Renal: Glomerular Disease

🫘 Glomerular disease is damage to the kidney's filters. Some diseases make the filter leaky to protein (nephrotic); others cause inflammation that lets blood through and reduces filtering (nephritic). Some are slow and benign; others (vasculitis, anti-GBM disease) can destroy the kidneys in days. Most diagnoses need a kidney biopsy, but the blood tests -ANCA, anti-GBM, complement, anti-PLA2R -point you in the right direction.
Your four questions for every patient: Is the picture nephrotic, nephritic, or mixed? How fast is kidney function changing? Is there a systemic disease (vasculitis, lupus, myeloma, infection, cancer)? Does this need urgent treatment before the biopsy?

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How Glomerular Disease Presents

Feature	What to look for
Nephrotic syndrome	Heavy proteinuria (over 3 g/day; PCR over 300 mg/mmol), low albumin (under 30 g/L), oedema, often high cholesterol. Little blood in the urine; kidney function often normal at first.
Nephritic syndrome	Haematuria (dysmorphic red cells, red cell casts), hypertension, reduced kidney function or AKI, oliguria, some oedema, proteinuria usually under 3 g/day.
Rapidly progressive GN	Nephritic picture with kidney function falling over days to weeks; crescents on biopsy -an emergency.
Isolated urine abnormality	Invisible haematuria and/or mild proteinuria found by chance.
Visible haematuria episodes	Typically IgA nephropathy, with throat infections.
CKD	Slow decline with proteinuria, hypertension and small kidneys.

• Mainly nephrotic: minimal change disease, FSGS, membranous nephropathy, diabetic kidney disease, amyloidosis.
• Mainly nephritic: IgA nephropathy, post-infectious GN, ANCA vasculitis, anti-GBM disease.
• Either or both: lupus nephritis, MPGN and C3 glomerulopathy.

💡 Clinical Pearl: In nephrotic syndrome the filter's barrier is damaged (podocytes); in nephritic syndrome there is inflammation in the glomerulus. Think "nephrotic = protein" and "nephritic = inflammation".

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Haematuria and Proteinuria

• Haematuria:
  • Visible (macroscopic) or non-visible (dipstick 1+ or more, confirmed on repeat).
  • Exclude infection, menstruation and exercise; dipstick blood without red cells suggests myoglobin or haemoglobin.
  • Urology (cancer) route -NICE NG12 suspected cancer pathway:
    • Age 45 or over with unexplained visible haematuria (without UTI, or persisting after UTI treatment).
    • Age 60 or over with unexplained non-visible haematuria plus dysuria or a raised white cell count.
  • Nephrology route -think glomerular if there is:
    • Proteinuria (ACR 30 or more).
    • Low or falling eGFR.
    • Hypertension.
    • Dysmorphic red cells or red cell casts.
    • Visible haematuria with a throat infection.
    • Younger age, or systemic symptoms.
  • Isolated non-visible haematuria with normal BP, eGFR and ACR -monitor yearly (BP, eGFR, ACR). Often thin basement membrane disease (now often recognised as a mild form of Alport-type collagen IV disease).
• Proteinuria:
  • Quantify with ACR (or PCR for heavy proteinuria).
  • Transient causes -fever, exercise, UTI, heart failure.
  • Orthostatic proteinuria in young people -present on standing only (normal early-morning sample).
  • Overflow -light chains in myeloma (Bence Jones protein) aren't detected well by dipstick.
  • Tubular proteinuria -low-molecular-weight proteins; PCR much higher than ACR.

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Tests and Complement

• Urine: Dipstick, microscopy (red cell casts), ACR and PCR.
• Blood:
  • U&E, albumin, lipids, FBC, glucose and HbA1c.
  • ANCA (PR3 and MPO).
  • Anti-GBM antibodies.
  • ANA, dsDNA, ENA.
  • Complement C3 and C4.
  • Anti-PLA2R antibodies (membranous).
  • Serum free light chains, protein electrophoresis, immunoglobulins.
  • Hepatitis B and C, HIV.
  • ASOT and anti-DNase B (streptococcus).
  • Cryoglobulins.
• Ultrasound -kidney size; two kidneys present before biopsy.

