Glomerular Disease (Glomerulonephropathies)

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A comprehensive topic overview

Introduction

Glomerulonephropathies are a set of diseases which cause in
variety of di
patient with suspected glomerular disease.

Classi

Diseases of the glomerulus can be broadly divided into nephrotic syndrome and nephritic syndrome. A syndrome is a
group of symptoms which consistently occur together.
In the case of nephrotic and nephritic syndromes, these are descriptive terms for a group of symptoms caused by di
diseases. For example, a patient is not diagnosed with nephrotic syndrome. Instead, they are diagnosed with nephrotic
syndrome caused by minimal change disease or membranous glomerulonephropathy.
Nephrotic syndrome is an important and well-de
patients.
The term ‘nephritic’ refers to glomerulonephritis (i.e. in
present in the urine dip and often reduced kidney function. Nephritic syndrome is a less commonly used term clinically
and refers to severe and usually acute presentations of glomerulonephritis causing hypertension and reduced urine
output.
However, it is still helpful to think about nephritic syndrome to split the di
While some diseases generally cause either nephrotic syndrome or nephritic syndrome, many can overlap and have
features of both. Some conditions may also present with mild proteinuria +/- haematuria that would not meet the
nephrotic or nephritic syndrome de
Table 1. Nephrotic vs nephritic syndrome
Nephrotic syndrome Nephritic syndrome
1. Proteinuria
. Proteinuria (>3.5gram protein/24hrs)
. Hypoalbuminemia
. Oedema
2. Haematuria
3. Hypertension
4. Oliguria
Diseases of the glomerulus can also be classi
Primary diseases a
causes are when the kidney disease is driven by another disease or process (e.g. cancers, drugs, infections).
Pathology
The terminology used when describing the disease which a
diagnoses. The only real exception to this is focal segmental glomerulosclerosis (FSGS), a disease entity causing
nephrotic syndrome de
Terms used to describe glomerular disease\:
Focal\: a
Di
Segmental\: a
Global\: a
Proliferative\: increase in the number of cells in the glomerulus
Crescent\: a proliferation of cells within the bowman’s capsule that squashes the glomerular capillaries, giving a crescent
appearance

Nephrotic syndrome

Nephrotic syndrome is typically caused by diseases which damage the
membrane and is de
Proteinuria (>3.5gram protein/24hrs)
Hypoalbuminemia
Oedema
Clinical features1
Proteinuria
Nephrotic range proteinuria is de
or excess protein is detected on urine sampling. This equates to a urine protein\:creatinine ratio (PCR) of approximately
300mg/mmol.
Proteinuria is caused by increased basement membrane permeability, causing increased urinary loss of protein (including
albumin).
Hypoalbuminemia
Loss of albumin in the urine. Usually, the liver would be able to compensate by increasing albumin production. However,
for unknown reasons, the liver cannot compensate in patients with nephrotic syndrome.
Oedema
2
Classically, oedema is thought to be related to hypoalbuminemia, causing reduced plasma oncotic pressure and, therefore,

