Acute Glomerulonephritis

Updated: Dec 15, 2020
  • Author: Malvinder S Parmar, MBBS, MS, FRCPC, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
  • Print

Practice Essentials

Acute glomerulonephritis (GN) comprises a specific set of renal diseases in which an immunologic mechanism triggers inflammation and proliferation of glomerular tissue that can result in damage to the basement membrane, mesangium, or capillary endothelium. Acute nephritic syndrome is the most serious and potentially devastating form of the various renal syndromes. Acute glomerulonephritis progresses to chronic glomerulonephritis in about 30% of adults. [1]

Acute poststreptococcal glomerulonephritis (PSGN) is the archetype of acute GN. In recent decades, however, the incidence of PSGN has fallen in the United States and other developed countries, while GN associated with staphylococcal infection has risen, due to the increase in antibiotic-resistant Staphylococcus aureus infections. [2, 3, 4]

Acute GN is defined as the sudden onset of hematuria, proteinuria, and red blood cell (RBC) casts in the urine. This clinical picture is often accompanied by hypertension, edema, azotemia (ie, decreased glomerular filtration rate [GFR]), and renal salt and water retention. Acute GN can be due to a primary renal disease or to a systemic disease. Most original research focuses on acute PSGN.

Treatment of PSGN is mainly supportive, because there is no specific therapy for renal disease. When acute GN is associated with chronic infections, the underlying infections must be treated. This article addresses the aspects of GN that are relevant to its acute management.

Go to Emergent Management of Acute Glomerulonephritis and Acute Poststreptococcal Glomerulonephritis for complete information on these topics.



Hippocrates originally described the natural history of acute GN, writing of back pain and hematuria followed by oliguria or anuria. Richard Bright (1789-1858) described acute GN clinically in 1827, which led to the eponymic designation Bright disease. With the development of the microscope, Theodor Langhans (1839-1915) was later able to describe these pathophysiologic glomerular changes.



Glomerular lesions in acute GN are the result of glomerular deposition or in situ formation of immune complexes. On gross appearance, the kidneys may be enlarged up to 50%. Histopathologic changes include swelling of the glomerular tufts and infiltration with polymorphonucleocytes (see Workup: Histologic Findings). Immunofluorescence reveals deposition of immunoglobulins and complement.

In PSGN, involvement of derivatives of streptococcal proteins has been reported. A streptococcal neuraminidase may alter host immunoglobulin G (IgG). IgG combines with host antibodies. IgG/anti-IgG immune complexes are formed and then collect in the glomeruli. In addition, elevations of antibody titers to other antigens, such as antistreptolysin O or antihyaluronidase, DNAase-B, and streptokinase, provide evidence of a recent streptococcal infection.

GN associated with staphylococcal infection occurs in the setting of an active infection.  Immunofluorescence microscopy of kidney biopsy specimens in these cases show deposits that stain in a dominant or co-dominant fashion for IgA and the C3 component of complement. [3]  

Stamatiades et al determined that in PSGN and other type III hypersensitivity reactions, vascular endothelial cells in the kidney actively transport circulating immune complexes from the capillaries to the peritubular interstitial space, where they are detected and scavenged by resident macrophages. Uptake of these immune complexes by the resident macrophages triggers the release of pro-inflammatory cytokines, which in turn results in recruitment of monocytes and neutrophils into the kidney from the circulation. [5]

Structural and functional changes

Acute GN involves both structural changes and functional changes.

Structurally, cellular proliferation leads to an increase in the number of cells in the glomerular tuft because of the proliferation of endothelial, mesangial, [6] and epithelial cells. The proliferation may 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 is indicated by the presence of neutrophils and monocytes within the glomerular capillary lumen and often accompanies cellular proliferation.

Glomerular basement membrane thickening appears as thickening of capillary walls on light microscopy. On 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. Electron-dense deposits can be subendothelial, subepithelial, intramembranous, or mesangial, and they correspond to an area of immune complex deposition.

Hyalinization or sclerosis indicates irreversible injury. These structural changes can be focal, diffuse or segmental, or global.

Functional changes include proteinuria, hematuria, reduction in GFR (ie, oliguria or anuria), 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

Streptococcal M-protein was previously believed to be responsible for PSGN, but the studies on which this belief was based have been discounted. Nephritis-associated streptococcal cationic protease and its zymogen precursor (nephritis-associated plasmin receptor [NAPlr]) have been identified as a glyceraldehyde-3-phosphate dehydrogenase that functions as a plasmin(ogen) receptor.

