Glomerular Disease

Glomerular Disease

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Glomerulonephropathies are diseases which cause inflammation in the glomeruli. These can be divided into nephrotic and nephritic syndrome, and this article will cover the causes and management of a patient with suspected glomerular disease.



Nephrotic syndrome and nephritic syndrome are terms describing a group of symptoms caused by different diseases. Nephrotic syndrome is an important clinical entity and a well-defined group of symptoms. Nephritic syndrome is less commonly used and typically refers to severe and acute presentations of glomerulonephritis with hypertension and reduced urine output. However, many glomerulopathies can present with both nephrotic and nephritic features or mild proteinuria and haematuria not meeting the definition of either syndrome.

Glomerulopathies can further be classified as primary or secondary, with primary diseases directly affecting the kidneys and secondary diseases caused by another disease or process.


When describing diseases of the glomerulus, terminology can be confusing. Terms are used when describing histological patterns on kidney biopsy and usually are not specific diagnoses. The only exception is focal segmental glomerulosclerosis (FSGS), a type of nephrotic syndrome defined by focal and segmental glomerulosclerosis on histology.

Terms Used to Describe Glomerular Disease

  • Focal: Affecting some glomeruli
  • Diffuse: Affecting all glomeruli
  • Segmental: Affecting part of the glomerulus only
  • Global: Affecting the entire glomerulus
  • 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 filtration barrier at the glomerular basement membrane and is defined by a triad of proteinuria, hypoalbuminemia and oedema. Proteinuria is defined as a loss of 3.5g of protein per 24 hours, which equates to a urine protein:creatinine ratio of approximately 300mg/mmol. It is caused by increased basement membrane permeability, causing increased urinary loss of protein (including albumin). Hypoalbuminemia is caused by loss of albumin in the urine, usually compensated by the liver in healthy individuals, but unable to do so in nephrotic syndrome. Oedema is thought to be related to either hypoalbuminemia or excess salt and water retention in the kidney triggered by nephrotic syndrome, presenting with peripheral oedema.

Other Clinical Features

  • Hyperlipidaemia: Increased hepatic production of triglycerides
  • Thrombosis: Increased risk of VTE and often require anticoagulation
  • Immunodeficiency: Due to loss of immunoglobulins such as IgG and other immune proteins in the urine
  • Renal Impairment and Hypertension: Intrinsic damage to the kidney from the underlying disease process

Nephritic and Nephrotic Syndrome

Nephritic syndrome occurs due to inflammation and damage to endothelial cells of glomerular capillaries and can be triggered by several disease processes.

Clinical Features

Clinical features of nephritic syndrome include:

  • Proteinuria:this is usually, 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.

Types of Nephropathies

  • Minimal Change Disease
  • Primary or secondary to HIV, drugs (e.g. pamidronate), urinary reflux, sickle cell disease. Genetic factors such as APOL-L1 mutations are associated with an increased risk of FSGS and progression to end-stage kidney disease.
  • Focal collapse and sclerosis. Patchy involvement and may be missed on biopsy. Different histopathological subtypes have varying prognoses.
  • Not always steroid responsive. May require immunosuppression, renal replacement therapy and transplantation. Can recur in a transplant kidney.
  • Membranous Glomerulo-nephropathy
  • The commonest cause of nephrotic syndrome in adults.
  • 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.
  • Subepithelial deposition of immune complexes with basement membrane thickening -produces a spiked appearance on silver stain.
  • The prognosis depends on the cause. May remit spontaneously, but otherwise may need immunosuppression.
  • Amyloidosis
  • Amyloidosis involves extracellular protein deposits. This can deposit in multiple organs including the kidney.
  • Broadly split into AA Amyloid (associated with chronic inflammation) and AL amyloid (associated with haematological disorders). There are also a few rare genetic causes of amyloidosis.
  • Amyloid stains with Congo red, with apple-green birefringence on polarised light microscopy.
  • Depends on the underlying cause but renal amyloidosis generally carries a poor prognosis.
  • SLE (Lupus) Nephritis
  • Can present multiple histological findings and features of both nephrotic and nephritic syndromes.


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:

  • Salt and fluid restriction, diuretics (typically furosemide in the first instance): to reduce oedema
  • 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.

Rapidly Progressive Glomerulonephritis (RPGN)

Rapidly progressive glomerulonephritis (also known as crescentic glomerulonephritis) is a classification of acute glomerulonephritis that is associated with the presence of crescents on renal biopsy.

RPGN is characterized by a 50% decline in kidney function over a period of 3 months, or even faster, in a matter of days or weeks. It is not a single disease process, but rather a form of glomerulonephritis that presents very acutely, resulting in a rapid decline in kidney function and the presence of crescents (inflammation and proliferation of cells in the Bowman's space that compress the glomerulus).


The pathology of acute glomerulonephritis can be divided into three main categories: immune complex disease, vasculitis (often pauci-immune) and anti-GBM associated diseases.

Immune Complex Diseases

Immune complex diseases are caused by an activation of the complement system, where immune complexes deposit on the glomerular capillaries and lead to inflammation and damage. They can be identified by low levels of C3 and/or C4, depending on which arm of the complement system is activated. Examples include post-infectious glomerulonephritis (usually post-streptococcal infection), IgA nephropathy, and membranoproliferative glomerulonephritis (MPGN).

