Glomerulonephritis

Presentation

• >3-5 red cells in spun sediment
  • Gross haematuria usually only seen in post-streptococcal, IgA nephropathy and sickle cell disease
• Sustained proteinuria >1-2g/24 hours
  • Usually non-selective

Benign proteinuria

• Usually non-sustained, <1g/24 hours and sometimes called functional or transient
• Fever, exercise, obesity, sleep apnoea, emotional stress and CCF can cause this
• Orthostatic proteinuria can occur in upright posture only

Clinical syndromes

• Acute nephritic syndrome
  • 1-2g/24 hour proteinuria, haematuria with red cell casts, pyuria, HTN, fluid retention and rise in serum creatinine with fall in GFR
  • If develops rapidly within days = rapidly progressive GN (histopathological crescentic GN)
  • RPGN with lung haemorrhage = pulmonary-renal syndrome
• Nephrotic syndrome
  • >3g/24 hours proteinuria, HTN, dyslipidaemia, hypoalbuminaemia, oedema/anasarca and microscopic haematuria
  • If only proteinuria without rest of diagnostic criteria = nephrotic-range proteinuria
  • GFR may be normal, higher than normal but typically declines over months to years
• Not mutually exclusive

6 general syndromes

• Acute nephritic syndrome
  • Post-strep GN, subacute bacterial endocarditis, lupus nephritis, antiglomerular BM disease, IgA nephropathy, ANCA vasculitis, HSP, cryoglobulinaemia, membranoproliferative, mesangioproliferative
• Pulmonary-renal syndromes
  • Goodpasture, ANCA vasculitis, HSP, cryoglobulinaemia
• Nephrotic syndrome
  • Minimal change disease, focal segmental glomerulosclerosis, membraneous GN, diabetic nephropathy, amyloidosis
• Basement membrane syndromes
  • Anti-GBM disease, Alport’s syndrome, thin basement membrane disease, nail-patella disease
• Glomerular vascular syndromes
  • Atherosclerotic nephropathy, hypertensive nephropathy, cholesterol emboli, sickle cell disease, thrombotic microangiopathies, ANCA, HSP, cryoglobulinaemia, amyloidosis
• Infectious-disease associated syndromes
  • Post-strep GN, subacute bacterial endocarditis, HIV, HepB/C, syphilis, leprosy, malaria, schistosomiasis

Acute nephritic syndromes

• Post-streptococcal GN
  • Usually children 2-14 yo (10% of patients >40yo)
  • Mostly males
  • Skin and throat infections with nephritogenic strains of strep
  • 2-6 weeks after impetigo and 1-3 weeks after strep pharyngitis
  • Immune-mediated disease due to M protein mimicry
  • Presents with haematuria, pyuria, red cell casts, oedema, HTN, oliguric renal failure and perhaps RPGN severity
  • Headache, malaise, anorexia and flank pain (renal capsule swelling) in 50%
  • Low C3 and normal C4 in 90% of patients in first week

Acute nephritic syndromes

• Post-strep GN
  • Strep culture may represent colonisation
  • ASOT rises with pharyngitis (but not skin infection)
  • Anti-DNAse B usually positive after skin infection
  • Positive strep cultures in 10-40%, Anti-streptolysin O titre in 30% and anti-DNAse in 70%
  • Treat all patients for strep infection + supportive
  • No role for immunosuppression
  • Risk of immunosuppression (loss of complement and antibodies), thrombosis and bleeding (coagulation factor loss)
  • Complete resolution in 3-6 weeks is expected (permanent renal dysfunction in 1-3% and even less in kids)

Acute nephritic syndromes

• Subacute bacterial endocarditis
  • Due to renal deposition of circulating immune complexes with complement activation +- septic emboli
  • Present with haematuria, pyuria, mild proteiburia
  • Treatment focuses on underlying infection

