• Nephritic syndrome: Characterised by haematuria, sub-nephrotic proteinuria, hypertension, and variable renal impairment.
• Nephrotic syndrome: Marked by heavy proteinuria (≥3.5 g/day), hypoalbuminaemia, oedema, and hyperlipidaemia.
• Rapidly progressive GN: A severe form with rapid decline in renal function over weeks to months, often with crescent formation on biopsy.
  
  

• Primary: Confined to the kidney, e.g., minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy.
• Secondary: Due to systemic conditions such as systemic lupus erythematosus, vasculitis, infections (e.g., post-streptococcal), or malignancies.
  
  

Classification Based on Underlying Cause

Infectious Causes

• Caused by nephritogenic strains of group A beta-haemolytic Streptococcus.
• Two main serotypes:
  • Serotype 12: Associated with pharyngitis (winter peak).
  • Serotype 49: Linked to skin infections (summer/fall peak).
• Typically presents 1–3 weeks after infection.
  
  

• Staphylococcus aureus, diplococci, Salmonella typhosa, Mycobacterium tuberculosis, Treponema pallidum, Corynebacterium, and actinobacilli.
  
  

• Cytomegalovirus, Epstein-Barr virus, coxsackievirus, hepatitis B and C, rubella, mumps, parvovirus B19, rickettsiae.
  
  

• Plasmodium falciparum, Schistosoma mansoni, Toxoplasma gondii, Trichinella, Trypanosoma, Wuchereria bancrofti, and Coccidioides immitis.
  
  
  
  

Non-Infectious Causes

• Systemic lupus erythematosus (SLE)
• Granulomatosis with polyangiitis
• Microscopic polyangiitis
• Anti-glomerular basement membrane disease (Goodpasture syndrome)
• Cryoglobulinaemia
• IgA vasculitis (Henoch-Schönlein purpura)
• Polyarteritis nodosa
• Hypersensitivity vasculitis
  
  

• Diabetes mellitus
• Hypertension
• Autoimmune thyroiditis
  
  

• Lung and colorectal carcinomas
• Hodgkin and non-Hodgkin lymphomas
• Melanoma
• Thymoma
• Leukaemia
  
  

• Gold salts
• Hydralazine
• Lithium
• Propylthiouracil
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• COVID-19 vaccines (rare reports)
• Cetuximab (via EGFR inhibition)
  
  

• Alport syndrome (type IV collagen defect)
• Fabry disease
• Thin basement membrane disease
• Nail-patella syndrome
• Genetic complement pathway disorders
  
  

• Amyloidosis
• Monoclonal immunoglobulin deposition disease (MIDD)
  
  

Classification by Immune Pathogenesis

• IgA nephropathy, lupus nephritis, infection-related GN, IgA vasculitis, fibrillary GN
  
  

• Characterised by linear IgG deposition targeting type IV collagen
  
  

• Typically ANCA-associated (e.g. PR3-ANCA, MPO-ANCA); minimal immune deposition
  
  

• Includes proliferative GN with monoclonal IgG, MIDD, and immunotactoid GN
  
  

• Dense deposit disease and C3 GN; driven by alternative complement dysregulation
  
  

Classification by Clinical Syndrome

• Minimal change disease
• Focal segmental glomerulosclerosis
• Membranous nephropathy
• Membranoproliferative GN (also presents with nephritic features)
• HIV-associated nephropathy
• Diabetic nephropathy
• Amyloidosis
  
  

• IgA nephropathy
• Henoch-Schönlein purpura
• Post-streptococcal GN
• Anti-GBM disease
• Rapidly progressive GN
• Granulomatosis with polyangiitis
• Eosinophilic granulomatosis with polyangiitis
• Polyarteritis nodosa
• Lupus nephritis
• Hepatitis C-associated GN
  
  

Immune-Mediated Injury

• Immune complexes may form in situ or be deposited from circulation.
• Intrinsic autoantigen reactions: Seen in anti-GBM disease and membranous nephropathy, where antibodies bind directly to antigens in the GBM.
• Entrapped antigens: As in post-infectious GN, where foreign antigens are deposited and elicit immune response.
• Preformed circulating immune complexes: Formed in conditions like cryoglobulinaemia or SLE and deposited in the glomeruli.
  
