Chapter 18
Renal Failure
1
Section I .
Introduction
2
Kidneys are the principal excretive organs
Not only excrete waste metabolic products
to remove various harmful substances,
But also regulate a variety of material in plasma
to maintain the homeostasis of internal environment
(osmolality and acid-base balance)
Besides, kidneys also produce some bioactive substances
renin, prostaglandins (regulation of blood pressure)
erythropoietin (formation of matured RBCs)
active vitamin D (metabolism of calcium and phosphorus)
3
Kidneys are the principal excretive organs
Not only excrete waste metabolic products
to remove various harmful substances,
But also regulate a variety of material in plasma
to maintain the homeostasis of internal environment
(osmolality and acid-base balance)
Besides, kidneys also produce some bioactive substances
renin, prostaglandins (regulation of blood pressure)
erythropoietin (formation of matured RBCs)
active vitamin D (metabolism of calcium and phosphorus)
4
The following pathologic process is termed ''renal failure'':
Various causes
Severely impair renal function
Glomerular filteration rate↓
Retention of metabolic wastes, Disturbanc of internal environment
a serial of clinical manifestations
Renal Failure
Acute renal failure (ARF)
(CRF) Cronic renal failure
Uremia
5
1. Causes of renal dysfunction
(1) Primary renal disease
(2) Renal injury secondary to systemic diseases.
6
1. Causes of renal dysfunction
(1) Primary renal disease
(2) Renal injury secondary to systemic diseases.
1) Glomerular disease
glomerulonephritis; nephrotic syndrome
2) Renal tubular disease renal glucosuria;
aminoaciduria, renal tubular acidosis
3) Interstitial nephritis
acute or chronic interstitial inflammation
4) Others: renal injury, tumor, calculus;
obstructive nephropathy;
vascular nephropathy
7
1. Causes of renal dysfunction
(1) Primary renal disease
(2) Renal injury secondary to systemic diseases
.
1) Circulatory system diseases: Shock, AS, thrombosis, etc.
2) Auto-immune and connective tissue diseases:
Lupus nephritis, renal injury by rheumatoid arthritis, etc
3) Metabolic diseases: Nephropathy caused by amyloidosis,
diabetic or hyperuricemia
4) Hematological diseases: Renal injury by plasmacyte disease,
multiple myeloma or leukemia
5) Others: Heart failure, hepatic disease, endocrine disease
and malignant tumors
8
2. The basic manifestation of RF
The anatomic and functional unit of kidney is nephron, which
consists of glomerulus and renal tubule. Each human kidney
has approximately 1 million nephrons. The glomerular function
is to form original urine by filtration, while the tubule perform
reabsorption and secretion. The basic presentation of RF include:
(l) Dysfunction of glomerule
(2) Dysfunction of renal tubules
(3) Dysfunction of renal endocrine
9
(l) Dysfunction of glomerule
20% of CI
Renal blood flow
Effective filtration pressure of the glomerule 
Kf (LPA, permeability and total filtration area) 
GFR 
125ml/min
180L/day
99%
Alteration of urinary quantity
Permeability 
(of glomerular filtration membrane)
Abnormality of urinary quality
(hematuria & proteinuria)
1.5L/day
10
(2) Dysfunction of renal tubules
The secretion and reabsorption function are very important
for maintain the homeostasis of internal environment
l ) Principal influencing factors
① Renal tubular EC (may impaired by ischemia,
hypoxia, infection and toxins)
180L/d
99%
② Neuro-humoral factors
(Aldosterone, ADH, ANP, PTH etc.)
③ Concentration and flow rate of the initial urine
(ANP: atrium natriuretic peptide; PTH: parathyroid hormone)
1.5L/d
11
2) Types of renal tubular dysfunction
① Dysfunction of reabsorption
Proximal convoluted tubule: glucosuria, phosphuria,
aminoaciduria, Na+ and H2O retention, renal tubular acidosis
② Dysfunction of concentration and dilution
Henle’s (medullary) loop and collecting tubule:
polyuria, Isosthenuria (isotonic), Hyposthenuria (hypotonic)
③ Acid-base Disturbances
Proximal tubule (secrete H+, NH4+, NH3 ; reabsorb HCO3–);
Medullary loop (reabsorb b HCO3– and NH3)
Distal tubule (secrete H+)
12
(3) Dysfunction of renal endocrine
① Increased secretion of rennin
Renin 
② Declined Kallikrein-kinin system (KKS)
Kinin 
③ Increased secretion of endothelin
ET 
④ Inadequate synthesis of prostaglandins
from arachidonic acid
PGE2 , I2 
Renal Hypertension
13
⑤ Decreased eryhropoietin
EPO 
(90% formed in kidney)
Renal aneamia
⑥ Decreased 1-a-hydroxylase
⑦ Weakened inactivation to PTH
1,25-(OH)2- D3 
PTH 
Renal osteodystrophy
⑧ Weakened inactivation to gastrin
HCI 
Ulceration
14
Section 2.