Complement levels narrow the list:

Complement	Think of
Low C3 and low C4	Lupus nephritis; cryoglobulinaemia (hepatitis C); immune-complex MPGN; endocarditis and shunt nephritis
Low C3, normal C4	Post-streptococcal GN; C3 glomerulopathy
Normal	IgA nephropathy; ANCA vasculitis; anti-GBM disease; minimal change; FSGS; membranous

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Kidney Biopsy

• When:
  • Nephrotic syndrome in adults (in children, minimal change is assumed and steroids given first).
  • Unexplained AKI or rapidly progressive GN.
  • Haematuria with significant proteinuria or falling eGFR.
  • Kidney involvement in systemic disease (lupus, vasculitis).
  • Transplant dysfunction.
• What it shows:
  • Light microscopy -structure, crescents, scarring.
  • Immunofluorescence -deposits (IgA, IgG, C3, light chains; linear IgG in anti-GBM disease).
  • Electron microscopy -podocyte foot process effacement (minimal change), deposit location.
  • Chronic damage (scarring, tubular atrophy) predicts how much recovery is possible.
• Before biopsy:
  • Check platelets, clotting, and Hb; group and save.
  • BP controlled (e.g. under 160/90).
  • Stop anticoagulants and antiplatelets (according to local protocol).
  • Consent -bleeding is the main risk (visible haematuria, perinephric haematoma; transfusion or embolisation about 1 in 100; nephrectomy and death very rare).
• After: Bed rest, observations, check urine for blood and Hb.
• Relative contraindications: Single kidney, small scarred kidneys, uncontrolled BP, bleeding disorder, active infection.

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Nephrotic Syndrome -General Care

Complications:

• Venous thromboembolism -loss of anticoagulant proteins (antithrombin) in the urine and high liver production of clotting factors:
  • DVT, PE, renal vein thrombosis (loin pain, haematuria, worsening kidney function).
  • Highest risk in membranous nephropathy and when albumin is very low.
• Infection -loss of immunoglobulins; cellulitis, spontaneous bacterial peritonitis (pneumococcus), especially in children.
• High cholesterol.
• AKI -volume depletion from over-diuresis, renal vein thrombosis, drugs.
• Loss of binding proteins -low total thyroxine and vitamin D.

Supportive treatment (alongside treatment of the cause):

• Oedema:
  • Salt restriction.
  • Loop diuretic -often high doses (e.g. furosemide 80–250 mg), sometimes IV because gut oedema reduces absorption. Add a thiazide or amiloride if needed.
  • Aim for weight loss of 0.5–1 kg/day; daily weights.
  • Mild fluid restriction.
  • IV albumin with diuretics only in selected severe cases.
• Proteinuria and BP -ACE inhibitor or ARB (may wait in minimal change disease, which usually responds quickly to steroids).
• Anticoagulation:
  • Consider prophylactic anticoagulation when albumin is very low (e.g. under 20–25 g/L, or higher in membranous nephropathy) and bleeding risk is low -LMWH or warfarin; DOACs used in some units.
  • Treat established clots as usual.
• Statin if nephrotic syndrome persists.
• Vaccines -pneumococcal and influenza.
• Bone protection during long steroid courses; PJP prophylaxis with intensive immunosuppression.

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Minimal Change Disease

• Who: The cause of about 90% of nephrotic syndrome in young children, and 10–15% in adults.
• Causes (usually none found):
  • NSAIDs.
  • Hodgkin lymphoma (and other lymphomas).
  • Allergies, bee stings.
  • Lithium.
  • Recent infection.
• Features:
  • Sudden severe nephrotic syndrome -over days, with heavy oedema.
  • Normal BP and kidney function (AKI can occur in adults).
  • Little or no blood in the urine.
• Biopsy: Normal on light microscopy; podocyte foot process effacement on electron microscopy. Anti-nephrin antibodies are found in many patients.
• Treatment:
  • Children -prednisolone (60 mg/m² daily for 4 weeks, then on alternate days and tapered) without biopsy; about 90% respond.
  • Adults -prednisolone 1 mg/kg daily (maximum 80 mg) until remission (can take up to 16 weeks in adults), then tapered over months.
  • Frequent relapses or steroid dependence -rituximab, calcineurin inhibitors (tacrolimus, ciclosporin), cyclophosphamide or mycophenolate.
• Prognosis: Good -kidney failure is rare, but relapses are common.