  

• Involves infiltration by T lymphocytes, monocytes, and macrophages, which mediate tissue damage through direct cytotoxicity and cytokine secretion.
• Pauci-immune GN (e.g. ANCA-associated vasculitis) exemplifies cell-mediated glomerular damage, often with minimal immune deposition.
• Platelet activation may amplify injury via release of monocyte chemoattractant protein-1 and other inflammatory mediators.
  
  
  

Non-Immune Mechanisms

• Metabolic: Chronic hyperglycaemia in diabetic nephropathy alters GBM composition.
• Haemodynamic stress: Sustained hypertension increases intraglomerular pressure, fostering injury.
• Toxic injury: Drugs or nephrotoxins can directly damage glomerular structures.
• Hereditary: Mutations in type IV collagen (e.g. Alport syndrome) or lysosomal enzymes (e.g. Fabry disease) compromise structural integrity of the GBM.
  
  
  

Complement Activation and Fibrosis

• Recruitment of inflammatory cells (neutrophils, monocytes)
• Glomerular endothelial and mesangial proliferation
• Release of matrix proteins contributing to glomerulosclerosis

Histopathological and Structural Changes

• Endocapillary proliferation: Proliferation within glomerular capillary tufts.
• Extracapillary proliferation: Expansion in Bowman’s space, leading to crescent formation—hallmark of rapidly progressive GN.

• Subendothelial: Often seen in lupus nephritis
• Subepithelial: Typical in membranous nephropathy
• Intramembranous: Associated with dense deposit disease
• Mesangial: Common in IgA nephropathy
  
  

• Uniform thickening (e.g. diabetic nephropathy)
• Electron-dense deposits indicating immune deposition
  
  

• Hyalinisation and glomerulosclerosis (segmental or global)
• Progressive fibrosis and atrophy indicate chronic damage
  
  
  

Functional Changes

• Proteinuria: Due to podocyte injury and GBM disruption
• Haematuria: With dysmorphic RBCs and RBC casts
• Reduced glomerular filtration rate (GFR): Leads to oliguria or anuria
• Salt and water retention: Resulting in intravascular volume expansion, systemic hypertension, and oedema
  
  

Post-Infectious GN as a Paradigm

• Nephritogenic antigens (e.g. nephritis-associated plasmin receptor, NAPlr) facilitate immune complex formation
• NAPlr maintains glomerular plasmin activity, contributing to inflammation
• Immunofluorescence shows C3 and IgG or IgA deposition depending on the pathogen (e.g. Streptococcus or Staphylococcus)

Contribution to Chronic and End-Stage Kidney Disease

• GN accounts for 10–15% of ESRD cases in the United States, ranking third after diabetes mellitus and hypertension.
• Chronic GN constitutes approximately 25–30% of all patients on dialysis, particularly among those with rapidly progressive or untreated disease.
• In young adults, GN is the leading cause of ESRD, highlighting its clinical relevance in early-onset kidney failure.
  
  

Global Prevalence and Patterns

• IgA nephropathy (IgAN) is recognised as the most common cause of primary GN globally. It predominates in East Asia (China, Japan), parts of Europe, and Australia.
• Post-streptococcal GN (PSGN) remains the leading cause of acute GN in children, particularly in low- and middle-income countries.
• Membranous nephropathy (MN) was historically the most frequent biopsy diagnosis in adults, especially in white men over 40 years. Its prevalence has declined in some regions due to better infectious disease control and improved biopsy practices.
  
  

Geographic Variations

• In high-income countries, a decline in PSGN has been observed since the 1990s. For example, in Japan, post-infectious GN now comprises only 40–50% of cases, compared to nearly all cases in the 1970s. This decline coincides with a rise in Staphylococcus aureus–associated nephritis (30%) and hepatitis C–related GN.
• In contrast, PSGN continues to be endemic in parts of the Caribbean, Africa, South Asia (India, Pakistan), Papua New Guinea, South America, and Malaysia.
• In Port Harcourt, Nigeria, the annual incidence of acute GN in children aged 3–16 is 15.5 cases/year, with a near-equal gender ratio.
  
  
  

Regional Biopsy Trends

• In the southeastern United States, focal segmental glomerulosclerosis (FSGS) is the most common GN identified via kidney biopsy.
• In Australia and France, IgA nephropathy is the predominant histological diagnosis.
• A large review from China noted:
  • IgAN was the most common GN in children.
  • MN remained the leading primary GN in adults.
    
