Nephrotic syndrome massive

proteinuria (> 3.5 g/day),

hypoalbuminaemia, oedema,
lipiduria and hyperlipidaemia.
Acute glomerulonephritis (acute nephritic
syndrome) abrupt onset of glomerular
haematuria (RBC casts or dysmorphic RBC),
non-nephrotic range proteinuria, oedema,
hypertension and transient renal impairment.
Nephrotic syndrome refers to the secondary
phenomena that occur when substantial amounts
of protein are lost in the urine .
Dependent oedema accumulates predominantly in
the lower limbs in adults, extending to the
genitalia and lower abdomen as it becomes more
severe.
In the morning, the upper limbs and face may be
more affected.
In children, ascites occurs early and oedema is
often seen only in the face.
Overt proteinuria-usually > 3.5 g/24 hrs
(urine may be frothy)
Hypoalbuminaemia (< 30 g/l)
Oedema and generalised fluid retention
Intravascular volume depletion with
hypotension, or expansion with hypertension,
may occur

Feature mechanism consequence manageme
nt
Hypoalbuminaemia Urinary protein losses exceed
synthetic capacity of liver
Reduced oncotic
pressure
Oedema
Diuretics
and a low-
sodium
diet*
Avid sodium
retention
Low oncotic pressure and
intravascular volume
Secondary hyperaldosteronism
Primary defect in renal
sodium excretion
edema
Hypercholesterolae
mia
Non-specific increase in
lipoprotein synthesis by liver
in response to low oncotic
pressure
High rate of
atherosclerosis
Lipid-
lowering
drugs (e.g.
HMG CoA
reductase
inhibitors,
Feature mechanism consequence managemen
t
Hypercoagulabi
lity
Relative loss of inhibitors of
coagulation (e.g.
antithrombin II, protein C
and S) and increase in liver
synthesis of procoagulant
factors
Venous
thromboembolis
m
Case for
routine
anticoagulatio
n in all
patients with
chronic or
severe
nephrotic
syndrome
Infection Hypogammaglobulinaemia
(urinary losses)
Pneumococcal
infection
Consider
vaccination,
particularly in
children
The diseases that cause nephrotic syndrome always affect
the glomerulus and tend to be non-inflammatory, or
subacute examples of inflammatory glomerulonephritis.
Diabetes mellitus and amyloidosis can also cause nephrotic
syndrome.
In children, because minimal change glomerulonephritis is
the most common diagnosis, initial management includes
administration of high-dose corticosteroids.
In older patients, and in children where this therapy is
unsuccessful, a renal biopsy is required unless there is
strong evidence for a specific aetiology (e.g. a long history
of diabetes with other microvascular complications and a
demonstrated progression from microalbuminuria, and
with hypertension but no haematuria).
Nephritic syndrome
Haematuria (brown urine)
Oedema and generalised fluid retention
Hypertension
Oliguria

