AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Bright initially described acute glomerulonephritis (GN) in 1927. Acute poststreptococcal glomerulonephritis (PSGN) is the archetype of acute GN. Acute nephritic syndrome is the most serious and potentially devastating form of various renal syndromes. Acute GN is characterized by the abrupt onset of hematuria and proteinuria, often accompanied by azotemia (ie, decreased glomerular filtration rate [GFR]) and renal salt and water retention.

Pathophysiology

Acute GN has 2 components: structural changes and functional changes.

Structural changes

• Cellular proliferation: This leads to an increase in the number of cells in the glomerular tuft because of the proliferation of endothelial, mesangial, and epithelial cells. The proliferation could be endocapillary (ie, within the confines of the glomerular capillary tufts) or extracapillary (ie, in the Bowman space involving the epithelial cells). In extracapillary proliferation, proliferation of parietal epithelial cells leads to the formation of crescents, a feature characteristic of certain forms of rapidly progressive GN.
• Leukocyte proliferation: This is indicated by the presence of neutrophils and monocytes within the glomerular capillary lumen and often accompanies cellular proliferation.
• Glomerular basement membrane thickening: This development appears as thickening of capillary walls using light microscopy. Using electron microscopy, this may appear as the result of thickening of basement membrane proper (eg, diabetes) or deposition of electron-dense material, either on the endothelial or epithelial side of the basement membrane.
• Hyalinization or sclerosis: These conditions indicate irreversible injury.
• Electron-dense deposits: Such deposits could be subendothelial, subepithelial, intramembranous, or mesangial, and they correspond to an area of immune complex deposition.
• These structural changes could be focal, diffuse or segmental, and global.

Functional changes

Functional changes include proteinuria, hematuria, reduction in GFR (ie, oligoanuria), and active urine sediment with RBCs and RBC casts. The decreased GFR and avid distal nephron salt and water retention result in expansion of intravascular volume, edema, and, frequently, systemic hypertension.

Poststreptococcal glomerulonephritis

M-protein of the organism was previously believed to be responsible for PSGN. These studies have been discounted recently. Nephritis-associated streptococcal cationic protease and its zymogen precursor (NAPR) have been identified as a glyceraldehyde-3-phosphate dehydrogenase that functions as a plasmin(ogen) receptor. This binds to plasmin and activates complement via alternate pathway. Antibody levels to NAPR are elevated in streptococcal infections (of group A, C, and G) associated with glomerulonephritis but are not elevated in streptococcal infections without glomerulonephritis, whereas anti-streptolysin-O titers are elevated in both circumstances. These antibodies to NAPR persist for years and perhaps are protective against further episodes of PSGN. In a recent study in adults, the 2 most frequently identified infectious agents were streptococcus (27.9%) and staphylococcus (24.4%).¹

Frequency

United States

GN comprises 25-30% of all cases of end-stage renal disease (ESRD). About one fourth of patients present with acute nephritis syndrome. Most cases that progress do so relatively quickly, and end-stage renal failure may occur within weeks or months of acute nephritic syndrome onset. Asymptomatic episodes of PSGN exceed symptomatic episodes by a ratio of 3-4:1.

International

Geographic and seasonal variations in the prevalence of PSGN are more marked for pharyngeally associated GN than for cutaneously associated disease.

Race

Postinfectious GN has no predilection for any racial or ethnic group. A higher incidence (related to poor hygiene) may be observed in some socioeconomic groups.

Sex

Acute GN predominantly affects males (ie, 2:1 male-to-female ratio).

Age

Postinfectious GN can occur at any age but usually develops in children. Outbreaks of PSGN are common in children aged 6-10 years.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Taking a proper history is important and helpful.

• Determine onset of disease: Ask the patient about onset and duration of illness.
• Identify a possible etiologic agent (eg, streptococcal throat infection [pharyngitis], skin infection [pyoderma]): Recent fever, sore throat, joint pains, hepatitis, travel, valve replacement, and/or intravenous drug use may be causative factors. Rheumatic fever rarely coexists with acute PSGN.
• Identify systemic disease (eg, arthralgia, diabetes).
• Assess the consequences of the disease process (eg, uremic symptoms): Inquire about loss of appetite, generalized itching, tiredness, listlessness, nausea, easy bruising, nose bleeds, facial swelling, leg edema, and shortness of breath.
• Identify clinical features: Inquire about edema, decreased volume and frequency of urination, systemic hypertension, uremic symptoms, costovertebral tenderness (ie, enlarged kidneys [rare]), and gross hematuria. Gross hematuria is the most common abnormality observed in patients with acute PSGN and often manifests as smoky-, coffee-, or cola-colored urine.