    
    

Age, Gender, and Demographic Patterns

• Acute GN can occur at any age, though certain types show age predilection:
  • PSGN typically affects children aged 5–15, with peaks around 6 years of age.
  • Only ~10% of PSGN cases occur in individuals over 40.
• Males are more frequently affected than females, particularly in acute post-infectious GN (male-to-female ratio approximately 2:1).
• Despite global demographic variation, no clear racial or ethnic predilection has been consistently established for most forms of GN.
  
  
  

Subclinical Disease Burden

• For each patient with overt clinical GN, an estimated 5–10 individuals may harbour subclinical glomerular disease. These may only be identified through microscopic haematuria or incidental findings on routine urinalysis.
• The increasing use of kidney biopsy and changes in diagnostic thresholds have likely contributed to the observed rise in GN diagnoses in some regions.
  
  
  
  

Demographics and Patient Profile

• Children (2–14 years): Acute GN commonly presents as facial puffiness or periorbital oedema following a recent streptococcal infection. Dark, scanty urine and elevated blood pressure may be noted.
• Middle-aged or older adults: Particularly those with diabetes mellitus may present with GN associated with concurrent Staphylococcus aureus infection (e.g., pneumonia, endocarditis, osteomyelitis, or skin abscesses).
  
  
  

Temporal Profile and Symptom Onset

• Abrupt symptom onset is typical in acute GN.
• Latent periods:
  • Post-pharyngitis: 1–2 weeks before renal symptoms appear.
  • Post-dermal infection (e.g., pyoderma): 2–4 weeks delay.
  • Immediate onset (<4 days) suggests pre-existing renal disease.
    
    

Recent Infections and Risk Factors

• Sore throat (suggestive of streptococcal pharyngitis)
• Skin infections (e.g., impetigo)
• Respiratory or gastrointestinal infections
• Endocarditis (ask about heart valve surgery, prosthetics)
• IV drug use or travel history
• Hepatitis B or C exposure
• HIV risk factors
  
  

Renal Symptomatology

• Haematuria: Present in almost all cases; may be microscopic or macroscopic (“cola-coloured” urine).
• Oliguria: Reduction in urine output; may suggest declining GFR.
• Oedema: Facial or peripheral swelling; present in ~85% of paediatric cases.
• Hypertension: May manifest with headache or confusion (malignant hypertension).
• Flank pain: Possible due to renal capsular stretch.
• Dark, frothy urine: Indicative of haematuria and/or proteinuria.
  
  

Uraemic and Systemic Symptoms

• Loss of appetite
• Generalised pruritis
• Tiredness or lethargy
• Nausea and vomiting
• Easy bruising or epistaxis
• Weight loss
• Dyspnoea on exertion or orthopnoea (from fluid overload)
  
  
  

Clues to Systemic Disease as Underlying Cause

• Granulomatosis with polyangiitis: Sinusitis, haemoptysis, nephritis.
• Henoch-Schönlein purpura: Abdominal pain, nausea, purpura.
• Polyarteritis nodosa: Systemic symptoms with evidence of vasculitis.
• Hypersensitivity vasculitis: Skin rash, arthralgia, haematuria.
  
  

• Systemic lupus erythematosus: Joint pains, rash, serositis.
• Cryoglobulinaemia: Recurrent purpura, arthralgia, weakness.
  
  

• Goodpasture syndrome: Haemoptysis with glomerulonephritis.
  
  

• Solid tumours (e.g., lung, colorectal cancer) or haematological cancers (e.g., Hodgkin’s, non-Hodgkin lymphoma, leukaemia) may induce secondary GN.
  
  

 Medication and Drug Exposure

• Gold sodium thiomalate
• Hydralazine
• Lithium
• Propylthiouracil
• Non-steroidal anti-inflammatory drugs (NSAIDs)
  
  
  

Common General Findings

• Periorbital oedema: Often the earliest and most recognisable sign, particularly in children.
• Peripheral oedema: Pedal or dependent swelling; may progress with fluid retention.
• Ascites and pleural effusion: Possible in severe volume overload.
  
  

• Common due to salt and water retention secondary to reduced glomerular filtration.
• May result in headache, confusion, or even hypertensive encephalopathy.
  
  

• Suggests rapidly progressive renal dysfunction or severe glomerular injury.
• Accompanied by weight gain due to fluid accumulation.
  
