diagnosis and investigations og glomerulonephritis

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Glomerulonephritis — Diagnosis & Investigations

Definition & Clinical Presentation

Glomerulonephritis (GN) refers to a group of immune-mediated inflammatory conditions of the glomerulus. The classic clinical presentation is nephritic syndrome, defined as:
  • Glomerular hematuria — dysmorphic RBCs and/or RBC casts in urine
  • Hypertension
  • Edema
  • Reduced GFR (with or without oliguria)
  • Non-nephrotic-range proteinuria
When GFR declines rapidly over days to weeks in this setting, it is termed Rapidly Progressive Glomerulonephritis (RPGN).
National Kidney Foundation Primer on Kidney Diseases, 8e

Classification (Etiology-Based)

CategoryExamples
Immune complex-mediatedPost-infectious GN, lupus nephritis, IgA nephropathy, cryoglobulinemia, MPGN
Pauci-immune / ANCA-associatedMicroscopic polyangiitis (MPO-ANCA), Granulomatosis with Polyangiitis (PR3-ANCA)
Anti-GBM antibody-mediatedGoodpasture disease/syndrome
Complement-mediatedC3 glomerulopathy
Monoclonal gammopathy-associatedMIDD, cryoglobulinemic GN
National Kidney Foundation Primer on Kidney Diseases, 8e; Smith & Tanagho's General Urology, 19e

Diagnosis

History & Physical Exam

  • Recent throat/skin infection (1–4 weeks prior) → post-streptococcal GN
  • Concurrent infection (active) → infection-associated GN
  • Systemic symptoms (joints, skin, lungs) → vasculitis, lupus
  • Family history → hereditary nephritis (Alport syndrome)
  • Drugs (gold, penicillamine, NSAIDs) → secondary membranous nephropathy

Investigations

1. Urinalysis & Urine Microscopy

  • Dysmorphic RBCs (acanthocytes) and RBC casts — pathognomonic for glomerular origin of hematuria
  • Proteinuria — usually sub-nephrotic in nephritis; nephrotic range warrants evaluation for podocytopathy
  • Urine culture — to exclude infection
"In glomerulonephritis, the urinalysis demonstrates macroscopic or microscopic hematuria, RBC casts, and proteinuria. Microscopic examination of urinary sediment shows dysmorphic RBCs and RBC casts." — Tintinalli's Emergency Medicine

2. Blood Tests

Basic Panel

TestRelevance
Serum creatinine / eGFRAssess degree of renal impairment
BUNElevated in renal failure
ElectrolytesMetabolic acidosis, hyperkalemia
CBCAnemia of chronic disease
ESR / CRPElevated in vasculitis, infection

Serological Panel (Key to Subtype Diagnosis)

TestPositive In
ASO titre, anti-DNAse BPost-streptococcal GN
ANA, anti-dsDNA, extractable nuclear antigens (Ro, Sm, RNP)Lupus nephritis
Serum complement (C3, C4)Low in immune complex-mediated GN (see below)
ANCA (MPO/P-ANCA; PR3/C-ANCA)ANCA-associated pauci-immune GN
Anti-GBM antibodiesGoodpasture disease/RPGN type I
Anti-PLA2R, anti-THSD7AIdiopathic membranous nephropathy
Rheumatoid factor, cryoglobulinsCryoglobulinemic GN (especially with HCV)
Hepatitis B & C serologyHBV → membranous nephropathy/MPGN; HCV → cryoglobulinemic GN
HIV serologyHIVAN (collapsing FSGS)
Serum protein electrophoresis (SPEP), urine immunofixation (UIEP)Monoclonal gammopathy-related GN
SFLC (serum free light chain)Monoclonal gammopathy
National Kidney Foundation Primer on Kidney Diseases, 8e

3. Complement — A Key Diagnostic Discriminator

Complement LevelConditions
Low C3 & C4Lupus nephritis, cryoglobulinemic GN
Low C3, normal C4Post-infectious GN, MPGN type I/II, C3 glomerulopathy, cholesterol emboli, aHUS
Normal complementANCA-associated GN, anti-GBM GN, IgA nephropathy, HSP
"When hematuria accompanies AKI, acute glomerulonephritis should be suspected and can diagnostically be divided into low-complement GN (immune complex-mediated lesions such as lupus nephritis, postinfectious GN, and cryoglobulinemic GN) and normocomplementemic GN (classically seen in RPGN due to ANCA and anti-GBM antibody)." — Goldman-Cecil Medicine

