Post-infectious glomerulonephritis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Post-infectious glomerulonephritis is the classic delayed immune-complex response after infection, while the broader term infection-related GN includes disease arising during an active focus. Circulating or planted microbial antigens trigger immune and complement deposition in glomeruli. The result is a nephritic syndrome that may be mistaken for uncomplicated AKI from sepsis, particularly when urine microscopy is not performed.

Age and context shape the likely organism. A child with oedema and cola-coloured urine after impetigo fits post-streptococcal GN; an older person with diabetes, purulent skin disease and AKI may have IgA-dominant staphylococcal GN while infection persists. Endocarditis-associated GN may feature constitutional symptoms, murmurs, embolic signs, low complement and positive rheumatoid factor or ANCA, creating a dangerous vasculitis mimic.

Supportive renal treatment may include salt and fluid management, a loop diuretic, antihypertensive therapy and dialysis for standard urgent indications. Antibiotics eradicate an active source and prevent spread, although treatment given after the immune renal process begins does not instantly reverse glomerular inflammation. Improvement in urine, complement and kidney function is tracked; an atypical course prompts biopsy and renewed search for infection or complement dysregulation.

Key points

Infection-related glomerulonephritis may follow a resolved infection or occur while infection remains active; the latter is increasingly important in older adults, diabetes and frailty.
Classic post-streptococcal disease follows pharyngitis after roughly one to three weeks or skin infection after about three to six weeks rather than occurring simultaneously.
Haematuria, oedema, hypertension, reduced eGFR and variable proteinuria form the nephritic pattern; nephrotic-range protein loss can occur and does not exclude the diagnosis.
C3 is commonly low through alternative-complement activation and usually recovers within weeks; persistent hypocomplementaemia demands reassessment for C3 glomerulopathy, lupus or ongoing infection.
Antistreptolysin O supports recent pharyngeal streptococcal exposure, while anti-DNase B can be more helpful after skin infection; neither test alone proves renal causation.
Staphylococcal infection-related GN may be IgA-dominant and can arise during deep infection, endocarditis, osteomyelitis or an infected device.
Blood cultures and echocardiographic assessment are essential when endocarditis is plausible because immunosuppression before infection control can be catastrophic.
Treatment centres on eradication of active infection and management of fluid, blood pressure, potassium and uraemia; routine glucocorticoids have no established role.
Kidney biopsy is considered for atypical timing, severe or progressive failure, persistent complement consumption, marked proteinuria or diagnostic uncertainty.
Recovery is often good in children but less predictable in adults with comorbidity, severe AKI or chronic histological damage, so kidney follow-up must continue after infection resolves.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Latent post-streptococcal disease

Nephritis can follow pharyngeal or skin streptococcal infection after a symptom-free interval, when the original infection may already have resolved.

Active staphylococcal infection

Older, diabetic or frail adults may develop IgA-dominant glomerulonephritis during ongoing deep staphylococcal infection, including osteomyelitis or infection of an implanted device.

Endocarditis-associated disease

Persistent endovascular infection can drive immune-complex glomerulonephritis and may produce positive ANCA, making exclusion of infective endocarditis essential before vasculitis immunosuppression.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Microbial antigen exposure
Infection releases antigens that stimulate antibodies and form circulating or locally assembled immune complexes after microbial exposure.
2
Glomerular immune deposition
Complexes lodge in mesangial and capillary-wall sites, activating complement, commonly with a fall in circulating C3.
3
Endocapillary inflammation
Neutrophils and proliferating glomerular cells narrow capillary lumina and disrupt walls, causing haematuria, proteinuria and reduced filtration.
4
Resolution or persistent scarring
Removal of antigen permits complement and inflammation to recover, but ongoing infection or severe injury can leave glomerulosclerosis and chronic impairment.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Delayed post-streptococcal syndrome

Dark urine, periorbital oedema and hypertension after a symptom-free interval following sore throat or impetigo support classic post-infectious disease.

Active-infection phenotype

AKI and haematuria during cellulitis, osteomyelitis, abscess, infected prosthesis or deep staphylococcal infection suggest infection-related GN rather than a completed post-infectious event.

Endocarditis warningRed flag

Persistent fever, new murmur, embolic lesions, splenomegaly, weight loss or implanted cardiac material requires blood cultures and an endocarditis pathway before immune treatment.

Nephritic fluid overloadRed flag

Oedema, rising blood pressure, basal crackles and reduced urine output reflect sodium retention and may progress quickly to pulmonary oedema.

Hypertensive neurological emergencyRed flag

Severe headache, vomiting, confusion, visual change or seizure with marked hypertension can represent encephalopathy and requires monitored emergency treatment.