  
  

Signs of Fluid Overload

• Elevated jugular venous pressure
• Fine inspiratory crackles on chest auscultation (from pulmonary oedema)
• Dyspnoea or orthopnoea, reflecting impaired pulmonary compliance
• S3 gallop or displaced apex beat (in advanced cardiorenal syndrome)
  
  
  

Cutaneous and Mucosal Clues

• Typically found on the lower limbs in Henoch-Schönlein purpura (IgA vasculitis).
  
  

• Suggestive of systemic lupus erythematosus (SLE).
  
  

• May indicate underlying vasculitic disorders or cryoglobulinaemia.
  
  

• Associated with SLE and other connective tissue diseases.
  
  

• Impetigo or cellulitis may point toward preceding post-streptococcal GN.
  
  
  

Renal-Specific Signs

• Occasionally present, may reflect interstitial inflammation or infection.
  
  

• May be noted on inspection of urine sample or incontinence pads (cola- or tea-coloured).
  
  

Cardiopulmonary Clues

• May raise suspicion of infective endocarditis in GN linked to circulating immune complexes.
  
  

• Seen in Goodpasture syndrome or ANCA-associated vasculitis, often with haemoptysis and hypoxia.
  
  

• Suggests granulomatosis with polyangiitis in pulmonary-renal syndromes.
  
  
  

Neurological Abnormalities

• May indicate hypertensive encephalopathy or severe uraemia.
  
  

• Suggestive of advanced azotaemia.
  
  
  

Musculoskeletal and Systemic Signs

• Present in SLE, IgA vasculitis, and vasculitic GN.
  
  

• Due to anaemia of chronic disease or haematuria-associated iron loss.
  
  

• May indicate active infection, systemic vasculitis, or GN flare in autoimmune conditions.
  
  
  
  

Initial Urinary Assessment

• Key features:
  • Haematuria: Dysmorphic RBCs suggest glomerular origin.
  • Proteinuria: Typically sub-nephrotic; nephrotic range in specific subtypes.
  • RBC casts: Pathognomonic of GN.
  • Leukocyturia, granular casts, or acanthocytes may also be present.
• Specific gravity >1.020 indicates concentrated urine, often due to volume contraction.
  
  

• Preferred for quantifying proteinuria; nephrotic range defined as ≥3.5 g/24 hours.
  
  
  

• Alternative to 24-hour collection.
• Protein:Creatinine Ratio (PCR) ≥300 mg/mmol denotes nephrotic-range proteinuria.
  
  
  

Blood Investigations

• Complete Blood Count (CBC):
  • Anaemia may reflect chronic inflammation, blood loss, or dilution.
  • Leukocytosis suggests infection.
• Renal Function:
  • Elevated blood urea nitrogen (BUN) and serum creatinine indicate reduced GFR.
  • Estimated GFR (CKD-EPI equation) assesses stage and severity.
• Serum Electrolytes:
  • Hyperkalaemia is common in advanced renal impairment.
• Lipid Profile:
  • Hyperlipidaemia is associated with nephrotic syndrome.
    
    
    

• ESR and C-reactive protein (CRP): Raised in systemic inflammation or vasculitis.
  
  
  
  

Immunological and Serological Testing

• Low complement: Seen in lupus nephritis, post-streptococcal GN, cryoglobulinaemia, and membranoproliferative GN.
• Normal complement: Suggestive of polyarteritis nodosa, Goodpasture syndrome, and IgA nephropathy.
  
  

• ANA and anti-dsDNA: Support diagnosis of SLE.
• ANCA (c-ANCA, p-ANCA): Suggest ANCA-associated vasculitis.
• Anti-GBM antibodies: Diagnostic for Goodpasture syndrome.
• Rheumatoid Factor: May indicate cryoglobulinaemia or systemic rheumatic disease.
  
  

• Antistreptolysin O (ASO), anti-DNAase B, and antihyaluronidase titres support recent streptococcal infection.
  • ASO titres peak at 3–5 weeks and normalise within 6 months.
    
    

• Essential in evaluating potential viral-associated GN.
  
  

• Detect monoclonal or polyclonal gammopathies (e.g., MIDD, myeloma).
• Free light chain ratio: Altered in AL amyloidosis and plasma cell dyscrasias.
  
  

• Antiphospholipase A2 receptor antibodies: Positive in primary membranous nephropathy.
• Drug screen: Consider if GN is suspected secondary to nephrotoxic medications or illicit substance use.
  
  

Imaging

• Assesses kidney size, echogenicity, and obstruction.
  • Small kidneys may suggest chronicity or advanced fibrosis.
    