Acute Renal Failure
15
Various causes
Rapidly and severely decline of GFR
Kidneys fail to excretion and regulation in hours to days
Oliguria or anuria
Retention of nitrogenous wastes (azotemia)
water/electrolyte acid-base disturbance
Oliguria is usually emphasized in the past, but in some cases,
patients have high level BUN (azotemia) while urine volume
does not change. It is called non-oliguria ARF
16
l. Causes and classification
Acute renal failure (ARF) may result from a wide variety of
diseases (shock, heart failure, severe infection, hepatic diseases),
trauma, surgical procedures, drugs, renal toxins and urinary
tract obstruction.
According to causes, ARF may be divided into three main
categories: Prerenal
Intrarenal acute renal failure
Postrenal
17
( l ) Prerenal failure (functional RF or prerenal azotemia)
caused by any disorder external to the kidneys that rapidly
and severely decreases the blood supply to the nephron.
(2) Intrarenal failure (parenchymal RF)
caused by disease of the renal tissue itself, affecting the
blood vessels, glomeruli or tubules.
(3) Postrenal failure (Obstructive RF, Postrenal azotemia)
caused by obstructive disorders (uretal or urethral) that can
block or partially block urine flow, while the kidney's blood
supply and other functions are initially normal.
18
( l ) Prerenal failure
Hypovolemia, Acute heart failure
Sudden decrease of
renal perfusion
GFR↓
Na+, H2O reabsorption↑
Expanded vascular bed volume
(Hepatorenal syndrome
Anaphylactic shock, etc. )
Renal vascular blockage or
auto-regulation disturbances
Azotemia(urinary Cr/plasma Cr > 40 ) Oliguna (<400ml/day)
Urinary Na+<20 mmol/L
Urine gravity > 1.020
No RBC, WBC or cast in urine
19
(2) Intrarenal failure
Causes: intrinsic (parenchymal) renal diseases
1. Renal tubular diseases
Acute renal ischemia
Acute Tubular Necrosis
Acute renal poisoning
(most common)
Renal tubule blocked by Hb or Mb
2. Glomerular diseases
Glomerulonephritis, pye1onephritis, etc
3. Renal interstitial diseases
Severe infection, drug allergy, etc
4. Renal blood vessel diseases
Thrombosis, DIC, etc
20
Clinical features:
1. Oliguria or Non-oliguria
2. Isothenuria
the specific gravity of urine become fixed at 1.010 or 0.285
mOsm / L (equal to the osmotic concentration of plasma), implying
an inability of the kidney to concentration or dilute the urine.
3. Urinary Na+ >40mmo l/L (ability to reabsorb Na + )
4. Hematuria.
5. Azotemia(urinary Cr/plasma Cr < 20)
21
(3) Postrenal failure
Stone or tumor →Bilateral Obstruction
Renal pelvises hydropsy
increased renal interstitial pressure
increased intracapsular pressure →GFR↓↓
suddenly anuria and azotemia
22
2. Pathogenesis
There are three major factors may account
for the development of ARF(ATN):
1. Renal hemodynamic factors
1. Alteration of renal hemodynamics
2. Nephronal factors
2. Renal tubule injury
3. Filtration area and permeability
3. Decreased ultrafiltration coefficient (Kf) of glomeruli
23
2. Pathogenesis
1. Alteration of renal hemodynamics
2. Renal tubule injury
3. Decreased ultrafiltration coefficient (Kf) of glomeruli
24
(l ) Alteration of renal hemodynamics
The decreased renal perfusion caused by renal
vasoconstriction is the principal pathogenesis of ARF.
Effective filtration pressure, FF & Kf 
GFR
Oliguria or anuria
There are many factors may associated with renal
vasoconstriction:.
