OS 214: Renal Dr.

Agnes Mejia
Glomerulonephritis (GN) Exam 1&2

OUTLINE O2sat 92%) Severe

I. Introduction Uncompensated
II. Glomerulonephritis Metabolic acidosis (low
III. Pathogenesis of Glomerulonephritis pH, low HCO3;
IV. Approach to Patient with causes tachypnea)
CXR To rule out pneumonia Heart not enlarged but
Glomerulonephritis
with congestion
V. Forms of Glomerulonephritis Showed pulmonary
A. IgA Nephropathy edema
B. Poststreptococcal Glomerulonephritis EKG Check for hyperkalemia Peaked T waves
C. Membranous Glomerulonephritis (denotes hyperkalemia)
VI. Summary  you have to give
VII. Socioeconomic impact of calcium gluconate as
Glomerulonephritis treatment
VIII. Figures UTZ Visualize the kidney: Small shrunken kidney
If enlarged (e.g. 12 Cortex should at least be
cm)=acute GN, reversible 4.5cm thick
Note: The lecturer did not provide a powerpoint. Thank you to
If
Irving for sending pictures of the ppt for this trans. Please be
shrunken=ESRD,irreversi
reminded that the exam questions will come mainly from HPIM
ble
17th ed.; topics included are general information on glomerular
(Normal Filipino size:9.6
disease, GN, IgA nephropathy, PSGN and MGN.
cm in length; Normal
Caucasia:11-12 cm)
I. INTRODUCTION *Normal  globular, thick
A. Case of ER, presented with: cortex
o high BP (160/100), HR 104, RR 30/min Urinalysis “window to glomerular -low sp. gravity
o pale, sallow (in between pallor and jaundice) disease” -granular casts
o “peculiar fetor” – fruity smell -early morning urine -Increase RBC and
expected to have a dark, WBC
o evidence of cardiac damage (Grade II Av block intense color if kidney is -mucus threads rare
hypertensive) but not yet in CHF due to absence of able to concentrate urine denotes that urine was
s3 - concentrated (Sp. well collected
o no evidence of liver involvement gravity 1.020-1.030) -px has no fever but high
o ++ bipedal edema -Acute GN – red cell WBC may indicate
casts; RBCs degenerate sterile pyuria
o Dry skin, good and equal pulses
to fine/coarse granular
o Basal crepitant rales casts reflects chronicity
-Hyaline casts can be
B. Primary Impression: UREMIA (symptom diagnosis) found in a normal person
Symptoms seen in the ER -Most common cause of
o Vomiting pus cells non infective
o Tremors pyuria
o Anorexia
*if creatinine is high, BUN is expected to be abnormal; if BUN
o Weakness
is high, creatinine is not necessarily high
o SOB
*the presence of protein in the urine is not correlated with the
o Pruritus specific gravity of the urine since SG indicates the ability of
o Easy fatigability the kidneys to concentrate. Even if this is intact, the kidneys
o Irritability can still spill out urine.
*those in asterisks are the cheaper tests, so they are the most
Full blown Uremia (not seen in ER) economical and efficient in terms of information.
o Somnolence
o Seizures D. Final Diagnosis:
o Disorientation o Uremia secondary to ESRD (CKD Stage V)
o Coma secondary to Chronic Glomerulonephritis (CGN)

*Azotemia is a laboratory diagnosis Basis for diagnosis:

Uremia a clinical diagnosis CGN
o young adult, hypertension at age 19 (hypertensive
C. Labs Requested nephrosclerosis takes about 20 years to develop,
and so it is an unlikely ddx)
Lab Purpose Finding in ER o hematuria, pyuria
CBC Check for anemia due to Low Hg (7) o small kidneys (denotes a chronic problem, not acute)
pallor
BUN To asses kidney function, Elevated (60umol/L) ESRD
but creatinine is more
o shrunken kidneys
important
*Creatinine Single most important Increased (1800 umol/L) o uremia, anemia, low Ca
test for uremia (uremic if o Inc phosphorus
azotemic); if high, tells
you that px likely has *Single most important determinant of chronicity shrunken
kidney disease kidneys
Electrolytes To check for acidosis Decreased
Ca
Phosphorus *Severe renal failure Ca low, Phosphorus high
Elevated (6)
**K Needed if urgent action is Elevated (5.9)
required (can easily kill **ER is a UP student; inc BP at age 19 (140/90). ER was
the patient) erroneously treated as UTI for 3 years in a male with no
***ABG Needed if urgent action is (pH7.2; pCO235; symptoms and an abnormal urinalysis; ER passed
required pO294; HCO311; engineering boards 3 days before he underwent hemodialysis!