    

• Indicated when haemoptysis, pulmonary symptoms, or suspected pulmonary-renal syndrome present.
  • Assesses for infiltrates (e.g., Goodpasture syndrome, granulomatosis with polyangiitis).
    
    

• Performed if malignancy or abscess suspected.
• Non-contrast head CT advised in hypertensive encephalopathy or altered mental status.
  
  

• Assesses cardiac murmur, endocarditis, or pericardial effusion in suspected infective aetiologies.
  
  
  
  

Renal Biopsy

• Persistent proteinuria, haematuria, nephrotic-range proteinuria, rapidly progressive renal failure, or atypical presentation.
• Biopsy not typically required for classic post-streptococcal GN in children unless atypical.
  
  

• Light Microscopy:
  • Evaluates cellular proliferation (endocapillary or extracapillary), sclerosis, and crescents.
• Immunofluorescence:
  • Paterns of IgA, IgG, IgM, and complement deposition (e.g., “starry sky” IgG in PSGN).
• Electron Microscopy:
  • Identifies subepithelial humps, dense deposits, or podocyte effacement.
    
    
    

• Immune complex–mediated GN: e.g., PSGN, IgA nephropathy, lupus nephritis.
• ANCA-associated GN
• Anti-GBM GN
• Monoclonal immunoglobulin-related GN
• C3 glomerulopathy
  
  
  
  

Nephritic Syndrome Presentation

• In children, post-infectious glomerulonephritis is the most likely cause.
• In adults, IgA nephropathy should be prioritised when haematuria and mild proteinuria are present.
• Henoch-Schönlein purpura (IgA vasculitis) should be considered in paediatric patients with purpura and abdominal symptoms.
• In adults with systemic vasculitis, granulomatosis with polyangiitis is a key differential.
• Young women aged 20–30 are more likely to present with lupus nephritis.
  
  

Nephrotic Syndrome Presentation

• Minimal change disease is the leading cause in children presenting with nephrotic syndrome.
• In adults, membranous nephropathy becomes the most likely primary cause.
• Secondary causes such as diabetic nephropathy must be ruled out, particularly in patients with known metabolic disease or vascular complications.
  
  

Primary Glomerular Disease Subtypes

• Post-streptococcal glomerulonephritis
• IgA nephropathy
• Membranoproliferative glomerulonephritis
• Lupus nephritis
• Focal segmental glomerulosclerosis
• Crescentic or rapidly progressive GN
• Goodpasture syndrome
• Non-streptococcal infection-related GN
  
  

Non-Glomerular Mimics of GN

• Nephrolithiasis typically presents with colicky flank or groin pain; urinalysis shows haematuria without dysmorphic RBCs or casts, and diagnosis is confirmed with imaging.
• Bladder cancer presents with painless haematuria, often in older smokers; confirmed by cystoscopy and biopsy.
• Renal cell carcinoma may show haematuria, flank pain, and fever; CT imaging usually reveals a renal mass.
• Pre-renal acute kidney injury presents with symptoms of hypoperfusion such as dehydration or hypotension; urine sediment is bland and FENa is typically <1%.
• Post-renal obstruction causes decreased urine output; renal ultrasound or CT detects obstruction and hydronephrosis.
  
  

Chronic and Inherited Mimics

• Idiopathic haematuria presents with isolated red cells in urine without proteinuria or systemic features, especially in young patients.
• Chronic GN with acute exacerbation may mimic acute GN but is typically associated with a longer disease course.
• Familial nephritis (e.g., Alport syndrome) should be suspected in young males with haematuria and hearing loss.
• Anaphylactoid purpura (Henoch-Schönlein purpura) is characterised by purpura, abdominal pain, and nephritis in children.
  
  
  

Key Diagnostic Considerations

• Dysmorphic red blood cells and RBC casts in the urine support a glomerular origin.
• Absence of casts and dysmorphic cells points towards urological causes of haematuria.
• Systemic examination and targeted investigations help distinguish primary glomerular pathology from mimicking conditions.
• Renal biopsy remains essential when the diagnosis is uncertain or atypical features are present.
  
  

General Principles

• Treatment is tailored to the underlying cause (e.g., infection, autoimmune disease, or drug-induced).
• Supportive care remains foundational and includes management of hypertension, proteinuria, oedema, hyperlipidaemia, and risk of thrombosis.
• Renal function and proteinuria should be monitored closely to assess disease progression and response to therapy.
• Avoidance of nephrotoxic drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs), is essential.
• Lifestyle modifications, including smoking cessation, a low-salt diet, and increased physical activity, support overall renal and cardiovascular health.
  
