Acute Glomerulonephritis

Definitions
Acute glomerulonephritis (GN) is an inflammatory process involving the glomerulus of the kidney, resulting in a clinical syndrome consisting of hematuria, proteinuria, hypertension, and renal insufficiency.

Photomicrograph of a kidney biopsy from a patient with crescentic glomerulonephritisshowing prominent fibrocellular crescent formation and moderate mesangialproliferation in a glomerulus. Hematoxylin and eosin stain

Aetiology

Post-Streptococcal infection	Most commonly follows group A beta-hemolytic Streptococcus infection, but can occur as a result of other infections. Onset occurs 1–3 weeks after an infectious process (throat or skin). Accounts for 80% of acute GN in children Incidence: 5-10% in persons with pharyngitis and 25% in those with skin infections.
Nonstreptococcal postinfectious glomerulonephritis	Bacterial - Infective endocarditis, shunt nephritis, sepsis, pneumococcal pneumonia, typhoid, secondary syphilis, meningococcemia, and infection with methicillin-resistant Staphylococcus aureus (MRSA) Viral - Hepatitis B, infectious mononucleosis, mumps, measles, varicella, vaccinia, echovirus, parvovirus, and coxsackievirus Parasitic - Malaria, toxoplasmosis
IgA nephropathy	Relates to an abnormal glycosylation of IgA Most common form of primary acute GN Occurs mainly in the 2nd and 3rd decades Male:Female 3:1 Incidence differs geographically: Asia > US
Anti-GBM disease	Caused by autoantibodies that target type IV collagen of basement membranes Also known as Goodpasture disease A noted cause of the pulmonary–renal syndrome Occurs most commonly in the 2nd or 3rd decade Male:Female 6:1
ANCA-associated GN	Autoantibodies against neutrophil granules are involved in the pathogenesis Uncommon: Often has a relapsing and remitting course Three disease presentations:- Wegener granulomatosis, Churg-Strauss disease, Microscopic polyangiitis Older patients are more commonly affected, though this GN can affect any age group.
Membranoproliferative GN	An immune etiology is presumed, which triggers subendothelial deposits and inflammation. May be primary or secondary May present in the setting of a systemic viral or rheumatic illness
Lupus nephritis	An immune complex-mediated glomerular disease 30–70% of systemic lupus patients will have renal involvement
Cryoglobulin-associated vasculitis	An immune etiology is presumed, but not clearly defined. 80% of cases are associated with hepatitis C infection.
Miscellaneous	Guillain-Barré syndrome, radiation of Wilms tumor, diphtheria-pertussis-tetanus vaccine, serum sickness

Pathophysiology
2 components: structural changes and functional changes.

Structural changes (could be focal, diffuse or segmental, and global)	Cellular proliferation Leukocyte proliferation Glomerular basement membrane thickening Hyalinization or sclerosis Electron-dense deposits
Functional changes	proteinuria, hematuria, reduction in GFR (ie, oligoanuria), and active urine sediment with RBCs and RBC casts. he decreased GFR and avid distal nephron salt and water retention result in expansion of intravascular volume, edema, and, frequently, systemic hypertension.

Pathology of post-streptococcal AGN (Common in Malaysia)
-Poststreptococcal glomerulonephritis follows infection(ie. throat, skin infection) with only certain strains of streptococci (Group A Streps)
- immune complex containing a streptococcal antigen is deposited in the affected glomeruli.
- The GBM pore sizes in children and adults are 2-3 nm and 4-4.5 nm, respectively.
- the immune complex molecule can be more easily rodded into the glomerulus in children
- A latent period (1-2 weeks after a throat infection and 3-6 weeks after a skin infection) always occurs between the streptococcal infection and the onset of signs and symptoms of acute glomerulonephritis.

