the renal tubulus, this
secondary phosphate binds a proton and the result is H2PO4−. The newly formed
primary phosphate cannot be reabsorbed and with the help of phosphate excretion, a
proton is eliminated.

Bicarbonate Reabsorption:

Glomerular filtered bicarbonate is reabsorbed in the proximal tubule via the

following mechanism: the filtered HCO3− and secreted H+ from the tubular cell
(Na-H exchanger) forms with the help of luminal carbonic anhydrase H2CO3, which
dissociates to CO2 ad H2O. The CO2 enters easily into the tubule cell and binds
with OH− (remnants of the H+ secretion) to bicarbonate (HCO3−). With the help of
the Na+/HCO3−-cotransporter in the basal membrane, bicarbonate is returned into
the blood. In the case of alkalosis, bicarbonate can be secreted to balance the acid-
base homeostasis.

Ammonium Excretion:

The ammonium excretion can be 10-fold increased in case of acidosis. NH3 is

formed in the kidney by deamination of glutamine by the tubular cells and can
diffuse into the tubular lumen. In the renal tubules, NH3 forms together with a
proton NH4+, which cannot be reabsorbed.

15
Glucose Reabsorption in the Kidney

Glucose reabsorption happens to 100% in the proximal tubule using the sodium-
glucose-cotransporter. In the case of too high glucose concentration in the serum,
this mechanism is subject to saturation and glucosuria results. The threshold
concentration for this saturation is 10 mmol/l (180 mg/dl) of glucose in the serum.

Amino Acid Reabsorption in the Kidney

Different sodium-amino acid cotransporter are responsible for the reabsorption of

amino acids in the proximal tubule. So far, seven different transporters have been
described: for acidic amino acids (Glu, Asp), basic amino acids (Arg, Lys, Orn) and
five other systems for neutral amino acids. There are similar principles for the
saturation of the amino acid transport as for glucose reabsorption (see above). The
failure of amino acid cotransporter, usually for genetic reasons or side effects of
medication, causes selective aminoaciduria (Cystinuria, Hartnup's disease, Fanconi
syndrome).

Urea Transport of the Kidney

About 50 g of urea are filtered per day, of which approximately 25–40 g are
excreted in the urine. The reabsorption of urea (proximal tubule, collecting ducts)
and active secretion of urea (Henle loop) leads to a urea circulation between the

16
lumen of the nephron and renal medulla, which is an important element of the renal
urine concentration.

Urea is freely filtered, 50% are reabsorbed in the proximal tubule with the
reabsorption of water (solvent drag). Urea is secreted in the thin ascending limb of
Henle loop, so significant amounts of urea reach the distal nephron. In the collecting
ducts, urea is reabsorbed together with water. These mechanisms enable the
formation of a high-osmolar urea gradient in the renal medulla, which is important
for the renal urine concentration. If the absorption of urea (and water) is stopped in
the collecting duct, the osmolarity of the medulla decreases and the concentration
mechanisms collapse.

Uric acid transport of the kidney

Uric acid is filtered completely and is partially absorbed in the proximal tubule. In
addition, uric acid is secreted in the proximal tubule. Uric acid is has a good
solubility in form of sodium urate. To prevent calcium urate crystals in the course of
the urine concentration, various complexing agents such as calcium citrate, calcium-
binding proteins and mucopolysaccharides are necessary.

Mechanism of the Urine Concentration

In the case of water deficiency, the human kidney can concentrate the urine up to 4
times of the plasma osmolarity of 290 mosmol/l. With antidiuresis, the daily urine

17
volume is 0.5–1 l. A complex countercurrent system, which includes the Henle
loops, Vasa recta and collecting ducts, generates a hypertonic renal medulla of 1200
mosmol/l. The high osmolarity of the renal medulla enables a urine concentration
with a urine osmolarity up to these values.

Renal Countercurrent System

The motor of the renal countercurrent system and the urine concentration is the
NaCl reabsorption of the thick ascending loop (TAL) of Henle. The active Na+ and
Cl−transport in the watertight ascending Henle loops leads to an increase in
osmolarity of the renal interstitium. Another mechanism of the high osmolarity of
renal medulla is the reabsorption of urea (proximal tubule, collecting ducts) and
active secretion of urea (Henle loop). The urea circulation between proximal and
distal nephron helps to establish the gradual increase in osmolarity in the direction
of the renal papillae.

