Rapidly Progressive Glomerulonephritis

Overview

Definition

Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months.

• Associated with nephritic syndrome Nephritic syndrome Nephritic syndrome is a broad category of glomerular diseases characterized by glomerular hematuria, variable loss of renal function, and hypertension. These features are in contrast to those of nephrotic syndrome, which includes glomerular diseases characterized by severe proteinuria, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephritic Syndrome
• A manifestation of various diseases, not an etiology
• Histologically characterized by the presence of crescents:
  • Proliferated cells (predominantly epithelial), with infiltration of monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation and macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation in the Bowman space
  • Also called crescentic glomerulonephritis
• Generally, biopsies of < 10% crescents are not included in the category.

Classification

Most cases are from immunological injury of the glomeruli. The mechanisms and findings are classified as:

• Anti-glomerular basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN) (anti-GBM) antibody disease:
  • A rare disease characterized by vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus of the small vessels
  • Can affect glomerular and pulmonary capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology 
• Immune-complex mediated injury: immune complex deposition in the glomeruli
• Pauci-immune necrotizing and crescentic glomerulonephritis:
  • Glomerulonephritis with minimal or no detectable antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (anti-GBM) or immune complex deposits on immunofluorescence or electron microscopy
  • Most cases are ANCA-positive.
• Double antibody-positive disease (very rare): features of both ANCA-positive RPGN and anti-GBM antibody disease
• Idiopathic Idiopathic Dermatomyositis, including:
  • An immune complex disease Immune complex disease Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other immune system diseases including glomerulonephritis, systemic lupus erythematosus (lupus erythematosus, systemic) and polyarteritis nodosa. Membranoproliferative Glomerulonephritis not belonging to the identifiable categories
  • ANCA-negative pauci-immune disease

Epidemiology

• Annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 7 cases per 1 million individuals
• White individuals affected > Black individuals
• Rare in the pediatric population
• Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: middle of the 6th decade

Etiology

• Anti-GBM antibody-mediated disease (≤ 10% of cases):
  • Anti-GBM glomerulonephritis (without lung hemorrhage)
  • Goodpasture syndrome Goodpasture Syndrome Goodpasture syndrome, also known as anti-glomerular basement membrane (GBM) disease, is an autoimmune disease characterized by circulating antibodies directed against glomerular and alveolar basement membranes. Affected individuals present with symptoms of rapidly progressive glomerulonephritis and alveolar hemorrhage. Goodpasture Syndrome with lung hemorrhage
• Immune complex-mediated injury (≤ 40% of cases):
  • Postinfectious causes:
    • Poststreptococcal glomerulonephritis Poststreptococcal Glomerulonephritis Post-streptococcal glomerulonephritis (PSGN) is a type of nephritis that is caused by a prior infection with group A beta-hemolytic Streptococcus (GAS). The clinical presentation of PSGN can range from asymptomatic, microscopic hematuria to full-blown acute nephritic syndrome, which is characterized by red-to-brown urine, proteinuria, edema, and acute kidney injury. Postinfectious Glomerulonephritis
    • Infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
    • Vascular prosthetic nephritis
    • Viral hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus
  • Others:
    • Lupus nephritis Lupus nephritis Glomerulonephritis associated with autoimmune disease systemic lupus erythematosus. Lupus nephritis is histologically classified into 6 classes: class I – normal glomeruli, class II – pure mesangial alterations, class III – focal segmental glomerulonephritis, class IV – diffuse glomerulonephritis, class V – diffuse membranous glomerulonephritis, and class VI – advanced sclerosing glomerulonephritis (the world health organization classification 1982). Diffuse Proliferative Glomerulonephritis 
    • IgA-associated vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus glomerulonephritis
    • Cryoglobulinemic glomerulonephritis
    • IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions nephropathy
    • Membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis (MPGN) is also known as mesangiocapillary glomerulonephritis. Membranoproliferative glomerulonephritis is a pattern of glomerular injury characterized by mesangial hypercellularity, endocapillary proliferation, and thickening of the glomerular basement membrane (double contour formation). Membranoproliferative Glomerulonephritis
    • Idiopathic Idiopathic Dermatomyositis crescentic glomerulonephritis (rare)
• Pauci-immune disease (up to 50% of cases):
  • GPA GPA A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (vasculitis) leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies (antineutrophil cytoplasmic antibodies) against myeloblastin. Granulomatosis with Polyangiitis
  • Microscopic polyangiitis Microscopic polyangiitis A primary systemic vasculitis of small- and some medium-sized vessels. It is characterized by a tropism for kidneys and lungs, positive association with anti-neutrophil cytoplasmic antibodies (ANCA), and a paucity of immunoglobulin deposits in vessel walls. Vasculitides

