glomerular diseases

The nephritic spectrum — active sediment (dysmorphic RBCs, RBC casts), AKI, hypertension, and sub-nephrotic proteinuria — spans a range from indolent IgA nephropathy to fulminant RPGN. Complement levels at presentation stratify the differential efficiently: low C3 alone (post-infectious, C3 glomerulopathy), low C4 ± C3 (lupus, cryoglobulinaemia, MPGN), or normal complements (ANCA vasculitis, anti-GBM, IgA nephropathy). For nephrotic-spectrum disease, see nephrotic syndrome.

do not miss

Pulmonary-renal syndrome (haemoptysis + haematuria + AKI) → anti-GBM or ANCA vasculitis — same-day nephrology, ICU, urgent PLEX/immunosuppression
RPGN (creatinine doubling over days–weeks with active sediment) → delays cost nephrons; send ANCA, anti-GBM, C3/C4, ANA and arrange urgent biopsy
Anti-GBM with dialysis-dependent AKI and no pulmonary haemorrhage → immunosuppression unlikely to recover renal function; discuss goals early

nephritic vs nephrotic

feature	nephritic (proliferative)	nephrotic (non-proliferative)
sediment	dysmorphic RBCs, acanthocytes, RBC casts	oval fat bodies, fatty casts, maltese crosses
proteinuria	sub-nephrotic (usually <3.5 g/day)	nephrotic-range (≥3.5 g/day)
blood pressure	often hypertensive	variable
renal function	AKI common	may be preserved early
oedema	mild–moderate	often severe / anasarca

Overlap exists — lupus nephritis class III/IV and MPGN can present with both nephritic and nephrotic features.

complement-based classification

Branch point for nephritic-spectrum GN:

low C3, normal C4

Post-infectious GN — 2–3 weeks after pharyngitis or skin infection; elevated ASOT/anti-DNase B; “lumpy-bumpy” subepithelial deposits on EM. Supportive management; most recover spontaneously
C3 glomerulopathy (C3GN / dense deposit disease) — persistent low C3, alternative pathway dysregulation; renal biopsy required; may need eculizumab

low C4 ± low C3

Lupus nephritis — ANA, anti-dsDNA, low C3/C4; biopsy-guided by ISN/RPS class (see below)
Cryoglobulinaemic GN — strongly associated with HCV; check cryoglobulins, rheumatoid factor, HCV serology. Treat with DAAs ± rituximab/PLEX if severe RPGN
MPGN pattern — not a single disease; secondary causes (HCV, autoimmune, paraprotein) must be excluded before considering primary

normal complements

ANCA vasculitis (GPA / MPA / EGPA) — pauci-immune crescentic GN (see below)
Anti-GBM disease — linear IgG on IF; anti-GBM antibody (see below)
IgA nephropathy — mesangial IgA on IF; most common GN worldwide (see below)

specific disease management

IgA nephropathy

Synpharyngitic haematuria (concurrent with URTI, not delayed like post-infectious GN). Highly variable course — 20–40% progress to ESKD over 20 years.

Supportive care first (all patients):

BP target ≤120/70 mmHg
Maximum tolerated ACEi or ARB; sparsentan (Filspari) — dual endothelin–angiotensin receptor antagonist — PROTECT (2023) showed greater proteinuria reduction vs irbesartan
SGLT2i — DAPA-CKD IgAN subanalysis (2024) showed 71% reduction in kidney composite endpoint
Sodium restriction <2 g/day

Disease-specific therapy — if proteinuria ≥0.75–1.0 g/day persists after ≥3 months of optimised supportive care:

Targeted-release budesonide (Nefecon) 16 mg/day × 9 months — NefIgArd (2023) showed sustained eGFR benefit; acts on gut mucosal IgA production with less systemic steroid exposure
Reduced-dose systemic corticosteroids: methylprednisolone 0.4 mg/kg/day tapered over 6–9 months — TESTING (2022) showed benefit with reduced-dose protocol (full-dose had excess serious infections)
Mycophenolate not effective in non-Asian populations — STOP-IgAN (2015)

ANCA vasculitis (GPA / MPA)

Pauci-immune crescentic GN — few/no immune deposits on IF. Check PR3-ANCA (GPA) and MPO-ANCA (MPA).