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Focal Segmental Glomerulosclerosis

• What it is: Scarring of some glomeruli (focal), affecting part of each glomerulus (segmental). It is a pattern of injury with different causes.
• Types:
  • Primary -a circulating factor (anti-nephrin antibodies in some); full nephrotic syndrome, sudden onset.
  • Secondary (adaptive) -obesity, reduced kidney mass (reflux nephropathy, single kidney), hypertension, sickle cell disease. Usually sub-nephrotic proteinuria with normal albumin.
  • Viral and drug-related -HIV (collapsing type), parvovirus, COVID-19, heroin, pamidronate, lithium, interferon, anabolic steroids.
  • Genetic -podocyte gene mutations; APOL1 risk variants in people of West African ancestry.
• Treatment:
  • All -ACE inhibitor or ARB, SGLT2 inhibitor, BP control.
  • Primary FSGS -high-dose steroids (prednisolone 1 mg/kg for up to 16 weeks); calcineurin inhibitors if steroid-resistant or steroids aren't suitable; rituximab in some.
  • Secondary FSGS -treat the cause (weight loss); no immunosuppression.
  • Genetic -doesn't respond to immunosuppression; genetic testing helps avoid unnecessary treatment.
• Prognosis: A common cause of kidney failure; primary FSGS can recur in a kidney transplant (sometimes within days).

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Membranous Nephropathy

• Who: The commonest cause of nephrotic syndrome in white adults; peak age 40–60, more often men.
• Causes:
  • Primary (about 75%) -autoantibodies against a podocyte protein: anti-PLA2R (about 70–80%), anti-THSD7A.
  • Secondary:
    • Cancer -lung, bowel, breast, prostate (especially over 60; screen as age-appropriate).
    • Infection -hepatitis B, hepatitis C, syphilis, malaria.
    • Lupus (class V).
    • Drugs -NSAIDs, gold, penicillamine.
    • Other autoimmune disease (thyroid, Sjögren's).
• Biopsy: Thickened basement membrane; IgG deposits under the podocytes ("spikes" on silver stain); PLA2R staining.
• Anti-PLA2R antibodies:
  • A positive test with typical features can avoid the need for biopsy in some patients.
  • Levels track disease activity -falling titres predict remission.
• Course -"rule of thirds" (roughly): one-third remit spontaneously, one-third have persistent proteinuria, one-third progress to kidney failure.
• Treatment:
  • Supportive for all -ACE inhibitor or ARB, diuretics, statin, anticoagulation (highest VTE risk of all causes; consider when albumin is under about 25 g/L).
  • Low risk (normal eGFR, proteinuria under 3.5 g/day) -supportive care and watch (often 6 months).
  • Moderate to high risk -rituximab (MENTOR trial -better than ciclosporin).
  • High risk or failing kidney function -cyclophosphamide with steroids (modified Ponticelli regimen, alternating months); calcineurin inhibitors as an alternative.
  • Secondary -treat the cause (remove the tumour, antivirals for hepatitis B, stop the drug).

⚠️ Safety Pearl: Sudden loin pain, visible haematuria and a fall in kidney function in a patient with membranous nephropathy suggest renal vein thrombosis -request CT venography and anticoagulate.

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Diabetic Kidney Disease

• The commonest cause of kidney failure in the UK.
• Natural history:
  • Early hyperfiltration (high GFR).
  • Moderately increased albuminuria (ACR 3–30).
  • Severely increased albuminuria (ACR over 30), then nephrotic-range proteinuria.
  • Falling eGFR, then kidney failure.
  • In type 2 diabetes, some patients lose GFR without much albuminuria.
• Biopsy (not usually needed) -thickened basement membrane, mesangial expansion, Kimmelstiel–Wilson nodules.
• Consider another cause (and refer for biopsy) if:
  • No diabetic retinopathy (especially in type 1 diabetes).
  • Rapid decline in eGFR or sudden nephrotic syndrome.
  • Haematuria or red cell casts.
  • Short duration of diabetes (under 5 years in type 1).
  • Signs of another systemic disease.
• Treatment:
  • Glucose control (HbA1c target individualised).
  • BP control.
  • ACE inhibitor or ARB (ACR over 3).
  • SGLT2 inhibitor.
  • Finerenone (persistent albuminuria).
  • GLP-1 receptor agonist (semaglutide -kidney and cardiovascular benefits).
  • Statin.
  • See the CKD chapter.

