Nephritic Syndrome

Nephritic syndrome is a broad category of glomerular diseases characterized by glomerular hematuria, 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 loss of renal function, 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. These features are in contrast to those of 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, which includes glomerular diseases characterized by severe proteinuria, although there is sometimes overlap of > 1 glomerular disease in the same individual. The clinical presentations of nephritic syndrome are highly varied, from asymptomatic with urinary abnormalities to life-threatening critical illness. Diagnosis is suggested by hematuria, mild-to-moderate proteinuria, and certain serologies (e.g., ANCA); kidney biopsy is necessary in most cases. Management varies as widely as the clinical presentations, from watchful waiting in mild cases to immunosuppression and plasmapheresis in aggressive disease.

Last update:

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Overview

Definition

Nephritic syndrome is defined by some or all of the following findings: 

  • Glomerular hematuria: active urine sediment
    • Dysmorphic RBCs
    • RBC casts
  • Mild-to-moderate proteinuria (500–3500 mg/day called “subnephrotic”)
  • Hypertension due to:
    • Volume overload/Na retention
    • Suppression of the RAAS
  • Azotemia:
    • Elevated BUN
    • BUN-to-creatinine ratio > 15
  • Oliguria: < 500 mL of urine/day

Etiology

  • Acute glomerulonephritis (GN; presents with mild-to-moderate 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):
    • IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy (also chronic)
    • Poststreptococcal GN ( 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. Poststreptococcal Glomerulonephritis)
    • Lupus nephritis (also chronic)
    • Membranoproliferative GN ( 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; immune complex– and complement-mediated)
    • Rapidly progressive GN ( 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) can be seen with:
      • Anti–glomerular basement membrane (GBM) disease ( 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)
      • Immune complex GN (due to lupus nephritis, IgA, poststreptococcal, 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, and pauci-immune GN seen with ANCA-associated vasculitis)
  • Chronic GN (presents in 3 ways):
    • Incidentally discovered microscopic hematuria +/– mild proteinuria
    • Episodic gross hematuria

Classification

  • Primary GN:
    • IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy
    • 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
    • Anti-GBM disease ( 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)
  • Hereditary disorders:
    • Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome
    • Thin basement membrane disease
  • Secondary GN:
    • Infectious and postinfectious causes:
      • 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 
      • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or "walking" pneumonia. Mycoplasma 
      • Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella typhi
      • Staphylococcal infections (including bacterial 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)
      • Visceral abscesses due to gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
      • Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria
      • Schistosomiasis Schistosomiasis Schistosomiasis is an infection caused by Schistosoma, a trematode. Schistosomiasis occurs in developing countries with poor sanitation. Freshwater snails are the intermediate host and are transmitted to humans through skin contact with contaminated fresh water. The clinical presentation occurs as a result of the host's immune response to antigens from the eggs. Schistosoma/Schistosomiasis
      • Coxsackievirus Coxsackievirus Coxsackievirus is a member of a family of viruses called Picornaviridae and the genus Enterovirus. Coxsackieviruses are single-stranded, positive-sense RNA viruses, and are divided into coxsackie group A and B viruses. Both groups of viruses cause upper respiratory infections, rashes, aseptic meningitis, or encephalitis. Coxsackievirus
      • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus
      • EBV
      • 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 C 
      • Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus
      • Mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps
      • Varicella
    • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue disorders: 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
    • Vasculitides Vasculitides Vasculitides are a group of conditions characterized by vasculitis, ischemia, and damage to the organs supplied by the affected vessels. The affected arteries are of different sizes and locations and vary by the type of vasculitis. Vasculitides
      • Eosinophilic granulomatosis with polyangiitis Granulomatosis with Polyangiitis Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease of unknown etiology. It leads to a necrotizing granulomatous inflammation of small and medium-sized blood vessels of the nose, sinuses, throat, lungs, and kidneys. Granulomatosis with Polyangiitis (EGPA; formerly, Churg-Strauss syndrome)
      • Microscopic polyangiitis (MPA)
      • Granulomatosis with polyangiitis
      • IgA-associated vasculitis, also known as Henoch-Schönlein purpura Henoch-Schönlein Purpura Henoch-Schönlein purpura (HSP), also known as immunoglobulin A vasculitis, is an autoimmune small-vessel vasculitis that typically presents as a tetrad of abdominal pain, arthralgia, hematuria, and purpuric rash. Henoch-Schönlein Purpura (not the same as IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy)
      • Polyarteritis nodosa
    • Hematologic dyscrasias:
      • Mixed IgG–IgM cryoglobulinemia
      • Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura–hemolytic uremic syndrome (TTP-HUS)
Urine microscopy - normal and dysmorphic rbcs

Urine microscopy:
Normal RBC with circular appearance (left)
The 3 images to the right show dysmorphic RBCs. Note the blebs on the membrane and the “Mickey Mouse” cells.