Atypical non-recovery

Persistently low C3, progressive creatinine, prolonged heavy proteinuria or recurrent episodes after infection control argues for biopsy and an alternative diagnosis.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Urinalysis and urine microscopyFirst step
Why
Identify glomerular haematuria, red-cell casts and the amount and character of protein loss.
Interpretation and limitations
Dysmorphic erythrocytes and casts support GN, while coincident bacteriuria must not be assumed to explain a nephritic sediment.
02
Creatinine, electrolytes and serial urine output
Why
Grade AKI and detect potassium, acid–base and volume indications for urgent therapy.
Interpretation and limitations
Trajectory determines urgency; severe complications require renal replacement assessment regardless of whether immune markers are pending.
03
C3 and C4
Why
Assess complement consumption and follow expected recovery.
Interpretation and limitations
Low C3 with relatively preserved C4 is common; failure to normalise over roughly six to eight weeks should trigger specialist reconsideration rather than indefinite observation.
04
Streptococcal antibodies
Why
Support recent group A streptococcal exposure when cultures from the original illness are no longer positive.
Interpretation and limitations
ASO is more informative after pharyngitis and anti-DNase B after skin disease; titre timing and background exposure affect specificity.
05
Blood and focus-specific cultures
Why
Identify ongoing bacteraemia, endocarditis or a deep source before antimicrobial therapy when safe.
Interpretation and limitations
Obtain several blood-culture sets in suspected endocarditis, but never delay immediate sepsis antibiotics in an unstable patient.
06
Echocardiography and source imaging
Why
Find valvular infection, abscess, bone infection or infected hardware when clinical clues exist.
Interpretation and limitations
A negative transthoracic study may not exclude endocarditis; microbiology and cardiology determine need for transoesophageal imaging.
07
Immune and infection serology
Why
Evaluate lupus, ANCA vasculitis, anti-GBM disease, hepatitis and other mimics in an atypical or severe case.
Interpretation and limitations
ANCA positivity can accompany endocarditis; interpret antibodies within cultures, imaging and biopsy rather than treating the laboratory result.
08
Kidney biopsy
Why
Confirm immune-complex GN and distinguish infection-related disease from C3 glomerulopathy or pauci-immune inflammation.
Interpretation and limitations
Diffuse proliferative or exudative change, granular immune staining and subepithelial humps may support the diagnosis, but pathology must be integrated with active infection evidence.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

IgA nephropathy

Haematuria concurrent with a mucosal infection and normal complement favours IgA nephropathy, whereas a latent interval and transient low C3 support classic post-infectious disease.

C3 glomerulopathy

Persistently depressed complement or continuing nephritis after infection control suggests alternative-complement dysregulation rather than a resolving infection-triggered process.

Lupus nephritis

Systemic lupus features, ANA and dsDNA activity and broader complement consumption with full-house deposits favour lupus.

ANCA-associated glomerulonephritis

Pulmonary, ENT, neural or cutaneous vasculitis with pauci-immune biopsy supports ANCA disease, but endocarditis can generate ANCA and must be excluded.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Acute nephritic illnessStabilise before labelling the causeFirst stepHaematuria, oedema, hypertension and AKI appear after or during an infection.

1Assess ABCDE, pulmonary oedema, blood pressure, potassium, acid–base state and urine output, treating immediate renal emergencies and involving nephrology early.
2Send microscopy, quantitative protein, complement, cultures and exposure-directed serology, and examine carefully for skin, dental, cardiac, bone, line or prosthetic infection.
3Use timing and infection status to distinguish delayed post-streptococcal disease from ongoing infection-related GN, arranging biopsy if severity or uncertainty makes histology actionable.

02Ongoing infectionEradicate the antigen sourceCultures, examination or imaging suggests endocarditis, abscess, osteomyelitis or another active focus.

1Take appropriate cultures promptly, then start local empiric antimicrobial therapy according to sepsis severity, likely source, allergy and kidney function.
2Engage microbiology and the relevant source-control team for drainage, device management, dental treatment or endocarditis care and narrow antibiotics when results return.
3Avoid empirical immunosuppression unless nephrology and infection specialists judge a biopsy-defined exceptional indication after adequate infection control.

03Supportive renal careControl fluid and pressureSodium retention, hypertension or kidney dysfunction persists while the immune process resolves.

1Restrict dietary sodium and tailor fluids to clinical volume, measuring weight, blood pressure, intake, output, creatinine and electrolytes.
2Use a loop diuretic and an appropriate antihypertensive under the acute renal plan, avoiding ACE inhibitor or ARB initiation during unstable AKI or hyperkalaemia.
3EscalationEscalate for dialysis when refractory pulmonary oedema, hyperkalaemia, acidosis or uraemic complications occur; no creatinine threshold substitutes for clinical indications.