Renin-Angiotensin System
Catecholamine
Prostaglandins, etc.
25
1) Renin-angiotension system
Toxin , Ischemia
Impairing
proximal convoluted tube and
ascending limb of medullary lope
vasoconstriction
Reabsorption of Na+ 
Na+ in distal convoluted tube
(T-G feedback)
Stimulating macula densa
of juxtaglomerular apparatus
Renal perfusion pressure 
stimulating
juxtaglomerular cells
in afferent arteriole
Activating RAS
26
2) Catecholamine (CA)
Effective circulating blood flow↓ or toxin
3) Prostaglandins
(PG)
→ excitation
of sympathetic-adrenomedullary system
→ CA↑→vasoconstriction
of 2renal
Decreased synthesis
of PG → PGI2/TXA
↓ cortex
especially
afferent
arteriole
4) Endothelin (ET)
→ofrenal
vasoconstriction
Renal diseases may stimulate blood vessel EC to secrete ET.
During ARF the level of plasma ET and the ability of ET-R to
5) Others:
combine ET are all increased, which will directly or indirectly
NO synthesis↓, ADH, PAF and TNF↑and ischemialead to renal vasoconstriction
reperfusion injury → promote ATN
All these go into a vicious circle
and cause increasingly severe damage
27
(2) Renal tubule injury
1) Renal tubule obstruction
Cast formation
2) Renal tubule backflow of original urine
Loss of tubule integrity
28
Renal tubule injury
Renal tubule EC necrosis
Basement membrane broken down
Loss of tubule integrity
Dead and Filtered protein
detached ECs (HB or MB)
Backleak of original urine
into renal interstitium
Cast formation
Interstitial edema formation
Tubule obstruction
Intracapsular pressure 
Effective filtration p 
Oppressing
renal tubule
Aggravate
tubule obstruction
GFR 
Oppression
renal capillary
Aggravate
renal ischemia
Oliguria
29
(3) Decreased ultrafiltration coefficient (Kf)
of renal glomeruli
Decreased filter area↓
structural destruction of filter membrane
Ultrafiltration Coefficient↓
30
3. Clinical course and manifestation
(l) Oliguria type of ARF
(2) Nonoliguria type of ARF
31
(l) Oliguria type of ARF
When various diseases lead to destruction of the tubular
cells of the nephron (as typically occurs in cases of ATN),
a characteristic response pattern is noted.
It usually develops in three stages:
Oliguria phase  diuresis phase  recovery phase
32
l) Oliguria phase
Oliguria:
Urine volume < 400 ml / day, or <50ml / day (anuria)
It usually occurs in one day after renal damage and lasting l-2
weeks. The longer the time last, the worse the prognosis is
A duration more than one month indicates that the necrosis of
tubule is very severe.
33
As the urine formation rapidly diminished, the wastes of
protein metabolism and water, electrolytes accumulate in
extracellular fluid, which is often characterized by:
1. Azotemia
Progressive elevation of NPN (Urea, creatinine, etc.)
2. Hyperkalemia
May lead to ventricular fibrillation and cardiac arrest
(No.1 cause of death)
3. Metabolic acidosis
May depress CNS and heart, aggravate hyperkalemia
4. Retention of water and sodium
Edema, hyponatremia and even water intoxication
would occur if there is water and salts overload
34
2. Hyperkalemia
3. Metabolic acidosis
2. Hyperkalemia
Death Triangle
4.
Edema, hyponatremia and Water intoxication
35
Differences between functional and parenchymal ARF
INDEXES
F - ARF
Urine specific gravity
> l .020
Urine osmolality
> 500 mmol / L
Urine Na+
< 20 mmol / L
Urine Cr / Plasma Cr
> 40
Renal failure index (RFI)
<l
FENa
<l
Urinary sediment
Normal
urine Na+
RFI = urine Cr/plasma Cr;
P - ARF
< l .0l 5
< 350 mmol / L
> 40 mmol / L
< 20
>2
>2
Proteins, cells, casts
urine Na+ /serum Na+
FENa = urine Cr/plasma Cr
36
2) Diuresis phase
If the patient pass through the oliguria phase safely, the tubular
EC may regenerate and the renal function would recover gradually.
An increasing urine volume is a signal of renal EC healing, and
suggests the start-up of diuresis phase if it is more than 400 ml per
day. After then, the urine volume increasing doubly up to 3-5L/day
and may last about one month.