retention in the kidney triggered by nephrotic syndrome. Patients present with gross peripheral oedema.
Other clinical features
Other clinical features of nephrotic syndrome may include\:
Hyperlipidaemia\: increased hepatic production of triglycerides. This is poorly understood but thought to be due to
hypoalbuminemia and changes to albumin-bound lipids. Hyperlipidaemia leads to an increased cardiovascular risk
pro
Thrombosis\: caused by loss of antithrombotic factors in the urine and increased production of prothrombotic factors in
the liver. Patients are at increased risk of VTE and often require anticoagulation.
3
Immunode
Renal impairment and hypertension\: intrinsic damage to the kidney from the underlying disease process. The
presence/degree of renal impairment depends on the disease.
Predominantly nephrotic disease
Table 2. Conditions which predominantly cause nephrotic syndrome.
4,5
Disease Overview Aetiology Histology TreatmentMinimal change
nephropathy
Focal segmental
glomerulosclerosis
Membranous
glomerulo-
nephropathy
Amyloidosis
The most common
cause of nephrotic
syndrome in
children. Typically
presents around 2
years old with
facial swelling.
Abrupt onset
Can progress to
chronic renal
failure.
The commonest
cause of nephrotic
syndrome in
adults.
Amyloidosis
involves
extracellular
protein deposits.
This can deposit in
multiple organs
including the
kidney.
Primary or secondary to
things such as
NSAIDs/lymphoma/allergy.
Several genetic causes are
recognised and are often
refractory to treatment.
Primary or secondary to
HIV, drugs (e.g.
pamidronate), urinary re
sickle cell disease. Genetic
factors such as APOL-L1
mutations are associated
with an increased risk of
FSGS and progression to
ESKD
Primary or secondary. 70%
of primary cases are
associated with anti-PLA2R
antibodies. Other causes
include malignancy, drugs,
infections (e.g. viral
hepatitis) or SLE.
Broadly split into AA
Amyloid (associated with
chronic in
AL amyloid (associated with
haematological disorders).
There are also a few rare
genetic causes of
amyloidosis.
Light microscopy
normal. Electron
microscopy shows
podocyte foot
process e
Focal collapse and
sclerosis. Patchy
involvement and
may be missed on
biopsy. Di
histopathological
subtypes have
varying prognoses.
Subepithelial
deposition of
immune complexes
with basement
membrane
thickening -
produces a spiked
appearance on silver
stain.
Amyloid stains with
Congo red, with
apple-green
birefringence on
polarised light
microscopy.
Usually very steroid
responsive but can
relapse. May require
further
immunosuppression.
Not always steroid
responsive. May
require
immunosuppression,
renal replacement
therapy and
transplantation. Can
recur in a transplant
kidney.
The prognosis
depends on the
cause. May remit
spontaneously, but
otherwise may need
immunosuppression.
Depends on the
underlying cause but
renal amyloidosis
generally carries a
poor prognosis
Can present multiple histological
syndromes.
SLE (lupus)
nephritis
(speci
subtype)
Management
Treatment varies depending on the cause of nephrotic syndrome. However, treatment can be divided into
general/supportive measures and immunosuppression.
General/supportive measures for nephrotic syndrome include\:
9
Salt and
Commence ACE inhibitor/ARB\: to reduce proteinuria
Consider VTE prophylaxis\: due to hypercoagulability
Pneumococcal vaccine\: due to immunosuppression
Commence statin\: to manage dyslipidaemia and reduce cardiovascular risk
Unless the patient is deemed high-risk, supportive measures may be tried to see if remission occurs without the need for
immunosuppression.
Immunosuppression regimens vary depending on the cause of nephrotic syndrome\:Minimal change disease and FSGS\: usually initially treated with steroids (prednisolone)\: further immunosuppression is
considered if failure to achieve remission or if there is a relapse
Membranous nephropathy\: treatment depends on the severity of the disease, but may include steroids and
cyclophosphamide, or rituximab
Other agents that may be used (particular if treating resistant or relapsing diseases) include calcineurin inhibitors (e.g.
tacrolimus), mycophenolate mofetil, azathioprine and rituximab.