Acute nephritic syndromes

• Lupus nephritis
  • Common and serious complication of SLE
  • 30-50% have renal involvement at time of diagnosis and 60% of adults/80% of children develop renal impairment in lifetime
  • Results from immune complex deposition
  • Proteinuria is most common but haematuria, HTN, renal failure and red cell casts can occur
  • Anti-dsDNA antibodies that fix complement correlate best with renal disease
  • Hypocomplementaemia is common

Acute nephritic syndrome

• Anti-glomerular basement membrane disease
  • If lung haemorrhage = Goodpasture’s
  • Seen in young men in their 20’s and older men and women in 60s and 70s
  • Disease in younger group is usually explosive with haemoptysis, drop in Hb, fever, dyspnoea and haematuria
  • Older patients typically present with prolonged asymptomatic renal injury
  • Lung haemorrhage responds to plasmapheresis and steroids +- cyclophosphamide

Acute nephritic syndrome

• IgA nephropathy
  • Follows viral infection with intermittent gross haematuria. Peaks in young males 10-30 years old
  • Similar to HSP
  • Two most common presentations are recurrent gross haematuria in children following viral infection or asymptomatic microscopic haematuria in adults
  • Once haematuria persists, get rise in proteinuria (nephrotic syndrome levels uncommon)
  • Progresses to renal failure in 30% over 20-25 years
  • ACEi may be of benefit
  • Steroids, cytotoxics and plasmapheresis if RPGN

Acute nephritic syndrome

• ANCA small-vessel vasculitis
  • Includes Wegener’s, Churg-Strauss and microscopic polyangiitis
  • Can all be p- or c-ANCA positive
  • Need induction hterapy of plasmapheresis, methylprednisolone and cyclophosphamide
  • Wegener’s gramulatosis
    • Fever, purulent rhinorrhoea, nasal ulcers, sinus pain, polyarthralgia, cough, haemoptysis, SOB, microscopic haematuria and 0.5-1g/24hr proteinuria
    • CXR often reveals nodules and persistent infiltrates
  • Microscopic polyangiitis
    • Present similar to Wegener’s but without lung disease or destructive sinusitis
  • Churg-Strauss
    • Present with persistent eosinophilia, cutaneous purpura, mononeuropathy, asthma and allergic rhinitis

Acute nephritic syndrome

• Membranoproliferative GN
  • Thicking of glomerular BM due to mesangioproliferative changes
  • 70% have reduced serum complement

Nephrotic syndrome

• All patients need supportive therapy including
  • Lipid-lower therapy
  • Salt and water restriction + diuretics
  • DVT prophylaxis
  • ACEi

nephrotic syndrome

• Minimal change disease
  • Causes 70-90% of nephrotic syndrome in childhood but only 10-15% in adults
  • Presents with abrupt onset oedema and nephrotic level proteinuria
  • May also have hypertension, microscopic haematuria, atopy and reduced renal function
  • In children, proteinuria is usually albumin-selective
  • Treat with steroids
    • 95% of children have complete remission within 8 weeks
    • 85% of adults will have complete remission within 20-24 weeks
  • Relapses occur in 75% of children

Nephrotic syndrome

• Focal segmental glomerulosclerosis
  • Up to 1/3 of nephrotic syndrome in adults
  • Diagnosed on biopsy

Nephrotic syndrome

• Membraneous glomerulonephritis
  • 30% of cases in adults
  • Rare in childhood

Nephrotic syndrome

• Diabetic nephropathy
  • Single most common cause of chronic renal failure
  • Morphological changes arise within 1-2 years of diagnosis of DM
  • Degree of glomerular hyperfiltration correlates with risk of clinically significant diabetic nephropathy
  • Microalbuminuria
    • 30-300mg/24 hours
    • Seen in 5-10 years from diagnosis
    • Potent risk factor for cardiovascular disease and death
  • Macroalbuminuria > 300mg/24 hours
  • 50% of patients reach renal failure in 5-10 years from diagnosis of proteinuria >500mg/24 hours
  • Strict blood sugar control, blood pressure control and ACEi all prevent progression

Last Updated on October 9, 2020 by Andrew Crofton