4. Urine Quantification

  • 24-hour urine protein — nephrotic range (>3.5 g/day) vs. nephritic range (<3.5 g/day)
  • Urine protein:creatinine ratio (PCR) — practical alternative to 24-hour collection
  • Split urine collection — to exclude orthostatic proteinuria (supine vs. upright)

5. Imaging

  • Renal ultrasound — assess kidney size, echogenicity, hydronephrosis, structural abnormalities; guides biopsy safety
  • Chest CT — in suspected pulmonary-renal syndrome (ANCA vasculitis, anti-GBM disease); shows lung nodules, infiltrates, cavities, or alveolar hemorrhage

6. Renal Biopsy — Definitive Investigation

Indications:
  • Proteinuria with declining GFR
  • Nephrotic-range proteinuria (>3.5 g/day)
  • Proteinuria + features of glomerular source (albuminuria, acanthocytes, RBC casts)
  • Persistent proteinuria with SLE or other rheumatologic condition
  • Unexplained hematuria with proteinuria
Three modalities are required:
ModalityWhat It Shows
Light microscopyArchitecture — mesangial proliferation, endocapillary proliferation, crescents, sclerosis, necrosis
Immunofluorescence (IF)Pattern and class of immune deposits — granular (immune complex), linear (anti-GBM), pauci-immune (ANCA)
Electron microscopy (EM)Location of deposits — subepithelial "humps" (post-infectious), subendothelial, mesangial, intramembranous
"Specific diagnoses of renal disease require targeted immunofluorescent techniques for demonstrating a variety of antigens, antibodies, and complement fractions. Electron microscopy has complemented these immunologic methods." — Smith & Tanagho's General Urology, 19e

Immunofluorescence Patterns by GN Type

IF PatternGN Type
Linear IgG along GBMAnti-GBM disease / Goodpasture
Granular IgG + C3 (subepithelial/subendothelial)Post-infectious GN, lupus nephritis
Mesangial IgAIgA nephropathy, HSP
Granular IgG + C3 (subepithelial "spikes")Membranous nephropathy
Pauci-immune (few/no deposits)ANCA-associated GN
Mesangial IgA + C3 + IgM (schistosomal)Schistosomal GN

Diagnostic Algorithm Summary

Hematuria + AKI
     │
     ├─ Low complement ──► Immune complex GN
     │                      (Lupus, PSGN, Cryo)
     │
     └─ Normal complement ──► ANCA-associated GN (check MPO/PR3)
                               Anti-GBM disease (check anti-GBM Ab)
                               IgA nephropathy

Hematuria WITHOUT AKI ──► Chronic GN (IgA, thin GBM disease)

Proteinuria > 3.5 g/day ──► Nephrotic syndrome
                              (Biopsy if ANA, anti-PLA2R, viral serologies)
Goldman-Cecil Medicine; National Kidney Foundation Primer on Kidney Diseases, 8e

Specific Types at a Glance

TypeKey Diagnostic Feature
Post-streptococcal GN↑ASO titre, ↓C3, "subepithelial humps" on EM
IgA nephropathyMesangial IgA on IF; synpharyngitic hematuria
Lupus nephritisANA+, anti-dsDNA+, ↓C3/C4; WHO class I–VI
ANCA-associated GNC-ANCA (PR3) or P-ANCA (MPO); pauci-immune on IF; crescentic GN
Anti-GBM (Goodpasture)Anti-GBM Ab+; linear IgG on IF; pulmonary hemorrhage + RPGN
Membranous nephropathyAnti-PLA2R+; subepithelial "spike and dome" deposits
Cryoglobulinemic GNRF+, ↓C3/C4, HCV+; "intraluminal thrombi" on LM
MPGN↓C3; mesangial and endocapillary proliferation; "tram-tracking"

non pharmacological treatment fo this diases

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Non-Pharmacological Treatment of Glomerulonephritis

Non-pharmacological (supportive/conservative) management is the foundation of treatment for most forms of GN, especially post-infectious GN, and forms an essential adjunct in all other types. It targets the major consequences of GN: fluid overload, hypertension, uremia, and progression to CKD.