37
The mechanisms for diuresis including:
a) The RBF & GFR recovered gradually while the reabsorption
function of regenerating immature tubules keep on abnormal.
b) The high level of metabolic products retained during the
oliguria phase resulted in a hyperosmolarity diuretic effect.
c) The tubular integrity recovered, interstitial edema subsided, the
casts to be washed out and the tubular obstruction relieved.
38
During this stage, the excretion of urea and other nitrogenous
compounds lags behind that of salt and water as reflected by the
continual rise in the concentrations of these substances for
several days after the onset of the diuresis.
The reason is the incomplete recovery of GFR. Nevertheless,
the tubular function also not well recovered, the kidney still
work as a simple filter. Salt and water loss could occur and lead
to dehydration, hypokalemia and hyponatremia.
39
Therefore, this stage is also considered to be a critical phase,
and it has been pointed out that approximately 25 percent of the
deaths in ARF occurred following the onset of the diuresis.
40
3) Recovery phase
The improvement of renal function leads to a gradual
reduction of BUN and correction of water, electrolytes and
acid-base imbalance. The full recovery is depends on the
healing of tubular ECs.
This process may take up three months to one year.
Unfortunately, not all individuals are restored to health and
may become chronic renal failure due to serious damage of
the renal tubular EC and the fibrosis of renal tissue.
41
(2) Nonoliguric type of ARF
While oliguria is a hallmark of ARF, some patients will develop
an acute lose of renal function without oliguria. The common
cause of this type is renal toxic substances, especially the
aminoglycoside antibiotics and radiography contrast agents.
It is suggested that in such cases, GFR has not been reduced
severely and might remain partial tubule function, but its ability
of concentration is impaired. The urine volume may be more
(about 400-1000ml / day) and the concentration of Na+ in urine
may be lower, while azotemia is still existed.
42
The prognosis of which is better than that of oliguria type. It
might be related to either a milder renal injury or fewer
complications because of better water/ electrolyte and acid-base
balance. However, both types may transform each other, the
nonoliguria type will become oliguria type if having not pay
attention and treat properly.
43
4. Principles of prevention and treatment
(l) Etiologic treatment (shock, infection, DIC, kidney disease,
recover renal perfusion, eliminate tubule obstruction, etc.)
(2) Diuresis (osmolar diuretic: improving perfusion,
excreting toxin and alleviating tubular obstruction)
(3) Maintaining water and electrolytes balance,
correcting hyperkalemia.
(4) Dialysis (peritoneal dialysis or hemodialysis)
44
Summary for ARF
Various causes
Rapidly and severely decline of GFR
Kidneys fail to excretion and regulation in hours to days
Oliguria or anuria
Retention of nitrogenous wastes (azotemia)
water/electrolyte acid-base disturbance
Acute Renal Failure
Intrarenal failure
Acute Renal Failure
RF) Postrenal failure
Prerenal failure (parenchymal
Intrarenal failure
(functional RF)
RF)
(Obstructive RF)
Acute(parenchymal
Tubular Necrosis
Acute Tubular Necrosis
45
Summary for ARF
Pathogenesis
Toxin , Ischemia
renal tubule injury
Renal hemodynamic alteration
Backleak of original urine
into renal interstitium
Tubule obstruction
Oliguria
effective
filtration pressure
GFR
renal vasoconstriction
renal perfusion 
glomerular Kf 
46
Summary for ARF
Clinical course and manifestation
(l) Oliguria type of ARF
Oliguria phase  diuresis phase  recovery phase
hyperkalemia
Metabolic acidosis
water intoxication
Differences between functional and parenchymal ARF
( Urine specific gravity, osmolality, Na+, Cr , sediment )
(2) Nonoliguric type of ARF
GFR has not been reduced severely and might remain partial
tubule function, but its ability of concentration is impaired
47
Today’s question
(l) What are the primary causes of death in
oliguria type of ARF?
Hyperkalemia; metabolic acidosis; water intoxication
(2) How to differentiate the functional and
parenchymal ARF
INDEXES
Urine specific gravity
Urine Na+
Urine Cr / Plasma Cr
Urinary sediment
F - ARF
> l .020
< 20 mmol / L
> 40
Normal
P - ARF
< l .0l5
> 40 mmol / L
< 20
Proteins, cells, casts
48
Section 3.
