ACUTE NEPHRITIS SYNDROME

BY: DR. NURUL NAZIFAH AZIZ

Comprises of: Hematuria

presence of at least 5 red blood cells (RBCs) per microliter of urine

Proteinuria non-nephrotic range proteinuria (<2 g in 24 hrs). Hypertension

Oedema(periorbital, leg or sacral)

Temporarily oliguria and uremia urine output that is less than 1 mL/kg/h in infants, less than 0.5 mL/kg/h in children, and less than 400 mL/d in adults

Disease associated with acute nephritis syndrome

Infective causes Post streptococcal glomerulonephritis Non streptococcal post infectious glomerulonephritis

Staphylococcus, pneumococcus, legionella, syphilis, mumps, varicella, hepatitis B and C, echovirus, Epstein barr virus, toxoplasmosis, malaria, schistosomiasis, trichinosis

 Non infective Multisystem

Vasculitis (eg wagener granulomatosis) Collagen vascular disease (eg SLE) Henoch schonlein purpura Polyarteritis nodosa Cryoglobulinemia Goodpasture syndrome

Primary renal disease

MPGN IgA nephropathy (berger disease) Idiopathic RPGN

epidemiology
Worldwide, Berger disease is the most common

cause of GN the incidence of PSGN has fallen in most Western countries. PSGN remains much more common in regions such as Africa, the Caribbean, India, Pakistan, Malaysia, Papua New Guinea, and South America the incidence of acute GN in children aged 3-16 years was 15.5 cases per year, with a male-to-female ratio of 1.1:1

Post streptococcal glomerulonephritis

etiology

Group A beta hemolytic streptococcus PSGN usually develops 1-3 weeks after acute infection with specific nephritogenic strains of group A beta-hemolytic streptococcus Only few strains of streptococci are nephritogenic, eg. Type 4 and 12 causing pharyngitis and type 49 causing pyoderma. The incidence of GN is approximately 5-10% in persons with pharyngitis and 25% in those with skin infections.

pathogenesis

glomerular-immune complex formation

immune complexes formed from antigen,

antibodies, and complement, get trapped in kidney filters (Glomeruli).

The filters become inflamed, which leads to

ineffective kidney function.

pathology
Histopathology- glomeruli appear enlarged and

shows diffuse mesangial cell proliferation with invasion of acute inflammatory cells Immunofluorescence- C3 and IgG deposition on glomerular BM and in the mesangium. Electron microscopy- electron dense deposits or hump like deposits of immunocomplexes seen on epithelial side of GBM Changes usually restricted to mesangium and endothilium with minimal epithilial proliferation

PSGN - hypercellular glomerulus with proliferating endothelial and mesangial cells, and neutrophil infiltration.

PSGN- granular bumpy pattern of immune deposits on immunofluorescence

Clinical presentation

This disorder may begin to develop one to two

weeks after an untreated throat infection

three to four weeks after an untreated skin

infection.

mostly common in children ages five to twelve.

Clinical presentation
3 phase sequence: infection - interval - nephritic syndrome The severity of renal involvement varies from asymptomatic

microscopic hematuria with normal renal function to acute renal failure

Abrupt onset of:

Hematuria(cola coloured) Oliguria( Reduced GFR) Oedema (Salt and water retention) periorbital puffiness and pedal edema Hypertension

Diagnosis
Urinalysis

Rbc Frequently in association with rbc casts Mild proteinuria Polymorp leukocytes

A mild normochromic anemia may be present

from hemodilution and low-grade hemolysis.

 The serum C3 level is usually reduced in the acute phase and

returns to normal 68 wk after onset

positive throat culture report may support the diagnosis

The antistreptolysin O titer is commonly elevated after a

pharyngeal infection
anti-deoxyribonuclease (DNase) B level after cutaneous

infection.

Indications for renal biopsy

Renal biopsy should be considered only in the

presence of acute renal failure, nephrotic syndrome, absence of evidence of streptococcal infection, or normal complement levels. In addition, renal biopsy is considered when hematuria and proteinuria, diminished renal function, and/or a low C3 level persist more than 2 mo after onset

treatment
Focused on treating acute effects of renal insufficiency and

hypertension
Restriction of salt and fluid Antibiotics (ex. Penicillin), for streptococcal bacteria- to limit

spread of organism
Blood pressure medications

calcium channel blocker-nifedipine

diuretic medications may be needed to control swelling and

high blood pressure.

prognosis
Usually mild disease recovery typically within weeks ( 95% ) 1 week: onset of diuresis

4 weeks: normalization of renal function

3-6 months: resolution of hematuria

Possible complications
Congestive heart failure pulmonary edema Hyperkalemia High blood pressure (hypertension) Acute renal failure Chronic glomerulonephritis

IgA nephropathy

IgA nephropathy
Pathogenesis Focal and segmental proliferative glomerulonephritis with mesangial deposit of polymeric IgA

Etiology Unknown May be a result of an exaggerated bone marrow and tonsillar IgA immune response to viral or other antigens

Clinical and lab manifestation

Tends to occur in children and young males > 80% children have experience of

gross hematuria (in U.S.)