Pathophysiology

• Crescents form in response to injury to the glomerular capillary wall, which can be damaged by:
  • Immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency
  • Anti-GBM antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (cross-react with the basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN) of the pulmonary alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) and lead to pulmonary hemorrhage)
• Followed by a nephritogenic inflammatory response mediated by Th1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions
• Focal gaps (also known as rents) in the glomerular capillary wall are produced, allowing entry of the following into the Bowman space:
  • Coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis (e.g., fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis) → fibrin formation
  • Fibrinolytic inhibitory factors
  • Cellular elements (e.g., macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions)
  • Proinflammatory cytokines Proinflammatory Cytokines Metabolic Syndrome
• Crescents can cause obliteration of the urinary space.

Clinical Presentation

• Manifestations of RPGN:
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma with urine RBC casts
  • Proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children (up to 30% reaching nephrotic range)
  • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension may or may not be present.
• Insidious onset
• Symptoms include:
  • Oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation
  • Arthralgia Arthralgia Pain in the joint. Rheumatic Fever
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Abdominal pain Abdominal Pain Acute Abdomen, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
• Individuals with anti-GBM disease, granulomatosis with polyangiitis Granulomatosis with Polyangiitis A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (vasculitis) leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies (antineutrophil cytoplasmic antibodies) against myeloblastin. Granulomatosis with Polyangiitis ( GPA GPA A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (vasculitis) leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies (antineutrophil cytoplasmic antibodies) against myeloblastin. Granulomatosis with Polyangiitis), and microscopic polyangiitis Microscopic polyangiitis A primary systemic vasculitis of small- and some medium-sized vessels. It is characterized by a tropism for kidneys and lungs, positive association with anti-neutrophil cytoplasmic antibodies (ANCA), and a paucity of immunoglobulin deposits in vessel walls. Vasculitides ( MPA MPA A primary systemic vasculitis of small- and some medium-sized vessels. It is characterized by a tropism for kidneys and lungs, positive association with anti-neutrophil cytoplasmic antibodies (ANCA), and a paucity of immunoglobulin deposits in vessel walls. Vasculitides) may have hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis from pulmonary involvement Pulmonary involvement Coccidioides/Coccidioidomycosis.

Diagnosis

Laboratory evaluation

• Serum creatinine: almost always elevated
• Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children:
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
  • Dysmorphic RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
  • Sediment with multiple elements (e.g., WBCs, RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, and other casts)
• CBC may show:
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types 
  • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus
• Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess): usually elevated
• Serologic testing (as indicated by clinical presentation) may include:
  • Anti-GBM antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions for anti-GBM antibody disease
  • Antistreptolysin Antistreptolysin Antibodies specific to streptolysins which indicate streptococcal infections. Postinfectious Glomerulonephritis O antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions for postinfectious RPGN
  • Anti-dsDNA antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions for lupus-related RPGN
  • Cryoglobulins for cryoglobulinemia 
  • ANCA titer for pauci-immune RPGN
• Serum complement levels for hypocomplementemia in immune-complex RPGN 
• Other tests:
  • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus (associated with polyarteritis nodosa Polyarteritis nodosa A form of necrotizing non-granulomatous inflammation occurring primarily in medium-sized arteries, often with microaneurysms. It is characterized by muscle, joint, and abdominal pain resulting from arterial infarction and scarring in affected organs. Polyarteritis nodosa with lung involvement is called churg-strauss syndrome. Vasculitides)
  • Hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus (associated with cryoglobulinemia)
  • Urine and serum electrophoresis Electrophoresis An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. Blotting Techniques for suspected multiple myeloma Multiple myeloma Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
• Imaging:
  • Renal ultrasound:
    • To exclude obstructive etiology
    • To determine the presence of 2 functional kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy (needed with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma).
  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests or CT: the presentation includes hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis or pulmonary symptoms

Renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

• Pathologic findings:
  • The proliferation of glomerular epithelial cells 
  • Crescentic cellular mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast fills the Bowman space (may be defined as either 50% of the glomeruli or > 10%).
  • Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage in the glomerular tuft 
• Immunofluorescence microscopy:
  • Anti-GBM antibody disease: linear or ribbon-like deposition of IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis along the GBM 
  • Immune complex RPGN: granular or irregular mesangial IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis and C3 deposits 
  • Pauci-immune RPGN: negative immune staining, no deposits
  • Double antibody RPGN: linear staining of the GBM
  • Idiopathic Idiopathic Dermatomyositis RPGN: varies (with or without immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency)

