module-gna by xiaopangnv


                             Contributor: dr. Krisni S ., Sp.A(K)


After completing this module, the students be able to:

    1. Describe the acute glomerulonephritis
    2. Explain the pathophysiology of acute glomerulonephritis
    3. Describe many causes of acute glomerulonephritis
    4. Describe the complication of acute glomerulonephritis
    5. Plan assessement of acute glomerulonephritis
    6. Communicate and taking history with acute glomerulonephritis


            Knowledge & Attitude                               Skill & attitude

    1.   Overview lecture                          1. Overview lecture of History taking in
    2.   Self directed learning                       acute glomerulonephritis
    3.   Small class discussion                    2. History taking formative assessement
    4.   Instructure lecture                          (checklist)
    5.   Assessement                               3. OSCE summative assessement in
                                                      the last semester


         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 glomerulus is manifested
by proliferation of cellular elements secondary to an immunological mechanism. 1



Acute GN has 2 components: structural changes and functional changes.

Structural changes

•   Cellular proliferation: This leads to an increase in the number of cells in the glomerular
    tuft because of the proliferation of endothelial, mesangial and epithelial cells. The

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    proliferation could be endocapillary (ie, within the confines of the glomerular capillary
    tufts) or extracapillary (ie, in the Bowman space involving the epithelial     cells).      In
    extracapillary proliferation, proliferation of parietal epithelial cells leads to the
    formation of crescents, a feature characteristic of certain forms                of rapidly
    progressive GN.

•   Leukocyte proliferation: This is indicated by the presence of neutrophils and monocytes
    within the glomerular capillary lumen and often accompanies cellular proliferation.

•   Glomerular basement membrane thickening: This development appears as thickening
    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 endothelial or epithelial side of   the
    basement membrane.

•   Hyalinization or sclerosis: These conditions indicate irreversible injury.

•   Electron-dense deposits: Such deposits could be subendothelial, subepithelial,
    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

    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.

Poststreptococcal glomerulonephritis

    M-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 glyceraldehyde-3-phosphate
dehydrogenase that functions as a plasmin(ogen) receptor.2 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 glomerulonephritis but are
not elevated in streptococcal infections without glomerulonephritis, whereas anti-streptolysin-
O titers are elevated in both circumstances.3 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 staphylococcus



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, travel, valve
    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): Inquire
    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-,
    coffee-, or cola-colored urine.


•          Signs of fluid overload

           o        Periorbital and/or pedal edema

           o        Edema and hypertension due to fluid overload (in 75% of patients)

           o        Crackles (ie, if pulmonary edema)

           o        Elevated jugular venous pressure

           o        Ascites and pleural effusion (possible)

•          Rash (ie, vasculitis, Henoch-Schönlein purpura)

•          Pallor

•          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
noninfectious groups.

       • Infectious

       o    Streptococcal: Poststreptococcal GN usually develops 1-3 weeks following
            acute infection with specific nephritogenic strains of group A beta-hemolytic
            streptococcus. The incidence of GN is approximately 5-10% in persons with
            pharyngitis and 25% in those with skin infections. 5

       o    Nonstreptococcal postinfectious glomerulonephritis

            Bacterial - Infective endocarditis, shunt nephritis, sepsis, pneumococcal
               pneumonia, typhoid, secondary syphilis, meningococcemia, and infection with
               methicillin-resistant Staphylococcus aureus (MRSA)

            Viral - Hepatitis B, infectious mononucleosis, mumps, measles, varicella,
               vaccinia, echovirus, parvovirus, and coxsackievirus

            Parasitic - Malaria, toxoplasmosis

       • Noninfectious

       o    Multisystem systemic diseases - Systemic lupus erythematosus, vasculitis,
            Henoch-Schönlein         purpura,        Goodpasture          syndrome,         Wegener

       o    Primary glomerular diseases - Membranoproliferative GN (MPGN), Berger
            disease     (ie,   immunoglobulin    A   [IgA]    nephropathy),      "pure"    mesangial
            proliferative GN.

       o    Miscellaneous - Guillain-Barré syndrome, radiation of Wilms tumor,            diphtheria-
            pertussis-tetanus vaccine, serum sickness

Differential Diagnoses
Glomerulonephritis, Crescentic                               Goodpasture Syndrome
Glomerulonephritis, Diffuse Proliferative                    Hemolytic-Uremic Syndrome
Glomerulonephritis, Membranoproliferative                    Nephritis, Interstitial
Glomerulonephritis, Poststreptococcal                        Nephritis, Lupus
Glomerulonephritis, Rapidly Progressive

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Laboratory Studies

      Urinalysis and sediment examination

            o   These tests are crucial in the evaluation of patients with acute nephritic

            o   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.

            o   Finding RBC casts is an almost pathognomonic sign of GN.

            o   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)

            o   Low C3 levels are found in almost all patients with acute poststreptococcal
                nephritis; C4 levels may be slightly low. Hypocomplementemia is noted in
                73.9% of adult patients.

            o   Type III cryoglobulinemia may be present.

