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S ., Sp.
After completing this module, the students be able to:
escribe many causes of
scribe the complication of
lan assessement of
and taking history
Self directed learning
Small class discussion
Overview lecture of History taking in
History taking formative assessement
OSCE summative assessement in
Acute glomerulonephritis (AGN) is a disease characterized by the sudden
appearance of edema, hematuria, proteinuria, and hypertension. It is a representative
disease of acute nephritic syndrome in which inflammation of the glom
erulus is manifested
by proliferation of cellular elements secondary to an immunological mechanism.
Acute GN has 2 components: structural changes and functional changes.
Cellular proliferation: This leads to an increase in the number of cells in the
tuft because of the proliferatio
n of endothelial, mesangial
and epithelial cells. The
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proliferation could be endocapillary (ie, within the confines of the glomeru
tufts) or extracapillary (ie, in the Bowman space involving the
extracapillary proliferation, proliferation of parietal epithelial cells leads to
formation of crescents, a feature characteristic of certain forms
Leukocyte proliferation: This is indicated by the presence of neutrophils and
within the glomerular capillary lumen and often accompanies cellular
Glomerular basement membrane thickening: This
development appears as
of capillary walls using light microscopy. Using electron microscopy, this may
appear as the result of thickening of basement membrane proper (eg, diabetes) or
deposition of electron
dense material, either on the endot
helial or epithelial side of
Hyalinization or sclerosis: These conditions indicate irreversible injury.
dense deposits: Such de
posits could be subendothelial,
intramembranous, or mesangial, and they correspond to an area of immune complex
These structural changes could be focal, diffuse or segmental, and global.
Functional changes include proteinuria, hematuria, reduction in
GFR (ie, oligoanuria),
and active urine sediment with RBCs and RBC casts. The decreased GFR and avid distal
nephron salt and water retention result in expansion of intravascular volume, edema, and,
frequently, systemic hypertension.
protein of the organism was previously believed to be responsible for PSGN, but
these studies have been discounted. Nephritis
associated streptococcal cationic protease
and its zymogen precursor (NAPR) have been identified as a glyceralde
dehydrogenase that functions as a plasmin(ogen) receptor.
This binds to plasmin and
activates complement via alternate pathway. Antibody levels to NAPR are elevated in
streptococcal infections (of group A, C, and G) associated with glomer
ulonephritis but are
not elevated in streptococcal infections without glomerulonephritis, whereas anti
O titers are elevated in both circumstances.
These antibodies to NAPR persist for years and
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perhaps are protective against further episodes
of PSGN. In a study in adults, the 2 most
frequently identified infectious agents were streptococcus (27.9%) and staphyl
Taking a proper history is important and helpful.
Determine onset of disease: Ask the patient about onset and duration of illness.
Identify a possible etiologic agent (eg, streptococcal throat infection [pharyngitis], skin
infection [pyoderma]): Recent fever, sore throat, joint pains, hepatitis, trave
replacement, and/or intravenous drug use may be causative factors. Rheumatic fever
rarely coexists with acute PSGN.
Identify systemic disease (eg, arthralgia, diabetes).
Assess the consequences of the disease process (eg, uremic symptoms):
about loss of appetite, generalized itching, tiredness, listlessness, nausea, easy
bruising, nose bleeds, facial swelling, leg edema, and shortness of breath.
Identify clinical features: Inquire about edema, decreased volume and frequency of
urination, systemic hypertension, uremic symptoms, costovertebral tenderness (ie,
enlarged kidneys [rare]), and gross hematuria. Gross hematuria is the most common
abnormality observed in patients with acute PSGN and often manifests as smoky
Signs of fluid overload
Periorbital and/or pedal edema
Edema and hypertension due to fluid overload (in 75% of patients)
Crackles (ie, if pulmonary edema)
Elevated jugular venous pressure
pleural effusion (possible)
Rash (ie, vasculitis, Henoch
Renal angle (ie, costovertebral) fullness or tenderness, joint swelling, or tenderness
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The causal factors that underlie this syndrome can be broadly divided
into infectious and
Streptococcal: Poststreptococcal GN usually develops 1
3 weeks following
acute infection with specific nephritogenic strains of group A beta
streptococcus. The incidence of GN is appr
10% in persons with
pharyngitis and 25% in those with skin infections.
Nonstreptococcal postinfectious glomerulonephritis
Infective endocarditis, shunt nephritis, sepsis, pneumococcal
pneumonia, typhoid, secondary syphili
s, meningococcemia, and infection with
resistant Staphylococcus aureus (MRSA)
Hepatitis B, infectious mononucleosis, mumps, measles, varicella,
vaccinia, echovirus, parvovirus, and coxsackievirus
Multisystem systemic diseases
Systemic lupus erythematosus, vasculitis,
Schönlein purpura, Goodpasture syndrome, Wegener
Primary glomerular diseases
Membranoproliferative GN (MPGN), Berger
(ie, immunoglobulin A [IgA] nephropathy), "pure" mesangial
Barré syndrome, radiation of Wilms tumor,
tetanus vaccine, serum sickness
Glomerulonephritis, Diffuse Proliferative
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Urinalysis and sediment examination
These tests are crucial in the evaluation of patients with acute nephritic
Look for protein, blood, RBCs and WBCs, dysmorphic red cells,
acanthocytes, cellular (ie, RBC, WBC)
casts, granular casts, and oval fat
bodies. In some instances, marked sterile pyuria is present.