Physical

• Signs of fluid overload
• • Periorbital and/or pedal edema
  • Edema and hypertension due to fluid overload  (in 75% of patients)
  • Crackles (ie, if pulmonary edema)
  • Elevated jugular venous pressure
  • Ascites and pleural effusion (possible)
• Rash (ie, vasculitis, Henoch-Schönlein purpura)
• Pallor
• Renal angle (ie, costovertebral) fullness or tenderness, joint swelling, or tenderness

Causes

The causal factors that underlie this syndrome can be broadly divided into infectious and noninfectious groups.

• Infectious
• • Streptococcal: Poststreptococcal GN usually develops 1-3 weeks following acute infection with specific nephritogenic strains of group A beta-hemolytic streptococcus. The incidence of GN is approximately 5-10% in persons with pharyngitis and 25% in those with skin infections.
  • Nonstreptococcal postinfectious glomerulonephritis
    • Bacterial - Infective endocarditis, shunt nephritis, sepsis, pneumococcal pneumonia, typhoid, secondary syphilis, meningococcemia, and infection with methicillin-resistant Staphylococcus aureus (MRSA)
    • Viral - Hepatitis B, infectious mononucleosis, mumps, measles, varicella, vaccinia, echovirus, parvovirus, and coxsackievirus
    • Parasitic - Malaria, toxoplasmosis
• Noninfectious
• • Multisystem systemic diseases - Systemic lupus erythematosus, vasculitis, Henoch-Schönlein purpura, Goodpasture syndrome, Wegener granulomatosis
  • Primary glomerular diseases - Membranoproliferative GN (MPGN), Berger disease (ie, immunoglobulin A [IgA] nephropathy), "pure" mesangial proliferative GN
  • Miscellaneous - Guillain-Barré syndrome, radiation of Wilms tumor, diphtheria-pertussis-tetanus vaccine, serum sickness

DIFFERENTIALS

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Other Problems to be Considered

• Postinfectious GN must be differentiated from the following conditions:
• • IgA nephritis: The latent period between infection and onset of nephritis is 1- 2 days, or it may be concomitant with upper respiratory tract infection (ie, "synpharyngitic" in contrast to 1-3 wk "postpharyngitic nephritis" in PSGN).
  • MPGN (type I, type II): This is a chronic disease, but it can manifest with an acute nephritic picture with hypocomplementemia; failure of acute nephritis to resolve should prompt consideration of this possibility.
  • Lupus nephritis: Gross hematuria is unusual in lupus nephritis.
  • GN of chronic infection: This can manifest as acute nephritis. Unlike PSGN, in which the infection may have resolved by the time nephritis occurs, patients with nephritis of chronic infection have an active infection at the time nephritis becomes evident. Circulating immune complexes play an important role in the pathogenesis of acute GN in these diseases.
  • Vasculitis: Nephritis of MRSA may have vasculitic lesions of the lower extremities.
  • Predominantly nonglomerular diseases: Thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, atheroembolic renal disease, and acute hypersensitivity interstitial nephritis may present with features of acute nephritic syndrome and should be differentiated.

WORKUP

Section 5 of 11  

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Lab Studies

• Urinalysis and sediment examination
• • These tests are crucial in the evaluation of patients with acute nephritic syndrome.
  • Look for protein, blood, RBCs and WBCs, dysmorphic red cells, acanthocytes, cellular (ie, RBC, WBC) casts, granular casts, and oval fat bodies. In some instances, marked sterile pyuria is present.
  • Finding RBC casts is an almost pathognomonic sign of GN.
  • Urine electrolytes, urine sodium, and fractional excretion of sodium (FENa) assays are needed to assess salt avidity.
• Blood, urea, and nitrogen (BUN); serum creatinine; and serum electrolytes (especially serum potassium level)
• Complete blood cell count
• Erythrocyte sedimentation rate
• Complement levels (C3, C4, CH50)
• • Low C3 levels are found in almost all patients with acute poststreptococcal nephritis; C4 levels may be slightly low. Hypocomplementemia is noted in 73.9% of adult patients.
  • Type III cryoglobulinemia may be present.
• Twenty-four–hour urine test for total protein and creatinine clearance: Remember that creatinine clearance is a "steady-state" measurement. The creatinine clearance may not reveal the true picture because of rapidly changing renal function; therefore, it is better to wait until renal function has stabilized before performing creatinine clearance.
• Antistreptolysin-O titer (ASOT) or streptozyme titer: Increasing titer levels confirm recent infection. In patients with skin infection, anti-DNase B titers are more sensitive than ASOT for infection with Streptococcus.
• Antibody to NAPR: Levels are elevated in streptococcal infections with GN but not in streptococcal infections without GN.
• If MRSA is the inciting agent, then hypocomplementemia is usually not present, but plasma immunoglobulins, especially IgA, are markedly elevated.
• Qualitative estimation of proteinuria: Determination of high-molecular weight (HMW) protein, like fractional excretion of IgG (FEIgG), and low-molecular weight (LMW) protein, like alpha-1-microglobulin, may help predict the clinical outcome and may help in guiding steroid and immunosuppressive therapy, especially in patients with primary glomerular diseases with nephrotic syndrome.

