Nephrotic and Nephritic

Syndromes
13/7/14

What are they, and why do we care?

The nephrotic and nephritic syndromes are distinct
clusters of symptoms caused by various glomerular
diseases.
For each syndrome, there is a set of possible underlying
causes.
So while the syndromes are not diagnoses, identifying
whether your patient is nephrotic or nephritic can narrow
down the DDx.
The syndromes may overlap, and some diseases can
cause either.

glomerular
disease:

Silly picture
A

presentation:

DDx:

nephritic

nephrotic

ABCD

CDEF

Nephritic syndrome
-itic like -itis means inflammation, so think of a
glomerulus damaged by inflammation.
Such a glomerulus will be leaking
inappropriately, i.e.:
1. Leaking things it shouldnt be (blood)
2. Not leaking things it should be (GFR).

GFR leads to too much fluid on one side

(hypertension) and less than normal on the
other side (oliguria).

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

plasma creatinine
and urea
(uremia)

oliguria

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

plasma creatinine
and urea
(uremia)

severe GFR activates

RAAS system, as it should

oliguria

Na+ retention

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

plasma creatinine
and urea
(uremia)

severe GFR activates

RAAS system, as it should

oliguria

Na+ retention occurs even if GFR is not

significantly reduced. Appears to be due
to upregulation of basolateral Na+/K+
ATPase in late DT, but the mechanism
by which glomerular damage causes this
is unknown.

Na+ retention

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

severe GFR activates

RAAS system, as it should

Na+ retention occurs even if GFR is not

significantly reduced. Appears to be due
to upregulation of basolateral Na+/K+
ATPase in late DT, but the mechanism
by which glomerular damage causes this
is unknown.

Na+ retention

water retention

plasma creatinine
and urea
(uremia)

plasma volume
oliguria

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

severe GFR activates

RAAS system, as it should

Na+ retention occurs even if GFR is not

significantly reduced. Appears to be due
to upregulation of basolateral Na+/K+
ATPase in late DT, but the mechanism
by which glomerular damage causes this
is unknown.

Na+ retention

water retention

plasma creatinine
and urea
(uremia)

plasma volume
oliguria
?edema
hypertension
JVP, cardiomegaly

Pathogenesis of nephritic syndrome

underlying cause

glomerular damage with

inflammation
(GFR but glomerulus
becomes very leaky to
other things)

?minor proteinuria
hematuria with RBC casts
GFR

severe GFR activates

RAAS system, as it should

Na+ retention occurs even if GFR is not

significantly reduced. Appears to be due
to upregulation of basolateral Na+/K+
ATPase in late DT, but the mechanism
by which glomerular damage causes this
is unknown.

Na+ retention

water retention

plasma creatinine
and urea
(uremia)

plasma volume
oliguria
?edema
hypertension
JVP, cardiomegaly

Nephritic syndrome summary

Defining symptoms:
Hematuria
Hypertension
Oliguria.

A quick way to remember:

H2O.

Nephrotic syndrome
The glomerulus is damaged but not inflamed,
so it leaks things it shouldnt, but otherwise filters
normally.
The damage is more subtle than nephritic, so
proteins can leak, but not usually blood.
Symptoms are all consequences of this protein
loss.

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)

hypoalbuminemia
?anemia
(loss of transferrin)

proteinuria

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

proteinuria

Na+ retention

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

proteinuria

Glomerular damage may cause

Na+ retention by additional
mechanisms, but this is poorly
understood.

Na+ retention

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

proteinuria

Glomerular damage may cause

Na+ retention by additional
mechanisms, but this is poorly
understood.

Na+ retention

water retention

plasma volume

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

proteinuria

Glomerular damage may cause

Na+ retention by additional
mechanisms, but this is poorly
understood.

Na+ retention

water retention

plasma volume

plasma oncotic
pressure

edema

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

proteinuria

Glomerular damage may cause

Na+ retention by additional
mechanisms, but this is poorly
understood.

Na+ retention

water retention

plasma volume

plasma oncotic
pressure

edema

In the setting of plasma

oncotic pressure, extra fluid
moves straight into
interstitium, so BP is rarely/
barely raised.

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

Liver makes more

proteins (not just
albumin)

plasma LDL
(hyperlipidemia)

proteinuria

Glomerular damage may cause

Na+ retention by additional
mechanisms, but this is poorly
understood.

Na+ retention

water retention

plasma volume

plasma oncotic
pressure

edema

In the setting of plasma

oncotic pressure, extra fluid
moves straight into
interstitium, so BP is rarely/
barely raised.

Pathogenesis of nephrotic syndrome

underlying cause

protein filtration

glomerular damage
without inflammation
(preserves GFR but makes
glomerulus leaky to protein)
Filtered proteases
cleave inactive
ENaC in late DT

hypoalbuminemia
?anemia
(loss of transferrin)

Liver makes more

proteins (not just
albumin)

plasma LDL
(hyperlipidemia)

proteinuria

Glomerular damage may cause

Na+ retention by additional
mechanisms, but this is poorly
understood.

Na+ retention

water retention

plasma volume

plasma oncotic
pressure

edema

In the setting of plasma

oncotic pressure, extra fluid
moves straight into
interstitium, so BP is rarely/
barely raised.

Summary of nephrotic syndrome

Defining symptoms:
Hypoalbuminemia
Edema
Lipids
Proteinuria 3.5g/day (equivalently, protein/
creatinine ratio 350mg/mmol)

A quick way to remember:

HELP

Summary and comparison

Nephritic
Inflammatory causes

Nephrotic
Non-inflammatory causes

Hematuria
Hypertension
Oliguria
+Maybe edema and mild
proteinuria

Hypoalbuminemia
Edema
Lipids
Proteinuria

Potential confusing things

Nephritic

Nephrotic

In nephritic, Na+ and water

retention lead to hypertension.
But in nephrotic, which also
involves these processes, the
BP is usually normal. (This is
because the low plasma
oncotic pressure allows the
extra fluid to go straight into
the interstitium, so it doesnt
hang around long enough to
raise BP).

Glomerulus is damaged enough to

let big RBCs through, so youd
think proteins would easily pass
through. However proteinuria is
not usually seen, and if it is
present, its mild.

In the next episode

Explore some of the different types of
glomerulonephritis (GN).
For each type of GN, learn whether it
typically presents as nephrotic or nephritic
syndrome, and why.