Chronic Renal failure
49
CRF is characterized by progressive and irreversible loss
of large numbers of functioning nephrons, which lead to a very
significant reduction in GFR. The remnant nephron fail to
excrete waste metabolic product and keep the constancy of
internal environment.
Various diseases (kidney or kidney-related diseases)
progressive irreversible destruction of nephron
CRF
Retention of waste metabolic products
Water/electrolyte and acid-base imbalance
Disturbance of renal endocrine
50
A wide variety of renal disorders, including disorders of
the blood vessels, glomeruli, tubules, renal interstitium
and lower urinary tract, can cause CRF.
Common causes:
Primary--Chronic glomerulonephritis, interstitial nephritis;
Secondary--diabetic or hypertensive nephropathy
(The incidence of secondary CRF is increasing recently, about 36% and
30% of CRF caused by diabetes and hypertension respectively in USA.)
CRF is the ultimate common outcome of various kidney or
kidney-related diseases and have been called:
End-stage renal disease (ESRD).
51
1. Process of disease
The general course of progressive renal failure may be divided into 4 stages
Stages
Compensatory Stage
GFR
(ml/min)
BUN
(mmol/L)
BCr
(umol/L)
>50
<9
<178
25~50
9~20
178~445
Renal failure
<25
20~28
451~707
Uremia
<10
>28.6
>707
Decompensatory Stage
(renal insufficiency)
BCr = blood level of creatinine
52
Compensatory
Stage
Clinical manifestation
(1)
Uremic stage
Renal failure stage
Asymptomatic
Decompensatory stage
Compensatory stage
% of normal clearance rate of Cr
CCr GFR
BUN
BCr
(%) (ml/min) (mmol/L) (umol/L)
>30
>50
<9
<178
Clinical
Asymptomatic
53
Decompensatory
Stage
Clinical manifestation
(2)
Uremic stage
Renal failure stage
Asymptomatic
Decompensatory stage
Compensatory stage
% of normal clearance rate of Cr
CCr GFR
BUN
BCr
(%) (ml/min) (mmol/L) (umol/L)
25~30 25~50
9~20
178~445
Clinical
Lassitude, Mild anemia, Nocturia,
Alimental tract discomfort
54
Renal failure
Stage
Clinical manifestation
(3)
Uremic stage
Renal failure stage
Asymptomatic
Decompensatory stage
Compensatory stage
% of normal clearance rate of Cr
CCr GFR
BUN
BCr
(%) (ml/min) (mmol/L) (umol/L)
20~25 <25
20~28 451~707
Clinical
Anemia, Acidosis, Cl－↑, Na+↓
Hypocalcemia, Hyperphosphatemia
55
Uremic Stage
Clinical manifestation
(4)
Uremic stage
Renal failure stage
Asymptomatic
Decompensatory stage
Compensatory stage
% of normal clearance rate of Cr
CCr GFR
BUN
BCr
(%) (ml/min) (mmol/L) (umol/L)
<20
<10
>28.6
>707
Clinical
Various uremic symptoms
56
2. Pathogenesis
Despite primary causes, the pathogenesis of CRF is a process
in which
the nephrons to be damaged continually
the renal function to be declined progressively until failed.
The remnant nephrons (so called intact nephrons) are
compensatory hypertrophy, but their number decreasing
day by day and finally become decompensatory.
The degree of renal dysfunction depends on the number
of intact nephron
57
There are two principal types of nephron injury:
(1) Glomerulosclerosis
(2) Tubulointerstitial injury
1) Alteration of glomerular basement membrane permeability
2) Hemodynamic alterations of intact nephrone
Injuries → basement membrane permeability↑


Mesangial cells overload and damaged
Proteinuria


Mesangial cells proliferation and increased Cast formation
production of extracellular matrix
Tubule blocked


Glomerulosclerosis
58
There are two principal types of nephron injury:
(1) Glomerulosclerosis
(2) Tubulointerstitial injury
1) Alteration of glomerular basement membrane permeability
2) Hemodynamic alterations of intact nephrone
The number of nephron decreasing day by day
→ pressure and flow in glomerular capillary of
remnant nephron↑
→ glomerular hyperfiltration
→ further glomerular injury
59
There are two principal types of nephron injury:
(1) Glomerulosclerosis
(2) Tubulointerstitial injury
Compensatory hypertrophy
in remnant nephron
metabolism 
oxygen consumption 
free radical production 
Tubulointerstitial injury
60
There are two principal types of nephron injury:
(1) Glomerulosclerosis
(2) Tubulointerstitial injury
Compensatory hypertrophy
in remnant nephron
metabolism 
oxygen consumption 
Inflammatory response
fibrin deposition
in tubules and
surrounding interstitium
free radical production 
Tubulointerstitial injury
61
There are two principal types of nephron injury:
(1) Glomerulosclerosis
(2) Tubulointerstitial injury
Loss of some nephrons leads to compensatory
hyperfunction of others, increasing their vulnerability
to damage and going to a vicious cycle—the nephrons
to be continuously lost and the GFR progressively
decreased until the renal function failed.