Clinical Features

  • Hypertension: This occurs due to salt and water retention, in part mediated by glomerular damage causing activation of the renin-angiotensin-aldosterone (RAAS) system. Hypertension can be so severe it can result in hypertensive encephalopathy.
  • Renal impairment & oliguria: Oliguria occurs as a reduction in glomerular filtration, in severe or advanced cases.
  • Pyuria: Pyuria can present and will be sterile (with no organisms present), indicating inflammation and producing white cell 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 classified as acute glomerulonephritis. If the symptoms occur over months to years with little reduction in kidney function, then it is chronic glomerulonephritis.

Overview of Nephritic Syndrome

Nephritic syndrome is a histological finding which can be caused by a variety of underlying diseases. These include paraprotein-producing malignancies, autoimmune diseases, chronic viral infections (e.g. hepatitis C), small vessel, medium vessel or large vessel vasculitis, as well as diseases with ANCA antibodies and anti-GBM antibodies.

Pauci-Immune Vasculitis

Vasculitis can also cause nephritic syndrome. It is a systemic disease which affects other organs, or can be renal-specific. Complement levels will be normal. Vasculitis is classified by the size of the vessels involved or their immunofluorescence pattern on histology. Diseases associated with renal vasculitis include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (eGPA) and microscopic polyangiitis (MPA). These are pauci-immune diseases as there is a relative lack of immune deposits on immunofluorescence. The associated ANCA antibodies (cANCA or pANCA) can be useful in monitoring treatment response.

Anti-GBM Disease

Anti-GBM disease can also 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. Lung involvement may present as massive haemoptysis. Linear GBM staining can be seen on immunofluorescence.

Predominantly Nephritic Diseases

Conditions which predominantly cause nephritic syndrome include immune complex diseases such as post-streptococcal GN and IgA GN (previously Berger's disease), as well as membranoproliferative glomerulonephritis, systemic lupus erythematosus (SLE), shunt nephritis from infected ventricular peritoneal shunts.

Post-Streptococcal GN

  • Pathology: due to group A streptococcal infection (GAS).
  • Clinical features: low C3/4. Positive ASOT. Presents two to three 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 specific cases.

Membranoproliferative Glomerulonephritis (MPGN)

  • 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.


Glomerulonephropathies are a set of diseases which affect the glomeruli. Two of the most common manifestations are nephrotic syndrome and nephritic syndrome.

Nephrotic Syndrome

Nephrotic syndrome typically presents with proteinuria, hypoalbuminemia and oedema. Common causes include:

  • Focal segmental glomerulosclerosis (FSGS)
  • Membranous nephropathy
  • Minimal change disease
  • Diabetic nephropathy
  • Amyloidosis
  • Bacterial endocarditis
  • Cryoglobulinaemia (typically causes MPGN pattern of injury)

Nephritic Syndrome

Nephritic syndrome typically presents with proteinuria, haematuria, hypertension and oliguria (in severe cases). Common causes include:

  • IgA nephropathy
  • Antiglomerular basement membrane (anti-GBM) disease and Goodpasture's syndrome
  • 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)


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.

If severe renal impairment then dialysis may be required. Transplantation may be considered later as long as the disease process is controlled.

Key Points

  • Glomerulonephropathies are a set of diseases which affect the glomeruli.
  • 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.


  1. Macé C, Chugh SS. Nephrotic syndrome: components, connections, and angiopoietin-like 4-related therapeutics. J Am Soc Nephrol. 2014 Nov;25(11):2393-8.
  3. Rondon-Berrios H. New insights into the pathophysiology of oedema in nephrotic syndrome. Nefrología (English Edition). 2011 Mar 1;31(2):148-54.
  5. Al-Azzawi HF, Obi OC, Safi J, Song M. Nephrotic syndrome-induced thromboembolism in adults. Int J Crit Illn Inj Sci. 2016 Apr-Jun;6(2):85-8.

What is Glomerulonephritis?

Glomerulonephritis is a type of kidney disease that affects the glomeruli, which are the tiny filters located in the kidneys. Injured or damaged glomeruli can no longer filter waste products, electrolytes and fluid from the bodies blood. This type of kidney disease is caused by the immune system attacking the glomeruli, usually as a reaction to an infection, or by deposits of immune complexes.

Glomerulonephritis can be classified into four main categories:

  • IgA nephropathy
  • Focal segmental glomerulosclerosis (FSGS)
  • Membranous Nephropathy (MN)
  • Membranoproliferative Glomerulonephritis (MPGN)

IgA nephropathy is the most common type of glomerulonephritis. It is caused by an accumulation of a certain type of antibody, IgA. IgA nephropathy has been linked to certain infections and immune disorders. FSGS is a type of glomerulonephritis that affects the glomerular basement membranes. It is caused by a defect in the filtration process, and it is the leading cause of chronic kidney disease in adults. MN is a type of glomerulonephritis that affects the glomeruli and is caused by deposits of antibodies in the kidney's basement membrane. MPGN affects the immune cells in the glomeruli, leading to excessive inflammation and damage to the kidneys.

Glomerulonephritis can lead to a number of serious health complications. These complications can include hypertension (high blood pressure), proteinuria (increased protein in the urine), fluid overload, and electrolyte problems. Treatment for glomerulonephritis typically includes medications that help reduce inflammation, protect the kidneys, and control blood pressure levels.


  • Kidney Health Australia. Understanding FSGS. 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].

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