Image: “Isomorphic red blood cells (RBCs) and dysmorphic RBCs, 400×” by Chu-Su Y., et al. License: CC BY 4.0, cropped by Lecturio.

Pathophysiology

The 2 main mechanisms of glomerular injury in the nephritic syndromes are immune complex–mediated and complement dysregulation. Hereditary forms of GN (e.g., Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome) have different pathophysiologies.

Nephron Nephron The functional units of the kidney, consisting of the glomerulus and the attached tubule. Kidneys anatomy and physiology

  • Glomerular barrier: filtration structure of the nephron that surrounds the glomerular 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 and includes the following 3 layers:
    • Capillary endothelium: walls of the capillary vessels
    • GBM: formed by the capillary endothelial and podocyte basal laminas
    • Epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium (podocytes): attached to the GBM with multiple foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot processes
  • Nephritic syndrome primarily involves the capillary endothelium and GBM.
  • Nephrotic syndrome primarily involves the epithelial layer with podocytes.
Glomerular barrier

Diagram of the glomerular barrier:
A: Fenestrated endothelium of the glomerular 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
B: Basal membrane
C: Epithelial layer demonstrating podocyte foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot processes and structural proteins creating the slit diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm

Image by Lecturio.

Pathophysiology

  • Immune complex–mediated:
    • Antigen:
      • Can be foreign (e.g., bacterial) or self (e.g., autoimmune disease)
      • Can be circulating in the bloodstream or fixed in tissues 
    • Antigen + antibody = immune complex → inflammatory response → neutrophils and other inflammatory factors are recruited → tissue damage
      • Can form in the circulation (e.g., 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. Poststreptococcal Glomerulonephritis)
      • Can also form directly in tissues (e.g., anti-GBM disease)
  • Complement dysregulation:
    • Normal complement system/process:
      • Complement is a component of the humoral immune system.
      • Cascade ends with the formation of a membrane attack complex (MAC) → compromises the integrity of the foreign cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane → cell lysis
    • Dysregulation in GN:
      • Compromises the integrity of the glomerular filtration Glomerular filtration The kidneys are primarily in charge of the maintenance of water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. Glomerular filtration is the process of converting the systemic blood supply into a filtrate, which will ultimately become the urine. Glomerular Filtration unit → RBC and protein leak into the urine → glomerular filtration rate Glomerular filtration rate The volume of water filtered out of plasma through glomerular capillary walls into bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests decreases
      • The alternative pathway is overactive → inappropriate inflammatory response and neutrophil recruitment → tissue damage 
Primary pathways of the complement system

Primary pathways of the complement system
MBL: monoclonal B-cell lymphocytosis Lymphocytosis WBCs develop from stem cells in the bone marrow and are called leukocytes when circulating in the bloodstream. Lymphocytes are 1 of the 5 subclasses of WBCs. Lymphocytosis is an increase in the number or proportion of the lymphocyte subclass of WBCs, often as a result of an immune response to infection (known as reactive lymphocytosis). Lymphocytosis

Image by Lecturio.

Types of Nephritic Syndrome

The primary and secondary causes of GN vary by etiology but have hematuria and 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 degrees of proteinuria in common. Biopsy findings differ and are important to know.

IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy

  • Presentation:
    • Most commonly presents as chronic GN:
      • 40% present with gross hematuria. 
      • 30% are found incidentally with persistent microscopic hematuria. 
      • May present in association with a concurrent upper respiratory infection 
    • Presents much less commonly as acute GN or 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 (approximately 5%–10%)
  • Diagnosis:
    • Labs: normal serum complement levels
    • Kidney biopsy findings:
      • Light microscopy: mesangial hypercellularity
      • Immunofluorescence: positive for IgA in the mesangium
      • Electron microscopy: mesangial immune deposits
  • Management:
    • Observation if creatinine is normal and proteinuria is < 500 mg/day
    • ACEi if proteinuria is 500 mg–1000 mg/day
    • Steroids for progressive disease
    • Transplantation if progression to end-stage renal disease (ESRD)

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. Poststreptococcal Glomerulonephritis