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Amyloidosis

• What it is: Misfolded proteins deposit as fibrils in organs. The kidneys are often affected, usually with nephrotic syndrome.
• AL amyloidosis (light chain):
  • From a plasma cell clone -MGUS or myeloma.
  • Features:
    • Nephrotic syndrome; normal-sized or large kidneys.
    • Heart -restrictive cardiomyopathy, heart failure, low-voltage ECG (the main cause of death).
    • Peripheral and autonomic neuropathy, carpal tunnel syndrome.
    • Macroglossia; periorbital purpura ("raccoon eyes").
    • Large liver.
  • Treatment: Chemotherapy against the plasma cell clone -daratumumab with bortezomib, cyclophosphamide and dexamethasone; stem cell transplant for some.
• AA amyloidosis (serum amyloid A):
  • From chronic inflammation -rheumatoid arthritis, IBD, familial Mediterranean fever, bronchiectasis, TB, injecting drug use (chronic skin infections).
  • Treatment: Control the inflammation (biologics; colchicine for FMF).
• Diagnosis:
  • Biopsy (kidney, fat pad, or rectum) -Congo red stain with apple-green birefringence under polarised light.
  • Typing (which protein) -essential for treatment.
  • Serum free light chains; SAP scan (National Amyloidosis Centre, London).

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Myeloma and Paraprotein Kidney Disease

• Myeloma cast nephropathy ("myeloma kidney"):
  • Free light chains block the tubules -AKI, often with high calcium and dehydration.
  • Little albuminuria (light chains are poorly detected by dipstick); PCR much higher than ACR.
  • Treatment: IV fluids, correct calcium, stop nephrotoxic drugs, and urgent anti-myeloma treatment (bortezomib-based regimens with dexamethasone) to cut light chain levels fast.
• Light chain deposition disease -nodular glomerular deposits, proteinuria.
• AL amyloidosis -see above.
• Monoclonal gammopathy of renal significance (MGRS) -a small plasma cell or B cell clone (not enough to be myeloma) that damages the kidney. It is treated with chemotherapy to protect the kidney.
• Other myeloma-related kidney problems -high calcium, Fanconi syndrome (proximal tubule damage), NSAIDs, contrast, bisphosphonates.
• See the Lymphoma and Myeloma chapter.

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IgA Nephropathy

• Who: The commonest glomerulonephritis worldwide; young men; more common in East Asia.
• What it is: Abnormal IgA1 molecules form immune complexes that deposit in the mesangium.
• Features:
  • Visible haematuria within 1–2 days of a sore throat or other infection ("synpharyngitic") -compare post-streptococcal GN, which follows 1–3 weeks after.
  • Persistent invisible haematuria and proteinuria found at a check-up.
  • Hypertension; slow CKD.
  • Occasionally nephrotic, or rapidly progressive (crescentic).
• Tests: Complement normal; serum IgA raised in about half (not diagnostic).
• Biopsy: Mesangial IgA deposits on immunofluorescence; MEST-C score predicts outcome.
• Treatment:
  • Supportive care -the main treatment for all:
    • ACE inhibitor or ARB at maximum dose.
    • SGLT2 inhibitor.
    • BP control (under 130/80 if proteinuria).
    • Statin; lifestyle; stop smoking.
  • Persistent proteinuria (e.g. over 0.5–1 g/day) despite supportive care -newer options:
    • Targeted-release budesonide (Kinpeygo; NICE TA937) -acts on gut lymphoid tissue where abnormal IgA is made; a 9-month course.
    • Sparsentan (NICE TA1074) -a dual endothelin and angiotensin receptor antagonist, used in place of an ACE inhibitor or ARB.
    • Systemic steroids -selected high-risk patients (TESTING trial showed benefit, but with serious infections at higher doses).
  • Crescentic IgA -treated like ANCA vasculitis (steroids and cyclophosphamide).
  • Tonsillectomy -used in Japan; not routine in the UK.
• Prognosis: About 20–40% reach kidney failure within 20 years. Worse with heavy proteinuria, high BP, and low eGFR at diagnosis.

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IgA Vasculitis

• What it is: Small-vessel vasculitis with IgA deposits (formerly Henoch–Schönlein purpura). The kidney lesion looks like IgA nephropathy.
• Who: Mainly children aged 3–15, often after an upper respiratory infection; less common but more severe in adults.
• Features:
  • Palpable purpura on the buttocks and legs (with a normal platelet count).
  • Joint pain (knees, ankles).
  • Abdominal pain, GI bleeding, intussusception (children).
  • Nephritis -haematuria and proteinuria in up to half.
  • Scrotal swelling.
• Management:
  • Usually self-limiting -supportive care (simple analgesia; avoid NSAIDs if the kidneys are involved).
  • Monitor BP and urine for at least 6 months (kidney involvement can appear later).
  • Refer if there is significant proteinuria, nephrotic or nephritic syndrome, high BP, or reduced kidney function.
  • Steroids and immunosuppression for severe kidney disease.