March 6, 2009/Friday Page 1 of 7

Seth, Ian
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis (GN) Exam 1&2

*Immunofluorescence can be used to determine whether

immune complexes are in-situ or circulating

My Goals (which I guess have to be our goals) *Overlapping etiologies may produce similar glomerular
1. To be aware lesions display common patterns of injury (syndrome); this is
2. To be suspicious evident in microscopy:
3. To Set the Alarm IgA paramesangial; can still see spaces in glomerulus; most
common in Asians
II. Glomerulonephritis
-inflammation of the glomerular capillaries Poststrep GN (PSGN) – same pattern of injury can be seen in
lupus; immune-complex GN; most common post infectious
a. Normal Kidneys:
o smooth surface Membranous GN (MGN) –same pattern can be seen in
o pinkish cortex idiopathic, Hepatitis, and drug-induced; just hits the basement
o reddish medulla membrane, causing it to thicken; most common in men
o yellow calyces, pelvis
o In GN: kidneys are pale IV. Approach to Patient with Glomerulonephritis

*Kidney disease has 10 types but can manifest the same way. A. History and PE (what to look at)
But if you look inside the kidneys, the pathology is actually o confined to the kidneys or systemic? acute or
different. They hit different parts of the kidney thus histology chronic?
is important! o signs and symptoms (what to ask the px)
• dysuria – pain during urination?
b. Glomerulus • nocturia – urination at night?
o 600 thousand – 2 million (all in all) in a normal • hematuria – blood in the urine? (2 kinds gross
individual and microscopic)
*prematures have less glomeruli  higher tendency • retention/incontinence – incomplete
for hypertension  higher tendency for renal disease voiding?
at age 50 • frequency – urinating more often?
o is a ball of capillaries (“berries”) with afferent and • Sediments- may “latak” sa ilalim ang ihi?
efferent arterioles (histology: stalk – where efferent
• frothy urine – like beer?
and afferent arterioles run)
o glomerular capillaries filter 120-180 L/d of plasma • edema
water o last known urinalysis/creatinine
o filtration occurs through a physicochemical barrier o pregnancy status (preeclampsia); birth control pills
governed by pore size and negative electrostatic o last normal BP
charge o Blood pressure
o glomerulus is an imperfect barrier • must give exact value, not just saying
*e.g. albumin-despite its negativity, readily passes normal or high, because what is high for
through due to its small radius (3.6nm vs. 4nm radius one person may be normal for another
of glomerular basement mebrane (GBM) slit-pores); o Urinalysis
albumin is reabsorbed in the proximal tubules (urine • window to glomerular disease
normally contains only 8-10 mg) • Quality of urine: clear, cloudy or bloody
(gross hematuria)
*Glomerulonephritis can affect any part of the glomerulus *if with gross hematuria and is painless consider
(mesangium, parietal epithelium, basement membrane, malignancy until proven otherwise; if painful,
podocytes) and will manifest differently. consider urethritis
In GN: the glomeruli are full of scars
*Dilute urine  yellow concentrated
Pathogenesis:
*Cloudy tea colored
(1) (2) *Bloody gross hematuria
Circulating immune complexes In-situ immune complexes
Table 277-1. Urine assays for albumin/proteinuria (HPIM 17th ed)
T-cells (CD 4/8) activation 24Hr Albumin/ Dipstick 24Hh
Albumin creatinine proteinuri Urine
Loca activation of toll-like receptors on Glomerular Cells (mg/24h) ratio a Protein
(mg/G) (mg/24h)
Deposition of Immune Complexes
Normal 8-10 <30 - <150
Complement injury Microalbu 30-300 30-300 -/trace/1+ -
minuria
Glomerular injury Proteinuria >300 >300 Trace-3+ >150
Mononuclear infiltration
V. Forms of Glomerulonephritis (Patterns of Clinical GN)
Cytokine release

Attract more inflammatory cells Form Prototype Disease

Acute Nephritic IgA Nephropathy
Glomerular damage Infectious Disease PostStreptococcal GN
Associated; Nephritic (PSGN)
*In summary, GN may be caused by circulating or in situ Nephrotic Membranous GN
immune complexes, but whichever the cause is, they both
follow the path of inflammation via T-cell activation Basement membrane Alport’s syndrome
Glomerular Vascular Disease ANCA small vessel vasculits

