Approach to Glomerular Disease

Outline
Glomerular Anatomy and Function
Over view of Pathogenesis of Glomerular Disease
Clinical presentation
• Asymptomatic Hematuria & Macroscopic Hematuria
• Asymptomatic Proteinuria & Nephrotic Syndrome
• Nephritic syndrome-RPGN
• Chronic GN
Evaluation of pts with Glomerular Disease
Treatment of Glomerular Disease
Glomerular Anatomy
Glomerular Anatomy
I. THE GLOMERULAR TUFT
Normal structure of the glomerulus
Glomerular capillary wall
 Composed of three layers
 Fenestrated
endothelial cells
 GBM and
 Epithelial cells
Basic renal processes:
Four processes in forming urine
1.Filtration of plasma by the glomerulus
2.Reabsorption of solute and water
3.Secretion of solute
4.Excretion of urine
 Renal function is estimated by using GFR

(amount of filtrate formed in all nephrons)

 Normal value ranges from 120 – 180L/d(≈ 125ml/min) even if it varies with wt, age,
sex, race, . . .Eg.F=95±20,M=120±25
Glomerular function…
Glomerular function…
b. Size selectivity
 Molecules of small mole wt are easily filtered

c. Charge selectivity
 Cationic molecules are usually filtered

 Other functions of the glomerulus include:

 Synthetic- epithelial cells synthesize GBM, endothelium regulates
vasomotor tone via release of prostacyclin, endothelin, & nitric oxide
 Phagocytic- mesangial cells
 Endocrine- Erythropoietin, renin(JGA), …
Glomerular disease
Glomerular injury
 Glomerulonephritis – inflammation of the glomeruli
Glomerulopathy – disease of the glomeruli
Impairment of selective filtering properties of the kidney
leading to a decreased GFR
Molecules normally not filtered such as constituents of
the blood, pass into the urine and are excreted
Nomenclature
Primary – confined to the kidney
Secondary – due to a systemic disease
Acute (days-wks),subacute(wks-mon),chronic(mon-yrs)
Focal vs diffuse
segemental vs global
Proloferative- endo/extra capillary
Membernous
Sclerosis
Fibrosis
Cresent
Nomenclature of glomerular diseases
MCD
Focal Segmental GlomeruloSclerosis
MembernoGlomerlonephrtis
MembernoProlifertive GN
Cresentic GN(RPGN)
Pathogenesis of Glomerular
Disease
Pathogenesis of Glomerular Disease
 The pathogenesis of glomerular diseases are variably linked to
the presence of:
 Genetic mutation.
 Autoimmunity
 Infection & toxin exposure
 Diabetic nephropathy
 Hypertension & Atherosclerosis
Emboli /thrombosis
Pathogenesis--- Genetic mutation

 Genetic mutation –
 congenital nephrotic syndrome from mutations in NPHS1(nephrin)
& NPHS2(podocin) affect the slit-pore membrane at birth. –
 Alport’s syndrome, from mutations in genes encoding for the
chains of type IV collagen, produces split-basement membranes
with glomerulosclerosis.
 mutations in complement factor H associate with membranoproliferative
glomerulonephritis(MPGN) or atypical hemolytic uremic syndrome (aHUS),
Hypertension & Atherosclerosis – systemic HTN &
atherosclerosis can produce pressure stress, ischemia, or
lipid oxidants that lead to chronic glomerulosclerosis.

Diabetic nephropathy – is an acquired sclerotic injury

associated with thickening of the GBM secondary to
 the long-standing effects of hyperglycemia,
advanced glycosylation end-products, and
reactive oxygen species.
Infection & toxin – Bacteria, fungi, & viruses can directly
infect the kidney producing their own antigen, some antigens
causing cross reactivity.
Most glomerular or mesangial antigens involved in
immune-mediated glomerulonephritis are unknown