Asymptomatic microscopic hematuria or recurrent macroscopic

hematuria following URTI or GI viral infection

Proteinuriaoften, but severity < nephrotic, often <1g/24h Hypertensionmild to moderate Normal serum C3 Serum IgA levels have no diagnostic value because they are

elevated in only 15 of patients.

 Although IgA nephropathy does not lead to significant

kidney damage in most children, progressive disease develops in 2030% of children at 1520 yr after disease onset.

Poor prognostic indicators include persistent hypertension,

diminished renal function, and heavy or prolonged proteinuria. A worse prognosis is suggested by histologic evidence of diffuse mesangial proliferation, extensive glomerular crescents, glomerulosclerosis, and tubulointerstitial changes, including inflammation and fibrosis.

treatment
Primary treatment is proper blood pressure control Fish oil, which contains anti-inflammatory omega-3

polyunsaturated fatty acids, decreases the rate of renal progression

Immunosuppressive therapy with corticosteroids Angiotensin-converting enzyme inhibitors and angiotensin II

receptor antagonists are effective in reducing proteinuria and retarding the rate of renal progression when used as single agents or in combination. the rate of renal disease progression

Tonsillectomy may reduce the frequency of gross hematuria and

Henoch schonlein purpura

Henoch schonlein purpura

a small vessel vasculitis characterized by a purpuric rash, arthritis,

abdominal pain, and glomerulonephritis HSP nephritis and IgA nephropathy demonstrate identical renal pathologic findings, but systemic findings are only seen in HSP nephritis

pathogenesis
The pathogenesis of HSP nephritis remains

unknown this disease appears to be mediated by the formation of immune complexes containing polymeric IgA1 within capillaries of the skin, intestines, and glomerulus.

Clinical and lab manifestation

The symptoms and signs of HSP nephritis typically

appear 13 wk after an upper respiratory tract infection gross hematuria is seen in 2030% of cases patients may also present with isolated microscopic hematuria, hematuria and proteinuria. Renal manifestations of HSP nephritis occur up to 12 wk after the initial presentation of HSP

treatment
Symptomatic Some studies suggest that short courses of low-dose

prednisone initiated at diagnosis reduce the subsequent risk of developing any clinical signs of nephritis

Rapidly progressive glomerulonephritis

a syndrome of the kidney that is characterized by a rapid

loss of renal function, (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies.

Crescentic glomerulonephritis (PAS stain). Note the collapsed glomerular tufts and the crescent-shaped mass of proliferating cells and leukocytes internal to Bowman capsule

ANTI-GBM ANTIBODYMEDIATED RPGN 20% Goodpasture syndrome Idiopathic anti-GBM nephritis Membranous nephropathy with crescents RPGN ASSOCIATED WITH GRANULAR IMMUNE DEPOSITS 40% Postinfectious Poststreptococcal glomerulonephritis Bacterial endocarditis Shunt nephritis Visceral abscesses, other nonstreptococcal infections Noninfectious Systemic lupus erythematosus Henoch-Schnlein purpura Mixed cryoglobulinemia Solid tumors Primary Renal Disease Membranoproliferative glomerulonephritis IgA nephropathy Idiopathic immune-complex nephritis RPGN WITHOUT GLOMERULAR IMMUNE DEPOSITS 40% Vasculitis Polyarteritis Hypersensitivity vasculitis Wegener granulomatosis Idiopathic RPGN

 Sign & symptoms The clinical picture is consistent with nephritic syndrome, although the degree of proteinuria may occasionally exceed 3 g/24 h, a range associated with nephrotic syndrome Diagnosis The presence of anti-Glomerular basement membrane (GBM) antibodies suggests type I RPGN;antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus and type II RPGN; and type III and idiopathic RPGN are frequently associated with anti-neutrophil cytoplasmic antibodies (ANCA)-positive serum.

 Treatment

Excellent therapeutic response using a combination of corticosteroids and cytotoxic therapy with cyclophosphamide often occurs in patients with systemic lupus erythematosus, IgA nephropathy, and Henoch-Schnlein purpura nephritis Plasmapheresis beneficial in patients with systemic vasculitides and Goodpasture syndrome

 THANK YOU.

References
Nelson Textbook Of Paediatric 18th Ed. Kumar & Clarks Clinical Medicine 7th Ed. Ghais Essential Paediatric 7th Ed.

Emedicine.medscape.com