Non-inflammatory and subacute inflammatory/proliferative glomerular
disorders may present with substantial proteinuria resulting in nephrotic
syndrome.
Inflammatory glomerular disorders more typically cause haematuria in
association with early signs of disturbed renal function, such as
hypertension.
If progressive, obvious signs of impaired excretion of water and solutes
develop.
The onset of these features in close succession has been described as
the nephritic syndrome , but in pure form this condition is rarely seen,
except in countries where post-infectious glomerulonephritis is common.
Mixed inflammatory and nephrotic features are more common.
It is important to recognise such disease, especially if renal impairment
is progressing, as the inflammatory group includes some renal disorders
which are amenable to treatment.
MANAGEMENT
dietary sodium restriction and a thiazide diuretic (e.g.
bendroflumethiazide 5 mg daily).
Unresponsive patients require furosemide 40120 mg
daily with the addition of amiloride (5 mg daily), with
the serum potassium concentration monitored
regularly.
Nephrotic patients may malabsorb diuretics (as well
as other drugs) owing to gut mucosal oedema, and
parenteral administration is then required initially.
Patients are sometimes hypovolaemic, and moderate
oedema may have to be accepted in order to avoid
postural hypotension.
Normal protein intake is advisable.
A high-protein diet (8090 g protein daily)
increases proteinuria and can be harmful in the
long term.
Infusion of albumin produces only a transient
effect. It is only given to diuretic resistant
patients and those with oliguria and uraemia in
the absence of severe glomerular damage, e.g. in
minimal-change nephropathy.
Albumin infusion is combined with diuretic
therapy and diuresis often continues with diuretic
treatment alone.
Hypercoagulable states predispose to venous
thrombosis.
The hypercoagulable state is due to loss of clotting
factors (e.g. antithrombin) in the urine and an
increase in hepatic production of fibrinogen.
Prolonged bed rest should therefore be avoided as
thromboembolism is very common in the nephrotic
syndrome.
In the absence of any contraindication, longterm
prophylactic anticoagulation is desirable.
If renal vein thrombosis occurs, permanent
anticoagulation is required.
Sepsis is a major cause of death in nephrotic
patients.
The increased susceptibility to infection is partly
due to
loss of immunoglobulin in the urine.
Pneumococcal infections are particularly common
and pneumococcal vaccine should be given.
Early detection and aggressive treatment of
infections, rather than long-term antibiotic
prophylaxis, is the best approach.
Lipid abnormalities are responsible for an
increase in the risk of cardiovascular disease
in patients with proteinuria.
Treatment of hypercholesterolaemia starts
with an HMG-CoA reductase inhibitor.
ACE inhibitors and/or angiotensin II receptor
antagonists (AIIRA) are used for their
antiproteinuric properties in all types of GN.
These groups of drugs reduce proteinuria by
lowering glomerular capillary filtration
pressure; the blood pressure and renal
function should be monitored regularly.

Acute Glomerulonephritis
Postinfectious acute glomerulonephritis is due to
immune attack on the infecting organism in which
there is cross-reactivity between an antigen of the
infecting organism (eg, of group A beta-hemolytic
streptococci) and a host antigen.
The result is deposition of immune complexes and
complement in glomerular capillaries and the
mesangium.
Symptoms and signs typically occur 710 days after
onset of the acute pharyngeal or cutaneous infection
and resolve over weeks after treatment of the
infection.
Causes of proteinuria
Orthostatic proteinuria
Glomerular abnormalities
Minimal change disease
Glomerulonephritis
Abnormal glomerular basement membrane (familial
nephritides)
Increased glomerular perfusion pressure
Reduced renal mass
Hypertension
Tubular proteinuria

Clinical signs of the nephrotic syndrome
are:
periorbital oedema (particularly on waking),
the earliest sign
scrotal or vulval, leg and ankle oedema
ascites
breathlessness due to pleural effusions and
abdominal distension.

AGN
This comprises:
haematuria (macroscopic or microscopic) red-cell
casts are typically seen on urine microscopy
proteinuria
hypertension
oedema (periorbital, leg or sacral)
temporarily oliguria and uraemia.
The histological pattern is characterized by cellular
proliferation (mesangial and endothelial) and
inflammatory cell infiltration (neutrophils,
macrophages).
Diseases commonly associated
with acute nephritic syndome
the acute nephritic syndrome
Post-streptococcal glomerulonephritis
Non-streptococcal post-infectious glomerulonephritis,
e.g. Staphylococcus, pneumococcus, Legionella,
syphilis, mumps, varicella, hepatitis B and C,
echovirus, EpsteinBarr virus, toxoplasmosis, malaria,
schistosomiasis, trichinosis
Infective endocarditis
Shunt nephritis
Visceral abscess
Systemic lupus erythematosus
HenochSchnlein syndrome
Cryoglobulinaemia



Post-streptococcal
glomerulonephritis
usually a child, suffers a streptococcal infection 13
weeks before the onset of the acute nephritic
syndrome.
Streptococcal throat infection, otitis media or cellulitis
can all be responsible.
The infecting organism : Lancefield group A -
haemolytic streptococcus of a nephritogenic type.
This is diagnosed by evidence of a recent
streptococcal infection (culture of the
organism, raised ASO titre) and low
complement C3 levels that return to normal
after 3-4 weeks.
Long-term prognosis is good.