Glomerular epithelial or mesangial cells may shed them or

express epitopes that mimic other immunogenic proteins
made elsewhere in the body.
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 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.
Pathogenesis…
Autoimmune response – autoimmune events that damage
glomeruli classically produce a humoral immune response.
 ideopathic MGN or MPGN are confined to kidney, while systemic
inflammatory diseases like lupus nephritis & Wegner’s
granulomatosis→ 2˚ injury.
 PSGN, lupus nephritis, & idiopathic membranous nephritis typically
are associated with immune deposits along GBM
 while anti-GBM antibodies are produced in anti-GBM disease
producing Goodpasture's syndrome primarily injures both the lung
and kidney .
Persistent damage to glomerular capillaries
spreads to the tubulointerstitium in association with
1. proteinuria.
2. efferent arterioles l
leading from inflamed glomeruli carry forward
inflammatory mediators, which induces
downstream interstitial nephritis, resulting in
fibrosis
Glomerular injury
 Glomerulonephritis – inflammation of the glomeruli
Glomerulopathy – disease of the glomeruli
Impairment of selective filtering properties of the kidney
leading to a decreased GFR
Molecules normally not filtered such as constituents of the
blood, pass into the urine and are excreted
Pathogenesis…
Autoimmune response – autoimmune events that
damage glomeruli classically produce a humoral immune
response.
 PSGN, lupus nephritis, & idiopathic membranous nephritis
typically are associated with immune deposits along GBM
 while anti-GBM antibodies are produced in anti-GBM disease.
Glomerular disease presentaion
Possible Clinical Manifestations
Haematuria – asymptomatic
Proteinuria – asymptomatic
Hypertension
Nephrotic syndrome
Nephritic syndrome
Acute renal failure
Rapidly progressive renal failure
End stage renal failure
Glomerular disease
Asymptomatic urine abnormalities are much more
common but less specific.

Patients with glomerular disease usually have some

hematuria with varying degrees of proteinuria.
Glomerular disease
Presence of glomerular disease as opposed to
tubulointersititial or vascular disease is suspected from
history
 Haematuria (especially dysmorphic red cells)Red cell casts
 Lipiduria (glomerular permeability must be increased to
allow the filtration of large lipoproteins)
 Proteinuria (may be in nephrotic range of >3.5 g/24hours)
 Hematuria
 An acceptable definition of hematuria is more than
two red cells per high-power field in centrifuged urine

 The urinary dipstick detects one to two red cells per

high power field and results in a very sensitive test. A
negative dipstick examination virtually excludes
hematuria
 Microscopic -mostly in GN. Exceptions r IgA,SCD
 Hematuria
 Hematuria is present in about 5% to 6% of the general
population and 4% of school children.

 Up to 80% of children and 15% to 20% of adults with

hematuria will have no identifiable cause

 Less than 10% of hematuria is caused by glomerular

bleeding
Non-glomerular hematuria
 neoplasms,
 trauma,
 metabolic defects such as hypercalciuria,
 vascular diseases including renal infarctions and renal vein
thrombosis,
 cystic diseases of the kidney including PCKD, medullary
cystic disease and medullary sponge kidney, and
 interstitial kidney disease such as papillary necrosis,
hydronephrosis, and drug-induced interstitial nephritis.
Renal Disease in Patients with Hematuria Undergoing Renal
Biopsy
 Isolated hematuria…
The differential pathologic diagnosis of glomerular
hematuria without proteinuria, renal insufficiency, or red
blood cell casts is
IgA nephropathy
thin basement membrane nephropathy,
hereditary nephritis, or
histologically normal glomeruli
Pyuria
Some patients with inflammatory glomerular disease, such as
acute PSGN or MPGN, have pyuria characterized by the
presence of considerable numbers of leukocytes.