  • Presentation:
    • Most common cause of acute nephritic syndrome (but not concurrently) in children
    • Can present 1–3 weeks after a throat infection caused by specific nephritogenic strains of 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 
    • Can present 3–6 weeks after a skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin infection ( impetigo Impetigo Impetigo is a highly contagious superficial bacterial infection typically caused by Staphylococcus aureus (most common) and Streptococcus pyogenes. Impetigo most commonly presents in children aged 2 to 5 years with lesions that evolve from papules to vesicles to pustules, which eventually break down to form characteristic "honey-colored" crusts. Impetigo): caused by group A 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 or Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
  • Diagnosis:
    • Labs: 
      • Streptozyme test: measures 5 different 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 including antistreptolysin-O after pharyngeal infection
      • Urinalysis: hematuria with RBC casts, +/– proteinuria
    • Kidney biopsy findings:
      • Light microscopy: diffuse endocapillary proliferation with neutrophils
      • Immunofluorescence: C3 positive; granular IgG “lumpy-bumpy” or “starry sky” pattern
      • Electron microscopy: subepithelial “hump-like” immune complex deposits
  • Management:
    • Supportive care
    • Antibiotics: only if the strep infection is still present at the time of diagnosis
    • Treat 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/or 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:
      • Loop diuretics Loop diuretics Loop diuretics are a group of diuretic medications primarily used to treat fluid overload in edematous conditions such as heart failure and cirrhosis. Loop diuretics also treat hypertension, but not as a 1st-line agent. Loop Diuretics (e.g., furosemide)
      • Sodium and water restriction

Lupus Nephritis

  • Presentation:
    • Variable; can present as acute/chronic GN or as 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
    • Commonly will have a relapsing and remitting pattern once established
    • Can overlap with 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
  • Diagnosis:
    • Lab findings:
      • Classical complement pathway pattern (low C3 and C4)
      • Specific diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests: ANA, double-stranded DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure (dsDNA)
    • Kidney biopsy findings (differ by class):
      • Class III (focal proliferative GN): < 50% glomeruli involvement with cellular proliferation; “wire loops”
      • Class IV (diffuse proliferative GN): > 50% glomeruli involvement with cellular proliferation; “wire loops”
      • Class V (membranous nephropathy): Thickened basement membrane
  • Management:
    • Class I and II: conservative treatment with ACEi for 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
    • Class III and IV: add immunosuppressant drugs (steroids and cyclophosphamide).
    • Class V: steroids + mycophenolate mofetil + ACEi for proteinuria
Renal histopathologic findings in a patient with systemic lupus erythematosus

Renal histopathologic findings in 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:
Light micrographs of a glomerulus show diffuse thickening of the glomerular basement membrane (periodic acid–silver methenamine stain; ×400) (a) with mesangial hypercellularity and mesangial matrix expansion (periodic acid–Schiff stain; ×400) (b). Electron microscopic analyses show numerous subepithelial and mesangial electron-dense deposits, as well as deposits within the glomerular basement membrane with extensive fusion of foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot processes (×5000) (c).

Image: “Renal histopathological findings” by Su X., et al. License: CC BY 4.0

Anti–glomerular basement membrane disease ( 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)

  • Presentation:
    • Only presents as 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 (medical emergency)
    • 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 (also called crescentic):
      • Refers to renal and pulmonary involvement (pulmonary–renal syndrome)
      • Presents with 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 in 25%–60%
      • More likely in individuals < 30 years old
      • Older individuals > 50 years are more likely to have isolated GN.
  • Diagnosis:
    • Normal serum complement levels
    • Specific diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests:
      • Serum anti-GBM antibody
      • Serum ANCA (up to half will be positive = overlap syndrome with ANCA vasculitis)
      • Chest x-ray/CT: Assess for pulmonary hemorrhage.
      • Bronchoalveolar lavage for definitive diagnosis
    • Kidney biopsy findings:
      • Light microscopy: crescents, necrosis
      • Immunofluorescence: linear IgG deposition 
      • Electron microscopy: nonspecific findings
  • Management: 
    • Plasmapheresis
    • 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
    • Transplantation in individuals who develop ESRD

Immune complex–mediated 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

  • Presentation:
    • Variable; can be triggered by a multitude of underlying diseases
    • Can present as acute/chronic GN or as 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
    • Membranoproliferative glomerulonephritis often overlaps with 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.
    • Commonly associated with mixed cryoglobulinemia with 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
  • Diagnosis:
    • Labs:
      • Classical complement pathway pattern (low C3, low C4)
      • 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 C 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
    • Biopsy findings:
      • Light microscopy: double-contour “tram-track” of GBM
      • Immunofluorescence: varies depending on etiology
      • Electron microscopy: subendothelial deposits
  • Management:
    • Acute GN: steroids + mycophenolate mofetil (avoid with very poor renal function)
    • 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: IV steroids plus cyclophosphamide