04Atypical courseChallenge the initial diagnosisComplement stays low, kidney function worsens or urinary abnormalities fail to improve after infection treatment.

1Repeat complement, cultures and urine-protein and eGFR trends, verifying that the suspected infection has truly been eradicated.
2Reassess for C3 glomerulopathy, membranoproliferative patterns, lupus, cryoglobulinaemia, endocarditis and ANCA-associated disease using focused testing.
3Arrange nephrology review and kidney biopsy when safe, then direct any immunotherapy to the revised clinicopathological diagnosis rather than the original label.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Eradicates active infection, prevents further antigen exposure and treats sepsis or an infective focus.

Source-directed antibiotic

Choose agent, route and duration through local microbiology guidance, cultures, source and current renal dosing.

Obtain cultures first when this is safe, adjust for changing kidney function, check allergy and interactions, and arrange source control because antibiotics alone may fail.

Treats pulmonary and peripheral fluid overload while glomerular filtration and sodium handling recover.

Loop diuretic

Titrate the local oral or intravenous regimen to congestion, diuretic exposure, perfusion and kidney response.

Monitor blood pressure, weight, sodium, potassium and creatinine; excessive removal causes hypovolaemia and can worsen infection-associated AKI.

Reduces complications from severe nephritic hypertension while the underlying salt retention is corrected.

Acute antihypertensive therapy

Select oral or monitored intravenous treatment according to end-organ injury and the local hypertension emergency protocol.

Avoid precipitous unmonitored pressure reduction; choice changes with pulmonary oedema, bradycardia, pregnancy, AKI and possible neurological emergency.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute kidney injury

Severe endocapillary inflammation can sharply reduce filtration, producing hyperkalaemia, acidosis, uraemia and a temporary need for dialysis.

Hypertension and pulmonary oedema

Glomerular filtration loss drives sodium retention, leading to severe blood-pressure elevation, peripheral oedema and potentially respiratory compromise.

Persistent chronic kidney disease

Adults with comorbidity, severe AKI or chronic biopsy damage may retain proteinuria and reduced filtration after the infection resolves.

Uncontrolled source infection

Failure to recognise active endocarditis, osteomyelitis or device infection permits sepsis, embolic disease and continued immune-complex renal injury.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During the acute phase record blood pressure, weight, oxygenation, fluid balance and urine output frequently enough to detect pulmonary oedema or oliguria early.
Trend creatinine, potassium, bicarbonate and sodium through sepsis treatment, diuresis and antimicrobial dose changes.
Follow C3 to recovery and reopen the differential if it remains depressed beyond the expected several-week course.
Document culture clearance and source resolution in bacteraemia or endocarditis rather than equating defervescence with cure.
Repeat quantitative proteinuria and haematuria after clinical recovery; persistent abnormalities require renal follow-up even when creatinine normalises.
Monitor antimicrobial toxicity and interactions, especially during prolonged therapy for endocarditis, bone infection or infected devices.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The infection may still be present

In modern adult infection-related GN, immune-complex kidney injury often develops during active staphylococcal or deep infection rather than after a clean latent interval.

Complement is a clock

Early C3 consumption fits the diagnosis, but failure to recover is a temporal clue to ongoing antigen, lupus or dysregulation of the alternative complement pathway.

ANCA can mislead

Endocarditis may produce positive ANCA and a nephritic sediment, so cultures and cardiac assessment are essential before giving vasculitis induction therapy.

Antibiotics and renal recovery differ

Successful microbial eradication stops further stimulus but cannot instantly remove deposited immune complexes or reverse established glomerular and interstitial scarring.

Children and adults diverge

A child with classic post-streptococcal disease often recovers fully, while comorbidity, ongoing infection and chronic damage make adult prognosis less favourable.

Biopsy humps are supportive

Subepithelial humps are a useful electron-microscopy pattern but not an isolated diagnosis; complement-dominant diseases and infection history still require integration.

11Common pitfallsFrequent interpretation and management errors.

01
Using a positive ASO titre as proof that streptococcus caused the current kidney injury.
02
Starting glucocorticoids for ANCA positivity before excluding infective endocarditis.
03
Assuming nephritic AKI after infection is only haemodynamic and omitting urine microscopy.
04
Waiting for serology before treating haemodynamic sepsis or an obvious deep bacterial focus.
05
Discharging after creatinine improves without confirming blood-pressure, complement and urinary recovery.
06
Calling persistently low C3 normal for post-infectious disease and missing C3 glomerulopathy.