This finding has to be distinguished from urine infected with

bacteria.
Proteinuria
 Abnormal proteinuria is defined as excretion of >150 mg/day
 Microalbuminuria is defined as daily urinary albumin excretion of 30
to 300 mg/day
 24-hour protein excretion remains the reference (‘‘gold standard’’)
method for:
 quantification of proteinuria in patients with GN.
 averaging the variation of proteinuria due to the circadian rhythm,
physical activity, and posture.
 Albumin-creatinine ratio on a random (‘‘spot’’) urine sample, or
a first morning urine sample, is a practical alternative to 24-
hour urine collection
Proteinuria…
Components of Protienuria
There are three major components of proteinuria as the
amount of protein in the urine depends
 the filtered load- on how much gets there
 Glomerular permeability- how well it passes through
the glomerular barrier
 proximal tubule - whether or not the proximal tubule
degrades it if the protein does get into the glomerular
filtrate.
Types of Protienuria
Overflow Protienuria
Tubular Protienuria
Glomerular Proteinuria
Overflow Protienuria
typical of urinary light chain excretion. Eg. Myeloma

Tubular Protienuria
 occurs when there is impaired tubular reabsorption of
normally filtered proteins.
associated with low grade proteinuria(<2g/d)
Tubular protein, albumin
If with glomerular proteinuria- adverse prognostic sign.
Tubular Protienuria….
 The distinction between "glomerular" proteinuria
and "tubular" proteinuria is based on the quantity
and quality of the proteins measured in the
urine.
 The appearance in the urine of serum proteins with a
molecular weight in excess of 40,000 to 50,000 Da is
an early marker of glomerular damage.
 The commonly measured high-molecular-weight
proteins include albumin,transferrin and IgG
Glomerular proteinuria
 In general, Proteinuria >3 g/day is virtually always
glomerular.
 Proteinuria <3 g/ day is nondiagnostic and could
represent a prerenal, glomerular, or tubular origin

If the origin of the proteinuria is unclear, the

source of the urinary protein may next be evaluated
by urine protein electrophoresis.
If the protein is >70% albumin, the source is glomerular.

A tubular source will cause excretion of globulins more

than albumin, with multiple peaks (representing a number
of different proteins).

 A prerenal source protienuria usually reveals a single

globulin peak, representing the protein whose plasma
concentration is unusually high.
Glomerular proteinuria is further classified into
that
 which is transient or hemodynamic (functional),
 which is present only during the day (orthostatic),
 which is persistent or fixed

Functional proteinuria
 Transient, non-nephrotic proteinuria(generally <1 g/24 h)
 Is benign
 Hemodynamic in origin
Eg. Fever ,exercise, CHF , obesity, sleep apnea, emotional
stress, hyper adrenergic state, hyperrenin state
Proteinuria
Orthostatic(Postural)proteinuria
 No proteinuria in recumbent position
 Prognosis good, biopsy not needed.
Fixed non- nephrotic proteinuria:
 Usually due to glomerular disease
 If GFR preserved and proteinuria<1g/d biopsy not
indicated
 No treatment is necessary
 Only prolonged follow up.
Clinical Syndromes
 Six general categories of clinical syndromes are
 Acute nephritic syndrome
 pulmonary-renal syndrome
 Nephrotic syndrome
 Basement membrane syndrome
 Glomerular-vascular syndrome
 Infectious disease-associated syndrome
 These general categories of syndromes are usually determined at the bedside
with the help of a history and physical examination, blood chemistries,
renal ultrasound, and urinalysis
Anti-GBM disease
Alport's syndrome
Thin basement membrane disease
Nephrotic Syndrome
Nephrotic Syndrome
Characterized by:
 Massive proteinuria(>3.5g/24hr/1.73m2)
or 3+ on urine dipstick
 Hypoproteinemia, esp. alb
 Edema
 Hyperlipidemia
 Lipiduria
 UA- oval fat bodies, most specific
Pathogenesis
Protienuria – filtration barrier losses its charge and
size selectivity.
Hypoalbuminemia- result of massive protienuria
Nephrotic edema- result from
decrease oncotic pressure and
 retention of salt water due to decrease
eeffective circulatory fluid volume
Clinical feature
Significant periorbital ,leg and abdominal edema
(ansarca)
Hypertension/Hematuria is not common
JVP is not raised
Pulmonary congestion is not common
Nephrotic Syndrome
Can be due to systemic (Secondary)or local(Primary) renal disease
Common etiologies…
Primary- Secondary-
 minimal change disease,
DM,
Amyloid,
focal segmental glomerulosclerosis,
SLE,
 membranous nephropathy,
neoplasms(HD)
membranoproliferative glomerulonephritis drugs
Age and race- in primary causes
children<10,MCD Vs. adult 10-15% of NS
Caucasian adults- MGN( 40%)
African Americans- FSGS (50%)
Investigation
1. Urinalysis -
A. 24 hour total protein determination
B. dipstick from urine sample
2. serum protein and albumin determination
3. renal function test
4. ultrasound of kideny
5. serology : ANA.Anti DNAase,HBsag,AntiHCV,VDRL
6.renal biopsy
Minimal Change Disease
Also called nil disease
causes 70–90% of nephrotic syndrome in childhood
but only 10–15% of nephrotic syndrome in adults.
usually presents as a primary renal disease
 but can be associated with several other conditions, including
Hodgkin's disease,
allergies, or
use of nonsteroidal anti-inflammatory agents;
Significant interstitial nephritis often accompanies cases
associated with nonsteroidal use.
MCD presents clinically with the abrupt onset of edema
and nephrotic syndrome accompanied by urinary
sediment.
Less common clinical features include
 hypertension (30% in children, 50% in adults),
microscopic hematuria (20% in children, 33%
in adults),
atopy or allergic symptoms (40% in children,
30% in adults), and
 decreased renal function (<5% in children,
30% in adults).
MCD on renal biopsy
shows no obvious glomerular lesion by light microscopy
and
 is negative for deposits by immunofluorescent
microscopy
Electron microscopy, however, consistently demonstrates
an effacement of the foot process supporting the
epithetlial podocytes with weakening of slit-pore
membranes.
 