March 6, 2009/Friday Page 2 of 7

Seth, Ian
 OS 214: Renal
Glomerulonephritis (GN)
Pumonary-Renal Goodpasture’s disease
*just focus on the first three as said by the lecturer, ayt?
A. IgA Nephropathy
CASE:
31 female
Routine annual Physical checkup
Urinalysis
- RBC –TNTC
- WBC – 0-3
- Protein (-)
- Casts (-)
BP  120/70
o immune complex mediated GN defined by the
presence of diffuse mesangial IgA deposits often
associated with mesangial hypercellularity
o circulating immune complexes get deposited in the
mesangium or podocytes (not the basement
membrane [BM])
o IgM, IgG, C3, or immunoglobulin light chains can be
codistributed with IgA
o Mild – do not undergo dialysis
o RPGN (rapidly progessive)- end up in dialysis after 6
mos
• POSTstrep GN - tea colored urine happens 2
weeks after infection
• In IgA – happens with the infection
• Pathogenesis: defective immune response formation of
immune complex proinflammatory, proproliferative,
proapoptotic, profibrotic + milieu in glomeruli
mesangial/podocyte injury, capillary hypertension, altered
perm selectivity, glomerulosclerosis, tubulo-interstitial
fibrous hematuria, proteinuria, decreased GFR
• Epidemiology
o most common form of GN worldwide
o 30% in Asia and Pacific RimEast > West
o 20% in southern Europe
o low prevalence in N. Europe & N. America
o Male > Female
o peak incidence: 2nd-3rd decade of life
o rare familial clustering
• Presentation
o most common presentations are:
• recurrent episodic macroscopic hematuria
following a respiratory infection in children
• asymptomatic microscopic hematuria seen
in adults
o between episodes, urinalysis is normal
o in persistent hematuria, increasing proteinuria is
found
• Differentials
o Henoch-Schonlein Purpura- can be
distinguished for IgA Nephropathy by prominent
systemic sx, younger onset (<20yrs old),
preceding infection and abdominal complaints
o Crohn’s disease, chronic lover disease, GI
adenocarcinoma, etc –also present with IgA
deposition in mesangium; can be differentiated
due to absence of significant glomerular
inflammation.
• Progression
o generally a benign disease, but 25-30%
progress to renal failure over 20-25 yrs.
o 5-30% go into complete remission
March 6, 2009/Friday
Dr. Agnes Mejia
Exam 1&2
o sometimes recur post transplant
o risk factors for renal failure: HPN, proteinuria,
absence of episodic macroscopic hematuria,
male, older age of onset, sever renal biopsy
changes
o “Point of no return” – stage where treatment is
insufficient usually when creatinine is at least 2
o the clinical prognostic index (CPI) of GN–made
in Verona, Italy; a scoring system that predicts
the prognosis of GN
• 2pts for Serum Creatinine> 1.4mg/dl
• 1pt for Proteinuria> 1g/24 hrs
• 1pt for presence of HPN
• 1pt patient > 30 years old
o Score of 0-2*: higher 10-year renal survival; 3-5:
lower 10-year renal survival; most likely to end
up in dialysis; hence, creatinine is the single
most impt predictors of survival since it
automatically gives you 2pts if abnormal
*Immunoflourescence  positive for IgA
• Treatment
o Evidence-based: ACEI-ARB, Steroids, fish oil
(severe only), sequential, cyclophosphamide:
azathioprine (progressive only)
o Non-evidence Based: azathioprine/MMF, CNI
(CsA Tacro), IVIg, Leflunomide,
heparin/warfarin/dipyridamole, tonsillectomy
*IgA GN is common, progressive, but treatable
B. PostStreptococcal Glomerulonephritis (PSGN)
CASE:
22 male
1 month impetigo in L leg
Pus, crust, swelling, redness, fever  tea colored urine, dec
outpu, puffy eyelids, anorexi, easy fatigability, inc BP
o also known as Postinfectious GN
o prototype for acute endocapillary proliferative GN
o classically not a nephritic syndrome
• Pathogenesis: putative streptococcal antigens circulating
1-C, activation of complement with cell mediated injury
deposition in GBM
• Epidemiology
o typically sporadic
o children between 2-14 yrs (10% in px>40yrs)
o Males > Females
o 10% pts>40yrs
o familial/cohabitant incidence is high-40%
o M types of Streptococci (nephritogenic strains)
o impetigo- M types 2, 47, 49, 55, 57, 60;
PSGN develops 2-6 wks after a skin infection
o Pharyngitis (nephritogenic strain)- M types
1,2, 3, 4, 12, 25, 49; PSGN develops 1-3 wks
after strep upper respiratory infection
(pharyngitis)
• Labs
o Decreased CH50, decreased C3
o Inconsistently positive culture (10-70%)
o Increased ASO titers (30%)
o Anti-DNase (70%)
o Antihyaluronidone Ab (40%)
• Presentation
Page 3 of 7
Seth, Ian
 OS 214: Renal
Glomerulonephritis (GN)