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Post-infectious Glomerulonephritis

• Post-streptococcal GN (mainly children):
  • 1–3 weeks after a sore throat, or 3–6 weeks after a skin infection (impetigo), with group A streptococcus.
  • Features: Nephritic syndrome -cola-coloured urine, oedema (periorbital), hypertension, oliguria, AKI.
  • Tests:
    • Low C3 with normal C4 (C3 recovers within 6–8 weeks -if not, think C3 glomerulopathy).
    • Raised ASOT (throat) or anti-DNase B (skin).
  • Biopsy (if done): Inflamed glomeruli with "humps" (deposits under the epithelium).
  • Treatment: Supportive -salt and fluid restriction, loop diuretics, BP control; penicillin to clear the infection; dialysis rarely.
  • Prognosis: Excellent in children; less good in older adults.
• Infection-related GN in adults:
  • Often during the infection (not after) -staphylococcal infection (skin, bone, endocarditis), especially in diabetes, alcohol excess and older people.
  • May show IgA-dominant deposits.
  • Treat the infection; avoid immunosuppression.
• Endocarditis and shunt nephritis -immune complex GN with low C3 and C4.

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Anti-GBM Disease

• What it is: Autoantibodies against type IV collagen (alpha-3 chain) in the glomerular and alveolar basement membranes. "Goodpasture's disease" is the name used when the lungs are involved.
• Who: Two peaks -young men (20s–30s, more lung haemorrhage) and older women (60s–70s, more kidney-only disease). Smoking and inhaled hydrocarbons increase lung bleeding.
• Features:
  • Rapidly progressive GN -kidney failure over days.
  • Lung haemorrhage (in about half) -haemoptysis, breathlessness, anaemia, infiltrates on chest X-ray, raised transfer factor (KCO).
  • Few systemic symptoms.
• Tests:
  • Anti-GBM antibodies in the blood (urgent).
  • Biopsy -linear IgG along the basement membrane; crescents.
  • ANCA -about 30–40% are also ANCA-positive ("double positive"), with a risk of relapse like vasculitis.
• Treatment (urgent, before biopsy if suspected):
  • Plasma exchange -daily, to remove antibodies (usually for about 14 days or until antibodies are gone).
  • High-dose steroids -IV methylprednisolone then oral prednisolone.
  • Cyclophosphamide (rituximab as an alternative).
  • Stop smoking.
• Prognosis:
  • Kidney recovery is unlikely if the patient needs dialysis at presentation and nearly all glomeruli have crescents -though treatment is still given for lung haemorrhage.
  • Relapse is rare (unlike ANCA vasculitis), except in double-positive patients.
  • Transplant only after antibodies have been undetectable for at least 6 months.

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ANCA-associated Vasculitis

• What it is: Small-vessel vasculitis with antibodies against neutrophil enzymes. The kidney lesion is a pauci-immune (few deposits) necrotising crescentic GN.
• Types:
  • Granulomatosis with polyangiitis (GPA) -usually PR3-ANCA (c-ANCA):
    • Ear, nose and throat -crusting, nosebleeds, sinusitis, deafness, saddle-nose.
    • Lungs -nodules, cavities, haemorrhage.
    • Kidneys -GN.
    • Eyes (scleritis, orbital mass), subglottic stenosis.
  • Microscopic polyangiitis (MPA) -usually MPO-ANCA (p-ANCA): kidney and lung (haemorrhage, fibrosis); no granulomas; older people.
  • Eosinophilic GPA (EGPA) -asthma, nasal polyps, eosinophilia, neuropathy (mononeuritis multiplex), heart involvement; MPO-ANCA in about 40%; kidney disease less common.
• General features: Fever, weight loss, joint pains, purpuric rash, mononeuritis multiplex, raised CRP, anaemia.
• Drug-induced -hydralazine, propylthiouracil, levamisole-contaminated cocaine, minocycline.
• Treatment (KDIGO 2024, BSR):
  • Induction:
    • Steroids -IV methylprednisolone then oral prednisolone, using a reduced-dose taper (PEXIVAS -as effective, with fewer infections).
    • Plus rituximab or cyclophosphamide (rituximab preferred for relapsing disease, PR3-ANCA, younger people wanting fertility).
    • Avacopan (NICE TA825) -a C5a receptor blocker, with rituximab or cyclophosphamide, for severe active GPA or MPA; allows much less steroid.
    • Plasma exchange -consider with creatinine over about 300 µmol/L, rapidly falling function or dialysis, or lung haemorrhage with hypoxia.
  • Maintenance (for 2–4 years):
    • Rituximab every 6 months (better than azathioprine -MAINRITSAN).
    • Azathioprine or methotrexate as alternatives.
  • EGPA -steroids; mepolizumab (anti-IL-5) for relapsing or refractory disease.
  • Prophylaxis:
    • Co-trimoxazole (PJP prophylaxis).
    • Bone protection.
    • Vaccines (before rituximab).
    • Check immunoglobulins (rituximab can cause low IgG).
• Prognosis: Mostly good with treatment, but relapse is common (especially PR3); infection is a major cause of death in the first year.