Immunofluorescence staining of renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in early-phase acute PSGN, and glomerular plasmin activity was almost identical to NAPlr deposition in renal biopsy tissues of acute PSGN patients. These data suggest that NAPlr may contribute to the pathogenesis of acute PSGN by maintaining plasmin activity. [26]  However, the unique glomerular staining patterns of NAPlr and plasmin activity have also been reported in patients with other glomerular diseases in which a preceding streptococcal infection was suggested. [7]

Antibody levels to nephritis-associated protease (NAPR) are elevated in streptococcal infections (group A, C, and G) associated with GN but are not elevated in streptococcal infections without GN, 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 study in adults, the two most frequently identified infectious agents were streptococci (27.9%) and staphylococci (24.4%). [8]

Go to Acute Poststreptococcal Glomerulonephritis for complete information on this topic.



The causal factors that underlie acute GN can be broadly divided into infectious and noninfectious groups.


The most common infectious cause of acute GN has historically been infection by Streptococcus species (ie, group A, beta-hemolytic). Two types have been described, involving different serotypes:

  • Serotype 12 - Poststreptococcal nephritis due to an upper respiratory infection, occurring primarily in the winter months

  • Serotype 49 - Poststreptococcal nephritis due to a skin infection, usually observed in the summer and fall and more prevalent in southern regions of the United States

PSGN usually develops 1-3 weeks after 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 GN may also result from infection by other bacteria, viruses, parasites, or fungi. Bacteria besides group A streptococci that can cause acute GN include the following:

  • Staphylococci
  • Diplococci
  • Other streptococci
  • Mycobacteria
  • Salmonella typhosa
  • Brucella suis
  • Treponema pallidum
  • Corynebacterium bovis
  • Actinobacilli

Cytomegalovirus (CMV), coxsackievirus, Epstein-Barr virus (EBV), hepatitis B virus (HBV), [9] rubella, rickettsiae (as in scrub typhus), parvovirus B19, [10] and mumps virus are accepted as viral causes only if it can be documented that a recent group A beta-hemolytic streptococcal infection did not occur. Acute GN has been documented as a rare complication of hepatitis A. [11]

Attributing glomerulonephritis to a parasitic or fungal etiology also requires the exclusion of a streptococcal infection. Identified organisms include Coccidioides immitis and the following parasites:

  • Plasmodium malariae
  • Plasmodium falciparum
  • Schistosoma mansoni
  • Toxoplasma gondii
  • Wuchereria bancrofti
  • Trichinella roundworms
  • Trypanosomes


Noninfectious causes of acute GN may be divided into primary kidney diseases, systemic diseases, and miscellaneous conditions or agents.

Multisystem systemic diseases that can cause acute GN include the following:

  • Vasculitis (eg, granulomatosis with polyangiitis [Wegener granulomatosis]) - This causes glomerulonephritis that combines upper and lower granulomatous nephritides).

  • Collagen-vascular diseases (eg, systemic lupus erythematosus [SLE]) – This causes glomerulonephritis through renal deposition of immune complexes).

  • Hypersensitivity vasculitis – This encompasses a heterogeneous group of disorders featuring small vessel and skin disease.

  • Cryoglobulinemia – This causes abnormal quantities of cryoglobulin in plasma that result in repeated episodes of widespread purpura and cutaneous ulcerations upon crystallization.

  • Polyarteritis nodosa - This causes nephritis from a vasculitis involving the renal arteries.

  • Henoch-Schönlein purpura – This causes a generalized vasculitis resulting in glomerulonephritis.

  • Goodpasture syndrome – This causes circulating antibodies to type IV collagen and often results in a rapidly progressive oliguric renal failure (weeks to months).

Primary renal diseases that can cause acute GN include the following:

  • Membranoproliferative glomerulonephritis (MPGN) - This is due to the expansion and proliferation of mesangial cells as a consequence of the deposition of complements. Type I refers to the granular deposition of C3; type II refers to an irregular process.

  • Immunoglobulin A (IgA) nephropathy (Berger disease) - This causes GN as a result of diffuse mesangial deposition of IgA and IgG.

  • “Pure” mesangial proliferative GN [6]

  • Idiopathic rapidly progressive glomerulonephritis - This form of GN is characterized by the presence of glomerular crescents. Three types have been distinguished: Type I is an antiglomerular basement membrane disease, type II is mediated by immune complexes, and type III is identified by antineutrophil cytoplasmic antibody (ANCA).

Miscellaneous noninfectious causes of acute GN include the following:

  • Guillain-Barré syndrome

  • Irradiation of Wilms tumor

  • Diphtheria-pertussis-tetanus (DPT) vaccine

  • Serum sickness

  • Epidermal growth factor receptor activation, [12] and possibly its inhibition by cetuximab [13]



United States statistics

GN represents 10-15% of glomerular diseases. Variable incidence has been reported, in part because of the subclinical nature of the disease in more than half the affected population. Despite sporadic outbreaks, the incidence of PSGN has fallen over the past few decades. Factors responsible for this decline may include better health care delivery and improved socioeconomic conditions.

