Membranoproliferative Glomerulonephritis

Overview

Definition

Membranoproliferative glomerulonephritis (MPGN) is a glomerular injury characterized by 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) (GBM) thickening (“membrano-”) and increased endocapillary and mesangial cellularity (“proliferative”).

• The GBM thickens from deposits of 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, complement factors, and/or interposed cells (between the GBM and endothelial cells).
• Proliferation of mesangial cells and 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 contributes to increased cellularity, creating a lobulated glomerular tuft.
• MPGN is a histologic finding and not a specific disease; thus, it is associated with multiple etiologies.
• Also called mesangiocapillary glomerulonephritis

Epidemiology

• Accounts for 7%–10% of cases of biopsy-confirmed glomerulonephritis
• The idiopathic Idiopathic Dermatomyositis or primary form affects the younger population (8–30 years of age).
• The secondary form is seen predominantly in individuals > 30 years of age.

Pathophysiology and Etiology

Glomerular injury

• Pathogenetic mechanisms:
  • Immune complex/monoclonal Ig-mediated mechanism:
    • Deposition of 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 or monoclonal Ig Ig X-linked Agammaglobulinemia
    • Leads to complement activation Complement Activation The sequential activation of serum complement proteins to create the complement membrane attack complex. Factors initiating complement activation include antigen-antibody complexes, microbial antigens, or cell surface polysaccharides. Systemic Lupus Erythematosus
  • Complement-mediated mechanism:
    • Alternative complement pathway (where C3 is at a constant low level in circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment) becomes dysregulated, causing persistent activation.
    • Deposition of complement products in the glomeruli (capillary walls and mesangium Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of glomerular mesangial cells and their extracellular matrix. IgA Nephropathy)
  • Unrelated to complement or Ig Ig X-linked Agammaglobulinemia deposition (seen in the case of endothelial injury)
• Insults to the glomeruli and mesangium Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of glomerular mesangial cells and their extracellular matrix. IgA Nephropathy result in:
  • Acute mesangial and capillary injury from the deposition of 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, monoclonal Igs Igs 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, or complement factors
  • Influx of inflammatory cells
  • Histologic changes:
    • New mesangial matrix is produced → mesangium Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of glomerular mesangial cells and their extracellular matrix. IgA Nephropathy expands → glomerular tuft becomes lobular
    • New GBM is formed that looks like a 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) with a double contour → “tram track”

Classification (electron microscopy)

Traditionally, MPGN was classified based on electron microscopy findings (old classification):

• Based on electron microscopy:
  • MPGN type I:
    • Characterized by immune deposits in the subendothelial space (subendothelial deposits) and mesangium Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of glomerular mesangial cells and their extracellular matrix. IgA Nephropathy (mesangial deposits)
    • Seen in 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, infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • MPGN type II:
    • Dense deposit disease (DDD)
    • Additional intramembranous deposits
    • Along the GBMs, tubules, and Bowman’s capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides, continuous dense ribbon-like deposits are seen.
    • Associated with C3 nephritic factor (C3NeF)
  • MPGN type III: similar to MPGN type I, but with subendothelial, mesangial, and subepithelial deposits
• Overlapping features of the different types are noted (e.g., type I can be found to have features of complement-mediated or immune complex-mediated MPGN).

Classification (immunofluorescence microscopy) and etiology

A different classification based on the pathogenetic process helps point to the underlying etiology or disease, thus directing treatment.