💡 Clinical Pearl: An older person with "pneumonia that doesn't respond to antibiotics", a rising creatinine, and blood and protein on dipstick has ANCA vasculitis until proven otherwise.

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Lupus Nephritis

• Who: About 40–50% of people with SLE develop kidney involvement, usually in the first 5 years; more common and severe in people of African, Caribbean and Asian descent.
• Screen all SLE patients regularly -BP, urine dipstick, ACR or PCR, eGFR.
• Signs of activity:
  • Proteinuria (PCR over 50 mg/mmol is an indication for biopsy), haematuria, casts.
  • Rising creatinine.
  • Low C3 and C4.
  • Rising anti-dsDNA.
• Classes (ISN/RPS, on biopsy):
  • I–II -mesangial (mild); no specific immunosuppression for the kidney.
  • III (focal) and IV (diffuse) proliferative -the most serious; nephritic picture; needs immunosuppression.
  • V -membranous -nephrotic syndrome; immunosuppression if heavy proteinuria.
  • VI -advanced scarring (over 90% sclerosed); prepare for kidney failure.
• Treatment (class III, IV, and V with heavy proteinuria):
  • Induction:
    • Steroids -IV methylprednisolone then oral prednisolone, tapered.
    • Plus mycophenolate (MMF) or low-dose IV cyclophosphamide (Euro-Lupus regimen).
    • Add-on options -voclosporin (with MMF; NICE TA882) or belimumab.
    • Rituximab for refractory disease.
  • Maintenance -MMF (or azathioprine, especially in pregnancy) for at least 3 years.
  • Hydroxychloroquine for all (reduces flares).
  • ACE inhibitor or ARB, BP control, statin.
  • Pregnancy -plan when disease is quiet for 6 months or more; switch MMF to azathioprine; aspirin; watch for flares and pre-eclampsia.
• Antiphospholipid syndrome can cause kidney thrombotic microangiopathy in SLE -anticoagulation.

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MPGN and C3 Glomerulopathy

• Membranoproliferative GN (MPGN) -a pattern of injury with thickened capillary walls ("tram-track" appearance) and increased cells. Mixed nephrotic and nephritic picture, often with low complement.
• Immune-complex MPGN (low C3 and C4) -look for a cause:
  • Hepatitis C with cryoglobulinaemia -purpura, joint pain, neuropathy, low C4; treat with direct-acting antivirals.
  • Hepatitis B; endocarditis; other chronic infections.
  • Monoclonal gammopathy (MGRS).
  • Autoimmune disease (lupus, Sjögren's).
• C3 glomerulopathy (low C3, normal C4):
  • Over-activity of the alternative complement pathway -often C3 nephritic factor (an autoantibody) or genetic defects.
  • Includes dense deposit disease (linked to partial lipodystrophy and retinal drusen).
  • Often presents after an infection, like post-streptococcal GN -but C3 stays low beyond 8–12 weeks.
  • Treatment: Supportive care; mycophenolate with steroids; complement inhibitors (e.g. iptacopan is licensed; NICE was unable to make a recommendation -TA1102).
  • Recurs often after transplant.

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Infection-related Kidney Disease

• Hepatitis B -membranous nephropathy (children), MPGN, polyarteritis nodosa. Treat with antivirals.
• Hepatitis C -cryoglobulinaemic MPGN. Treat with direct-acting antivirals; rituximab for severe vasculitis.
• HIV:
  • HIV-associated nephropathy (HIVAN) -collapsing FSGS, heavy proteinuria, large echogenic kidneys, rapid kidney failure; mainly people of African ancestry (APOL1).
  • Immune complex disease; drug toxicity (tenofovir disoproxil -Fanconi syndrome, AKI).
  • Antiretroviral therapy improves HIVAN.
• Endocarditis -immune complex GN, emboli, drug-induced AIN and antibiotic toxicity (gentamicin, vancomycin).
• Syphilis, malaria, schistosomiasis -membranous or other glomerular disease (travel history).
• Hantavirus and leptospirosis -interstitial disease and AKI.

