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Glomerulonephritis - Mechanism of Damage to the Nephrons

Last Updated on Feb 29, 2016
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What is Glomerulonephritis?

Glomerulonephritis (glo·mer·u·lo·ne·phri·tis) is a word used to describe a group of kidney diseases that result in damage of glomeruli due to inflammation - the functional units of the kidney that filter blood. The damage is not due to infection but mostly attributed to the immune system of the body.


When the kidney is damaged, it cannot get rid of wastes and extra fluid in the body. If the illness continues, the kidneys may stop working completely. The damage can cause leakage of protein and sometimes the red cells into the urine.

Glomerulonephritis Types

The inflammation can affect all the million nephrons of the kidney. Each nephron contains a structure called the glomerulus which is actually a complex matrix of highly specialized blood vessels through which blood passes and the waste products of the body are purified. The condition is also called glomerular nephritis.

There are various types of glomerular diseases which are classified based on the type of mechanism of inflammation and section of the glomeruli that are affected. Broadly, the immune mechanism that causes the inflammation is of two types:

I. Antibody-mediated (Humoral) Immunity is the aspect of immunity mediated by the activity of B lymphocytes and circulating antibodies. The cells responsible for antibody-mediated immune response are:

  • B cells or lymphocytes are responsible for antibody responses.
  • Effector T cells for the cell-mediated immune response which is controlled by regulatory T cells.

Antibody-mediated immune response is as follows:

a) B cells are activated by antigen and helper T cells.

b) Antibodies against the antigen are produced by the plasma cells. These antibodies protect the host in 3 ways namely neutralization, opsonization and complement activation.

In neutralization, the antibodies bind to the pathogens and inhibit the toxic effects of the pathogen. In opsonization by coating the pathogens, antibodies ingest and kill the pathogen by a process known as opsonization. Antibodies trigger activation of the complement system (part of the immune system) which enhances opsonization and kills few bacterial cells.

II. Cell-mediated Immunity is an immune response triggered by phagocytes T cells and cytokines released in response to an antigen. T lymphocytes are responsible for cell-mediated immunity. Cell-mediated immunity does not involve antibodies.


Injury to glomeruli results in a variety of signs and symptoms of disease including:

Proteinurias caused by Altered permeability of capillary walls
Hematuria caused by Loss of capillary wall integrity
Azotemia caused by Impaired filtration and build-up of nitrogenous wastes
Oliguria or Anuria caused by Reduced glomerular filtration
Edema caused by Loss of intravascular oncotic pressure
Hypertension caused by Fluid retention & altered renal regulation of blood pressure

Several syndromes related to glomerulonephritis have been described.

a) Nephrotic Syndrome: Proteinuria in excess of 3.5 grams in 24 hours, accompanied by:

  • Proteinuria - passage of protein in the urine
  • Edema or swelling of the body due to fluid retention
  • Hypoalbuminemia or low albumin levels
  • Hyperlipidemia or high lipids (fats)
  • Lipiduria (passing of fat in the urine)

Urine is foamy and difficult to flush in the toilet due to the protein.

b) Acute Nephritis or Nephritic Syndrome:

  • Hematuria – traces of blood in the urine or blood stained urine
  • Variable proteinuria – protein in the urine
  • Azotemia – increase of urea
  • Hypertension – increase of blood pressure

Various types of glomerulonephritis include:

  • Rapidly Progressive Glomerulonephritis
  • Minimal Change Glomerulonephritis
  • Focal Segmental Glomerulosclerosis
  • Membranous Glomerulonephritis
  • Antibody-Mediated IgA Nephropathy
  • Membranoproliferative Glomerulonephritis
  • Post-Infectious Glomerulonephritis
  • Anti-Glomerular Basement Membrane Disease or Goodpasture’s syndrome

A description of the various types of glomerulonephritis is provided in brief.


Rapidly Progressive Glomerulonephritis

Results in hematuria, oliguria and acute renal failure.

Although much overlap exists, the various types of glomerular diseases may be classified by syndrome which manifests and provides the predominant clinical picture:

  Nephrotic Syndrome Nephritic Syndrome
Minimal change disease +++++ -
Membranous glomerulonephritis ++++ +
Focal segmental glomerulosclerosis ++++ +
IgA nephropathy +++ ++
Membranoproliferative GN ++ +++
Acute post-infectious GN + ++++

Minimal Change Glomerulonephritis

Minimal Change Disease - is the most common cause of the nephrotic syndrome in childhood. In a prospective study of untreated children with the nephrotic syndrome, minimal change disease was found in 76.6%.

