Glomerulonefrita Acuta Poststreptococica (GNAPS)-Engleza 2 (User-PC_s Conflicted Copy 2013-04-29)-1

8/13/2019 Glomerulonefrita Acuta Poststreptococica (GNAPS)-Engleza 2 (User-PC_s Conflicted Copy 2013-04-29)-1

1/37

Acute Poststreptococcal

GlomerulonephritisMirela Covacescu

Clinica II Pediatrie

IOMC Alfred Rusescu


2/37

Definition

Acute glomerulonephritis (AGN) is a

representative disease of acute nephritic

syndrome in which inflammation of the glomerulus

is manifested by proliferation of cellular elements

secondary to an immunologic mechanism.


3/37

4 major syndromes:

Fluid retention syndrome (edematous sd)

Urinary syndrome (albuminaemia, hematuria,

cylindruria)

Hypertensive and cardiovascular overloadsyndrome

Nitrogen retention syndrome (azotemia)

Definition


4/37

AGN etiology

Infectious and post infectious AGN:

Bacterial: Beta hemolytic streptococcus;

Staphylococcus , Pneumococcus, Meningococcus,

Salmonella, E coli

Viral: varicella zoster v., rubella v., mumps v., Epstein-

Bar v., Adenovirus, Coxsackie v., hepatitis B v.

Rickettsiaand parasites

Non infectious:serum sickness, snake venom, drugs

Primitive:unknown causes


5/37

Acute Poststreptococcal

Glomerulonephritis (APSGN)

APSGN results from an antecedent infection of the skin

or throat caused by nephritogenic strains of group A

beta-hemolytic streptococcus, secondary to an

immunologic mechanism, with a self-limited evolution

and favorable prognosis in most patients(more than

95%).

APSGN is the most common form of immune complex-

mediated nephritis in children, being the most frequent

postinfectious glomerulonephritis


6/37

Etiopathogenesis

APSGN= late complication after an infection of the skinor throat caused by nephritogenic strains of group Abeta-hemolytic streptococcus

Most of the serotypes are pharyngeal(A12- the mostknown, but also 1, 2, 4, 18, 25, 31, 52, 56, 59 and 61)

Serotypes 49, 55, 57 and 60 are also nephritogenic, but

are most commonly associated with skin infections(streptococcal impetigo, pyodermitis)

Features relating to the immune response of the host arealso involved


7/37

APSGN - mediated by an immune mechanism, both thehumoral and cellular immunity being involved in thepathogeny of this disease

Humoral immunity is mediated by in situ immuneantigen-antibody complexes formationof nephritogenicstreptococci and circulating immune complexes (CIC)

After 8-14 days from infection, specific antistreptococcalantibodies appear and bind to streptococcal antigensforming immune complexes.

The precise mechanism by which nephritogenic strains

of streptococci form immune complexes is stillincompletely understood.


8/37

streptococcal infection Agenters the

circulation

Stimulating humoral specific Ab

immunity

Complement Ag-Ab reaction

CIC- binding to the glomerular basement

membrane (GBM)


9/37

The most widely proposed theory - that

nephritogenic streptococci produce proteins with

unique antigenic determinantsthat have a

particular affinity for sites within the normal

glomerulus

Following release into the circulation, theantigens bind to these sites within the

glomerulus. Once bound to the glomerulus, they

activate the complementdirectly by interaction

with properdin


10/37

Two major antigens have presently been

identified :

I. Zymogen- precursor of exotoxin B namedSPEB [streptococcal pyrogenic toxin B] ornephritis strainassociated protein (NSAP)

II. NAPlr(Nephritis Associated Plasmin Receptor)

binds to activated plasminThis antigen is present in 100% of early renalbiopsies from APSGN


11/37

ICC activates local serum complement

Fact XII activation

Platelet aggregation

Intravasc localized

coagulation

microthrombosis of glomerularcapillary

Decrease in Surface of FG

Oliguria

Fluid and salt retention

Azotemia

Fix. and activ.complement(C)hipoC

Vasoactive and chemotact. leucocytefact release

Local crowding of pmn; phagocyte CI

Glomerular inflammation

Lysosyme enzime release

GBM permeability modification

Proteinuria

Hematuria

Cylindruria


12/37

Electron microscopy:

= The typical subepithelial "humps" located between

GBM and epithelial cells(the outer side of the

subepithelial basement membrane of glomerularcapillaries), consisting of soluble antigen-antibody

complex, typical for proliferative and exudative

APSGN


13/37

Susceptibility to this disease may be geneticallydetermined and dependent on each host

The disease is extremely rare under the age of 3

years.