      Twenty-four–hour urine test for total protein and creatinine clearance: Remember
       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 creatinine

      Antistreptolysin-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 Streptococcus.

      Antibody to 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-1-microglobulin, may help predict the clinical outcome and may
        help in guiding steroid and immunosuppressive therapy, especially in patients with
        primary glomerular diseases with nephrotic syndrome.

Imaging Studies

       Abdominal ultrasound

            o   Assesses renal size

            o   Assesses echogenicity of renal cortex

            o   Excludes obstruction


       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.

Histologic Findings

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. 4 In
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.


Medical Care

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.

•       Antimicrobial therapy

        o       Antibiotics (eg, penicillin) are used to control local symptoms and to prevent
                spread of infection to close contacts.

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           o      Antimicrobial therapy does not appear to prevent the development of GN,
                  except if given within the first 36 hours.

•          Loop diuretic therapy

           o      Loop diuretics may be required in patients who are edematous and
                  hypertensive in order to remove excess fluid and to correct hypertension.

           o      Relieves edema and controls volume, thereby helping to control volume-
                  related elevation in BP.

           o      Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may
                  be used if severe hypertension or encephalopathy is present.

           o      Glucocorticoids and cytotoxic agents are of no value, except in severe cases
                  of PSGN.


•          Sodium and fluid restriction - 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 circulatory congestion
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.

Antimicrobials (antibiotics)

In 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-Cillin K)

More resistant than penicillin G to hydrolysis 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 q6-8h


25,000-90,000 U/kg/d PO in 3-6 divided doses


Probenecid can increase effects; coadministration of tetracyclines can decrease effects;
aminoglycosides show synergistic bactericidal effect in vitro against some strains of
enterococci and viridans streptococci


Documented hypersensitivity

Loop diuretics

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.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding 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 for 4-6 h. Following IV administration
diuresis occurs within 30 min; duration of action is about 2 h; 66% of dose is excreted in the




Initial: 40-80 mg PO, titrate to satisfactory diuresis in 20- to 40-mg increments q6h; not to
exceed 200 mg per dose; once effective single dose determined, may repeat qd/tid


20-40 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 increasing the dose


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0.5-1 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 effect of
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 warfarin 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 nephrotoxicity 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 severe electrolyte depletion


•      Renal failure (rare)

•      Pulmonary edema

•      Generalized anasarca and hypoalbuminemia (secondary to severe proteinuria)

•      Hypertension

•      Hypertensive encephalopathy


•      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 renal failure.

•       Nephritis associated with MRSA and chronic infections usually resolves after
        treatment of the infection.

•       Immunity to type M protein is type-specific, long-lasting, and protective. Repeated
        episodes of PSGN are therefore unusual.

•       Approximately 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-
        40 years after the initial illness.

Patient Education

•       Counsel patients about the need for the following measures:

        o       Salt restriction during the acute phase to control edema and volume-related

        o       BP monitoring at periodic intervals

        o       Ongoing long-term monitoring of patients with persistent urinary abnormalities
                and elevated BP

        o       Consideration of protein restriction and angiotensin converting enzyme
                inhibitors (in   patients who show evidence of persistent abnormalities or in
                those who develop late evidence of progressive disease)

        o       Early antibiotic treatment of close contacts

History taking about acute glomerulonephritis see attachment

An 7-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, cholesterol

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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 ?


 1. Discuss a problem of the scenario

 2. Explain the possibility mechanism, why the patient suffered from those symptoms?

 3. Can you draw the symptoms in your patient?

 4. What will the patient suffer from the next complication? How?

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 5. What is your opinion about the laboratory result?

 6. Do you need further examination to confirm your hypothesis about the patient problem?
      What for?

     Assessement system consist of: formative and summative ssessement.
     1. Formative assessement: student activity during discussion
     2. Summative assessement: MCQ examination after the completion of teaching-
        learning process.
     3. PBL assessment in the last semester

1.   Yoshizawa N. Acute glomerulonephritis. Intern Med. Sep 2000;39(9):687-94.

2.   Ahn SY, Ingulli E. Acute poststreptococcal glomerulonephritis: an update. Curr Opin
     Pediatr. Apr 2008;20(2):157-62

3.   Oda T, Yamakami K, Omasu F, et al. Glomerular plasmin-like activity in relation to
     nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis. J
     Am Soc Nephrol. Jan 2005;16(1):247-54.

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4.   Wen YK, Chen ML. The significance of atypical morphology in the changes of spectrum
     of postinfectious glomerulonephritis. Clin Nephrol. Mar 2010;73(3):173-9.

5.   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).
     Jan 2008;87(1):21-32

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