Management

Treatment approach

• Because RPGN progresses quickly, treatment should be initiated even while awaiting biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma interpretation (especially in severe disease).
• A delay in treatment may cause irreversible renal damage.
• Initial goals:
  • Remove circulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions.
  • Decrease the inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.
• Treatment modalities:
  • Corticosteroids Corticosteroids Chorioretinitis: pulse methylprednisolone Methylprednisolone A prednisolone derivative with similar anti-inflammatory action. Immunosuppressants followed by prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants
  • Cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants
  • Alternatives to cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants:
    • Rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants
    • Mycophenolate Mycophenolate Immunosuppressants
  • Plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome:
    • Recommended for anti-GBM antibody disease
    • Allows the removal of free antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions, immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency, and inflammatory mediators
• Renal replacement therapy ( dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis or kidney transplantation Kidney Transplantation The transference of a kidney from one human or animal to another. Organ Transplantation)

Specific treatments

• Anti-GBM disease:
  • Plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome with immunosuppressive therapy
  • May require respiratory support depending on the severity of hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis ( intubation Intubation Peritonsillar Abscess and mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing)
• ANCA-positive pauci-immune crescentic disease:
  • Induction with corticosteroids Corticosteroids Chorioretinitis combined with rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants or cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants
  • Use plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome in individuals with concomitant anti-GBM disease.
  • Plasmapheresis Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Stevens-Johnson Syndrome is controversial in other cases.
• Immune complex-mediated crescentic disease:
  • Poststreptococcal glomerulonephritis Poststreptococcal Glomerulonephritis Post-streptococcal glomerulonephritis (PSGN) is a type of nephritis that is caused by a prior infection with group A beta-hemolytic Streptococcus (GAS). The clinical presentation of PSGN can range from asymptomatic, microscopic hematuria to full-blown acute nephritic syndrome, which is characterized by red-to-brown urine, proteinuria, edema, and acute kidney injury. Postinfectious Glomerulonephritis: Recovery is typical (in adults, recovery may only be partial).
  • IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions nephropathy:
    • Start corticosteroids Corticosteroids Chorioretinitis in individuals at high risk of progression.
    • For individuals intolerant of corticosteroids Corticosteroids Chorioretinitis, mycophenolate Mycophenolate Immunosuppressants is an option.
  • Lupus nephritis Lupus nephritis Glomerulonephritis associated with autoimmune disease systemic lupus erythematosus. Lupus nephritis is histologically classified into 6 classes: class I – normal glomeruli, class II – pure mesangial alterations, class III – focal segmental glomerulonephritis, class IV – diffuse glomerulonephritis, class V – diffuse membranous glomerulonephritis, and class VI – advanced sclerosing glomerulonephritis (the world health organization classification 1982). Diffuse Proliferative Glomerulonephritis: corticosteroids Corticosteroids Chorioretinitis with cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants or mycophenolate Mycophenolate Immunosuppressants
  • Cryoglobulinemia:
    • Treat the underlying disease ( antiviral Antiviral Antivirals for Hepatitis B therapy for hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus).
    • Treat RPGN with corticosteroids Corticosteroids Chorioretinitis and rituximab Rituximab A murine-derived monoclonal antibody and antineoplastic agent that binds specifically to the cd20 antigen and is used in the treatment of leukemia; lymphoma and rheumatoid arthritis. Immunosuppressants.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• The likelihood of untreated cases progressing to end-stage renal disease within 6 months is high.
• Favorable prognostic features:
  • Anti-GBM disease (if treated early)
  • Postinfectious glomerulonephritis
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
  • GPA GPA A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (vasculitis) leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies (antineutrophil cytoplasmic antibodies) against myeloblastin. Granulomatosis with Polyangiitis
  • Microscopic polyangiitis Microscopic polyangiitis A primary systemic vasculitis of small- and some medium-sized vessels. It is characterized by a tropism for kidneys and lungs, positive association with anti-neutrophil cytoplasmic antibodies (ANCA), and a paucity of immunoglobulin deposits in vessel walls. Vasculitides
• Unfavorable prognostic features:
  • > 60 years of age
  • High serum creatinine level
  • Circumferential crescents in > 75% of glomeruli
  • Oliguric renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
  • No response to treatment in pauci-immune RPGN (seen in approximately 30% of individuals)
• Individuals with double antibody disease have a better renal prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas than individuals with only anti-GBM antibody disease.