Complement-mediated 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

  • Presentation:
    • Subtypes called dense deposit disease (DDD) and C3 glomerulonephritis are both rare.
    • Can present as acute/chronic glomerulonephritis or as 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
    • Drusen (fatty deposits in the retina) may be seen with DDD.
  • Diagnosis:
    • Labs:
      • Alternative complement pathway pattern (low C3, normal C4)
      • Serum C3 nephritic factor
      • Factor I/factor H mutations
    • Biopsy findings:
      • Light microscopy: double-contour tram-track of GBM
      • Immunofluorescence: C3 positive
      • Electron microscopy: intramembranous dense deposits (only with degenerative disk disease)
  • Management:
    • Conservative with ACEi if < 1.5 g/day proteinuria and normal creatinine
    • Steroids + mycophenolate mofetil if ≥ 1.5 g/day proteinuria or abnormal creatinine
    • Transplantation is an option, but recurrence is possible in the graft.

Differential Diagnosis

  • Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome: also known as hereditary nephritis. Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome is a genetic disease of type IV collagen of the basement membrane. Clinical presentation includes isolated microscopic hematuria initially, which may be confused for IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy or thin basement membrane disease. There is also characteristic sensorineural hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss, as well as ocular abnormalities. 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 develops over time and can progress to ESRD requiring transplantation.
  • Thin basement membrane disease: also known as benign familial hematuria. This genetic disease presents with isolated microscopic hematuria and may be confused with IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy or Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome. Kidney biopsy only shows diffuse thinning of the GBM on electron microscopy. The overall prognosis for thin basement membrane disease is good. Individuals should receive an ACEi and undergo long-term follow-up, as there may be overlap with Alport syndrome Alport Syndrome Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular and auditory findings. Alport Syndrome and some will develop 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.
  • Henoch-Schönlein purpura Henoch-Schönlein Purpura Henoch-Schönlein purpura (HSP), also known as immunoglobulin A vasculitis, is an autoimmune small-vessel vasculitis that typically presents as a tetrad of abdominal pain, arthralgia, hematuria, and purpuric rash. Henoch-Schönlein Purpura: also known as IgA vasculitis. Henoch-Schönlein purpura Henoch-Schönlein Purpura Henoch-Schönlein purpura (HSP), also known as immunoglobulin A vasculitis, is an autoimmune small-vessel vasculitis that typically presents as a tetrad of abdominal pain, arthralgia, hematuria, and purpuric rash. Henoch-Schönlein Purpura is primarily a pediatric disease and is the most common cause of vasculitis in children. This condition involves the deposition of IgA immune complexes in multiple vessels following a trigger (infection/environmental) and includes skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, GI, and musculoskeletal symptoms. The renal findings are very similar to those for IgA nephropathy IgA nephropathy IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. IgA Nephropathy, but the disease is often self-limited in children, and kidney biopsy and steroids are often not needed.

References

  1. Appel, G. B., Kaplan, A. A. (2020). Overview of the classification and treatment of rapidly progressive (crescentic) glomerulonephritis. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/overview-of-the-classification-and-treatment-of-rapidly-progressive-crescentic-glomerulonephritis
  2. Bomback, A. S., Appel, G. B. (2021). Lupus nephritis: diagnosis and classification. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/lupus-nephritis-diagnosis-and-classification
  3. Fervenza, F. C., Sethi, S. (2021). Membranoproliferative glomerulonephritis: Classification, clinical features, and diagnosis. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/membranoproliferative-glomerulonephritis-classification-clinical-features-and-diagnosis
  4. Fervenza, F. C., Sethi, S. (2020). Membranoproliferative glomerulonephritis: treatment and prognosis. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/membranoproliferative-glomerulonephritis-treatment-and-prognosis
  5. Kashtan, C. E., Simon, J. F. (2020). Isolated and persistent glomerular hematuria in adults. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/isolated-and-persistent-glomerular-hematuria-in-adults
  6. Kopel, T., Salant, D. J. (2020). C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/c3-glomerulopathies-dense-deposit-disease-and-c3-glomerulonephritis
  7. McAdoo, S. P., Pusey, C. D. (2017). Anti-glomerular basement membrane disease. Clinical Journal of the American Society of Nephrology 12:1162–1172. https://doi.org/10.2215/CJN.01380217
  8. Niaudet, P. (2020). Poststreptococcal glomerulonephritis. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/poststreptococcal-glomerulonephritis
  9. Radhakrishnan, J. (2021). Glomerular disease: Evaluation and differential diagnosis in adults. UpToDate. Retrieved October 25, 2021, from https://www.uptodate.com/contents/glomerular-disease-evaluation-and-differential-diagnosis-in-adults

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

0.0

()

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details