o classic presentation of acute nephritic px: HPN,
hematuria, RBC casts, pyuria, mild to moderate
proteinuria
o oliguric renal failure
o systemic symptoms include headache, malaise,
o anorexia, flank pain (swollen renal capsule) in 50%
of cases
o in the 1st week of symptoms: 90% have depressed
CH50, decreased C3 (because they are circulating
and get deposited in the GBM)
o positive strep cultures are inconsistent
Renal Biopsy
o diffuse proliferative: little bowman’s space seen
o hypercellularity of mesangial and endothelial cells
o glomerular infiltrates of PMN leukocytes
o granular subendothelial immune deposits of IgG,
IgM, C3, C4, C5-9
o subepithelial deposits-“humps”
o RPGN – with crescents
• Diagnosis
o renal biopsy is not necessary
o subclinical cases are reported to be more
common than clinical nephritis and
characterized by asymptomatic microscopic
hematuria and low serum complement levels
• Treatment
o supportive
• for HTN
• for Edema
• Dialysis if indicated (oliguric)
o antibiotic tx for strep infection for px and
cohabitants
o no role for immunosuppressive tx even if
crescents are present
o good prognosis, rare recurrence, permanent
renal failure is very uncommon (1-3%)
o complete resolution of hematuria and proteinuria
in children occur in 3- 6 weeks of onset of
nephritis
C. Membranous Glomerulonephritis (MPGN/MGN)
o also called Mebranous Nephropathy (MGN)
o in situ formation of immune complexes with megalin-
receptor associated protein as the putative agent
• Epidemiology
o 30% of nephrotic syndrome (NS) in adults
o rare in children but most common NS in the elderly
o peak incidence between 30-50 years
o Males > Females (2:1)
o 25-30% secondary to malignancy (tumors of lung,
breast, colon), infection (Hep B, malaria,
schistosomiasis), rheumatologic disorders (lupus)
o other etiologies are Drug-induced MGN
o Unknown/Idiopathic is still the most common MGN
Causes:
• Idiopathic
• Secondary: malignancy,infective Hep B,
Rheumatology (SLE), Drugs (Gold)  25-30% is
secondary
• Presentation
o 80% with nephrotic syndrome (NS)* and
nonselective proteinuria
o 50% with microscopic hematuria
Nephrotic Syndrome
March 6, 2009/Friday
Dr. Agnes Mejia
Exam 1&2
• heavy proteinuria (24h urine total protein > 3g),
minimal hematuria, hypoalbuminemia,
hypercholesterolemia, HPN
• if untreated leads to progressive glomerular
injury, decline in GFR and renal failure
Edema
There are 2 theories for the cause of edema due to NS:
1. Underfill  protein spillage  low albumin
(albumin acts as the magnet that attracts fluid)
 low oncotic pressure  low intravascular
volume  secondary sodium retention 
EDEMA
2. Overfill  low GFR  low RPF and low FF
primary Na retention  Expanded ECF volume
 EDEMA
Nephrotic syndrome (NS) is described as: 24hr total
Pr>3gm, hypertension, hypercholesterolemia,
hypoalbuminemia, edema/anasarca
*therapy of edema in NS: low Na diet, oral loop diuretic,
goal of 1-2lbs edema loss/day
Renal Biopsy
o LM: uniform thickening of the BM along the
peripheral capillary loops
o Immunoflorescence: diffuse granular deposits of
IgG and C3
o EM: electron dense subepithelial deposits
• Progression
o some reports suggest that degree of tubular
atrophy or interstitial fibrosis are better
predictors than the stage of glomerular disease
o high recurrence rates
o Abrupt onset of edema
o spontaneous remission occur in 20-30% of
patients and occur late in the course after year
of NS
o 1/3 have relapsing NS but maintain normal renal
functions
o 1/3 develop Renal failure of die of complications
of NS
o risk factors for worse prognosis: male, older age,
HPN, persistent proteinuria
o MGN has highest reported incidence of renal
vein thrombosis, pulmonary embolism and DVT
complications among NS
• Treatment
o symptomatic treatment: edema (oral loop
diuretics, low Na diet, target is loss of 1-2lbs or
fluid per day), HPN, dyslipidemia,
hypercholesterolinemia (lipid lowering agents to
decrease risk for CVS disease), proteinuria
(inhibition of RAS)
o immunosuppresive drugs (steroids and
cyclophosphamide, chlorambucil, cyclosporine,
tacrolimus, rituximab) for primary MGN and
persistent proteinuria (>3.0g/24hrs)
o experience with mycophenolate mofetil or anti-
CD20 antibody is limited
o prophylactic anticoagulation (controversial but
recommended) in px with sever proteinuria
Low risk
Normal renal function
Protein <4
Medium
Normal fxn
Page 4 of 7
Seth, Ian
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis (GN) Exam 1&2