In contrast, minimal change disease accounts for only 10% to 30% of adult cases of nephrotic syndrome. In both children and adults, these percentages vary in different parts of the world.

Minimal Change Glomerulonephritis

The clinical onset of nephrotic syndrome may be associated with an upper respiratory infection or with routine prophylactic immunizations. Other genetic and environmental factors may also be important.

Clinical Course: Most patients with minimal change disease develop mild edema around the eyes (periorbital) as the initial complaint.

The proteinuria in minimal change disease is said to be "selective", that is, it is composed primarily of albumin.

Microscopic hematuria or traces of blood in the urine is rare with reported frequencies of 13 to 36%.

Hypertension is also unusual in minimal change disease.

Treatment - Most patients (90%) respond to an 8 week course of steroids. Cytotoxic agents may be used in steroid resistant cases in less than 10 % and kidney failure from minimal change disease is rare, but relapses are common.

Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis is the most common cause of nephrotic syndrome in adults. It also comprises 10% of childhood disease.

Patients usually present with -

  • Proteinuria.
  • Sometimes with microscopic hematuria.
  • Hypertension is also common.
  • The pathogenesis of the sclerosing lesions and their progressive nature are debated.

Humans with idiopathic focal segmental glomerulosclerosis initially have a high glomerular filtration rate and evidence of hyperfiltration, suggesting that hyperfiltration and increased intercapillary glomerular pressure may be mediators of this disease.

A similar pattern of segmental sclerosis may be seen in a number of distinct glomerular diseases with different pathogenetic mechanisms and clinical courses (e.g. IgA nephropathy).

Clinical Course - Focal segmental glomerulosclerosis may be primary (idiopathic) or secondary to a number of etiologic agents including:

Steroid therapy may induce remission in 20-40% of children and fewer adults.

Adults may progress to renal failure rapidly over 2-3 years (15-20%) or more slowly over 10-12 years.

People of African descent tend to have worse outcomes.

Focal segmental glomerulosclerosis commonly recurs following transplantation (50-80%).

Membranous Glomerulonephritis

Membranous glomerulonephritis is an antibody-mediated disease. To understand the mechanism of damage requires some understanding of the glomerulus in detail.


The glomerulus is a cluster of capillaries involved in the filtration of the blood to form urine. The glomerulus is located within theBowman’s capsule within the kidney. The glomerulus was so named by the Italian anatomist Marcello Malpighi. Glomerulus receives blood from afferent arteriole and drains into efferent circulation. A glomerulus and a Bowman's capsule constitute a renal corpuscle, the initial blood-filtering component of a nephron. Glomerular filtration rate (GFR) is a test to check the function of the kidneys. The test estimates the rate at which blood is filtered through all of the glomeruli.

The immune complexes localize to the subepithelial aspect of the capillary loop. That is, between the outer aspect of the basement membrane and the podocyte (epithelial cell).

The immune complexes develop in situ or, less likely, by the deposition of circulating immune complexes of antibody and antigen.

Sometimes the antibody may bind to the glomerulus that acts like antigen or to a foreign antigen implanted on the capillary wall.

Approximately, 25 to 30% of cases are secondary. Common associations include:

  • Systemic lupus erythematosus and other connective tissue disorders
  • Drugs (gold, penicillamine, non-steroidal anti-inflammatory agents)
  • Hepatitis B, syphilis, quartan malaria, leprosy, schistosomiasis
  • Carcinoma, melanoma, leukemia, non-Hodgkin's lymphomas
Common Association in Glomerulonephritis Melanoma

Membranous glomerulonephritis is more common in adults and most patients are older than 30 years at diagnosis.

Membranous glomerulonephritis accounts for 35-50% of cases of the adult nephrotic syndrome.

Most patients present with -

Heavy proteinuria - most commonly in the nephrotic range that is insidious in onset.

A few patients have accompanying microscopic hematuria.

Clinical Course - The course of untreated idiopathic membranous glomerulonephritis is variable. Of patients presenting with the nephrotic syndrome and a normal serum creatinine:

  • 30% will have a spontaneous complete remission and a stable GFR for up to 20 years.
  • 25% will have a spontaneous partial remission with a stable GFR (Glomerular Filtration Rate).
  • 20-25% experience persistent nephrotic syndrome with stable or very slowly progressive loss of GFR.
  • 20 to 25% of patients progress to end-stage renal failure over a 20 to 30-year follow-up.

Patients in whom a causative agent is identified, usually respond to treatment of the underlying disorder, or withdrawal of the offending agent.