62
3. Alteration of function and metabolism
(1) Disturbance of water, electrolyte and acid-base balance
(2) Azotemia
(3) Renal hypertension
(4) Hematologic disorders
1) Renal anemia;
2) Tendency of bleeding
(5) Renal Osteodystrophy
63
(1) Disturbance of water, electrolyte
and acid-base balance
l) Water disturbance
Alteration of urine volume
Changes in urine osmotic pressure
2) Electrolyte disturbance
Natrium;
Potassium; Calcium & Phosphorus
3) Metabolic acidosis
64
l) Water disturbance
Alteration of urine volume
Changes in urine osmotic pressure
a) Nocturia (urine volume night > daytime, or > 750 ml)
b) Polyuria (>2000 ml per day in adult)
Mechanisms: ① Increased blood flow and rapid flow rate of
primary urine in the remnant nephrons; ② Hyperosmolarity
diuretic effect; ③ Decreased ability of urine concentration
caused by destruction of osmolar gradient in medulla.
c) Oliguria (< 400 ml per day in adult) when extremely few of
functional nephrons (GFR<5~10ml/min).
65
l) Water disturbance
Alteration of urine volume
Changes in urine osmotic pressure
Hyposthenuria:
urine specific gravity < 1.020 (nomal 1.002 ~ 1.035)
Isosthenuria:
urine specific gravity fixed at 1.010 or 0.285 mOsm / L
(equal to the osmotic concentration of plasma, implying
inability of the kidney to concentration or dilute the urine)
66
2) Electrolyte disturbance
Natrium
Regulation ability↓, may maintain normal at compensatory
stage but tend to depletion or retention at late stage.
Potassium
May maintain normal as long as the urine volume is not
decreased, although the regulation ability has been impaired.
Hyperkalemia may occur when oliguria, acidosis at late stage.
67
N
100
40 ①
70
Calcium & Phosphorus:
a) Hyperphosphatemia
L
20 ①
E
30
10
5
②
②
30
15
GFR↓→excretion of P↓① → [P]↑→[Ca]↓→ PTH↑
Inhibiting reabsorption of phosphorus by tubule②
phosphorus release from bone③
Early stage (GFR>30ml/min): ② ≥ ① → [P] remain normal
Late stage (GFR<30ml/min): ② ＜ ① → [P]↑+ ③ → [P]↑↑
68
b) Hypocalcemia
① Ingestion and absorption of Ca2+ inadequacy
② [P]↑→[Ca]↓to maintain [Ca][P] constant
↘ phosphorus excreting through intestine
→ interfering absorption of Ca2+
③ 1-hydroxylase↓→ 1,25-(OH)2-D3↓
↘
intestinal absorption of Ca2+ ↓
↗
④ Inactivation ↓ → PTH↑
69
3) Metabolic acidosis
when GFR<20ml/min, metabolic acidosis will occur
① Decreased ability of tubule to excrete acidic products
(HPO42+, SO42+, etc.)
AG↑, Cl－normal
② Decreased ability of tubule to
conserve HCO3－
③ Decreased ability to secrete H+
AG normal, Cl－↑
interstitial nephritis
70
(2) Azotemia
Non-protein nitrogen (NPN) > 28.6 mmol/L (40 mg/dl).
Urea, creatinine, uric acid
1) Blood urea nitrogen (BUN):
BUN is not a ideal index for renal function:
It is just increasing if the decrease of GFR more than 50%.
It may influenced by exogenous urea (protein intake) or
endogenous urea (infection, alimentary tract bleeding)
71
2) Creatinine (Cr):
Cr is end-product of creatine and phosphocreatine metabolism.