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Drug Reference Table

Drug	Key points
Prednisolone 1 mg/kg (maximum 80 mg)	Minimal change disease, primary FSGS; tapered after remission. Bone protection, glucose, infection.
Methylprednisolone IV	Induction in ANCA vasculitis, anti-GBM disease, lupus nephritis, crescentic GN.
Rituximab	Anti-CD20: membranous nephropathy, ANCA vasculitis (induction and maintenance), relapsing minimal change. Infusion reactions, low IgG, hepatitis B reactivation.
Cyclophosphamide	ANCA vasculitis, anti-GBM disease, lupus nephritis, high-risk membranous. Infertility, bladder toxicity, infection, cancer.
Mycophenolate mofetil	Lupus nephritis induction and maintenance; C3 glomerulopathy. Teratogenic, diarrhoea, low white cells.
Tacrolimus / ciclosporin	Calcineurin inhibitors: steroid-resistant FSGS, minimal change relapses, membranous. Nephrotoxic; levels needed.
Avacopan	C5a receptor antagonist for severe GPA/MPA with rituximab or cyclophosphamide (TA825); steroid-sparing; liver tests.
Voclosporin	Calcineurin inhibitor added to MMF for active lupus nephritis (TA882).
Belimumab	Anti-BLyS add-on for lupus nephritis.
Hydroxychloroquine	All lupus patients; yearly eye screening after 5 years.
Targeted-release budesonide	IgA nephropathy with persistent proteinuria (TA937).
Sparsentan	Dual endothelin/angiotensin receptor antagonist for IgA nephropathy (TA1074); replaces ACEi/ARB; liver tests, teratogenic.
Plasma exchange	Anti-GBM disease; selected severe ANCA vasculitis.
Co-trimoxazole	PJP prophylaxis during intensive immunosuppression.
Furosemide (high dose)	Nephrotic oedema; often IV initially; add thiazide if resistant.
LMWH / warfarin	Prophylactic anticoagulation in nephrotic syndrome with very low albumin, especially membranous.

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Spot the Diagnosis

Clue	Diagnosis
4-year-old with sudden heavy oedema, normal BP, no haematuria	Minimal change disease
Nephrotic syndrome in a young man with night sweats and neck lymph nodes	Minimal change disease with Hodgkin lymphoma
55-year-old nephrotic, anti-PLA2R positive	Primary membranous nephropathy
Membranous nephropathy, PLA2R negative, 68-year-old smoker	Consider underlying cancer (lung)
Obese man with proteinuria 2 g/day, normal albumin	Secondary (adaptive) FSGS
Heavy proteinuria, large echogenic kidneys, HIV not on treatment	HIVAN (collapsing FSGS)
Visible haematuria 2 days after a sore throat	IgA nephropathy
Cola-coloured urine 2 weeks after tonsillitis, low C3, normal C4	Post-streptococcal GN
Low C3 still present 4 months after an apparent post-infectious GN	C3 glomerulopathy
Child with purpura on buttocks, knee pain, abdominal pain and haematuria	IgA vasculitis
Young smoker with haemoptysis and AKI, linear IgG on biopsy	Anti-GBM (Goodpasture's) disease
Saddle nose, nosebleeds, lung cavities, AKI, PR3-ANCA	GPA
Asthma, eosinophilia, foot drop, MPO-ANCA	EGPA
SLE with low C3 and C4, rising dsDNA, PCR 180	Lupus nephritis -biopsy
Purpura, neuropathy, low C4 and hepatitis C	Cryoglobulinaemic MPGN
Nephrotic syndrome, macroglossia, periorbital purpura	AL amyloidosis
Nephrotic syndrome in long-standing rheumatoid arthritis	AA amyloidosis
Long-standing type 1 diabetes, retinopathy, ACR 120	Diabetic kidney disease

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Exam-style Scenarios

1. A 52-year-old man has leg oedema. Albumin 19 g/L, PCR 820 mg/mmol, creatinine normal, no haematuria. Anti-PLA2R is strongly positive.
Answer: Nephrotic syndrome from primary membranous nephropathy.