The blood supply of the renal medulla is scarce and also designed on the principle of
countercurrent; the high osmolarity is not washed out. The osmolarity increases in
the vasa recta in direction to the renal papillae and decreases in the outflow towards
the cortex. In principle, the osmotically active substances of the renal interstitium
circulate continuously. In the case of an increased renal blood flow, the renal
interstitium loses osmotically active substances. The result is a so-called pressure
diuresis, a mechanism to correct arterial hypertension.

18
Function of the Renin-Angiotensin-Aldosterone System
(RAAS)

The RAAS plays a central role in blood pressure regulation and consists of a
cascade of functional proteins (renin, angiotensinogen, angiotensin I and II)
[fig. cascade of the renin-angiotensin-aldosterone system]. The physiological
importance of the RAAS is the compensation of hypovolemia, hyponatremia and
hypotension. In people with normal blood pressure and a balanced salt homeostasis,
the RAAS is not activated. The RAAS receives pathophysiological significance in
incorrect activation, e.g. in renal artery stenosis, heart failure or advanced liver
disease.

Activation of the Renin-Angiotensin-Aldosterone System

(RAAS)

The cascade renin-angiotensin-aldosterone system begins with the cleavage

of angiotensinogen to angiotensin I (Ang.I), mediated by renin. This is the rate-determining step.
Next, angiotensin-converting enzyme (ACE) cleaves angiotensin I and produces angiotensin II
(Ang.II), an extremely potent vasoconstrictor. In addition, Angiotensin II stimulates the release
of aldosterone from the adrenal cortex.

19
fig. Cascade for the activation of the renin-angiotensin-aldosterone system (RAAS). Description see text.

Renin

Renin is an aspartyl protease, which specifically cleaves angiotensinogen into

angiotensin I (Ang.I). It is the rate-determining step of the RAAS. Renin is produced
in the juxtaglomerular cells of the afferent arteriole in the kidney, but is also detected
in other organs with a local RAAS.

Control of renin release:

The release of renin requires the uses the adenylate cyclase and formation of cAMP
as second messenger system. The following stimuli lead to a renin release with
activation of the renin-angiotensin-aldosterone system:

 Macula densa: reduced sodium and chloride concentration in the distal tubule

20
  Baroreceptors of the afferent arterioles: decreased blood pressure

 Neural mechanisms: the juxtaglomerular cells are innervated by abundant

beta-adrenergic sympathetic nerve fibers. Their activation leads to renin
secretion.

 Hormonal mechanisms: histamine, dopamine, epinephrine, prostaglandin I2

(prostacyclin) and E2 stimulate renin release. Inhibitory effects have
angiotensin II, ANF, endothelin and vasopressin.

Angiotensinogen

The function of angiotensinogen is a serine protease inhibitor. Renin cleaves

angiotensinogen into angiotensin I. Angiotensinogen is produced in the liver, but it is
also formed in the CNS, kidney, adrenal gland, leukocytes and heart. Angiotensin II,
estrogen and glucocorticoids stimulate the synthesis of angiotensinogen, whereas
renin is inhibitory.

Angiotensin converting enzyme (ACE)

Angiotensin converting enzyme (ACE) is a zinc-containing glycoprotein with

dipeptidyl-carboxy peptidase activity. ACE cleaves two amino acids from
angiotensin I, turning it into angiotensin II. Other proteases can also non-specifically
activate angiotensin II. Furthermore, ACE inactivates the bradykinin-kallikrein-kinin
system. ACE is produced by many endothelial and epithelial cells, the pulmonary

21
activity is very high. For the RAAS, the activity of ACE is not the rate-determining
step.

Angiotensin II (Ang.II)

Angiotensin II (Ang.II) is an octapeptide, which is produced by proteolytic cleavage

(ACE) of two amino acids from angiotensin I. The following functions are known:

Angiotensin II regulates the glomerular filtration rate:

With a reduced renal perfusion, Ang.II leads to a constriction of the vasa efferentes
and thus to an increased filtration pressure. ACE inhibitors can lead to acute renal
failure, when given in renal artery stenosis, because the renal perfusion is
completely dependent on the RAAS.

Angiotensin II increases the tubular sodium reabsorption and urine concentration:

Ang.II reduces the medullary blood flow; this increases the osmolarity of the renal
medulla, the tubular sodium reabsorption and the urine concentration.

Angiotensin II is a potent vasoconstrictor:

Ang.II directly stimulates the smooth muscle contraction in resistance vessels and
raises the blood pressure.

