ACUTE POST STREPTOCOCCAL GN ( PSAGN) Definition -GN -Variety of renal diseases in which there inflammation of the glomerulus, manifested by proliferation of cellular elements secondary to an immunologic mechanism. -Most incidents of AGN appear to be associated with a post infectious state ie post bacterial,viral and protozoan infection eg staphylococcal , pneumonococcal infections, coxsackievirus B, echovirus type 9, influenza virus, and mumps.PSAGN follows infection with group A beta hemolytic streptococci.Pathophysiology -Immune complexes, preformed by the combination of specific antibodies against streptococcal antigens, localize on the glomerular capillary wall and activate the complement system. -The immunologic system may also be activated by streptococcal antigens that adhere to the glomerular structures and act as "planted antigens" or by alterations in endogenous antigens. -The activation of the complement cascade then generates chemotactic -activated complement 5 (C5a) and platelet-derived inflammatory mediators. -Various cytokines and other cellular immunity factors initiate an inflammatory response manifested by cellular proliferation and edema of the glomerular tuft. -Only some strains of Grp A strep are nephrotogenic. Some non Grp A eg Grp C also cause PSGN. -At least 2 antigens isolated from nephritogenic streptococci, zymogen (a precursor of exotoxin B) and glyceraldehyde phosphate dehydrogenase (GAPDH), have been identified and are believed to be capable of initiating the immunologic response-Nodular deposits of immunoglobulin G (IgG) and the third component of complement (C3) on the capillary basement membrane. The finding of C3 in the renal glomerulus is usually associated with decreased serum concentrations of C3 and total hemolytic complement. -C3 levels return to normal in children in 6-8wks in children.C4 levels usually depressed too inconsistently.-PSAGN can occur in epidemics or, more commonly, it is be sporadic. -The sporadic form is seasonal; is associated with respiratory infection, and often associated with pyoderma. -Common group A beta hemolytic streptococci associated with nephritis from nasopharyngeal infections is type 12, type 49 is most often recovered during outbreaks of pyoderma-related PSAGN. -In individuals with pharyngitis-related AGN, the latent period is approximately 10 days, and more than 80% of patients exhibit a significant rise in serum titer of antistreptolysin-O (ASO). latent period is difficult to define in persons with impetigo-related AGN, and a rise in the titer of ASO only 50% of patientsOther streptococcal indicators (eg, antihyaluronidase [AH] titer, antideoxyribonuclease B titer [anti-DNase B]) elevated in either pharyngeal or skin infections. -When a variety of antibody titers is used, almost 95% of patients with PSAGN demonstrate evidence of a

Histology:The glomerular tufts usually appear enlarged and swollen; proliferation of mesangial and epithelial cells is present. Polymorphonuclear leukocytesImmunofluorescent microscopy Granular deposits of IgG and C3 ; other immunoglobulins (Igs) and fibrinogen often are observed. Electron microscopy of renal tissue from patients with PSAGN usually reveals subepithelial electron-dense deposits (humps)Usually, measurable reduction in volume of glomerular filtrate (GF) is present, and the capacity to excrete salt and water is usually diminished, leading to expansion of the extracellular fluid (ECF) volume. -The expanded ECF volume is responsible for edema and, in part, for hypertension, anemia, circulatory congestion, and encephalopathy.Mortality/Morbidity: Generally good prognosis-Depends largely on the severity of the initial insult. –In Very few of pts the initial injury is so severe that either persistent renal failure or progression to chronic renal failure occurs. -In most patients, histologic regression of the disease occur, and prognosis good. -Clinical manifestations of the disease rarely recur after the first 3 months, and second episodes of AGN are uncommon. -Poorer prognosis in adults, particularly in elderly individuals. Clinical course predictable:

Edema usually resolves within 5-10 days Gross hematuria usually disappears within

1-3 weeks BP usually returns to normal within 2-3

weeks though persistence of elevated pressures for as many as 6 weeks is compatible with complete resolution.