• Salt restriction, loop diuretic, ACE inhibitor or ARB, statin.
• Prophylactic anticoagulation (very low albumin, membranous -high VTE risk).
• Age-appropriate cancer screening; hepatitis B and C serology.
• Rituximab if high risk or not remitting; monitor PLA2R titres.

2. A 24-year-old man has visible haematuria a day after starting a cold. BP 142/90, ACR 60, eGFR 85, complement normal.
Answer: IgA nephropathy (synpharyngitic haematuria).

• Refer to nephrology for biopsy.
• ACE inhibitor or ARB to maximum dose; SGLT2 inhibitor; BP under 130/80.
• If proteinuria persists: targeted-release budesonide or sparsentan.

3. A 72-year-old woman has 6 weeks of malaise, arthralgia and weight loss. Creatinine is 410 µmol/L (was 80 a year ago). Dipstick 3+ blood, 2+ protein. MPO-ANCA positive.
Answer: Microscopic polyangiitis with rapidly progressive GN.

• Urgent nephrology admission; kidney biopsy; chest imaging.
• IV methylprednisolone then reduced-dose oral steroids, plus rituximab or cyclophosphamide; consider avacopan.
• Consider plasma exchange (creatinine over 300).
• Co-trimoxazole PJP prophylaxis; bone protection; maintenance rituximab.

4. A 28-year-old woman with SLE has new oedema, BP 150/95, PCR 250 mg/mmol, low C3 and C4.
Answer: Lupus nephritis.

• Kidney biopsy for class.
• Class III/IV: steroids with MMF (or low-dose cyclophosphamide); consider voclosporin or belimumab.
• Continue hydroxychloroquine; ACE inhibitor (with contraception advice); BP control.

5. A 9-year-old has periorbital swelling and dark urine 2 weeks after tonsillitis. BP 135/90. C3 low, C4 normal, ASOT raised.
Answer: Post-streptococcal glomerulonephritis.

• Supportive: salt and fluid restriction, loop diuretic, BP control; penicillin.
• Monitor U&E and fluid balance.
• Recheck C3 at 8–12 weeks -persistently low suggests C3 glomerulopathy.

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Key Points

• Nephrotic: proteinuria over 3 g/day, albumin under 30, oedema. Nephritic: haematuria, hypertension, falling eGFR.
• Low C3 and C4: lupus, cryoglobulinaemia, immune-complex MPGN. Low C3 only: post-streptococcal GN, C3 glomerulopathy.
• Minimal change: most childhood nephrotic syndrome; steroid-responsive; think NSAIDs and Hodgkin lymphoma in adults.
• FSGS: primary (steroids, calcineurin inhibitors) versus secondary (obesity, reduced nephrons -no immunosuppression) versus genetic.
• Membranous: anti-PLA2R; screen for cancer and hepatitis B; highest VTE risk; rituximab for higher-risk disease.
• Nephrotic syndrome care: salt restriction, high-dose loop diuretics, ACE inhibitor or ARB, statin, consider anticoagulation.
• IgA nephropathy: haematuria 1–2 days after infection; supportive care first; budesonide or sparsentan for persistent proteinuria.
• Post-streptococcal GN: 1–3 weeks after throat infection, low C3, supportive care.
• Anti-GBM disease: linear IgG, lung haemorrhage -plasma exchange, steroids, cyclophosphamide.
• ANCA vasculitis: steroids plus rituximab or cyclophosphamide; avacopan reduces steroid exposure; rituximab maintenance; relapses are common.
• Lupus nephritis classes III–IV need steroids plus MMF or cyclophosphamide; hydroxychloroquine for all.
• AL amyloid: nephrotic, heart, neuropathy, macroglossia -Congo red apple-green birefringence.
• Myeloma kidney: AKI with light chains -urgent anti-myeloma treatment.

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Guidelines and Further Reading

• KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases (and 2024 ANCA vasculitis and lupus nephritis updates; 2025 IgA nephropathy update)
• NICE NG12: Suspected cancer -recognition and referral (haematuria)
• NICE TA825 (avacopan), TA882 (voclosporin), TA937 (targeted-release budesonide), TA1074 (sparsentan), TA1102 (iptacopan for C3 glomerulopathy -no recommendation)
• British Society for Rheumatology guideline for ANCA-associated vasculitis
• UK Kidney Association and RaDaR (National Registry of Rare Kidney Diseases) resources
• BNF -for current doses

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