Angiotensin II stimulates aldosterone release:

22
Ang.II acts on the adrenal cortex, causing it to increase aldosterone production and
release.

Angiotensin II has effects on the central nerve system:

Ang. II stimulates the blood pressure, increases thirst and salt appetite.

Molecular mode of action of angiotensin II:

The effects of angiotensin II are mediated by angiotensin receptors (AT1 and AT2).
The vascular effects of Ang.II are mediated by AT1 receptors. The signal
transduction of AT1 receptors starts with G-protein receptors, this leads to an
intracellular activation of phospholipase C, DAG, IP3 and protein kinase C.
Antagonist to AT1 receptors are the sartans, e.g. losartan, which are used for
antihypertensive treatment.

Aldosterone

Aldosterone is a steroid hormone from the adrenal cortex, which important

influences on the water- and salt balance (mineralocorticoid).

Molecular mode of action of aldosterone:

Aldosterone is lipophil, enters easily the target cell and binds to the nuclear steroid
receptor proteins. The activated steroid receptors bind to specific DNA sequences
(hormone response elements, HRE) and lead to an increased gene expression.

23
Aldosterone promotes sodium and water retention, raises the blood pressure and
lowers the potassium concentration. The effects of aldosterone take place in several
organs:

 Kidneys: increased expression of sodium-potassium pumps, increased luminal

permability for Na+ .

 Sweat glands: stimulates Na+ and water reabsorption in exchange for K+

 Gastrointestinal tract: stimulates Na+ and water reabsorption in exchange for

K+

Erythropoetin (EPO)

Erythropoetin, also spelled Erythropoietin, is a growth hormone that controls

erythropoieses (formation of red blood cells). Target cells of Erythropoetin are the
red cell precursors in the bone marrow (colony forming unit-erythroid, CFU-E). The
duration of the erythrocyte development from precursors to the reticulocyte takes 7
days and includes 4–6 cell divisions.

24
Molecular Structure of Erythropoetin

Erythropoetin is a glycoprotein, the protein part consists of 165 amino acids and
mediates the cytokine function. The carbohydrate part of 40% protects the hormone
from proteolysis in vivo. Overall, Erythropoetin has a mass of 30 kDa. Minor
differences in the carbohydrate part between physiological and recombinant
Erythropoetin enables doping controls using electrophoresis.

Production Location of Erythropoetin

During fetal hematopoiesis, erythropoetin is formed in the liver. After birth, most of
the erythropoetin is produced in interstitial peritubular kidney cells (fibroblasts) in
the renal cortex. In small amounts, Erythropoetin is also produced in the CNS and
has functions in the neuroprotection.

Concentration of Erythropoetin

The concentration of Erythropoetin is expressed in Units (U). 1 U Erythropoetin

corresponds to the erythropoietic activity of 5 g cobalt chloride in animal
experiments. The normal concentration in blood is 5-25 U/l, during hypoxia or
anemia, the concentration increases up to 10 000 U/l.

25
Control of Erythropoetin

The physiological stimulus for the production and secretion of Erythropoetin is

hypoxemia and anemia. The signal transduction cascade for the activation of
Erythropoetin is complex and involves HIF 1–3 (hypoxia inducible factors) and
HRE (hypoxia response elements) sequences of the DNA. After the release,
Erythropoetin binds to the Erythropoetin receptor of the target cells CFU-E, which
is a tyrosine kinase receptor. The signaling prevents apoptosis of the target cell in
the bone marrow.

Endothelins

Endothelins are a group of peptide hormones, which are activated via a cascade
system like the renin-angiotensin-aldosterone system (RAAS). Functions of
endothelins are potent vasoconstriction, retention of sodium and raising the blood
pressure. Furthermore, endothelins have pathophysiological significance in kidney
diseases, heart failure, arteriosclerosis and pulmonary hypertension.

Further Endocrine Functions of the Kidney

Activation of Vitamin D

Hydroxylation of 25-hydroxyvitamin D3 to 1,25-hydroxyvitamin D3 (cholecalciferol

= calcitriol).

26
References

Benninghoff 1993 BENNINGHOFF, A.:

Makroskopische Anatomie, Embryologie und Histologie des Menschen.
15. Auflage.
München; Wien; Baltimore : Urban und Schwarzenberg, 1993

Jelkmann 2004 JELKMANN, W.:

Molecular biology of erythropoietin.
In: Intern Med
43 (2004), Nr. 8, S. 649–59
http://www.urology-textbook.com/

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