• Pathogenesis is identified based on immunofluorescence findings.
• Classification based on the pathogenesis (immune complex/monoclonal Ig Ig X-linked Agammaglobulinemia versus complement):
  • Immune complex/monoclonal Ig-mediated MPGN:
    • Chronic viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., 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 or C)
    • Chronic bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis, shunt nephritis, and abscesses)
    • Fungal and parasitic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency (e.g., 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, Sjögren syndrome Sjögren Syndrome Rheumatoid Arthritis, rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis)
    • Paraproteinemias (e.g., MGUS, Waldenstrom macroglobulinemia)
    • Malignancies (e.g., non-Hodgkin lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum)
    • Splenorenal shunt for portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension
    • Idiopathic Idiopathic Dermatomyositis/primary
  • Complement-mediated MPGN (less common):
    • C3 glomerulonephritis (C3GN)
    • C3 DDD: most cases have C3NeF → binds to alternative pathway Alternative pathway Complement activation initiated by the interaction of microbial antigens with complement C3b. When complement factor B binds to the membrane-bound C3b, complement factor d cleaves it to form alternative C3 convertase (c3bbb) which, stabilized by complement factor p, is able to cleave multiple complement C3 to form alternative C5 convertase (c3bbb3b) leading to cleavage of complement C5 and the assembly of complement membrane attack complex. Innate Immunity: Barriers, Complement, and Cytokines C3 convertase c3 convertase Serine proteases that cleave complement C3 into complement C3a and complement C3b, or cleave complement C5 into complement C5a and complement C5b. These include the different forms of C3/c5 convertases in the classical and the alternative pathways of complement activation. Both cleavages take place at the c-terminal of an arginine residue. Nephritic Syndrome → sustained C3 activation
    • C4 glomerulopathies (C4GN, C4 DDD)
    • Genetic causes
  • MPGN without Ig Ig X-linked Agammaglobulinemia or complement deposition (commonly from endothelial injury, followed by repair):
    • Thrombotic microangiopathies
    • Antiphospholipid antibody syndrome
    • After bone marrow transplantation Bone marrow transplantation Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation
    • Chronic kidney allograft nephropathy
    • Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma nephritis
    • Malignant hypertension Malignant Hypertension Hypertensive Retinopathy

Clinical Presentation and Diagnosis

Manifestations

• 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 (can present as acute/ rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. Rapidly Progressive Glomerulonephritis ( RPGN RPGN Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. Rapidly Progressive Glomerulonephritis) or as CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease)
• Typical findings:
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma: typically with dysmorphic red cells or red cell casts
  • Serum creatinine may be elevated or normal.
  • Proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children: sometimes similar to the levels seen in 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
  • 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
• Low complement levels or hypocomplementemia (↓C3 and ↓ CH50 CH50 Terminal Complement Pathway Deficiency levels) are common (although complement levels may be normal):
  • Immune complex-mediated MPGN:
    • Classic complement pathway is activated.
    • ↓ C3 and C4
  • Complement-mediated MPGN:
    • Alternative pathway Alternative pathway Complement activation initiated by the interaction of microbial antigens with complement C3b. When complement factor B binds to the membrane-bound C3b, complement factor d cleaves it to form alternative C3 convertase (c3bbb) which, stabilized by complement factor p, is able to cleave multiple complement C3 to form alternative C5 convertase (c3bbb3b) leading to cleavage of complement C5 and the assembly of complement membrane attack complex. Innate Immunity: Barriers, Complement, and Cytokines is activated.
    • ↓ C3, but normal C4
• Extrarenal manifestations: macular retinal deposits ( drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome) and upper body lipodystrophy in DDD

Diagnosis

• Although the clinical presentation may be suggestive, a biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is required for diagnosis:
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma establishes a histologic lesion but not a clinical diagnosis.
  • Further workup is needed to determine the underlying entity causing MPGN.
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma findings: based on histologic changes determined using light microscopy, immunofluorescence, and electron microscopy

Additional workup

Additional workup is indicated when biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma shows changes consistent with:

• Immune complex/monoclonal Ig-mediated MPGN; further tests may include:
  • Workup for infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Blood cultures
    • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus to determine 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 and 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 infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) and serologic tests to determine viral, bacterial, and fungal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in the relevant clinical context
  • Workup for autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency: screening Screening Preoperative Care for autoimmune diseases Autoimmune diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Selective IgA Deficiency, followed by specific tests as indicated
  • Workup for monoclonal gammopathies:
    • Serum protein 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 and immunofixation
    • Serum free light chains Light chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kda. There are two major types of light chains, kappa and lambda. Two ig light chains and two ig heavy chains (immunoglobulin heavy chains) make one immunoglobulin molecule. Immunoglobulins: Types and Functions
    • Urine protein 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 and immunofixation
    • Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis studies may also be indicated.
• Complement-mediated MPGN; check for:
  • Activation of the classic complement pathways: C3, C4, CH50 CH50 Terminal Complement Pathway Deficiency
  • Activation of the alternative complement pathway: AH50
  • Genetic analysis for mutations and allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics variants of complement factors
  • Autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques to complement regulating proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (e.g., factors H and I)
  • Testing for C3NeF
  • Serum levels of the membrane attack complex Membrane attack complex A product of complement activation cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target cell membrane and cell lysis. It is formed by the sequential assembly of terminal complement components (complement C5b; complement C6; complement C7; complement C8; and complement C9) into the target membrane. The resultant C5b-8-poly-c9 is the ‘membrane attack complex’ or MAC. Type II Hypersensitivity Reaction