Protein >=4 <8

High
Abnormal fxn
Protein >= 8

VI. SUMMARY

Be aware
o Family History: HTN, DM, CVD, Gout, Dialysis,
ESRD

Be suspicious
o BP > 140/90
o Frothy/cloudy urine
o Crea > 1.5 mg/dL or 132 umol/L
o GFR < 60
o Nocturia
o Dysuria

Set the Alarm

o Urinalysis
o BP >130/80
o Crea 1.5mg/dl, 132 mmol/L

3 Syndromes and their signs

Form Prototype Disease Proteinuria Albuminuria
Acute IgA Nephropathy +/++ +++
Nephritic
Infectious PSGN +/++ +++
Disease
Associated;
Nephritic
Nephrotic MGN ++++ +

*the GFR should be greatly decreased before creatinine

manifests with an abnormality. Hence, be suspicious agad!

*A normal creatinine doesn’t mean there’s normal kidney

function, so always compute!
Therapeutic Intervention
o AntiInflammatory: Prednisone, tacrolimus, MMF,
ritazimab
o Reduce Proteinuria: ACEI, ARB
e.g. FSGS-progression, remission, relapse if
mainatained on prednisone, but if given combination
therapy of prednisone and mycophenolate, disease
is kept in remission
Postinfectious (poststreptococcal) glomerulonephritis.The
glomerular tuft shows proliferative changes with numerous PMNs,
with a crescentic reaction in severe cases (A1). These deposits
localize in the mesangium and along the capillary wall in a
subepithelial pattern and stain dominantly for C3 and to a lesser
extent for IgG (A2). Subepithelial hump-shaped deposits are seen by
electron microscopy (A3).

VII. Socioeconomic impact of Glomerulonephritis

o Dialysis: Php40,000 per month
o Kidney transplant: Php1.2 M
o Maintenance medications: Php60,000 per month

*Hence: set the alarm! Because GN is a TREATABLE

disease; if treated early, there’s no need for these expensive
interventions.

VIII. Figures

March 6, 2009/Friday Page 5 of 7

Seth, Ian
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis (GN) Exam 1&2

IgA nephropathy
There is variable mesangial expansion due to mesangial
deposits, with some cases also showing endocapillary proliferation or
segmental sclerosis (C1). By immunofluorescence, deposits are
evident (C2).

Membranous glomerulopathy. Membranous glomerulopathy is due

to subepithelial deposits, with resulting basement membrane reaction,
resulting in the appearance of spike-like projections on silver stain
(B1). The deposits are directly visualized by fluorescent anti IgG,
Hyaline Cast
revealing diffuse granular capillary loop staining (B2). By electron
microscopy, the subepithelial location of the deposits and early
surrounding basement membrane reaction is evident, with overlying
foot process effacement (B3)

Berry-like configuration of the glomeruli.

March 6, 2009/Friday Page 6 of 7

Seth, Ian
 OS 214: Renal
Glomerulonephritis (GN)
Immunofluorescent staining of glomeruli with labeled anti-
IgG demonstrating linear staining (D1) from a patient with anti-
GBM disease or immune deposits from a patient with
membranous glomerulonephritis compared to IgG lumpy-
bumpy staining (D2). Preformed immune deposits can
preciptate from the circulation and collect along the glomerular
basement membrane (GBM) in the subendothelial space or
can form in situ along the subepithelial space.
March 6, 2009/Friday
Dr. Agnes Mejia
Exam 1&2
The mechanisms of glomerular injury have a complicated
pathogenesis. Immune deposits and complement deposition
classically draw macrophages and neutrophils into the
glomerulus. T lymphocytes may follow to participate in the injury
pattern as well.
*Amplification mediators such as locally
derived oxidants and proteases expand this
inflammation, and depending on the location
of the target antigen and the genetic
polymorphisms of the host, basement
membranes are damaged with either
endocapillary or extracapillary proliferation
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Seth, Ian