IgA nephropathy

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

IgA nephropathy arises from nephritogenic IgA-containing immune complexes depositing in the mesangium and triggering glomerular inflammation. The clinical course is highly variable: some people maintain normal kidney function for decades, whereas others progress despite quiet symptoms. A diagnosis therefore starts a longitudinal risk process, not a one-time reassurance after visible haematuria resolves.

The 2025 KDIGO update frames management around two simultaneous aims: reduce IgA-mediated glomerular injury and protect the remaining nephron from consequences of proteinuric CKD. Proteinuria should be reduced as low as practicable, with a contemporary target below 0.5 g/day and ideally below 0.3 g/day where safely achievable. Decisions incorporate time-averaged proteinuria, eGFR trajectory, biopsy context, comorbidities, treatment toxicity and access under current UK guidance.

Biopsy classification using MEST-C describes mesangial and endocapillary hypercellularity, segmental sclerosis, tubular atrophy/interstitial fibrosis and crescents. These findings contribute prognostic information, but chronic damage cannot be reversed by simply intensifying immunosuppression. Secondary IgA deposition associated with liver disease, infection, inflammatory bowel disease or other conditions and IgA vasculitis with systemic features must also be considered.

Key points

IgA nephropathy is defined by kidney-biopsy evidence of dominant or co-dominant mesangial IgA deposition in a compatible clinical setting; serum IgA is neither sensitive nor specific enough for diagnosis.
Visible haematuria often begins during or within days of an upper-respiratory infection, unlike the longer latent interval typical of classic post-streptococcal glomerulonephritis.
Presentation ranges from incidental microscopic haematuria to proteinuric CKD, nephrotic syndrome or rapidly progressive kidney failure, so the familiar young-adult vignette is incomplete.
Sustained proteinuria and eGFR slope are central modifiable prognostic signals; haematuria supports activity but cannot alone determine treatment intensity.
After biopsy, the International IgA Nephropathy Prediction Tool can inform shared prognostic discussion, but it does not prescribe a particular medicine.
Optimised supportive care includes blood-pressure control, a single ACE inhibitor or ARB when appropriate, dietary sodium reduction, smoking cessation and cardiovascular-risk management.
SGLT2 inhibition is considered for eligible CKD according to NICE and renal guidance, with sick-day, ketoacidosis and genital-infection counselling.
Targeted-release budesonide and sparsentan now have NICE technology-appraisal routes for defined adults; selection, contraindications and funding criteria require specialist confirmation.
Sparsentan replaces rather than accompanies ACE inhibitor or ARB therapy because of overlapping renin–angiotensin effects and requires pregnancy and liver-safety controls.
Systemic glucocorticoid benefit must be weighed against substantial infection and metabolic toxicity; it is not a reflex response to crescents or persistent microscopic haematuria.
Rapid eGFR decline with extensive crescents represents a distinct emergency and is managed through a specialist rapidly progressive GN pathway after excluding other causes.

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

Primary kidney-limited disease

Many patients have kidney-limited IgA nephropathy defined by dominant or co-dominant mesangial IgA deposition in a compatible clinical setting.

Secondary IgA deposition

Liver disease, chronic infection, inflammatory bowel disease and other systemic conditions can generate an IgA-dominant biopsy pattern that requires treatment of the underlying driver.

Systemic IgA-mediated disease

A renal IgA pattern may occur within IgA vasculitis when purpura, abdominal pain, arthralgia or gastrointestinal bleeding indicates systemic small-vessel involvement.

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

1
Mesangial IgA deposition
Dominant or co-dominant IgA deposits in the glomerular mesangium define IgA nephropathy when the clinical setting is compatible.
2
Active glomerular injury
Mesangial and endocapillary hypercellularity or crescents on biopsy indicate active inflammatory injury that can accompany haematuria and declining filtration.
3
Proteinuric progression
Sustained proteinuria and a negative eGFR slope are central prognostic signals, while haematuria alone does not determine treatment intensity.
4
Chronic renal scarring
Segmental sclerosis, tubular atrophy and interstitial fibrosis record chronic damage that cannot be reversed simply by intensifying immunosuppression.

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

Synpharyngitic haematuria

Tea- or cola-coloured urine appearing at the time of a mucosal infection is characteristic, often with loin discomfort, but infection-associated macroscopic haematuria is not disease-specific.

Silent proteinuric disease

Persistent microscopic haematuria and proteinuria on occupational, antenatal or primary-care testing may be the only signs while eGFR remains preserved.

Progressive phenotype

Rising time-averaged proteinuria, worsening hypertension and a negative eGFR slope identify ongoing risk even when visible haematuria has stopped.

IgA vasculitis clues

Palpable purpura, abdominal pain, arthralgia or gastrointestinal bleeding suggests systemic IgA vasculitis rather than kidney-limited disease and alters multidisciplinary assessment.

Macroscopic-haematuria AKIRed flag

Prolonged heavy haematuria can cause tubular obstruction and pigment injury, especially in older adults; a creatinine rise still requires exclusion of obstruction and crescentic disease.