Nephritic syndrome

Nephritic syndrome occurs due to in
triggered by several disease processes.
Clinical features6
Clinical features of nephritic syndrome include\:
Proteinuria\: this is typically, but not always, in the sub-nephrotic range
Haematuria\: can be micro or macroscopic haematuria. It can cause red cell casts which can be examined under
microscopy.
Hypertension\: this occurs due to salt and water retention, in part mediated by glomerular damage causing activation of
the renin-angiotensin-aldosterone (RAAS) system. Typically will occur in more acute or severe cases. Hypertension can
be so severe it can result in hypertensive encephalopathy.
7
Renal impairment & oliguria\: oliguria occurs as a reduction in glomerular
Pyuria\: can be present and will be sterile (i.e. no organisms present). This indicates in
casts in the urine that can be examined under microscopy.
Chronicity of disease is important in nephritic syndrome. If symptoms occur and renal function declines over days or
weeks, it can be classi
kidney function, then it is chronic glomerulonephritis.
Rapidly progressive glomerulonephritis (RPGN)
Rapidly progressive glomerulonephritis (synonymous with crescentic GN) is a sub-classi
glomerulonephritis which is associated with crescents on renal biopsy.
The de
matter of days/weeks).
RPGN is not a single disease process but describes glomerulonephritis, which presents very acutely with a rapid
decline in kidney function and the presence of crescents (in
space) compresses the glomerulus, giving the appearance of crescents) on histology.
6
Figure 1. Histopathological image of
crescentic glomerulonephritis in a patient
with rapidly progressive
glomerulonephritis
PathologyThe causes of acute glomerulonephritis can also be subclassi
vasculitis (often pauci-immune) and anti-GBM associated diseases.Immune complex diseases
Immune complex diseases are caused by an activation of the complement system by immune complexes that deposit on
the glomerular capillaries, leading to in
depending on which arm of the complement system is activated.
Diseases include post-infectious glomerulonephritis (usually post-streptococcal infection) and membranoproliferative
glomerulonephritis (MPGN). MPGN is a histological
autoimmune diseases and chronic viral infections (e.g. hepatitis C).
Pauci-immune vasculitis
Vasculitis can also cause nephritic syndrome. Vasculitis is a systemic disease involving other organ systems such as the
lung or skin but can involve the kidneys, or be renal-speci
Vasculitis can be split into small, medium or large vessel disease or be subclassi
immuno
Diseases typically associated with renal vasculitis are granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis
with polyangiitis (eGPA) and microscopic polyangiitis (MPA).
The term 'pauci-immune' refers to the relative lack of immune deposits on immuno
These are associated with ANCA antibodies which are often helpful in monitoring treatment response\:
GPA is associated with cANCA (anti-PR3)
MPA is associated with pANCA (anti-MPO)
Anti-GBM disease
Anti-GBM disease can cause nephritic syndrome, typically an RPGN. The complement levels will be normal. This is caused
by anti-GBM antibodies against the type IV collagen present in the kidneys and the lungs.
If the disease is associated with pulmonary and renal features it is called Goodpasture's disease, however, anti-GBM can
be kidney speci
massive haemoptysis.
Predominantly nephritic disease
Table 3. Conditions which predominantly cause nephritic syndrome
10
Immune complex diseases
Post-streptococcal GN
IgA GN
(previously Berger’s
disease)
Pathology\: due to group A streptococcal infection
(GAS).
Clinical features\: low C3/4. Positive ASOT. Presents
2-3 weeks after GAS infection. Nephritic symptoms.
Treatment\: treat GAS infection.
Pathology\: due to IgA deposition. Associated with
Henoch-Schonlein purpura.
Clinical features\: typically haematuria hours to days
after a recent respiratory tract infection. Can present
with just haematuria or nephritic syndrome. Raised
plasma IgA and IgA deposition with mesangial
expansion on renal biopsy.
Treatment\: ACE inhibitors, consider
immunosuppression in speci
glomerulonephritis
(MPGN)
8
Others
Pathology\: basement membrane and mesangial
thickening & proliferation on light microscopy with
“tram tracking” due to GBM expanding over the top of
immune deposits.
Clinical features\: nephritic or nephrotic clinical
picture. Associated with a number of conditions
including haematological malignancies, autoimmune
diseases, chronic viral infections, and genetic
abnormalities in the complement system.
Treatment\: treat the underlying cause (if secondary),
with immunosuppressive therapies.
SLE
Shunt nephritis (from infected ventricular
peritoneal shunts)
Bacterial endocarditis
Cryoglobulinaemia (typically causes MPGN
pattern of injury)
Pauci-immune diseases
Granulomatosis with polyangiitis\:
Invariably cANCA+ (anti-PR3)
Typically have ENT involvement and other constitutional symptoms
Eosinophilic granulomatosis with polyangiitis\:
Often pANCA+ (anti-MPO)
Atopy, eosinophilia
Microscopic polyangiitis\:
Invariably pANCA+
Renal involvement more common than with GPA
Anti-GBM associated diseases
Pathology\: caused by antibodies against the type IV
collagen which is located in the GBM and alveolar
capillaries.
Anti-GBM disease and
Goodpasture’s
syndrome
Clinical features\: either reno-speci
lungs. If the lungs are a
syndrome. RPGN picture usually. Lung involvement
may manifest as massive haemoptysis.
Treatment\: steroids, cyclophosphamide, plasma
exchange
Management
Like nephrotic syndrome, treatment varies depending on the underlying cause and severity.
For example, many patients with IgA nephropathy have a slowly progressive course where the only treatment is
supportive (e.g. ACE inhibitors for control of blood pressure and proteinuria). Conversely, anti-GBM disease typically
presents as an RPGN requiring immediate and intensive immunosuppression and plasma exchange.
For more information, see the Geeky Medics guide to glomerulonephritis.
If severe renal impairment then dialysis may be required. Transplantation may be considered later as long as the disease
process is controlled. For more information, see the Geeky Medics guide to chronic kidney disease.Key points
Glomerulonephropathies are a set of diseases which a
Nephrotic syndrome typically presents with proteinuria, hypoalbuminemia and oedema.
Nephritic syndrome typically presents with proteinuria, haematuria, hypertension and oliguria (in severe cases).
While some glomerular diseases generally cause either nephrotic syndrome or nephritic syndrome, there are many
which can overlap and have clinical features of both.
The management of glomerular disease depends on the underlying disease process but may involve
immunosuppression.