Sex ratio: M/F=2/1.

85% of AGN admitted to hospital are APSGN!


14/37

Clinical manifestations = Nephritic syndrome

Age-6- 12 years (5-15 years)

Medical history:develops 8-21 days after an antecedentstreptococcal pharyngitis or streptococcal pyoderma(detected by clinical history in 50% of cases)

The latent period between onset of the streptococcalinfection and development of clinical glomerulonephritis:asymptomatic or minor nonspecific signs(low fever,asthenia, anorexia, fatigue, arthralgia)

Onset: frequently acute; with fever, oliguria, hematuria,edema and rarely with neurological or circulatoryoverloading signs


15/37

The acute phase - 4 major syndromes

1. Edematous syndrome

Discrete/moderate edema

Renal edema characteristics= soft, white, first involvesthe periorbital area, pitting, more pronounced in the

morning

doesnt have the intensity and persistence of those in

NS Weight gain

May be unnoticed

exceptionally vast edema= anasarca


16/37

2. Urinary syndrome

the only manifestation in 10% of patients; missing very rarely

- oliguria< 180- 200 ml/m2/day (1 ml/kg/h)

- macroscopic hematuria (The urine is usually described as beingsmoky, cola colored, tea colored, rusty, dirty green;)

- or microscopichematuria (>1000 RBC/mmc; crenulated RBC;)

- cylindruria- hematic cylinders (50-85%), granulocytes.

- mild proteinuria 1020

- urinaryosmolarity > 500 mosm/l

oliguria ends in 4-7 days resumption of diuresispoliuria

macroscopic H-uria ends in 1-14 days microscopic H-uria may persist for several months (not defective

healing)


17/37

3. Hypertension and circulatory overload syndrome

reported in 50% of children who are hospitalized with

acute glomerulonephritis

Blood pressure moderately increased, oftenasymptomatic

Tends to be an inverse correlation between HTA and

the appearance of edema

Can exist circulatory overload signs with tachycardia,gallop, cardiomegaly, jugular stasis, hepatomegaly,

hepatojugular reflux;

Severe forms

Pulmonary edema

Hypertensive encephalopathy (headache, vomiting,

somnolence, agitation, coma, and seizures)


18/37

4. Nitrogen retention syndrome (azotemia)

Urea >40 mg% ;

Creatinine>1- 1,2mg%

Uric acid > 4 mg%

The acute period:

lasts between 4- 10 days;

the degree of symptom expression varies;

following resumption of diuresis, then polyuria with

regression of symptoms (edema and macroscopic

hematuria disappears,)

recovery phase


19/37

Lab exam:

Normochromic normocyticanemia

Inflammatory syndrome: WBC, erythrocyte sedimentation rate

(ESR), CRP, fibrinogen, alfa2 globulin increased

Urine examcertifies changes described at urinary syndrome

Azotemia-elevation in the serum concentrations of creatinine, urea

Renal function tests- low creatinine clearance

(normal Clr(mL/min)=0.55x lenght(cm) / blood creatinine (mg/dL))

Adiss test> 1000 RBC/min


20/37

Lab exam:

Proof of infection with A-BHS:

ASO (ASLO)

anti-DNase B

cultures from pharynx, rapid streptococcus test positive

cultures from skin Similar tests for other family members (streptococcus infection or

APSGN!)