Differential Diagnosis

• Diffuse proliferative glomerulonephritis Diffuse Proliferative Glomerulonephritis Diffuse proliferative glomerulonephritis (DPGN) is a histopathologic classification of glomerulonephritis (GN) characterized by an increased cellular proliferation affecting > 50% of the glomeruli. Mesangial, endothelial, and epithelial cells are notably increased. Diffuse Proliferative Glomerulonephritis ( DPGN DPGN Diffuse proliferative glomerulonephritis (DPGN) is a histopathologic classification of glomerulonephritis (GN) characterized by an increased cellular proliferation affecting > 50% of the glomeruli. Mesangial, endothelial, and epithelial cells are notably increased. Diffuse Proliferative Glomerulonephritis): a histopathologic classification of glomerulonephritis with increased cellular proliferation (mesangial, endothelial, and epithelial cells) affecting > 50% of the glomeruli. The most common causes are lupus nephritis Lupus nephritis Glomerulonephritis associated with autoimmune disease systemic lupus erythematosus. Lupus nephritis is histologically classified into 6 classes: class I – normal glomeruli, class II – pure mesangial alterations, class III – focal segmental glomerulonephritis, class IV – diffuse glomerulonephritis, class V – diffuse membranous glomerulonephritis, and class VI – advanced sclerosing glomerulonephritis (the world health organization classification 1982). Diffuse Proliferative Glomerulonephritis and IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions nephropathy. Symptoms include fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Microscopic findings show hypercellularity of the aforementioned cells with capillary loop thickening Capillary Loop Thickening Diffuse Proliferative Glomerulonephritis. Early and aggressive therapy is based on the specific etiology. 
• Poststreptococcal glomerulonephritis Poststreptococcal Glomerulonephritis Post-streptococcal glomerulonephritis (PSGN) is a type of nephritis that is caused by a prior infection with group A beta-hemolytic Streptococcus (GAS). The clinical presentation of PSGN can range from asymptomatic, microscopic hematuria to full-blown acute nephritic syndrome, which is characterized by red-to-brown urine, proteinuria, edema, and acute kidney injury. Postinfectious Glomerulonephritis ( PSGN PSGN Post-streptococcal glomerulonephritis (PSGN) is a type of nephritis that is caused by a prior infection with group A beta-hemolytic Streptococcus (GAS). The clinical presentation of PSGN can range from asymptomatic, microscopic hematuria to full-blown acute nephritic syndrome, which is characterized by red-to-brown urine, proteinuria, edema, and acute kidney injury. Postinfectious Glomerulonephritis): occurs after infection with a group A beta-hemolytic streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus. Diagnosis is by history, laboratory tests, urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children, and serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus testing. Treatment is supportive and the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is excellent. The majority of individuals recover without long-term complications. 
• Membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis (MPGN) is also known as mesangiocapillary glomerulonephritis. Membranoproliferative glomerulonephritis is a pattern of glomerular injury characterized by mesangial hypercellularity, endocapillary proliferation, and thickening of the glomerular basement membrane (double contour formation). Membranoproliferative Glomerulonephritis ( MPGN MPGN Membranoproliferative glomerulonephritis (MPGN) is also known as mesangiocapillary glomerulonephritis. Membranoproliferative glomerulonephritis is a pattern of glomerular injury characterized by mesangial hypercellularity, endocapillary proliferation, and thickening of the glomerular basement membrane (double contour formation). Membranoproliferative Glomerulonephritis): histologic renal lesions characterized by glomerular injury with GBM thickening and mesangial proliferation. The pathogenic process can either be immune complex-mediated or complement-mediated. Individuals can present with nephritic syndrome Nephritic syndrome Nephritic syndrome is a broad category of glomerular diseases characterized by glomerular hematuria, variable loss of renal function, and hypertension. These features are in contrast to those of nephrotic syndrome, which includes glomerular diseases characterized by severe proteinuria, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephritic Syndrome, variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, and decreased renal function. Renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis shows the pathologic renal lesion. Further investigation (i.e., laboratory tests) will point to the underlying cause (e.g., infection, autoimmune disease). Treatment is based on the etiologic disease. 
• Lupus nephritis Lupus nephritis Glomerulonephritis associated with autoimmune disease systemic lupus erythematosus. Lupus nephritis is histologically classified into 6 classes: class I – normal glomeruli, class II – pure mesangial alterations, class III – focal segmental glomerulonephritis, class IV – diffuse glomerulonephritis, class V – diffuse membranous glomerulonephritis, and class VI – advanced sclerosing glomerulonephritis (the world health organization classification 1982). Diffuse Proliferative Glomerulonephritis: glomerulonephritis caused by systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus. Clinical presentation can include hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome, and RPGN. Diagnosis is based on renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis, which will help to classify the disease, guide the management, and provide an indication of prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas. Management includes ACE inhibitors ACE inhibitors Truncus Arteriosus and immunosuppressant drugs.