ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (APSGN) IN CHILDREN

Group A beta-hemolytic Streptococci are the most common etiologic organism, pharingitis and pyoderma are the common antecendents of APSGN

Terminology Acute proliferative glomerulonephritis is charaterized by the histo-pathologic findings of capillary wall and mesangial hypercellularity accompanied by invading polymorpho-nuclear cells. Acute nephritic syndrome consist of haematuria, proteinuria, edema, hypertension, volume overload, and varying degree of renal insufficiency (oliguria, azotemia, hyper-creatininemia)

Epidemiology
Two antigenitically distinct proteins, M and T. Streptococcal pharyngitis occurs primarily in school-aged children from 5 to 6 years of age, most commonly in the winter and spring. Streptococcal-induced skin lesions, occur more often in the summer and fall in temperate climates, and are less seasonally associated in the tropical areas

Table Diseases Presenting with Acute Proliferative Glomerulonephritis and the Acute Nephritic Syndrome in Children.
Common Post infectious glomerulonephritis Poststreptococcal Other systemic infections Henoch-Schnlein purpura Less common Membranoproliferative glomewrulonephritides IgA nephropathy Systemic lupus erythematosus Familial nephritis Infective endocarditis-related Shunt nephritis Uncommon Wegeners granulomatosus Polyarteritis nodosa

Table : Organisms Implicated as Etiologic Factors in Acute Proliverative Glomerulonephritis Bacteria : Streptococcus, group A b-hemolyic Streptococcus viridans Streptococcus pneumonia Cytomegalovirus Staphylococcus aureus Staphylococcus epidermidis Corynebacterium Propionibacterium Atypical mycobacterium Mycoplasma Brucella rickettsiae Meningococcus Leptospira Viruses : Varicella Rubeolla

Epstein-Barr virus

Parasites Toxoplasma Trichinella Rickettsia R.

Pathology
The process is diffuse and generalised in that all the observed glomeruli and all the lobules in each glomerulus. During the acute stage, the glomeruli are enlarged, with pronounced lobular configuration that results from the proliferation. Thus, the designations of intracapillary and endocapillary glomerulonephritis are appropriate

Pathogenesis

The first element necessary in the production of disease are the host genetic factors that determine the immune response to the streptococcal antigen. The second element, the susceptible host must be presented with the inciting antigen. Hypothesis : the streptococcal antigens may deposit within glomeruli and stimulate the fixation of complement and specific antibody (1,2,3,4)

Pathophysiology

Glomerular filtration rate (GFR) is reduced Tubular function is preserved Oliguria results clinically due to enchanced absorption of fluid and solute in the distal tubule and collecting tubule. Hypertension and edema result from vascular, and subsequently, interstitial volume expansion Azotemia,acidemia, hyperkalemia, hyperphosphatemia

Frequency of clinical manifestations

~Gross hematuria ~Volume overload : Edema Hypertension ~Circulatory congestion (congestive heart failure, pulmonari edema) ~Central nerveous systems (headache, somnolence, coma, seizure) ~Back or abdominal pain, nausea, vomiting ~Anorexia, malaise, lethargy ~Acute nephritic syndrome, NS ~Rapidly progressive glomerulonephritis 25-33% 85% 60-80% 20% 10% occasionally uncommon some 1%

Laboratory Findings
Urinalysis :Early in the course of APSGN urine osmolality is high. Proteinuria usually light. Microscopic examination : * Red blood cells - mostly small - dysmorphic * Red blood cells cast in fresh urine (pathognomonic), hyaline cast granular cast * White blood cells.
xx Renal Function: Glomerular filtration rate, renal blood flow decreased. Serum urea nitrogen, creatinine usually elevated. Free water retension may lead to hyponatremia.

Complete Blood Count : Anemia caused by volume expansion. Trombocytopenia may be present. Leucocytosis is found in patients with intercurrent infection. Antistreptolysin O (ASO) titer will increase the precentage of positive diagnostic results. Third complement (C3) is generally but not universally profoundly decreased

Treatment
The treatment of the child with APSGN is largerly supportive. First comes the decision of whether hospitalization is required. Indication for hospitalization : Obvious edema, hypertension. Elevated blood urea nitrigen (BUN) and creatinine levels. No indication for hospitalization : Must be followed for frequent observation of deterioration. Evaluation must include the serologic examination that will substantiate the diagnosis of poststeptococcal disease. There is no reason to keep the children in bed.

For patient with acute nephritic syndrome : hypertension and other signs of volume overload, azotemia must be managed promptly and properly. There should be strict fluid and sodium restriction because volume overload is generally present.
Volume overload sufficient to produce congestive heart failure, severe hyperkalemia must be dialysed, which in children peritoneally is preferable

Table. Treatment Strategy for Acute Glomerulonephritis 1. Bed rest as necessary 2. Fluid and salt restriction 3. Specific intervention for the following : a.Hypertension and other signs of volume overload, including encephalopathy b.Hypercalemia c.Acidemia d.Hyperphosphatemia 4. Confirm likehood of psotstreptococcal disease 5. Watch for index of suspicion for diseases other than post streptococcal GN

Outcome of APSGN

There is a good correlation between the severity of the initial clinical syndrome, histologic abnormalities, and prolonged abnormal renal function.
Those patients with the most severe clinical findings - have the most severe histologic findings, with glomerular capillary obliteration and epithelial cell proliferation. - permanently decreased renal function. - yet, some of the patiens recovered. - 11% of patients did not heal within 3 years or more of the acute disease. Those with milder clinical features : all patients appear to improve. On the whole greater than 90% of APSGN should expected to recover. 0,5 - 2,0% may have a rapid progressive disease, reaching endstage within weeks to months

Course of Disease Process. In general, the acute phase of illness in APSGN with its most severe manifestations last 2-3 weeks. The frequency of need for follow-up examinations will depend on the individual patient and the severity of the disease

Groos haematuria Oliguria, azotemia Hypertension Depression of C3 Persistent proteinuria Microscopic haematuria Intermittent or orthostatic proteinuria 2 weeks 4 2 6 weeks months months year 1 years 2

Figure . Time course of resolution for the usual clinical/chemical features of post-streptococcal glomerulonephritis