Although Cr is rarely influenced by protein intake, it is also not
sensitive during early stage of CRF.
However, the clearance rate of Cr (CCr ) is closely related to
GFR, as it can be filtrated through glomerulus freely but can not
be reabsorbed by tubule, and only small amount may be secreted
by proximal tubule.
CCr = UV/ P
(U = urinary level of Cr, V = urine volume per min, P= plasma level of Cr)
72
(3) Renal hypertension
1) Sodium and H2O retention
(sodium-dependent hypertension)
2) Increased activity of renin-angiotensin system
(renin-dependent hypertension)
3) Decreased anti-hypertension agents secreted by kidney
(Kallikrein-kinin system and PG system)
73
(3) Renal hypertension
1) Sodium and H2O retention
(sodium-dependent hypertension)
2) Increased activity of renin-angiotensin system
(renin-dependent hypertension)
3) Decreased anti-hypertension agents secreted by kidney
(Kallikrein-kinin system and PG system)
Ability of excreting Na+, H2O↓→ Na+, H2O retention
→ blood volume↑→ cardiac output↑→ hypertension
↘more sensitive of blood wall → vasoconstriction ↗
74
(3) Renal hypertension
1) Sodium and H2O retention
(sodium-dependent hypertension)
2) Increased activity of renin-angiotensin system
(renin-dependent hypertension)
3) Decreased anti-hypertension agents secreted by kidney
(Kallikrein-kinin system and PG system)
Disorder of renal circulation → hypoxia → activating RAA
→AII↑→ vasoconstriction → peripheral resistance↑
↘
↘
Aldosterone ↑→ Na+, H2O retention → hypertension
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(3) Renal hypertension
1) Sodium and H2O retention
(sodium-dependent hypertension)
2) Increased activity of renin-angiotensin system
(renin-dependent hypertension)
3) Decreased anti-hypertension agents secreted by kidney
(Kallikrein-kinin system and PG system)
Renal dysfunction
Renal hypertension
(vicious circle)
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(4) Hematologic disorders
1) Renal anemia (97%)
Decreased production of RBC
① Synthesis of erythropoietin↓;
② Deficiency of hematopoietic material (iron, folic acid)
③ RBC-inhibiting factors inhibit RBC production;
④ Aluminium toxication (inhibiting synthesis of hematin,
interfering iron transfer and stem cells proliferation)
Increased destroy or loss of RBC
⑤ Hemolysis, Hypersplenism
(Toxic substances: Guanidines,
⑥ Bleeding
Amines, Phenols, PTH, Al, etc.)
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2) Tendency of bleeding (17-20%)
The main cause is the abnormality of platelet quality rather
than its quantity.
Uremia
CRF
Uremic toxins
(guanidines, phenol)
TXA2  ,PGI2 
Vasopressin receptor 
Platele dysfunction
Decreased adherence, aggregative function and release of PF3
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(5) Renal Osteodystrophy (renal osteopathy)
1) Disorder of Vitamin D metabolism
2) Disorder of Calcium and phosphorus metabolism and
secondly hyperparathyroidism
3) Aluminium accumulation
4) Acidosis
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Chronic RF (dysfunction of excretion and endocrine of kidney)
①
↓1,25-(OH)2-D3
Excretion of P↓
②
Hyperphosphatemia
↓absorption of Ca2+
hypocalcemia
④
Acidosis
bone lysis
Secondly hyperparathyroid
Calcification of bone↓
PTH↑
Ca2+ in bone↓
③
Aluminium accumulation
Renal osteodystrophy
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Section 4.
Uremia
81
End-Stage of ARF or CRF
Retention of metabolic end-product and endogenous toxin
Disturbance of water/electrolyte and acid-base balance
Disorder of endocrine function
a series of auto-toxic symptoms
Uremia
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1. Pathogenesis
(1) Uremic toxin: (more than 100)
(2) PTH
(3) Aluminium
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(1) Uremic toxin: (more than 100)
Urea; Guanidines; Amine and phenol；
Middle molecular weight toxins
1) Urea -principal end product of protein metabolism
May lead to headache, Anorexia, nausea, vomiting,
glucose tolerance↓ bleeding
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2) Guanidines –second abundant nitrogenous matter
The only confirmed pathway for guanidines synthesis is:
Arginine
(Normal pathway)
Guanidino acetic acid
Creatinine
Excretion
(RF)
Methyl guanidine
Guanidino succinic acid
Both with strong toxicity
May induce almost
symptoms of uremia.