Imaging Studies

• Abdominal ultrasound
• • Assesses renal size
  • Assesses echogenicity of renal cortex
  • Excludes obstruction

Procedures

• Generally, a renal biopsy is not necessary for a diagnosis of acute PSGN; however, in most cases, it is important because histology guides both prognosis and therapy.

Histologic Findings

Diffuse endocapillary proliferative changes are found (see Media files 1-2). The most common histologic patterns are diffuse (72.1%), focal (12.8%), and mesangial (8.1%) proliferative GN in adults.¹ In postinfectious GN, the glomerulus is hypercellular with marked cellular infiltration (ie, polymorphonuclear neutrophils, monocytes). Immunofluorescence may show fine granular deposits of immunoglobulin G in a "starry sky" appearance (see Media file 3). Large subepithelial deposits may be observed on electron microscopy (see Media file 4). Crescents may be observed.

TREATMENT

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Medical Care

Treatment of acute PSGN is mainly supportive because there is no specific therapy for renal disease. Treat the underlying infections when acute GN is associated with chronic infections.

• Antimicrobial therapy
• • Antibiotics (eg, penicillin) are used to control local symptoms and to prevent spread of infection to close contacts.
  • Antimicrobial therapy does not appear to prevent the development of GN, except if given within the first 36 hours.
• Loop diuretic therapy
• • Loop diuretics may be required in patients who are edematous and hypertensive in order to remove excess fluid and to correct hypertension.
  • Relieves edema and controls volume, thereby helping to control volume-related elevation in BP.
  • Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may be used if severe hypertension or encephalopathy is present.
  • Glucocorticoids and cytotoxic agents are of no value, except in severe cases of PSGN.

Consultations

Nephrologist

Diet

• Sodium and fluid restriction - For treatment of signs and symptoms of fluid retention (eg, edema, pulmonary edema)
• Protein restriction for patients with azotemia - If no evidence of malnutrition

Activity

Recommend bed rest until signs of glomerular inflammation and circulatory congestion subside. Prolonged inactivity does not benefit in the patient recovery process.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to eradicate the infection.

Drug Category: Antimicrobials (antibiotics)

In streptococcal infections, early antibiotic therapy may prevent antibody response to exoenzymes and render throat cultures negative, but may not prevent the development of PSGN.

Drug Category: Loop diuretics

Decrease plasma volume and edema by causing diuresis. The reduction in plasma volume and stroke volume associated with diuresis decreases cardiac output and, consequently, BP.

Drug Category: Vasodilators

Reduce SVR, which, in turn, may allow forward flow, improving cardiac output.

Drug Category: Calcium channel blockers

In specialized conducting and automatic cells in the heart, calcium is involved in the generation of the action potential. The calcium channel blockers inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Patients may require hospitalization for control of edema and hypertension.

Further Outpatient Care

• Monitor renal function, BP, edema, serum albumin, and urine protein excretion rate.

In/Out Patient Meds

• Patient may require medication to control BP.

Transfer

• The expertise available in the ICU may be needed for management of patients with hypertensive encephalopathy or pulmonary edema.

Deterrence/Prevention

• Early antibiotic therapy of streptococcal infection (ie, within 36 h of onset) may prevent development of PSGN.
• Antibiotic treatment of close contacts of the index case may help prevent development of PSGN.

Complications

• Renal failure (rare)
• Pulmonary edema
• Generalized anasarca and hypoalbuminemia (secondary to severe proteinuria)
• Hypertension
• Hypertensive encephalopathy

Prognosis

• Prognosis of acute PSGN is generally excellent in children.
• Within a week or so of onset, most patients with PSGN begin to experience spontaneous resolution of fluid retention and hypertension.
• C3 levels may normalize within 8 weeks after the first sign of PSGN.
• Proteinuria may persist for 6 months and microscopic hematuria for up to 1 year after onset of nephritis.
• Eventually, all urinary abnormalities should disappear, hypertension should subside, and renal function should return to normal.
• In adults with PSGN, full recovery of renal function can be expected in just over half of patients, and prognosis is dismal in patients with underlying diabetic glomerulosclerosis.
• Few patients with acute nephritis develop rapidly progressive renal failure.
• Nephritis associated with MRSA and chronic infections usually resolves after treatment of the infection.
• Immunity to type M protein is type-specific, long-lasting, and protective. Repeated episodes of PSGN are therefore unusual.
• Approximately 15% of patients at 3 years and 2% of patients at 7-10 years may have persistent mild proteinuria. Long-term prognosis is not necessarily benign. Some patients may develop hypertension, proteinuria, and renal insufficiency as long as 10-40 years after the initial illness.