The C3 concentration returns to normal by 6-8 weeks

Urinary abnormalities resolve at slower pace. Proteinuria may disappear within the first 2-3 months or may decrease slowly over 6 months. Intermittent or postural proteinuria has been noted in a few patients for as long as 1-2 years after onset.

Microscopic hematuria usually disappears after 6 months; however, its presence for as long as 1 year is not uncommon

Possibility that the disease has entered a chronic phase if both hematuria and proteinuria persist for more than 12 monthsAge: -Greatest frequency in children aged 4-12 years, with a peak prevalence in individuals aged approximately 5-6 years. Slight male predominance

prior streptococcal infectionClinical Presentation:Most patients with acute GN exhibit milder symptoms between 2 extremes;-Asymptomatic child whose disease is discovered only by examination of the urine. Based on surveillance studies of the siblings and/or household contacts of children affected with PSAGN, at least 50% of persons with laboratory evidence of nephritis (ie, abnormal urinalysis) appear to have no symptoms or signs of clinical illness- Severe disease manifested by oliguria, edema, hypertension, and azotemia and with proteinuria, hematuria, and urinary casts (cylindruria).-Latent period of 7-21 days between onset of the streptococcal infection and development of clinical GN is characteristic latent period, after pharyngeal infections , averages 10 days1.Gross hematuria and/or edema- the most common signs-Appear abruptly associated with various degrees of malaise, lethargy, anorexia, fever, abdominal pain, and headache-Gross hematuria occurs at onset in 30-50% of children The urine may be smoky, cola colored, tea colored, or rusty2. Oliguria. –decreased urine output.3.Edema -First involves the periorbital area, but it may be generalized. -The degree of edema varies and depends on a severity of glomerular involvement, the fluid intake, and the degree of hypoalbuminemia- Insidious onset of edema is more indicative of other forms of renal disease4.Hypertension- is the third cardinal feature of PSAGN and is reported in 50-90% -Multifactorial and related only in part to ECF volume expansion BP systolic pressures greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg -Rarely Hypertensive encephalopathy occur, most serious early complication of this disease.- Usually HTN is severe and CNS dysfunction signs as headache, vomiting, depressed sensorium, confusion, visual disturbances, aphasia, memory loss, coma, and convulsions.5.Circulatory congestion only rarely cause significant early symptoms. Dyspnea, orthopnea, and cough may be present. Pulmonary rales are often audible.In the patient with an otherwise normal cardiovascular system, cardiac failure is unusual. 6.Pallor is common at onset and is not explained entirely by the anemia.

Other postinfectious causes of AGN must be considered in the differential diagnosis (eg, Strep pneumoniae, Staph aureus, Staph epidermidis, Rickettsia rickettsiae, Mycoplasma species, Meningococcus species, Leptospira species).viral illnesses causing AGN; most common varicella-zoster virus, cytomegalovirus, and the Epstein-Barr virus1.IgA-associated GN -Urticarial or purpuric rashes, abdominal complaints, and arthritis and/or arthralgia -HTN and oedema less prominent. -No evidence of prior strep infection and c3 levels normal.2.Berger disease or IgA nepNephropathy presents as an episode of gross hematuria occurring during the early stages of a respiratory illness; no latent period exists, and hypertension or edema is uncommon. -Recurrence common. Unlike PSGN 3. Mesangiocapillary or membranoproliferative- GN (MPGN The initial manifestations are often more serious in persons with MPGN than in those with IgA nephropathy; the renal function is reduced markedly (ie, large elevation of serum creatinine). No evidence of strep infection, C3 depressed past 6wks, Urinary abn persist past time of resolution for PSGN.4.Crescentic GN is the term used to describe a histologic picture of severe proliferative GN. synechiae between the glomerular tuft and Bowman capsule. rapidly progressive GN and may be secondary to a number of causes, including an immune-complex mediated poststreptococcal nephritis. The initial clinical picture is generally severe, and resolution appears delayed.