References

Macé C, Chugh SS. Nephrotic syndrome\: components, connections, and angiopoietin-like 4-related therapeutics. J Am Soc
Nephrol. 2014 Nov;25(11)\:2393-8.
Rondon-Berrios H. New insights into the pathophysiology of oedema in nephrotic syndrome. Nefrología (English Edition).
2011 Mar 1;31(2)\:148-54.
Al-Azzawi HF, Obi OC, Sa
Apr-Jun;6(2)\:85-8.
Nephcure. FSGS. 2022. Available from\: [LINK]
Nephcure. Membranous nephropathy. 2022. Available from\: [LINK]
Saint, Sanjay and others (eds),
'Nephritic Syndrome'
, in Sanjay Saint, and Vineet Chopra (eds), The Saint-Chopra Guide to
Inpatient Medicine, 4 edn (New York, 2018; online edn, Oxford Academic, 1 Nov. 2018)
Ihm CG. Hypertension in Chronic Glomerulonephritis. Electrolyte Blood Press. 2015 Dec;13(2)\:41-5.
National Kidney Foundation. Membranoproliferative Glomerulonephritis. Available from\: [LINK]
Oxford Handbook of Clinical Specialities, 9th Ed. 2013.
Lionaki, S. , Skalioti, C. , Marinaki, S. , N. Boletis, J. . Pauci-Immune Vasculitides with Kidney Involvement. In\: Mohammed, R.
H. A. , editor. Vasculitis In Practice - An Update on Special Situations - Clinical and Therapeutic Considerations [Internet].
Image references

Related notes

Figure 1. KGH.Crescentic glomerulonephritis. License\: [CC BY-SA]
Acute Kidney Injury (AKI)

Reviewer

Chronic Kidney Disease (CKD)
Haemodialysis
Dr Mohammed Al-Talib
Henoch-Schönlein Purpura (IgA Vasculitis)
Renal Registrar
Hyperkalaemia

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Contents

Introduction
Classi
Nephrotic syndrome
Nephritic syndrome
Key pointsSource\: geekymedics.com