Finding RBC casts is an almost pathognomonic sign of GN.
Urine electrolytes, urine sodium, and fractional excretion of sodium (FENa)
assays are needed to
assess salt avidity.
Blood, urea, and nitrogen (BUN); serum creatinine; and serum electrolytes
(especially serum potassium level)
Complete blood cell count
Erythrocyte sedimentation rate
Complement levels (C3, C4, CH50)
Low C3 levels are found in almos
t all patients with acute poststreptococcal
nephritis; C4 levels may be slightly low. Hypocomplementemia is noted
73.9% of adult patients.
Type III cryoglobulinemia may be present.
hour urine test for total protein and creatinine clearance:
that creatinine clearance is a "steady
state" measurement. The creatinine clearance
may not reveal the true picture because of rapidly changing renal function; therefore,
it is better to wait until renal function has stabilized before performing
O titer (ASOT) or streptozyme titer: Increasing titer levels confirm
recent infection. In patients with skin infection, anti
DNase B titers are more sensitive
than ASOT for infection with
NAPR: Levels are elevated in streptococcal infections with GN but not in
streptococcal infections without GN.
If MRSA is the inciting agent, then hypocomplementemia is usually not present, but
plasma immunoglobulins, especially IgA, are markedly elevated.
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Qualitative estimation of proteinuria: Determination of high
molecular weight (HMW)
protein, like fractional excretion of IgG (FEIgG), and low
molecular weight (LMW)
protein, like alpha
microglobulin, may help predict the clinical outcome and may
in guiding steroid and immunosuppressive therapy, especially in patients with
primary glomerular diseases with nephrotic syndrome.
Assesses renal size
Assesses echogenicity of renal cortex
Generally, a renal biopsy is not necessary for a diagnosis of acute PSGN; however,
in most cases, it is important because histology guides both prognosis and therapy.
Diffuse endocapillary proliferative changes are found.
The most common histologic patterns
are diffuse (72.1%), focal (12.8%), and mesangial (8.1%) proliferative GN in adults.
postinfectious GN, the glomerulus is hypercellular with marked cellular infiltration (ie,
polymorphonuclear neutrophils, monocytes)
. Immunofluorescence may show fine, granular
deposits of immunoglobulin G in a "starry sky" appearance. Large subepithelial deposits may
be observed on electron microscopy.
Treatment of acute PSGN is mainly supportive because there
is no specific therapy for renal
disease. Treat the underlying infections when acute GN is associated with chronic infections.
Antibiotics (eg, penicillin) are used to control local symptoms and to prevent
spread of infection
to close contacts.
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Antimicrobial therapy does not appear to prevent the development of GN,
except if given within the first 36 hours.
Loop diuretic therapy
Loop diuretics may be required in patients who are edematous and
hypertensive in order to remove excess fluid and to correct hypertension.
Relieves edema and controls volume, thereby helping to control volume
related elevation in BP.
Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may
be used if severe hypertension or encephalopathy is present.
Glucocorticoids and cytotoxic agents are of no value, except in severe cases
Sodium and fluid
For treatment of signs and symptoms of fluid retention
(eg, edema, pulmonary edema)
Protein restriction for patients with azotemia
If no evidence of malnutrition
Recommend bed rest until signs of glomerular inflammation and ci
subside. Prolonged inactivity does not benefit in the patient recovery process.
The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to
eradicate the infection.
streptococcal infections, early antibiotic therapy may prevent antibody response to
exoenzymes and render throat cultures negative, but may not prevent the development of
Penicillin V (Pen VEE K, V
More resistant than penicillin G to hydro
lysis by acidic gastric secretions and is absorbed
rapidly after oral administration. 250 mg of penicillin V = 400,000 U of penicillin.
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500,000 U PO q6
90,000 U/kg/d PO in 3
6 divided doses
Probenecid can incr
ease effects; coadministration of tetracyclines can decrease effects;
aminoglycosides show synergistic bactericidal effect in vitro against some strains of
enterococci and viridans streptococci
Decrease plasma volume and edema by causing diuresis. The reduction in plasma volume
and stroke volume associated with diuresis decreases cardiac output and, consequently, BP.