The electrolyte profile- hyperkalemiaand dilution hyponatremia

(oliguric forms)

Lab exam:


21/37

Evidence of immune-complex disease:

Low serum complement level < 80 mg%

the complement activation occurs, resulting in decreased C3 for at

least 90% of patientsin the early phase of the disease(sometimes C4)

C3 levels generally return to normal by 10 days- 8 weeks after onset.

if it isn't determined in the early stage of the disease, low C3 sample

can be missed, being already normal in some cases

Early antibiotic treatment of streptococcal infection may shorten thelow C3 period so that it can not be proved anymore

There is no connection between the degree of decrease in C3 and

severity of the disease

if the value of C3 remains low after 8- 12 weeks after onset, adifferential diagnosis is made with other nephritic processes (LESother glomerulonephritis (renal biopsy!))


22/37

metabolic acidosisin severe forms of patients with

significant renal function impairment

urine protein electrophoresis- non-selected proteinuria

Others: CIC, IgG

Chest X-ray: +/- enlarged cardiac shadow

EKG- Hyperkalemia (K ): P wave; prolonged PR; QRS

widening; shortened QT; tall tented T waves

Fundic exam of eye (forms with neurological disorders orsevere hypertension)papilloedema, retinal stasis,

(AcuteHT)+/- retinal exudate and hemorrhage (cronical

HT)


23/37

Clinical forms with atypical manifestations:

Heart failure at onset

Brutal AHT- hypertension encephalopathy

Acute renal failure

AGN with minimal urinary syndrome


24/37

Positive diagnosis

Age:6-12 years

Evidence of a previous streptococcal infection with 1-2weeks before:

Medical history (scarlet fever, purulent tonsillitis,)

Throat exudate- BHS

Markers of strept. infection-ASLO (at 2-3 weeks afteronset) etc

Clinical:

Latent period: 10-20 days

Acute typical onset: fever, edema, oliguria, atypicalhematuria

Nephritic syndrome: the 4 cardinal syndromes

Immunological-low complement


25/37

Differential dg

Depends on the predominant manifestations: Edema- differential dg of edema

Hematuria- exclusion of other hematuria-associated causes

Difference between nephrotic and nephritic

syndrome


26/37

Differential diagnosis (hematuria)

1. Focal intra-infectious glomerulonephritis produced by

other causes besides streptococcus

Intra-infectious onset(non- strept. bacterial and viral

illnesses affecting the superior respiratory tract)

Usually only minor urinary syndrome (microscopic

hematuria, low proteinuria)

Commonly without edematous sdr, hypertensive sdr or

azotemia

C= N / increase

self limited benign evolution; may relapse2. Henoch-Schonlein nephritis

Characteristic clinical picture (purpura+ arthritis+ digest+

renal manif.)

C=N / increase


27/37

3. Hemolytic uremic syndrome (HUS)

- Young age: 6-12 months; occurs in evolution of severe infection

- Acute stage : hemolytic anemia

Hemorrhagic sdr -consumptive coagulopathy (Plt)

acute hematuric nephritis+ ARF (acute renal failure)

Neurological - coma, seizures

Unfavorable evolution- 50% irreversible ARF

Increase C

4. IgA nefrophathy (Berger disease)- benign recurrent hematuria

Episodes of Hematuria + Proteinuria without other manifestations

During viral infections of the superior respiratory tract; repetitivenature

APmesangioproliferative GN- mesangial interposition of IgA/

IgA+G

Benign evolution


28/37

5. Exacerbation of familial/non-familial chronic

glomerulonephritis

Family history of hereditary nephropathy History of nephropathy

Exacerbation during infections

Alterated renal function tests (it does not normalise!)

C=N / increase (except mbprolif GN) Histological- focal GN , diffuse prolif.

(ex. Alport sdr - deafness associated ; X-linked)

6. Persistent GNC from systemic disorders (LES, PAN)- multisystemic disease

- Lupus cell, AAN, anti DNA antibodies (double-stranded DNA )


29/37

7. Acute pyelonephritis (APN) or hemorrhagic cystitis

- viral or bacterial etiology

- Clinical signs of urinary infection -dysuria, pollakiuria, infectioustoxic syndrome