Patient Education

• Counsel patients about the need for the following measures:
• • Salt restriction during the acute phase to control edema and volume-related hypertension
  • BP monitoring at periodic intervals
  • Ongoing long-term monitoring of patients with persistent urinary abnormalities and elevated BP
  • Consideration of protein restriction and angiotensin converting enzyme inhibitors (in patients who show evidence of persistent abnormalities or in those who develop late evidence of progressive disease)
  • Early antibiotic treatment of close contacts
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Blood in the Urine.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to consider acute GN in the differential of patients presenting with hematuria, proteinuria, hypertension, facial or leg swelling, and renal insufficiency
• Failure to perform urinalysis, especially urine microscopy examination in patients presenting with passage of discolored urine or symptoms and signs suggestive of acute GN
• Failure to monitor renal function, electrolytes, and BP in patients with acute GN
• Failure to monitor and control BP effectively in patients with volume overload
• Failure to treat close contacts of patients with acute PSGN
• Failure to recommend long-term monitoring of patients with persistent urinary abnormalities and elevated BP

MULTIMEDIA

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Media file 1:  Light microscopy (hematoxylin and eosin stain X 25): Photograph showing enlargement of glomerular tuft with marked decrease of urinary space and hypercellularity. The hypercellularity is due to proliferation of endogenous cells and polymorphonuclear leukocyte infiltrate. Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
	View Full Size Image
Media type:  Photo

Media file 2:  Light microscopy (periodic acid-Schiff stain X 40): Photograph showing enlargement of glomerular tuft with marked decrease of urinary space and hypercellularity. The hypercellularity is due to proliferation of endogenous cells and polymorphonuclear leukocyte infiltrate. Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
	View Full Size Image
Media type:  Photo

Media file 3:  Immunofluorescence (X25): Fine granular deposits of immunoglobulin G (IgG) along the basement membrane and mesangium with "starry sky" appearance. Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
	View Full Size Image
Media type:  Photo

Media file 4:  Ultrastructure (electron microscopy): Photograph showing proliferation of endothelial cells and mesangial cells and leukocyte infiltrate associated with presence of large subepithelial electron-dense deposits (ie, "hump") (see arrow). Photograph courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
	View Full Size Image
Media type:  Photo

REFERENCES

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1. Nasr SH, Markowitz GS, Stokes MB, et al. Acute postinfectious glomerulonephritis in the modern era: experience with 86 adults and review of the literature. Medicine (Baltimore). Jan 2008;87(1):21-32. [Medline].
2. Arze RS, Rashid H, Morley R, et al. Shunt nephritis: report of two cases and review of the literature. Clin Nephrol. Jan 1983;19(1):48-53. [Medline].
3. Baldwin DS, Gluck MC, Schacht RG, et al. The long-term course of poststreptococcal glomerulonephritis. Ann Intern Med. Mar 1974;80(3):342-58. [Medline].
4. Bazzi C, Petrini C, Rizza V, et al. A modern approach to selectivity of proteinuria and tubulointerstitial damage in nephrotic syndrome. Kidney Int. Oct 2000;58(4):1732-41. [Medline].
5. Dodge WF, Spargo BH, Travis LB, et al. Poststreptococcal glomerulonephritis. A prospective study in children. N Engl J Med. Feb 10 1972;286(6):273-8. [Medline].
6. Neugarten J, Gallo GR, Baldwin DS. Glomerulonephritis in bacterial endocarditis. Am J Kidney Dis. Mar 1984;3(5):371-9. [Medline].
7. Oda T, Yamakami K, Omasu F, et al. Glomerular plasmin-like activity in relation to nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis. J Am Soc Nephrol. Jan 2005;16(1):247-54. [Medline].
8. Rodriguez-Iturbe B. Nephritis-associated streptococcal antigens: where are we now?. J Am Soc Nephrol. Jul 2004;15(7):1961-2. [Medline].
9. Rodríguez-Iturbe B. Epidemic poststreptococcal glomerulonephritis. Kidney Int. Jan 1984;25(1):129-36. [Medline].
10. Ronco P, Verroust P, Morel-Maroger L. Viruses and Glomerulonephritis. Nephron. 1982;31(2):97-102. [Medline].
11. Yoshizawa N, Yamakami K, Fujino M, et al. Nephritis-associated plasmin receptor and acute poststreptococcal glomerulonephritis: characterization of the antigen and associated immune response. J Am Soc Nephrol. Jul 2004;15(7):1785-93. [Medline].

Article Last Updated: Jul 2, 2008