Epidemiology
GN comprises 25-30% of all cases of end-stage renal disease (ESRD
M:F= 2:1
Postinfectious GN can occur at any age but usually develops in children. Outbreaks of PSGN are common in children aged 6-10 years

Presentation

Symptoms

Cola- or tea-colored urine and decreased urine volume. Edema occurs in many patients, typically face and lower extremities Shortness of breath may occur with significant fluid overload. Generalized malaise Patients may also present with complaints more specific to the associated disease: -Joint pain or rash in lupus nephritis -Hemoptysis in anti-GBM disease -Sinusitis and pulmonary infiltrates in ANCA-associated GN -Abdominal pain and purpura in IgA-Henoch Schönlein purpura -Purpura and skin vasculitis in cryoglobulinemia-associated GN

Signs

Signs of fluid overload  -Periorbital and/or pedal edema -Edema and hypertension due to fluid overload (in 75% of patients) -Crackles (ie, if pulmonary edema) -Elevated jugular venous pressure -Ascites and pleural effusion (possible) Acute nephritic syndrome presenting as edema, hematuria, and hypertension with or without oliguria is the most frequent presentation of APSGN Rash (ie, vasculitis, Henoch-Schönlein purpura) Pallor Renal angle (ie, costovertebral) fullness or tenderness, joint swelling, or tenderness

Investigation

Urinalysis and sediment examination	Dysmorphic red blood cells (RBCs) or RBC casts on urine microscopy indicate glomerular hematuria and suggest the diagnosis of an acute glomerulonephritis. Urine electrolytes, urine sodium, and fractional excretion of sodium (FENa) assays are needed to assess salt avidity.
	Blood, urea, and nitrogen (BUN); serum creatinine; and serum electrolytes (especially serum potassium level)
Complement levels (C3 and C4):	C3 complement levels are abnormal in postinfectious GN; C3 and C4 are abnormal in lupus nephritis and MPGN; C4 can be low in cryoglobulinemia.
Antistreptolysin O or Streptozyme titer	increasing titer levels confirm recent infectio
24-hour urine collection	to test for Proteinuria
Antinuclear antibody (and ANCA)	indications: Hematuria, proteinuria, unexplained renal failure
Miscellaneous	Anti-GBM antibody Hepatitis B antigen Hepatitis C antibody
Imaging	Abdominal ultrasound  -Assesses renal size -Assesses echogenicity of renal cortex -Excludes obstruction
Renal biopsy	If post-AGN, not needed, if unknown causes- biopsy

Management

Hypertension	Diuretics are useful, given that salt retention and edema are often present. Calcium channel blockers: Nifedipine (Adalat, Adalat CC, Procardia, Procardia XL), Hydralazine (Apresoline) Avoid ACEi if significant renal dysfunction is present.
Peripheral edema	Loop diuretics: Furosemide (lasix)
Antimicrobial therapy	eg, penicillin does not appear to prevent the development of GN, except if given within the first 36 hours.
Hyperkalemia:	Sodium polystyrene sulfonate (Kayexalate) resin: 15 g p.o. every day to q.i.d. in 10% sorbitol
Acidosis	Sodium bicarbonate 1–2 mEq/kg per dose (1–2 mmol/kg per dose) IV or p.o.
Diet	Sodium and fluid restriction Avoid high-potassium foods if significant renal dysfunction is present. Protein restriction for patients with azotemia
Second line treatment	Pulse methylprednisolone in rapidly progressing glomerulonephritis Alkylating agent - cyclophosphamide ANCA-associated renal disease, anti-GBM disease, and proliferative forms of lupus are treated with steroids plus either cyclophosphamide or mycophenolate Plasmapheresis in cases of pulmonary hemorrhage
Dialysis	Indication: uremia, hyperkalemia refractory to medical management, intractable acidosis, and diuretic-resistant pulmonary edema.
Admission Criteria	no urine output, significant hypertension, and suspicion of pulmonary hemorrhage or fluid overload that is compromising heart or respiratory function.
Follow-up	Monitor renal function, BP, edema, serum albumin, and urine protein excretion rate.

Complications
Hypertensive retinopathy and encephalopathy
Rapidly progressive glomerulonephritis
Microscopic hematuria may persist for years.
Chronic kidney disease
Nephrotic syndrome (~10%)



Prognosis
Prognosis of acute PSGN is generally excellent in children.
spontaneous resolution of fluid retention and hypertension after 1 week
C3 normalize within 8 weeks
Proteinuria may persist for 6 months and microscopic hematuria for up to 1 year
In adults with PSGN, full recovery of renal function in just over half of patients
Prognosis is poor in patients with underlying diabetic glomerulosclerosis.
Few patients with acute nephritis develop rapidly progressive renal failure.
Nephritis associated with MRSA and chronic infections usually resolves after treatment of the infection.