  
  

Mild Glomerulonephritis

• Patients typically present with isolated haematuria and minimal or no proteinuria, with preserved estimated glomerular filtration rate (eGFR).
• Treatment focuses on supportive measures and addressing reversible causes (e.g., treating infection, stopping offending drugs).
• Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be used to reduce proteinuria and control blood pressure.
• Combination therapy of ACEIs and ARBs should be avoided due to the risk of acute kidney injury and hyperkalaemia.
• Regular monitoring of renal function, blood pressure, lipid profile, and urinary protein excretion is necessary.

Moderate-to-Severe Glomerulonephritis

• Patients are often symptomatic with haematuria, significant proteinuria, and/or reduced renal function.
• Management includes the same supportive principles as in mild disease but with added intensity.
• In patients presenting with nephrotic syndrome, treatment includes:
  • Loop diuretics for fluid overload.
  • Statins for hyperlipidaemia.
  • Anticoagulation if thrombotic risk is elevated.
• Immunosuppressive therapy may be required, including corticosteroids, cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitors.
  
  
  

Rapidly Progressive Glomerulonephritis (RPGN)

• RPGN is a medical emergency marked by a rapid decline in renal function.
• Requires prompt immunosuppressive therapy, often with:
  • High-dose corticosteroids.
  • Cyclophosphamide.
  • Plasmapheresis for anti-GBM disease or ANCA-associated vasculitis.
• Treatment choice is guided by renal biopsy findings and serological markers.
  
  

Disease-Specific Management

• Start with ACEIs or ARBs for 3–6 months.
• If proteinuria persists >1g/day (with eGFR >50 mL/min), corticosteroids or fish oil may be added.
  
  

• Supportive care with blood pressure control and volume management.
• Antibiotics to eliminate nephritogenic streptococcal strains.
  
  

• Treated with plasma exchange, corticosteroids, cyclophosphamide, and rituximab.
  
  

• Managed with a combination of immunosuppressants including corticosteroids, mycophenolate mofetil, cyclophosphamide, and monoclonal antibodies.
  
  

• Corticosteroids with either cyclophosphamide or rituximab.
• Plasmapheresis may be considered in severe pulmonary or renal involvement.
  
  
  

Nephrotic Syndrome Management

• First-line therapy is prednisolone (1 mg/kg/day) for 4–16 weeks.
• For relapsing or steroid-dependent cases, options include cyclophosphamide or calcineurin inhibitors.
  
  

• Initial management with ACEIs/ARBs and blood pressure control.
• Additional treatments may include corticosteroids, calcineurin inhibitors, rituximab, or plasma exchange.
  
  

• Treated with ACEIs/ARBs and supportive care.
• Immunosuppression is considered when no secondary cause is identified.
• Experimental approaches targeting the complement system (e.g., C3 blockade) are under investigation.
  
  

• Continued monitoring of renal function, serum albumin, and urinary protein is essential.
• Hypertension should be managed aggressively, typically with ACEIs or ARBs.
• Diuretics and vasodilators may be used in cases of refractory hypertension or volume overload.
• Long-term complications, including anaemia, mineral bone disease, metabolic acidosis, and cardiovascular disease, require appropriate treatment.
• Dietary counselling and preparation for renal replacement therapy (RRT) should be initiated early in progressive cases.
  
  

Nephritic Spectrum Diseases

• In children, the prognosis is excellent, with most achieving full recovery within 6–8 weeks.
• In adults, around half may develop persistent proteinuria, hypertension, or reduced renal function.
  
  

• Frequently follows a benign course, especially in cases with minimal proteinuria and normal renal function.
• Progressive disease is associated with nephrotic-range proteinuria, hypertension, elevated serum creatinine, and interstitial fibrosis.
• The Oxford classification helps predict renal outcomes.
  
  

• Prognosis is favourable in patients without renal involvement, with complete resolution within approximately four weeks.
• Long-term outcome hinges on the extent of renal disease; about 1% progress to ESRD and require renal transplantation.
  
  

• With timely immunosuppressive treatment, remission is achieved in approximately 75% of cases.
• Untreated disease carries a poor prognosis, with rapid progression to renal failure.
  
  
  

• This condition frequently progresses to ESRD despite treatment.
• Post-transplant recurrence is also common, complicating long-term outcomes.
  