85
3) Amine and phenol
Produced by enteric germs, mainly toxic to nerve system
4) Middle molecular weight toxins (500-5000 Dalton)
Can removed by peritoneal dialysis but not hemodialysis
May lead to peripheral or central nerve disorder, RBC and
platelet injury, cellular immune and endocrine dysfunction, etc.
86
(2) PTH
1) Mechanism:
① hypocalcemia  stimulating thyroid proliferation 
secondly hyperparathyroidism  PTH↑
② decreased elimination and degradation of PTH by kidney
87
2) Toxicity of PTH:
① Inducing renal osteodystrophy
② Neural toxicity (decreasing neural transmission)
③ Anemia and bleeding
(inhibiting RBC production and Platelet aggregation)
④ Infection
(inhibiting WBC migrating, phagocytosis and Ab production)
⑤ Myocardium injury, vasodilation and B.P.↓
⑥ Soft tissue necrosis
⑦ Increasing protein catabolism nitrogenous substances↑
⑧ Increasing serum cholesterol and triglyceride
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(3) Aluminium
1) Mechanism:
95% of Al combined with transferrin in plasma, thus
difficult to remove by dialysis
2) Toxicity
Inhibiting enzymes, toxicity to cell nuclear
May induce dialytic encephalopathy,
osteomalacia and small-cell anemia.
89
2. Functional and metabolic alterations
System
Altered function
Manifestation
Nerve system Increase in metabolic
Uremic encephalopathy
products (urea, guanidine) Peripheral neuropathy
Cardiavascular Activation RAS
system
Excess ECF
Elevated BUN
Respiratory
system
Acidosis
Heart failure,
Na+/H2O retention
Hypoalbuminemia
Urea stimulation
Hypertension;
Congestive heart failure
Uremic pericarditis
Kussmaul’s respiration
Pulmonary edema
Uremic pleuritis
90
System
Digestive
system
Altered function
Manifestation
Urea → ammonia
Anorexia, nausea,
Vomiting, diarrhea
Ulceration
gastrin →HCl↑
Endocrine Ability of hormone
Disorder of endocrine
system
secretion or elimination↓ Sexual function impaired
Skin
Ca2+, urea deposition
Immune
Impaired cellular immunity Infection
Metabolism
Itch, urea cream
Glucose tolerance↓
Hypoproteinemia
Hypertriglyceridemia
91
3. Principles of prevention and treatment
(1) Preventing further renal
injury
(2) Dialysis (hemodialysis
or peritoneal dialysis)
(3) Renal transplantation
92
Summary for CRF
1. A pathologic process of retention of waste metabolic products,
water/electrolyte and acid-base imbalance, disturbance of renal
endocrine caused by progressive irreversible destruction of
nephrons in kidney or kidney-related diseases is called chronic
renal failure. It usually go through 4 stages: compensatory stage,
decompensatory stage, renal failure stage and uremia stage.
93
nephrons in kidney or kidney-related diseases is called chronic
renal failure. It usually
go throughfor
4 stages:
Summary
CRFcompensatory stage,
decompensatory stage, renal failure stage and uremia stage.
2. The pathogenesis of CRF include 2 types of nephron injury:
glumerulosclerosis and tubulointerstitial injury.
The functional and metabolic alterations in CFR primarily
include water, electrolyte and acid-base imbalance , azotemia ,
,renal
hematologic
disorders (
hypertension
renal anemia ,
bleeding tendency ), and renal osteodystrophy .
94
electrolyte and acid-base imbalance, azotemia, Renal
Summary
for CRF anemia, bleeding
hypertension, hematologic
disorders(Renal
tendency), and renal osteodystrophy
3. A series of auto-toxic symptoms at end-stage of RF caused by
retention of metabolic waste and endogenous toxin, disturbance
of water/electrolyte and acid-base balance, disorder of endocrine
function are called uremia. The pathogenesis include uremic
toxins ( urea , guanidines , amine and phenol , middle molecular .
weight toxins ), PTH and aluminium . Besides the symptomes
of CRF, functional and metabolic alterations in most organ
systems may occur.
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The End
Back to cover
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
A. Definition of terms （15％）

B. Fill in the blanks with suitable words (20%)

C. Answer questions (40%)

D. Case Presentation (25%)
97