Increases excretion of water by interfering with chloride
ding cotransport system,
inhibiting sodium and chloride reabsorption in ascending loop of Henle and distal renal
Rapidly absorbed from the GI tract. The diuretic effect is apparent within 1 h of PO
administration, peaks by second h and effect lasts
6 h. Following IV administration
diuresis occurs within 30 min; duration of action is about 2 h; 66% of dose is excreted in the
80 mg PO, titrate to satisfactory diuresis in 20
mg increments q6h; not to
exceed 200 mg per dose; once effective single dose determined, may repeat qd/tid
40 mg PO bid; titrated to desired response; if 40 mg PO bid does not lead to clinically
significant response, add another antihypertensive agent rather than i
ncreasing the dose
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1 mg/kg PO/IV; not to exceed 2 mg/kg PO qd or 1 mg/kg IV qd; in newborn and
premature babies, daily dose should not exceed 1 mg/kg
Metformin decreases concentrations; furosemide interferes with hypoglycemic eff
antidiabetic agents and antagonizes muscle
relaxing effect of tubocurarine; auditory toxicity
appears to be increased with coadministration of aminoglycosides and furosemide; hearing
loss of varying degrees may occur; anticoagulant activity of warfa
rin may be enhanced when
taken concurrently with this medication; increased plasma lithium levels and toxicity are
possible when taken concurrently with this medication; potentiate hypotensive effect of
various antihypertensive agents; may enhance the neph
rotoxicity of cephaloridine; sucralfate
may reduce absorption; increases risk of salicylate toxicity; NSAIDs, probenecid,
anticonvulsants may attenuate effect of furosemide
Documented hypersensitivity; hepatic coma, anuria, and state of s
evere electrolyte depletion
Renal failure (rare)
Generalized anasarca and hypoalbuminemia (secondary to severe proteinuria)
Prognosis of acute PSGN is generally excellent in children.
Within a week or so of onset, most patients with PSGN begin to experience
spontaneous resolution of fluid retention and hypertension.
C3 levels may normalize within 8 weeks after the first
sign of PSGN.
Proteinuria may persist for 6 months and microscopic hematuria for up to 1 year after
onset of nephritis.
Eventually, all urinary abnormalities should disappear, hypertension should subside,
and renal function should return to normal.
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In adults with PSGN, full recovery of renal function can be expected in just over half
of patients, and prognosis is dismal in patients with underlying diabetic
Few patients with acute nephritis develop rapidly progressive rena
Nephritis associated with MRSA and chronic infections usually resolves after
treatment of the infection.
Immunity to type M protein is type
lasting, and protective. Repeated
episodes of PSGN are therefore unusual.
ximately 15% of patients at 3 years and 2% of patients at 7
10 years may have
persistent mild proteinuria. Long
term prognosis is not necessarily benign. Some
patients may develop hypertension, proteinuria, and renal insufficiency as long as 10
after the initial illness.
Counsel patients about the need for the following measures:
Salt restriction during the acute phase to control edema and volume
BP monitoring at periodic intervals
term monitoring of patients with persistent urinary abnormalities
and elevated BP
Consideration of protein restriction and angiotensin converting enzyme
patients who show evidence of persistent abnormalities or in
those who deve
lop late evidence of progressive disease)
Early antibiotic treatment of close contacts
History taking about
year old boy, present with hematuria. A history of a recent throat infection + 14 days
before admission. Physical examination revealed temperature is 37,20C, blood pressure
140/100 mmHg, periorbita edema +. Laboratory examination revealed albumin, cho
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was normal. BUN : 168 mg/dl, creatinine serum : 4,8 mg/dl. ASO titer : 400 iu/ml, CRP :
negative. Urinalysis revealed albumin +2, dysmorphic erythrocyte, erythrocyte/granular casts
: +, leucocyte 3
5 /hpf. What is the diagnosis in this patient ?
Discuss a problem of
Explain the possibility mechanism, why the patient suffered from those symptoms?
Can you draw
in your patient?
What will the patient suffer from the next complication? How?
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What is your opinion about the laboratory result?
Do you need further examination to confirm your hypothesis about the patient problem?
Assessement system consist of: formative and summative ssessement.
tudent activity during discussion
Summative assessement: MCQ examination after the completion of teaching
PBL assessment in the last semester
Yoshizawa N. Acute glomerulonephritis. Intern Med. Sep 2000;39(9):687
Ahn SY, Ingulli E. Acute poststreptococcal glomerulonephritis: an update. Curr Opin
Pediatr. Apr 2008;20(2):157
Oda T, Yamakami K, Omasu F, et al. Glomerular plasmin
activity in relation to
associated plasmin receptor in acute poststreptococcal glomerulonephritis. J
Am Soc Nephrol. Jan 2005;16(1):247
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Wen YK, Chen ML. The significance of atypical morphology in the changes of spectrum
postinfectious glomerulonephritis. Clin Nephrol. Mar 2010;73(3):173
Nasr SH, Markowitz GS, Stokes MB, et al. Acute postinfectious glomerulonephritis in the
modern era: experience with 86 adults and review of the literature. Medicine (Baltimore).