Investigations:Urine output most often is reduced, and urine is concentrated and acidica) Urinalysis.

Proteinuria sometimes glycosuria. The urine reaction for protein rarely exceeds 3+ by dipstick, corresponding to fewer than 2 g/m2/d Abt 2-5% of children with PSAGN have massive proteinuria and a nephrotic picture.

Hematuria is the most consistent abnormality

Polymorphonuclear leukocytes and renal epithelial cells esp. during the early phase of the disease

Hyaline and/or cellular casts are almost always present.

RBC casts,b)Renal Function Tests.

The elevation in the serum concentrations of creatinine

Elevated blood urea nitrogen (BUN) is usually modest, although some patients may have severe azotemia at onset

c) Evidence of streptococcal infection in all patients. Culture of skin or pharnynx A number of laboratory tests can be used to

measure antibodies to a variety of streptococcal antigens (eg, ASO, AH, anti-DNase B) or to combinations of antigens (eg, streptozyme test). A rise in the titer of the antibody, measured at an interval of 2-3 weeks, is more meaningful than a single measurement.

d)Hemolytic complement. C3 and total hemolytic complement levels re low.C4 levels are most often normal.Serum levels of fifth component of complement (C5) and properdin are usually decreased.The complement levels generally return to normal by 6-8 weeks after onset.e)Electrolytes Hyperkalemia and metabolic acidosis are only present in patients with significant renal functional impairment. The same applies to hyperphosphatemia.Total serum calcium, but not ionized calcium levels, may be low in patients who have a nephrotic picturef)FHG A mild anemia (normocytic, normochromic) is common in persons in the early phase of AGN; its degree tends to parallel the degree of ECF volume expansion. Erythropoiesis may decline in the aftermath of AGN, particularly in individuals with severe cases.WBC and platelet counts are usually normal, even though an occasional patient exhibits a leukocytosis; rarely, a mild thrombocytopenia may be present.A few patients have hypoproteinemia and hyperlipidemia. A nephrotic picture has been reported in approximately 5% of hospitalized patients with PSAGN.

Imaging Studies: Renal ultrasonography generally demonstrates normal to slightly enlarged kidneys bilaterally with some evidence of increased echogenicity.Chest radiographs commonly demonstrate central venous congestion in a hilar pattern, the degree of which parallels the increase in ECF volume.Management Supportive and directed toward the potential complications 1.Severe hypertensionThat associated with signs of cerebral dysfunction, demands immediate attention. Three drugs are commonly cited as having a high benefit-to-risk ratio:

1. labetalol (0.5-2 mg/kg/h IV)2. diazoxide3. Nitroprusside (0.5-2 mcg/kg/min

The simultaneous intravenous (IV) administration of furosemide at doses of 2 mg/kg may be merited2.Mild-to- moderate HTN Bed rest, fluid restriction. Loop diuretics, such as furosemide (1-3 mg/kg/d PO, administered 1-2 times daily), may hasten resolution of the hypertension. Resistance either hydralazine or nifedipine is indicated. ACEI inhibitors are effective, although they have the potential to produce hyperkalemia and usually are not first-line drugs in AGN. Oedema and circulatory congestion also respond to the treatment.3.Course of penicillin can be administered to avoid contamination of contacts with a nephritogenic strain of streptococci4.Steroid therapy is indicated only in patients with severe crescent GN or in those with rapidly progressive GN. Complications

1. The most common acute complication is hypertension with or without central nervous system manifestations.

2. Anemia is common early and is due primarily to dilution. Anemia tends to resolve with diuresis. A few patients may have diminished erythropoiesis in the recovery phase and have some persisting anemia.

3. An occasional patient develops pulmonary edema because of the marked increase in vascular volume that is present in the early phase of the disease.

4. Congestive heart failure is rare but has been reported. Definite myocarditis also has been documented.

5. Chronic renal failure