Rapidly progressive diseaseRed flag

A substantial eGFR fall over weeks with active sediment and crescents is uncommon but time-critical; urgent biopsy-led nephrology treatment is required.

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, microscopy, ACR and PCRFirst step
Why
Document haematuria, quantify albumin and total protein and identify an active glomerular sediment.
Interpretation and limitations
Dysmorphic red cells support glomerular bleeding; serial quantitative protein values are more prognostic than dipstick fluctuations during an intercurrent infection.
02
Creatinine and serial eGFR
Why
Detect AKI and calculate the chronic direction and speed of kidney-function change.
Interpretation and limitations
One stable value cannot define risk; compare pre-illness results and establish slope after haemodynamic medicines have reached a steady state.
03
Blood pressure and cardiovascular assessment
Why
Identify a major driver and consequence of proteinuric kidney injury.
Interpretation and limitations
Use standardised readings and consider home or ambulatory data; treatment targets are individualised for tolerance, frailty and orthostatic symptoms.
04
Complement and immune serology
Why
Look for lupus, ANCA disease, anti-GBM disease and complement-consuming mimics when phenotype warrants.
Interpretation and limitations
Complement is usually normal in IgA nephropathy; an abnormal result should prompt reconsideration rather than being forced into the presumed diagnosis.
05
Infection and secondary-cause assessment
Why
Select tests for chronic liver disease, hepatitis, HIV, endocarditis or inflammatory disease from clinical clues.
Interpretation and limitations
Mesangial IgA can accompany systemic disease, so biopsy staining alone does not prove primary IgA nephropathy.
06
Kidney biopsy with MEST-C reporting
Why
Confirm dominant mesangial IgA and quantify active and chronic histological lesions.
Interpretation and limitations
MEST-C supports prognosis alongside clinical data but no isolated letter score automatically mandates systemic immunosuppression.
07
International IgAN Prediction Tool
Why
Estimate post-biopsy progression risk over a defined horizon using validated clinicopathological data.
Interpretation and limitations
Use the version appropriate to timing and population for shared decisions; predictions are uncertain and should not be used to deny follow-up.

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

Post-infectious glomerulonephritis

A latent interval after infection with low complement favours classic post-infectious disease, whereas haematuria concurrent with mucosal infection is more typical of IgA nephropathy.

IgA vasculitis

Purpura, abdominal symptoms, arthralgia or gastrointestinal bleeding indicate systemic small-vessel involvement rather than isolated renal IgA disease.

Collagen IV nephropathy

Lifelong familial haematuria, hearing loss or ocular features suggest Alport-spectrum disease; genetic testing and basement-membrane assessment distinguish it from mesangial IgA deposits.

IgA-dominant infection-related GN

Older age, diabetes, active staphylococcal or deep infection and low complement favour ongoing infection-related immune-complex disease over primary IgA nephropathy.

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

01Suspected IgANMove from haematuria to diagnosisFirst stepPersistent glomerular haematuria, proteinuria or recurrent infection-associated visible haematuria raises IgA nephropathy.

1AlternativeCheck blood pressure, kidney trajectory, quantitative proteinuria and urine microscopy, and assess for systemic vasculitis, liver disease, infection and alternative immune disease.
2Refer according to urgency and NICE kidney criteria; discuss biopsy when results would define diagnosis, prognosis or treatment and control bleeding risk before the procedure.
3After histological confirmation, document MEST-C, baseline eGFR slope and protein burden and agree an individual monitoring and supportive-care plan.

02Persistent proteinuriaOptimise kidney protectionBiopsy-proven disease has ongoing proteinuria or progressive CKD risk without a rapidly progressive presentation.

1Address dietary sodium, smoking, weight, exercise and blood pressure, and titrate one ACE inhibitor or ARB to the highest tolerated licensed dose with potassium and creatinine checks.
2Consider an SGLT2 inhibitor under current NICE CKD criteria and review adherence, home blood pressure and time-averaged proteinuria after a meaningful supportive-care interval.
3If residual risk remains, seek specialist selection for targeted-release budesonide, sparsentan or another current evidence-based option, following NHS eligibility, interaction and reproductive-safety requirements.

03Rapid declineTreat an IgAN renal emergencyKidney function deteriorates rapidly with active sediment, heavy haematuria or systemic illness.

1Admit or obtain urgent renal review, correct dangerous potassium, fluid or acid–base abnormalities and exclude sepsis, hypovolaemia, obstruction and nephrotoxic exposure.
2Repeat immune serology and arrange urgent biopsy when safe to distinguish crescentic IgA nephropathy, tubular injury from haematuria and a separate pulmonary–renal disease.
3Use glucocorticoid and cyclophosphamide-based RPGN treatment only when the specialist clinicopathological diagnosis supports it; provide infection and fertility safeguards.

04Pregnancy planningProtect kidneys and fetusA person with IgA nephropathy is planning pregnancy or could become pregnant during disease-modifying therapy.