  
  

Nephrotic Spectrum Diseases

• Prognosis is excellent across all age groups if there is a robust response to corticosteroids.
• Most morbidity stems from complications related to prolonged immunosuppressive therapy.
  
  

• Around one-third of patients with subnephrotic proteinuria achieve remission with conservative therapy.
• Even among those with heavy proteinuria, spontaneous remission may occur, although it often takes several months.
• Persistent nephrotic syndrome may require prolonged immunosuppression, with remission possible in up to 6 months.
  
  

• Antiretroviral therapy slows progression, but untreated cases frequently develop ESRD.
• Renal transplantation may be necessary in advanced stages.
  
  

• In AL (light-chain) amyloidosis, progression to ESRD typically occurs within 2–3 years.
• AA (serum amyloid A) amyloidosis may enter remission if the underlying inflammatory or infectious disease is effectively managed.
  
  

Key Prognostic Indicators Across GN Types

• Asymptomatic microscopic haematuria.
• Low-level proteinuria.
• Preserved estimated glomerular filtration rate (eGFR).
• Minimal histological damage on renal biopsy.
  
  

• Reduced eGFR at presentation.
• Severe or persistent proteinuria.
• Non-response to immunosuppressive therapy.
• Histological evidence of interstitial fibrosis or extensive glomerulosclerosis.
  
  

Acute Kidney Injury (AKI)

• AKI is a common early complication of rapidly progressive glomerulonephritis, particularly with crescent formation on biopsy.
• Conditions such as vasculitis and anti-glomerular basement membrane (anti-GBM) disease frequently present with AKI.
• Prompt diagnosis and immunosuppressive treatment are essential to prevent irreversible damage.
  
  

Chronic Kidney Disease and End-Stage Renal Disease

• Many forms of GN, especially if untreated or resistant to therapy, gradually progress to chronic glomerulonephritis and ultimately ESRD.
• Risk factors for progression include reduced eGFR at presentation, persistent proteinuria, failure to achieve remission, and histological evidence of interstitial fibrosis or glomerulosclerosis.

Hypertension

• Most patients with GN develop hypertension due to salt and water retention from impaired glomerular filtration.
• If uncontrolled, it increases the risk of cardiovascular events and accelerates renal deterioration.
• Management includes dietary sodium restriction, lifestyle modification, and antihypertensives such as ACE inhibitors or ARBs, often requiring combination therapy.

Volume Overload and Pulmonary Oedema

• Hypervolaemia arises from impaired sodium and water excretion.
• Pulmonary oedema may develop in severe cases, particularly in rapidly progressive or nephrotic presentations.
• Diuretics are the cornerstone of treatment.
  
  

Nephrotic Syndrome and Associated Complications

• Hypoalbuminaemia leads to anasarca and increases susceptibility to infections.
• Hyperlipidaemia, including hypercholesterolaemia and hypertriglyceridaemia, is due to increased hepatic lipid synthesis and urinary loss of regulatory proteins.
  • Though not directly renoprotective, lipid-lowering treatment reduces cardiovascular risk.
• Hypercoagulability is common due to urinary losses of antithrombin III and altered coagulation factors.
  • Thromboembolism risk is particularly high in membranous nephropathy and lupus nephritis.
  • Selected patients may benefit from anticoagulation prophylaxis.
• Increased infection risk arises from immunoglobulin loss in urine and the use of immunosuppressants.
  • Vaccinations should be up to date.
  • Pneumocystis prophylaxis is recommended in patients on agents like cyclophosphamide.
    
    

Hypertensive Retinopathy and Encephalopathy

• Sustained severe hypertension may result in end-organ complications such as visual impairment and altered mental status.
• These are more common in patients with poorly controlled blood pressure or malignant hypertension.
  
  

Cardiovascular Disease

• Long-term risk of cardiovascular morbidity is increased due to chronic hypertension, dyslipidaemia, hypervolaemia, and systemic inflammation.
• The underlying glomerular disease may also involve vascular endothelium, contributing to atherogenesis and cardiac involvement.
  
  
  

Rapidly Progressive Glomerulonephritis (RPGN)

• RPGN is both a clinical syndrome and a complication, characterised by rapid renal function decline and crescents on biopsy.
• It demands immediate immunosuppressive therapy and often plasmapheresis depending on the cause (e.g., ANCA vasculitis, anti-GBM disease).
  
  

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