Management

Treatment

• Treat the underlying disease (e.g., antiviral Antiviral Antivirals for Hepatitis B therapy for 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 or C, immunosuppression for autoimmune disorders).
• While most cases can be classified, the underlying disease is not found ( idiopathic Idiopathic Dermatomyositis) in a small number of cases.
  • Management depends on:
    • Proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children
    • Degree of kidney failure
  • In mild disease (normal kidney function, non-nephrotic–range proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children (< 3.5 g/day), and no significant hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma):
    • ACE inhibitors ACE inhibitors Truncus Arteriosus ( ACEis ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Angina Medication) or ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication
    • Regular Regular Insulin follow up of renal function (creatinine, 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, urine protein)
  • Upon deterioration (e.g., > 1.5 g/day proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children or abnormal creatinine), the therapeutic options considered are:
    • Immunosuppression ( corticosteroids Corticosteroids Chorioretinitis, mycophenolate Mycophenolate 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, cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants, tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants)
    • Plasma exchange Plasma exchange Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. Thrombotic Thrombocytopenic Purpura if C3NeF is present
    • Eculizumab (monoclonal antibody to C5)
  • Renal transplantation (recurrence possible in the graft Graft A piece of living tissue that is surgically transplanted Organ Transplantation)

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

• Poor prognostic factors:
  • 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
  • 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
  • Elevated creatinine
  • Crescents on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Tubulointerstitial disease
• Good prognostic factors:
  • Non-nephrotic range proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children
  • Normal blood pressure
  • Normal creatinine

Differential Diagnosis

• 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: a renal disease characterized by 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 deposition in the mesangium Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of glomerular mesangial cells and their extracellular matrix. IgA Nephropathy. Immunoglobulin A nephropathy frequently presents in the 2nd and 3rd decades of life and, historically, with a preceding upper respiratory or GI infection GI infection Microsporidia/Microsporidiosis. Presenting features are gross hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma or asymptomatic, microscopic hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma. The course is often benign Benign Fibroadenoma, with renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis performed only in cases of severe, progressive renal disease. Treatment depends on the severity of proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, renal function, and pathologic changes. To reduce disease progression, ACEis ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Angina Medication or ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication are often used. Immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants are administered to address persistent proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children and increasing creatinine levels.
• 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 presentations include hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, nephrotic range proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, and, in advanced disease, azotemia Azotemia A biochemical abnormality referring to an elevation of blood urea nitrogen and creatinine. Azotemia can be produced by kidney diseases or other extrarenal disorders. When azotemia becomes associated with a constellation of clinical signs, it is termed uremia. Acute Kidney Injury. Diagnosis is based on renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Treatment usually involves corticosteroids Corticosteroids Chorioretinitis and cytotoxic Cytotoxic Parvovirus B19 agents, or other immunosuppressant drugs.
• 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: a type of nephritis caused by a prior infection with 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 (GAS). The clinical presentation can range from asymptomatic, microscopic hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma to full-blown acute 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, which is characterized by red-to-brown urine, proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, 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, and AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury. The diagnosis is made based on clinical findings in the setting of a recent GAS infection. The management is supportive and involves treating the clinical manifestations. 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 generally favorable, especially in children.
•   RPGN RPGN Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. Rapidly Progressive Glomerulonephritis: a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. Rapidly Progressive Glomerulonephritis is a manifestation of different diseases. Histologically, crescents are found in the glomeruli. Crescents arise from immunologic injury, major mechanisms of which are classified into anti-GBM disease, pauci-immune crescentic disease, and immune complex-mediated injury. 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, 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, and 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 are the manifestations of RPGN RPGN Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. Rapidly Progressive Glomerulonephritis. Diagnosis is by presentation, laboratory tests, imaging, and renal biopsy Renal Biopsy Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Prompt treatment is essential and includes corticosteroids Corticosteroids Chorioretinitis, immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants, and 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, depending on the underlying disease.