Leucocyturia, Leuc. cylinders, flora

urine culture

8. Pure nephrotic syndrome- transienthematuria at onset

9. Other causes of hematuria-traumatic

- lithiasic -

- malformation

- haemostasis dis. Anamnesis- trauma, lithiasis

Clinical- hemorrhagic sdr associated, renal colic, etc

Renal X-ray, urography, renal ultrasound, urological exploration-

cystography, cystoscopy, etc

Screening hemostasis


30/37

Treatment

1. Hospitalization

2. Bed rest:

in acute forms (edema, AHT, cardiac failure,oliguria, N-emia)

Does not shorten evolution but can influence

the rate of complications ;

vertical position accentuates proteinuria andhematuria


31/37

3. Diet

Oligoanuria, hypertension

300 -400 Kcal/m2

/day Limitation of fluid intake - diuresis+ 300ml/m2

Limitation of salt intake 1g/day 0,3 g/day in severe

cases

excluding foods high in K low-protein diet 2g/Kg/day-urea 75mg%

0,5 g/Kg/day- urea>100mg%

Resumption of diuresis and decreasing urea- gradually diet,initially with proteins from vegetable then animal sources, with

hight biological value (cow cheese, meat, egg)

Convalescence period- normal protein and caloric intake,enriched in vitamins, moderate salt restriction

4 Anti-infective treatment


32/37

4. Anti-infective treatment

Preferably proper treatment (preventive) of streptococcal infection

Onset of GN-germs not found at the entrance gate anymore andrenal injury already established

Antibiotic treatment- without action on nephropathy or GN evolution

Administer antibiotics to ensure eradication of the streptococcusif

the disease is believed to be acute poststreptococcal

glomerulonephritis

Penicillin G for 10 days

50 000- 100 000/Kg/day, 4 doses (1 600 0002 400 000 ui/day)

or erythromycin 30 mg/kg/day, cephalexin 50 mg/kg/day then prophylaxis with penicillinV ormoldaminuntil discharge

(hospital- source of reinfection)


33/37

Treatment of complications

Circulatory congestion and edema

fluid and salt restriction

Furosemide 1-2 mg/kg/day (sometimes even 5mg/kg/day)

Left ventricular failure - digoxinloading dose 0,03 mg/kg/day

the maintenance dose according to creatinineclearance ( 50%- d 25%;

25%- d 20%;

20%-d 14%)

Acute pulmonary edema- fluid restriction + furosemide

Severe oliguria

mild fluid restriction, no K


34/37

Acute renal failure-

First days: diet without K; sufficient intake of iv glucose;

Hyper-Kemia treatment

Iv infusion in oligoanuric per : 25-40 ml/kg or 300-400

ml/m2; without electrolytes if ionogram is normal and there

are no losses; +/- mannitol to force diuresis 0,2 g/kg in 20min; dopaminein renal doses

HT encephalopathy- antiHT (labetalol, nitroprusiat, diazoxid,

captopril, enalapril, etc)


35/37

Evolution :

Signs of severity :

creatinine clrs < 60 ml/min

Urea>50 mg%

Oliguria 5mg%

K >8mEq/l non responsive to treatment Metabolic uncontrolled acidosis (bicarbonate


36/37

Typical evolutive presentation

1. Streptococcal infection

2. Latent period -7-21 days3. Active period 7-14 days- 4 cardinal syndromes

4. Improvement period (14-28 days)- no edema,macroscopic Huria , azotemia, AHT, circulatoryoverload; urine microscopic changes gradually resolve

in 70% of cases, complement becomes N5. Recovery period-variable duration up to 1 year since

onset; at 30% urine microscopic changes may persist(decreased albuminuria, microsc hematuria)

6. Complete recovery (90-95%) or defective recovery

(hematuria,residual proteinuria) at 1-10% of cases;5% evolve to rapidly progressive glomerulonephritis


37/37

Prognosis- good in general, largely depends on the

severity of the initial insult

Follow-up- 1 year; monthly urinalysis

Recovery criteria (at 1 year):Clinical - asymptomatic

Paraclinical - immunologicalC=N

- Fctal- renal fct tests N

- Urinary- urinary sdr (-) 90%- 10% defective healing- pyuria or isolated

residual hematuria

Documents

Glomerulonefrita Acuta Poststreptococica (GNAPS)-Engleza 2 (User-PC_s Conflicted Copy 2013-04-29)-1