1. Dietary Modifications

Salt (Sodium) Restriction

The cornerstone of managing both edema and hypertension in GN. Primary sodium retention by the kidney characterizes many forms of GN via incompletely understood mechanisms, with decreased GFR and filtrate-activated ENaC sodium channels playing a role.
"Hypervolemia usually responds to salt restriction and loop diuretics. Volume control is often sufficient to manage the new-onset hypertension." — National Kidney Foundation Primer on Kidney Diseases, 8e
  • Target: <2 g/day sodium (low-salt diet)
  • Reduces edema, controls BP, and lessens the need for diuretics

Protein Restriction

Indicated when BUN or creatinine is elevated (i.e., significant renal impairment is present).
"Symptomatic treatment should include bed rest and protein restriction (if the blood urea nitrogen or creatinine level is elevated)." — Swanson's Family Medicine Review
  • Reduces the production of nitrogenous waste
  • Helps manage uremia and reduces glomerular hyperfiltration
  • Typical target: 0.6–0.8 g/kg/day in significant renal impairment

Fluid Restriction

  • Indicated when significant edema or oliguria is present
  • Works synergistically with salt restriction and diuretics
  • Prevents volume overload and worsening hypertension

Potassium & Phosphate Restriction

  • Required in advanced renal failure (GFR significantly reduced)
  • Prevents hyperkalemia and hyperphosphatemia
  • Limit high-potassium foods (bananas, oranges, potatoes) and phosphate-rich foods (dairy, processed foods)

2. Rest

  • Bed rest is recommended during the acute phase of GN, particularly in PSGN
  • Helps control hypertension and reduces metabolic demand on kidneys
  • Activity can be gradually resumed as edema, hematuria, and hypertension resolve

3. Fluid & Edema Management (Non-Drug)

  • Fluid restriction combined with sodium restriction
  • Elevation of oedematous limbs where applicable
  • Monitoring daily weight and urine output to track fluid balance
  • Loop diuretics are the pharmacological adjunct to these measures — but the dietary sodium restriction is the non-pharmacological foundation

4. Blood Pressure Control (Non-Pharmacological Components)

Hypertension in GN is largely volume-dependent (due to sodium retention), so:
  • Salt restriction alone can normalize BP in many patients with PSGN
  • Weight management and reduced alcohol intake are standard lifestyle modifications
  • In most acute GN cases, BP resolves within 1–2 weeks as volume overload is corrected

5. Treatment/Control of the Underlying Infection (Infection-Associated GN)

  • In post-streptococcal GN: penicillin treats the streptococcal infection but does not alter the course of GN itself
  • Antibiotic prophylaxis of household/community contacts in epidemic PSGN can reduce disease incidence
  • For GN associated with active infection (e.g., endocarditis, abscesses): treating the source infection is the primary non-immunosuppressive strategy
"Although penicillin will eradicate the carrier state of group A β-hemolytic streptococci, it will not influence the course of the glomerulonephritis." — Swanson's Family Medicine Review

6. Renal Replacement Therapy (Dialysis)

When supportive measures fail and acute kidney injury is severe:
  • Haemodialysis or peritoneal dialysis may be required for:
    • Persistent volume overload unresponsive to diuretics
    • Severe uraemia (encephalopathy, pericarditis)
    • Severe hyperkalemia or metabolic acidosis refractory to medical management
  • Need for dialysis is more frequent in adults than children
"Dialysis may be necessary, and the need for dialysis is more frequent in adults." — National Kidney Foundation Primer on Kidney Diseases, 8e

7. Plasmapheresis (Plasma Exchange)

While not purely "non-pharmacological," it is a non-drug physical intervention:
  • Used as an adjunct in anti-GBM disease (Goodpasture syndrome) and select cases of ANCA-associated RPGN
  • Also reported as adjunct therapy in infective endocarditis-related GN when kidney function fails to improve despite antibiotics
  • Removes circulating antibodies (anti-GBM, ANCA, cryoglobulins) and immune complexes

8. Lifestyle Modifications (Long-Term / CKD Prevention)

For all GN patients, especially those at risk of progression:
MeasureRationale
Smoking cessationSmoking accelerates CKD progression and worsens cardiovascular risk
Weight reductionReduces proteinuria and glomerular hyperfiltration
Moderate physical activityImproves BP control and cardiovascular health once acute phase resolves
Avoidance of nephrotoxinsNSAIDs, contrast agents, and aminoglycosides worsen renal function
Avoidance of high-protein supplementsIncreases glomerular filtration load

Summary by Phase

PhaseKey Non-Pharmacological Measures
Acute phaseBed rest, fluid restriction, salt restriction, protein restriction (if uraemic)
Oedema managementLow-sodium diet, fluid restriction, limb elevation
HypertensionSalt restriction (often sufficient in volume-dependent hypertension)
Severe AKIDialysis
Long-termSmoking cessation, weight control, nephrotoxin avoidance
Infection-associated GNTreat underlying infection; antibiotic prophylaxis for contacts
National Kidney Foundation Primer on Kidney Diseases 8e; Goldman-Cecil Medicine; Swanson's Family Medicine Review; Brenner & Rector's The Kidney
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