Patients with idiopathic membranous require treatment with a course of steroids with cyclophosphamide for a period of at least 6 months.

Antibody Mediated IgA Nephropathy

IgA nephropathy, first described in 1968, is the most common form of primary glomerulonephritis in the world.

It is an antibody-mediated glomerular disease in which the immune deposits localize to the mesangium. It is not certain whether the deposits form in situ or from circulating immune complexes.

Patients with IgA nephropathy usually present with one of three syndromes:

  • Macroscopic hematuria or blood in the urine which means the urine is red along with an upper respiratory infection called syn-pharyngitic hematuria.
  • Asymptomatic microscopic hematuria (blood cannot be seen with the naked eye, but only under a microscope) seenand variable proteinuria.
  • Henoch-Schonlein purpura is the systemic form of the disease process causing IgA nephropathy and occurs more frequently in children than adults.

Patients with Henoch -Schonlein purpura manifest skin, joint and intestinal involvement.

A less common presentation is with the nephrotic syndrome - These patients may have advanced disease or normal renal function. In the latter case, the light microscopic features are of minimal change disease but with intense mesangial staining for IgA.

Clinical Course - Renal function progressively worsens in approximately 40% of patients, about half of whom reach end-stage renal failure after 20 years of clinically apparent disease.

Nearly 30% of patients exhibit a benign course with chronic microscopic hematuria, a normal serum creatinine and proteinuria usually less than 1 gram/day.

Hypertension is not uncommon and malignant hypertension develops in about 5% of patients.

Secondary deposits of IgA may occur in chronic liver disease, dermatitis herpetiformis, psoriasis, ankylosing spondylitis, inflammatory bowel disease, carcinoma, celiac disease, IgA monoclonal gammopathy, HIV infection and mycosis fungoides.

Membranoproliferative Glomerulonephritis

Membranoproliferative, or mesangiocapillary, glomerulonephritis (MPGN) is a chronic progressive glomerulonephritis that occurs in older children and adults.

Circulating immune complexes have been identified in 50% of patients and activation of the complement system with hypocomplementemia is a hallmark of MPGN.

The complement system is a part of the immune system that complements the ability of antibodies and the larger white cells to clear any foreign body or pathogens. Over 30 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. Sometimes the inflammation caused by antigen and antibody works against the body and the cascade of inflammation produced damages the tissues.

Idiopathic MPGN has several distinct histopathologic and immunopathologic features and three variants have been described.

  • Type I MPGN characterized by mesangial and subendothelial immune deposits.
  • Type II MPGN (dense deposit disease) characterized by interrupted linear deposits in the lamina densa of the basement membrane.
  • Type III MPGN, an uncommon variant, characterized by features of both type I MPGN and membranous GN, or by disruption of the glomerular basement membrane with an accumulation of new basement membrane material arranged in layers.

Clinical Course - Patients with MPGN may present with the nephrotic syndrome or an abnormal urinary sediment with non-nephrotic proteinuria or with acute nephritis. The diagnosis is suspected when serum complement levels are depressed.


Type I MPGN:

  • Is the most frequent primary MPGN.
  • Is also often associated with systemic disease, infection and neoplasms.
  • Membranoproliferative glomerulonephritis secondary to cryoglobulinemia is strongly associated with Hepatitis C virus infection.
  • The nephrotic syndrome is the most common presenting illness.
  • Type I MPGN is a slowly progressive disease; in 30-40% of patients, the disease remains stable despite persistent nephrotic range proteinuria. Median survival, free of renal failure in both children and adults ranges from 9 to 12 years.

In type II MPGN:

  • Acute nephritis and recurrent macroscopic hematuria are the most common presentations.
  • Most patients with type II MPGN are younger than 20 years of age, have more persistent C3 depression and more commonly present with nephritis.
  • Approximately, 20% of patients remain stable for many years and median survival, free of renal failure ranges from 5 to 10 years.

Post-Infectious Glomerulonephritis

Post-Infectious Glomerulonephritis - Infectious agents are the most common inciting antigens associated with immune complex- mediated glomerulonephritis.

Post-Sreptococcal Glomerulonephritis is the most common form of glomerulonephritis in children and occurs following a skin or throat or pharyngeal infection with Group A beta-hemolytic streptococci (a type of bacteria).

Post-Infectious Glomeruonephritis has also been associated with other bacterial, viral, parasitic, rickettsial and fungal infections.

The precise nature of the antigens involved in the formation of the immune complexes that deposit in the nephrons (nephritogenic) is unknown.

