Post Infection Glomerulonephritis

Post-Infectious Glomerulonephritis

Presenter

Dr. Mansour Alqurashi

Learning Objectives

  • Background
  • Pathophysiology
  • Histologic Findings
  • Clinical
    • History
    • Physical
    • Lab
  • Differential Diagnosis
  • Treatment
  • Follow Up

Background

  • Glomerulonephritis: Inflammation of the glomerulus, manifested by proliferation of cellular elements, secondary to an immunologic mechanism.
    • Most cases are associated with a post-infectious state.
    • Common in children aged 4-12 years, with a peak at 5-6 years.
    • Male to female ratio: 1.7-2:1.
    • Prognosis is generally good.


Filtration Barrier at the Glomerulus

  • Three Layers:
    • Capillary endothelium of glomerulus
    • Basement membrane of glomerulus
    • Visceral epithelium of Bowman’s capsule (podocytes with foot processes)


Pathogenesis

  • Strep Antigens: Trigger antibodies that cross-react with glomeruli.
  • Immune Complexes: Filtered by glomerulus and get stuck, activating complement.
  • Damage: Diffuse and generalized damage to glomeruli.
  • GFR and RBF: Decreased GFR due to inflammation; RBF decreases proportionally, maintaining normal filtration fraction.
  • Tubular Function: Preserved.
  • Plasma Renin and Aldosterone: Normal.


Incidence and Spectrum

epidemic form Decline in industrialized countries.

  • Post-Streptococcal Glomerulonephritis: 28-47%
  • Staph Aureus (Epidermidis): 12-24%
  • Gram-Negative Bacteria: 10-22%
  • Other Conditions: Bacterial endocarditis, shunt infections, atypical PIGN.

uacute endocapillary glomerulonephritis with mesangial and capillary granular immune deposition

General Symptoms

  • Fever, Headache, Malaise
  • Anorexia, Nausea, Vomiting
  • Pallor: Due to edema and/or anemia.
  • Confusion, Lethargy
  • Enlargement of the Liver

Signs and Symptoms

  • Gross Hematuria: 25-33%, dark brown or smoky urine.
  • Oliguria: Urine output < 400 ml/day.
  • Edema: 85%, starts in eyelids and face, then limbs, becomes generalized.; - Hypertensive encephalopathy, heart failure and acute pulmonary edema may occur in severe cases
  • Hypertension: 60-80%, mild to moderate.
  • CNS Symptoms: Seizures in 10%.
  • Nephrotic Syndrome: Rare.
  • ARF/Acute Renal Necrosis: Not uncommon, due to capillary injury or thrombosis.

Clinical Features - Examination

  • State of Patient:
    • Routine observations (temperature, HR, SBP, RR, SaO2).
    • Core-peripheral temperature
    • Serial plot of weights, heights
  • Hydration: Peripheral perfusion, JVP, edema.
  • Signs of Cardiac Failure
  • Multi-System Disease Clues: Rash, arthropathy, arthritis, oral lesions.
  • Palpable Kidneys or Masses

Mixed Nephritic and Nephrotic Syndromes

  • Nephritic Syndrome: Hematuria, proteinuria, oliguria, hypertension. Common Cause: PIGN/PSGN (Post-Infectious Glomerulonephritis

  • Nephrotic Syndrome:

    • Proteinuria > 40mg/m2/hour | > 1g/m2/day
    • hypoalbuminemia,
    • edema,
    • hyperlipidemia. Common Cause: MCNS (Minimal Change Nephrotic Syndrome).
  • Mixed Syndrome: Commonly caused by post-infectious GN.


Investigations

  • Blood Tests: Full blood count, ESR, coagulation screen, serum electrolytes.
  • Complement Assays: C3, C4, C3 nephritic factor. (C3: Decreased for few weeks.)
  • Serum electrolytes
    • U&Es, Cl, CO2, urea, creatinine, glucose
    • LFTs, CK, urate, bone profile
    • Ca, Mg, PO4, ALP, albumin
  • Immunoglobulins: Including IgA, (ASOT, antiDNAase B. (Measured at 2-3 weak intervals))
  • Autoimmune Profile: ANA, dsDNA, qDNA, ENA, ANCA, ACIgM/G.
  • Culture: From pharynx and skin.

Urine Tests

  • Urinalysis
  • Urine M,C&S
  • Urine Electrolytes
  • Fractional Excretion of Sodium (FENa): For evaluation of acute kidney failure .

Note that microscopic haematuria can persist for years following the acute episode.

Imaging and Biopsy

Renal ultrasound scan

  • bilateral echogenic kidneys

Percutaneous renal biopsy

  • confirm PIGN
  • exclude MPGN
  • consider crescentic GN.

The indications for renal biopsy are:

  • severe renal dysfunction at presentation
  • rapidly progressive acute renal failure
  • atypical presentation
  • delayed recovery
    • macroscopic haematuria for >1 month
    • low C3 levels for >6 months
    • heavy proteinuria for > 6 months

Differential Diagnosis

Hypocomplementemia

  • PIGN
    • Bacteria (GAS, S. viridans, pneumococcus, S. aureus, S. epi, atypical mycobacterium, meningococcus, Brucella, Leptospirosis, Propionibacterium)
    • Viruses (VZV, EBV, CMV, rubeola)
    • Parasites (Toxo, Trich, Riskettsia)
  • Membranoproliferative GN
  • SLE
  • Cryoglobulinemia
  • Bacterial Endocarditis
  • Shunt nephritis

Normal complement

  • HUS
  • IgA Nephropathy
  • HSP
  • Alport’s / TBMD
  • Nephrotic Syndrome

Treatment

Treatment of Underlying Infections in Acute GN

Antimicrobial Therapy
  • Antibiotics (e.g., penicillin) are used to control local symptoms and to prevent the spread of infection to close contacts.
  • Antimicrobial therapy does not appear to prevent the development of GN, except if given within the first 36 hours.
Loop Diuretic Therapy
  • Loop diuretics may be required in patients who are edematous and hypertensive in order to remove excess fluid and to correct hypertension.
  • Relieves edema and controls volume, thereby helping to control volume-related elevation in BP.
  • Vasodilator drugs (e.g., nitroprusside, nifedipine, hydralazine, diazoxide) may be used if severe hypertension or encephalopathy is present.
Diet
  • Sodium and fluid restriction
  • Protein restriction for azotemic patients
Activity
  • Recommend bed rest until signs of glomerular inflammation and circulatory congestion subside.

Follow Up

  • Prognosis: Usually excellent.

  • Mortality: 0.5% due to pulmonary edema or pneumonia.

  • Progression to CKD Stage 5: <1%.

  • Monitoring: Ensure control of hypertension, resolution of edema, hematuria, proteinuria, and normalization of creatinine.

  • Gross hematuria resolves within 2 weeks

  • Complement low for 6-8 weeks

  • Proteinuria remains upto 6 months

  • Hematuria remains upto 2 years

Differential