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

International statistics

Worldwide, IgA Nephropathy (Berger disease) is the most common cause of GN.

With some exceptions, the incidence of PSGN has fallen in most developed countries. Japanese researchers reported that incidence of postinfectious GN in their country peaked in the 1990s, and that PSGN, which accounted for almost all of the postinfectious GN cases in the 1970s, has decreased to approximately 40-50% since the 1990s, while the proportion of Staphylococcus aureus infection–related nephritis increased to 30%, and hepatitis C virus infection–associated GN also increased. [14]

PSGN remains much more common in regions such as Africa, the Caribbean, India, Pakistan, Malaysia, Papua New Guinea, and South America. In Port Harcourt, Nigeria, the incidence of acute GN in children aged 3-16 years was 15.5 cases per year, with a male-to-female ratio of 1.1:1; the current incidence is not much different. [15] A study from a regional dialysis center in Ethiopia found that acute GN was second only to hypovolemia as a cause of acute kidney injury that required dialysis, accoujting for approximately 22% of cases. [16]

Geographic and seasonal variations in the prevalence of PSGN are more marked for pharyngeally associated GN than for cutaneously associated disease. [15, 17, 18]

Age-, sex-, and race-related demographics

Postinfectious GN can occur at any age but usually develops in children. Most cases occur in patients aged 5-15 years; only 10% occur in patients older than 40 years. Outbreaks of PSGN are common in children aged 6-10 years. Acute nephritis may occur at any age, including infancy.

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



Most epidemic cases follow a course ending in complete patient recovery (as many as 100%). The mortality of acute GN in the most commonly affected age group, pediatric patients, has been reported at 0-7%.

Sporadic cases of acute nephritis often progress to a chronic form. This progression occurs in as many as 30% of adult patients and 10% of pediatric patients. GN is the most common cause of chronic renal failure (25%).

In PSGN, the long-term prognosis generally is good. More than 98% of individuals are asymptomatic after 5 years, with chronic renal failure reported 1-3% of the time.

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.

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. Immunity to type M protein is type-specific, long-lasting, and protective. Repeated episodes of PSGN are therefore unusual.

The prognosis for nonstreptococcal postinfectious GN depends on the underlying agent, which must be identified and addressed. Generally, the prognosis is worse in patients with heavy proteinuria, severe hypertension, and significant elevations of creatinine level. Nephritis associated with methicillin-resistant Staphylococcus aureus (MRSA) and chronic infections usually resolves after treatment of the infection.

In a pooled analysis of poststaphylococcal GN, only 44.7% of patients achieved remission; 22.9% progressed to ESRD and remained dialysis-dependent, and 14.5% died. Older age and diabetes mellitus were risk factors for adverse outcomes. [2]

Other causes of acute GN have outcomes varying from complete recovery to complete renal failure. The prognosis depends on the underlying disease and the overall health of the patient. The occurrence of cardiopulmonary or neurologic complications worsens the prognosis.

Murakami and colleagues examined the clinical characteristics and pathological patterns of postinfectious glomerulonephritis in 72 HIV-infected patients. The most common infectious agent was Staphylococcus. During a median of 17 months of follow-up, pathological patterns had no significant effects on renal outcomes. Mortality occurred in 14 patients overall, and mortality rates were significantly elevated among the 28 patients with healed postinfectious glomerulonephritis. [19]

In a retrospective study of 101 patients with severe lupus and rapidly progressive glomerulonephritis and 200 lupus patient controls who were followed for a median of 4 years, rapidly progressive glomerulonephritis was associated with poorer treatment response, atrophy and fibrosis, severe renal manifestations, serious sclerotic and crescentic glomeruli lesions, severe tubulointerstitial inflammation, and prominent leukocyte infiltration. Serum creatinine levels and the proportion of crescents were the most important predictors of developing end-stage renal disease. [20]

Xu et al reported an association between elevation in plasma phosphorus levels and adverse renal outcomes in Chinese patients with glomerulonephritis. In their prospective study, each 1 mg/dL elevation in baseline phosphorus was associated with a 1.33-fold higher risk of 50% reduction in eGFR, end-stage renal disease, or death. [21]


Patient Education

Counsel patients about the need for the following measures:

  • Salt restriction during the acute phase to control edema and volume-related hypertension

  • Blood pressure monitoring at periodic intervals

  • Ongoing long-term monitoring of patients with persistent urinary abnormalities and elevated blood pressure

  • Consideration of protein restriction and angiotensin-converting enzyme (ACE) 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 patient education resources, see Blood in the Urine.