Post-streptococcal Glomerulonephritis

Block VII: Bloody urine and Puffy eyelids Tutor: Dr. A. Quilala Prepared by: Goldie Hernandez DEFINITION AGN follows infection of the throat or skin by certain nephritogenic strains of group A -hemolytic streptococci This is a classic example of the acute nephritic syndrome characterized by the sudden onset of gross hematuria, edema, hypertension, and renal insufficiency. one of the most common glomerular causes of gross hematuria in children, surpassed only by IgA nephropathy. EPIDEMIOLOGY The incidence of poststreptococcal glomerulonephritis has dramatically decreased in developed countries and in these locations is typically sporadic; epidemics are less common. In underdeveloped countries usually affects children between the ages of 2 and 14 years, but in developed countries is more typical in the elderly, especially in association with debilitating conditions It is more common in males, and the familial or cohabitant incidence is as high as 40%. ETIOLOGY 2. Poststreptococcal glomerulonephritis follows infection of the throat or skin by certain nephritogenic strains of group A -hemolytic streptococci. Poststreptococcal glomerulonephritis commonly follows streptococcal pharyngitis during cold weather months and streptococcal skin infections or pyoderma during warm weather months. Skin and throat infections with particular M types of streptococci (nephritogenic strains) antedate glomerular disease M types 47, 49, 55, 2, 60, and 57 are seen following impetigo M types 1, 2, 4, 3, 25, 49, and 12 with pharyngitis. Poststreptococcal glomerulonephritis due to impetigo develops 26 weeks after skin infection and 13 weeks after streptococcal pharyngitis. immune complex containing a streptococcal antigen is deposited in the affected glomeruli. Two nephritogenic streptococci antigens are 1. cationic cysteine protease streptococcal pyrogenic exotoxin B 2. nephritis-associated streptococcal plasmin receptor, which is a plasmin-binding protein with glyceraldehyde phosphate dehydrogenase (also known as presorbing antigen or PA-Ag)

CLINICAL PRESENTATION 1. EDEMA ( periorbital edema) The onset of puffiness of the face or eyelids is sudden. It is usually prominent upon awakening and, if the patient is active, tends to subside at the end of the day. In some cases, generalized edema and other features of circulatory congestion, such as dyspnea, may be present. Edema is a result of a defect in renal excretion of salt and water Gross hematuria Smoky, tea-colored, cola-colored, or fresh bloody urine This is often the first clinical symptom. Dark urine is caused by hemolysis of red blood cells that have penetrated the glomerular basement membrane and have passed into the tubular system. Proteinuria usually normalize after 4 weeks Oliguria Hypertension mild to moderate, typically subsides promptly after diuresis Systemic symptoms of headache, malaise, anorexia, and flank pain (due to swelling of the renal capsule) are reported in as many as 50% of cases
The acute phase generally resolves within 68 wk. Although urinary protein excretion and hypertension usually normalize by 46 wk after onset, persistent microscopic hematuria may persist for 12 yr after the initial presentation.

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PATHOPHYSIOLOGY Post-streptococcus Glomerulonephritis is believed to be an immune-mediated disease, in which an

LABORATORY INVESTIGATIONS Urinalysis Results are always abnormal.

Hematuria and proteinuria are present in all cases. Urine sediment has red blood cells, red blood cell casts, white blood cells, granular casts, and, rarely, white blood cell casts. Dysmorphic red blood cells indicative of glomerular hematuria can usually be detected by performing phase-contrast microscopy. Red blood cell casts are best detected in first, early-morning urine specimens examined by the physician immediately after the patient voids. Proteinuria may be mild or so severe that it causes nephrotic syndrome. Evidence of preceding streptococcal infection A positive throat culture report may support the diagnosis or may simply represent the carrier state. a rising antibody titer to streptococcal antigen(s) confirms a recent streptococcal infection. antistreptolysin O titer is commonly elevated after a pharyngeal infection but rarely increases after streptococcal skin infections. The best single antibody titer to document cutaneous streptococcal infection is the anti-deoxyribonuclease (DNase) B level. The Streptozyme test is a useful and simple diagnostic test that detects antibodies to streptolysin O, DNase B, hyaluronidase, streptokinase, and nicotinamide-adenine dinucleotidase using a slide agglutination test. Renal function test This reflects the decrease in the glomerular filtration rate that occurs in the acute phase. The BUN concentration is elevated in 75% of patients, and serum creatinine level is increased in one half of the patients, but profound decrease in GFR is uncommon in children. Hyperkalemia, hypocalcemia, hyponatremia and metabolic acidosis are seen only in severe patients. Complete blood count A mild normochromic anemia may be present from hemodilution and low-grade hemolysis

Leukocytosis maybe present Serologic findings Low serum complement levels indicative of an antigen-antibody interaction are a universal finding in the acute phase of PSGN. Most patients have marked depression of serum hemolytic component CH50 and serum concentrations of C3 Positive rheumatoid factor (3040%), cryoglobulins and circulating immune complexes (6070%), Kidney ultrasound not necessary if patient has clear cut acute nephritic syndrome Renal biopsy Light microscopy glomeruli appear enlarged demonstrates hypercellularity of mesangial and endothelial cells, glomerular infiltrates of polymorphonuclear Electron Microscopy Subepithelial electron-dense deposits or humps are present which are observed on the epithelial side of the glomerular basement membrane Immunofluorescence microscopy Lumpy-bumpy deposits of immunoglobulin G and complement C3 along the capillary loops and within the mesangium

COMPLICATIONS Hypertension Acute renal failure Congestive heart failure

TREATMENT Treatment of PSGN is largely that of supportive care Patients undergo a spontaneous diuresis within 7-10 days after the onset of their illness Diuretics Diet Fluid restriction, sodium restriction (necessary) Antibiotics 10 day course of systematic antibiotic therapy with penicillin V is recommended to limit the spread of the nephritogenic organisms During the acute phase of the disease, restrict salt and water.

If significant edema or hypertension develops, administer diuretics. Loop diuretics increase urinary output and consequently improve cardiovascular congestion and hypertension. For hypertension not controlled by diuretics, usually calcium channel blockers or angiotensin-converting enzyme inhibitors are useful. For malignant hypertension, intravenous nitroprusside or other parenteral agents are used. Indications for dialysis include life-threatening hyperkalemia and clinical manifestations of uremia. Restricting physical activity is appropriate in the first few days of the illness but is unnecessary once the patient feels well