Induction:

Pulse IV methylprednisolone (500 mg–1 g × 3 days) then oral prednisone taper
Rituximab (Rituxan) or IV cyclophosphamide — RAVE (2010) showed rituximab non-inferior; preferred for relapsing disease and in women of childbearing potential
~~Avacopan (C5a receptor inhibitor)~~ — ADVOCATE trial retracted (NEJM, June 2026) due to data integrity concerns; FDA reviewing approval status. Not recommended pending resolution
PLEX: PEXIVAS (2020) showed no benefit on death/ESKD composite overall; KDIGO 2024 recommends consideration if SCr ≥300 µmol/L (absolute risk reduction for kidney failure ~5% at 300–500 µmol/L, ~16% above 500 µmol/L) or diffuse alveolar haemorrhage with hypoxaemia

Maintenance:

Rituximab 500 mg every 6 months (preferred) or azathioprine for ≥2 years after remission

cyclophosphamide toxicity

Cumulative cyclophosphamide dose drives haemorrhagic cystitis and bladder malignancy risk. Limit lifetime exposure; always co-prescribe mesna with IV dosing. Rituximab avoids these risks.

anti-GBM disease (Goodpasture syndrome)

Linear IgG along GBM on IF. Pulmonary haemorrhage when alveolar basement membrane is also targeted (classically in smokers).

Urgent: pulse IV methylprednisolone + oral cyclophosphamide + daily PLEX (14 sessions or until anti-GBM undetectable)
Renal prognosis poor if dialysis-dependent at presentation without pulmonary haemorrhage — discuss goals of immunosuppression
Recurrence rare; transplantation safe after anti-GBM undetectable for ≥6 months

lupus nephritis

Biopsy-guided management using ISN/RPS classification:

class	pattern	management
I–II	mesangial	supportive; RAS blockade
III–IV	proliferative (focal/diffuse)	induction: pulse methylprednisolone + mycophenolate (or cyclophosphamide) ± belimumab or CNI (see multi-target below); maintenance: mycophenolate
V	membranous	triple therapy (steroid + mycophenolate + CNI) if nephrotic
III/IV + V	mixed	treat as proliferative

Hydroxychloroquine for all lupus nephritis patients (renal-protective, reduces flares)
ACEi or ARB for proteinuria management
Multi-target initial therapy (KDIGO 2024 / KDOQI 2026) — belimumab or a CNI (voclosporin or tacrolimus) added to mycophenolate upfront for class III–V, not reserved as rescue:
- Voclosporin (Lupkynis) — AURORA 1 (2021) added to mycophenolate improved complete renal response (41% vs 23%); requires baseline eGFR ≥45 mL/min
- Belimumab (Benlysta) — BLISS-LN (2020) added to standard therapy improved renal response

lupus nephritis class transformation

Repeat biopsy is indicated for lupus flares or treatment non-response — class can transform over time (e.g. class V → class IV), changing management entirely.

traps

Attributing AKI + haematuria to “ATN” without checking sediment — RBC casts and dysmorphic RBCs mandate GN workup, not watchful waiting
Waiting for serology results before involving nephrology in suspected RPGN — arrange urgent biopsy in parallel; serology takes days, creatinine rises in hours
Using full-dose steroids for IgA nephropathy — TESTING showed excess serious infection with full-dose protocol; use reduced-dose regimen
Missing dual-positive anti-GBM + ANCA — ~30% of anti-GBM patients are also ANCA-positive; prognosis and relapse risk differ from single-positive anti-GBM
Forgetting HCV in MPGN/cryoglobulinaemia — treat the virus first with DAAs; immunosuppression alone is insufficient

key trials

trial	year	intervention	key result
RAVE	2010	rituximab vs cyclophosphamide in ANCA vasculitis	non-inferior for remission induction; superior in relapsing disease
TESTING	2022	reduced-dose methylprednisolone in IgA nephropathy	reduced kidney failure risk; reduced-dose protocol safer
PEXIVAS	2020	PLEX ± reduced-dose glucocorticoids in severe ANCA vasculitis	PLEX: no benefit on death/ESKD composite; reduced-dose steroids non-inferior
PROTECT	2023	sparsentan vs irbesartan in IgA nephropathy	greater proteinuria reduction; dual ERA/ARB mechanism
NefIgArd	2023	targeted-release budesonide in IgA nephropathy	sustained eGFR benefit with reduced systemic steroid exposure
AURORA 1	2021	voclosporin + mycophenolate vs mycophenolate in lupus nephritis	higher complete renal response (41% vs 23%)
BLISS-LN	2020	belimumab + standard therapy in lupus nephritis	improved primary efficacy renal response