1Review baseline creatinine, proteinuria, blood pressure and obstetric history with nephrology and maternal-medicine teams before conception where possible.
2Replace ACE inhibitor, ARB, sparsentan and other contraindicated medicines using a specialist pre-conception plan rather than stopping all therapy without alternatives.
3During pregnancy use obstetric-renal surveillance for pressure, proteinuria, kidney function, fetal growth and pre-eclampsia, recognising that baseline urinary abnormalities complicate interpretation.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Reduces proteinuria and intraglomerular pressure and provides foundational supportive treatment for suitable patients.

ACE inhibitor or ARB

Use one licensed agent, beginning cautiously and titrating to the highest tolerated dose with biochemical monitoring.

Check creatinine and potassium after changes; avoid dual blockade and do not use in pregnancy, severe hyperkalaemia or unstable hypovolaemic AKI.

Slows CKD progression and reduces kidney and cardiovascular events in eligible proteinuric chronic kidney disease.

SGLT2 inhibitor

Use the licensed once-daily CKD dose only when current NICE eligibility and eGFR criteria are met.

Counsel about temporary withholding during serious illness or fasting, genital infection and rare euglycaemic ketoacidosis; specialist advice may be needed at low eGFR.

Targets ileal mucosal immune activity to reduce pathogenic IgA production and progression risk in selected primary IgA nephropathy.

Targeted-release budesonide

A specialist prescribes the licensed nine-month course for adults meeting current NICE TA1128 criteria.

Despite targeted release, glucocorticoid effects, infection, liver disease, interactions and subsequent dose taper or monitoring require the product and specialist protocol.

Combines endothelin-A and angiotensin-receptor antagonism to lower proteinuria in selected adults with primary IgA nephropathy.

Sparsentan

Specialist initiation follows the licensed daily regimen and current NICE TA1074 proteinuria and kidney-function criteria.

Do not combine with ACE inhibitor or ARB; monitor blood pressure, potassium, kidney and liver function, oedema and strict pregnancy-prevention requirements.

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

Progressive chronic kidney disease

Sustained proteinuria, hypertension and negative eGFR slope reflect accumulating sclerosis and can culminate in kidney failure despite few symptoms.

Rapidly progressive glomerulonephritis

Uncommon extensive crescentic injury can cause a substantial fall in filtration over weeks, requiring urgent biopsy-led assessment for organ-saving treatment.

Macroscopic-haematuria AKI

Prolonged heavy glomerular bleeding can obstruct tubules and add pigment injury, particularly in older adults, even without widespread crescent formation.

Post-transplant recurrence

IgA deposits may recur in an allograft and occasionally impair graft function, although recurrence risk alone does not preclude transplantation.

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

Measure quantitative urine protein and eGFR often enough to establish time-averaged proteinuria and slope, increasing frequency after treatment changes or macroscopic haematuria.
Review standardised and home blood pressure, postural symptoms, adherence and dietary sodium before declaring supportive care unsuccessful.
Check creatinine and potassium after starting or increasing renin–angiotensin-active treatment and respond to the degree and context of any change.
During targeted-release budesonide monitor infection, blood pressure, glucose, weight, adrenal and other steroid toxicity according to specialist and product guidance.
During sparsentan follow liver tests, potassium, kidney function, fluid retention and pregnancy-prevention testing through the mandated specialist pathway.
Reassess diagnosis if complement falls, systemic symptoms emerge, nephrotic syndrome develops abruptly or eGFR declines faster than the established pattern.

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

Timing distinguishes classic vignettes

IgA macroscopic haematuria is usually concurrent with mucosal infection, whereas post-streptococcal disease follows a latent interval; neither timing pattern is perfectly specific.

Proteinuria integrates activity and damage

Persistent protein leak reflects modifiable haemodynamic stress as well as immune injury and scar burden, which is why it predicts outcome but does not select one treatment by itself.

Biopsy crescents need context

A small crescent component in otherwise stable disease is not equivalent to a rapidly progressive syndrome; clinical eGFR trajectory determines urgency and treatment framing.

New therapies are not stackable by default

Targeted-release budesonide, sparsentan, SGLT2 inhibition and conventional blockade have different eligibility and interaction rules; combinations require deliberate specialist review.

Tonsillectomy is region-specific

Evidence and practice differ geographically, and routine tonsillectomy solely to treat IgA nephropathy is not a standard UK intervention without another ENT indication.

Transplant does not erase recurrence

IgA deposits may recur in an allograft, but recurrence risk alone is not a contraindication to transplantation and post-transplant decisions remain centre-led.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing IgA nephropathy from a raised serum IgA concentration without kidney histology.
02
Calling every episode of haematuria after infection benign while creatinine and urine output deteriorate.
03
Treating the MEST-C score as a standalone instruction to prescribe systemic glucocorticoids.
04
Combining sparsentan with an ACE inhibitor or ARB and duplicating renin–angiotensin blockade.
05
Judging response from one dipstick rather than quantitative time-averaged proteinuria and eGFR slope.
06
Ignoring pregnancy planning when prescribing renin–angiotensin-active or disease-modifying medicines.