Streptococcal antigenic substances have been inconsistently detected in glomeruli and circulating immune complexes have been detected in some patients. Since streptococcal antigens do not always cause disease, other mechanisms may be involved, including alterations in IgG or glomerular components making them immunogenic. Antigens derived from infectious agents may bind to glomerular structures and induce development of in situ immune complexes.

Clinical Course - Post-streptococcal glomerulonephritis is primarily a disease of children, 6 to 7 years of age, although it may also be seen in adults and has a different clinical course in them.

The onset is usually abrupt, with a latent period of 7 to 21 days between infection and the development of nephritis. During epidemics, the clinical attack rate is 10-12%, but subclinical disease occurs four times more frequently than an overt disease. Asymptomatic contacts may have hematuria.

Common initial clinical manifestations of post-streptococcal glomerulonephritis are:

  • Hematuria (micro or macroscopic) - blood in urine
  • Edema or swelling of the body
  • Oliguria or less urine output
  • Hypertension
Evaluation of Glomerulonephritis Hypertension

The acute clinical episode of post-streptococcal glomerulonephritis is usually self-limited and complement levels return to normal within 6 weeks. In most patients, hematuria disappears by 6 months but proteinuria may persist for two years in a third of patients.

Early antimicrobial therapy in affected individuals and family members may prevent the spread of streptococcal infections. Treatment of established infection does not prevent the development of post-streptococcal glomerulonephritis, but may lessen its severity.

The prognosis for complete recovery is excellent in children, even in patients with the nephrotic syndrome or crescentic disease at presentation.

The prognosis in adults is less favorable, especially when accompanied by initial severe impairment in renal function, persistent proteinuria and the nephrotic syndrome. The development of crescents is more common in adults.

Anti-Glomerular Basement Membrane Disease (GBM)

It is also called Goodpasture's syndrome and is a clinical constellation of glomerulonephritis and pulmonary or lung hemorrhage, mediated by an anti-glomerular basement membrane antibody, which also reacts with the basement membrane of pulmonary capillaries.

Up to one-third of patients with rapidly progressive glomerulonephritis and anti-GBM antibodies, do not have detectable evidence of pulmonary involvement (anti-glomerular basement membrane disease).

Since the antibody response is directed toward a normal antigen present in the GBM, Goodpasture's syndrome and anti-GBM disease are classic examples of autoimmune disorders.

Clinical Course - Goodpasture's syndrome may occur at any time, but peaks in the spring and summer months are common. It frequently begins with a flu-like illness with evidence of pulmonary compromise.

  • Progressive dyspnea or breathing difficulty
  • Hemoptysis and occasionally ventilatory failure occur
  • Hematuria with red blood cell casts
  • Variable proteinuria

Treatment - Patients with Goodpasture's syndrome require immediate institution of plasma exchange and immunosuppressive therapy with steroids and cyclophosphamide.

Immunosuppressive Therapy for Goodpastures Syndrome

Prompt institution of therapy usually results in significant improvement in renal function. Patients with an initial serum creatinine less than 3 mg/dl and fewer than 30% crescents have a greater likelihood of responding favorably to therapy.

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i was diagnosed with mpgn type 2 at 4 yrs old... it all started with a persistant cold. My mom always thought i was pale but, she had no idea until she found me lethargic on the floor.. my blood pressure was sky high. my urine was black. my 14 yr treatment consisted of aggressive doses of prednisone and blood pressure medication. i also give all the credit in the world to the doctors and staff at the Motts childrens hospital in ann arbor michigan.

Tamara Harchanko

my stepmom has minimal change disease- she also has rhem.arthritis- last week relapsed into MCD- her ankles are swolen to painful- Is there anybody who knows what foods are for her to eat???? She also suffers from celiac and is under 100 lbs- Please help!!


to whom it may concern... I am a 20 year old servivor of MPGN. i was diagnosed at 4 and have now been in remission for 4 years. ive never had a transplant, and although i was very close to it ive never been on dialysis.


Hi bree. Glad to hear you are a survivor of MPGN. I am from ireland and my brothers little girl took this disease 9 weeks ago. She is on dialayis ever day and we are very concerned for her. I would be greatly obliged and grateful to hear the full story of your experiences and any advice you could offer me. Thankyou for you time and take care, colin


it all started with a persistant cold.. after about two months of an upper respertory infection my mom found me lethargic on the floor.. my urine was black it was mpgn type 2.


Hi Bree! My daughter was diagnosed with MPGN type 1 in 2004, she continues to have problems with anemia, seems to be getting worse. Just wondering if you had the same problem?

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