Pathophysiology
is due to immune attack on the infecting
organism in which there is cross-reactivity
between an antigen of the infecting organism
(eg, of group A beta-hemolytic streptococci)
and a host antigen.
The result is deposition of immune complexes
and complement in glomerular capillaries and
the mesangium.

Bed rest
Fluid restriction and monitoring of intake and output
Salt restriction
Prompt treatment of throat and skin infection with
antibiotics (Penicillin)
Antihpertensives
Loop diuretics (edema, raised blood pressure,
pulmonary congestion)
IgA Nephropathy
There is a focal and segmental proliferative
glomerulonephritis with mesangial deposits of
polymeric IgA1.
The disease may be a result of an
exaggerated bone marrow and tonsillar IgA1
immune response to viral or other antigens
and is associated with an abnormality in O-
linked galactosylation in the hinge region of
the IgA1 molecule
occur in children and young males.
asymptomatic microscopic haematuria or recurrent
macroscopic haematuria sometimes following an
upper respiratory or gastrointestinal viral infection.
Proteinuria occurs and 5% can be nephrotic.
The prognosis is usually good, especially in those with
normal blood pressure, normal renal function and
absence of proteinuria at presentation.
The risk of eventual development of end-
stage renal failure is about 25% in those with
proteinuria of more than 1 g per day, elevated
serum creatinine, hypertension, ACE gene
polymorphism (DD isoform) and
tubulointerstitial fibrosis on renal biopsy.
Patients with proteinuria over 13 g/day, mild
glomerular changes only and preserved renal function
should be treated with steroids.
Steroids reduce proteinuria and stabilize renal
function.
The combination of cyclophosphamide, dipyridamole
and warfarin should not be used, nor should
ciclosporin.
tonsillectomy can reduce proteinuria and haematuria
in those patients with recurrent tonsillitis.
All patients, with or without hypertension and
proteinuria, should receive a combination of ACE
inhibitor and angiotensin II receptor antagonist rather
than each agent alone because reduction of
proteinuria and preservation of renal function are
better with combination therapy despite similar blood
pressure control.

Henoch-Schnlein purpura is the combination
of:
characteristic skin rash
arthralgia
periarticular oedema
abdominal pain
glomerulonephritis.

between the ages of 3 and 10 years,
twice as common in boys
often preceded by an upper respiratory
infection.
the cause is unknown.
It is postulated that genetic predisposition and
antigen exposure increase circulating IgA
levels and disrupt IgG synthesis.
Renal biopsy shows diffuse, florid, acute
inflammation in the glomerulus (without
necrosis but occasionally cellular crescents),
with neutrophils and deposition of
immunoglobulin (IgG) and complement .
Ultrastructural findings are those of electron-
dense deposits, characteristically but not
solely in the subepithelial aspects of the
capillary walls.

The IgA and IgG interact to produce
complexes that activate complement and are
deposited in affected organs, precipitating an
inflammatory response with vasculitis.

Urinary protein loss of the order 3.5 g daily or
more in an adult is required to cause
hypoalbuminaemia.
In children, proportionately less proteinuria
results in hypoalbuminaemia.
The normal dietary protein intake in the UK is
of the order 70 g daily and the normal liver
can synthesize albumin at a rate of 1012 g
daily.
Nephrotic syndrome with
bland urine sediments
Primary glomerular disease
Minimal-change
glomerular lesion
Congenital nephrotic
syndrome
Focal segmental
glomerular sclerosis
Membranous
nephropathy

Secondary glomerular
disease
Amyloidosis
Diabetic nephropathy

Nephrotic syndrome with active
urine sediments (mixed
nephrotic/nephritic)
Primary glomerular disease
Mesangiocapillary
glomerulonephritis
Mesangial proliferative
glomerulonephritis

Secondary glomerular disease
Systemic lupus erythematosus
Cryoglobulinaemic disease
HenochSchnlein syndrome
Idiopathic fibrillary
glomerulopathy
Immunotactoid
glomerulopathy
Fibronectin
glomerulonephropathy