Nephrotic Syndrome
MCD-Treatment
Oral corticosteroids – prednisolone 1mg/kg/day
FSGN
Most common cause of idopatic nephrotic
syndrome in Africa American adults
 FSGS
 Can be secondary to HIV
infection, HBV infection,
heroin use
 Associated with other diseases
(morbid obesity, persistent
reflux nephropathy, sickle cell
disease, cyanotic congenital
heart disease)

 Can occur in MCD which

becomes resistant to
prednisolone
C/F
the clinical findings of FSGS largely manifest as
proteinuria. i.e Classic nephrotic syndrome and a
small amount of blood in the urine
Ass with progressive renal failure, hypertension,
FSGN
 Diagnosis – biopsy –
light microscopic pattern
of segmental or total
sclerosis
of glomerular tufts
Membranous Nephropathy
Most common cause of nephrotic syndrome in 40-
60 years
is typically a disease of adults (fewer than 3% of
cases are found in children)
It is rare in childhood and by far the most
common cause of nephrotic syndrome in the
elderly.
Membranous Nephropathy
 C/F

Usually frank nephrotic syndrome, low grade microscopic

haematuria, relatively preserved renal function
Some people asymptomatic
Others can lose 10-20g of protein a day and be quite sick
Rx
Acute and Chronic changes of renal function in NS
Acute and Chronic changes of Renal function in NS
CKD in NS
 Most causes of NS (except MCD) are associated with
some risk for dev’t of progressive renal failure.
 Risk increases with the degree of proteinuria.
 progressive CKD is not part of the natural history of
adults with MCD, and its occurrence suggests
underlying FSGS.
Treatment issue in NS
1. Rx of nephrotic edema
 Salt restriction
 Oral bid loop diuretic prefered due to longer effect
 Target- fluid removal of no more than 2kg/d.
 Combining a loop diuretic with a thiazide diuretic may overcome
diuretic resistance
 Diuretic resistant even if GFR in normal due to:
 Binding to albumine in tubular fluid
 Diuretic in the circulation is free

 Avid Na reabsorption due to ineffective circulatory volume

 Impaired absorption from GI b/c of mucosal congestion.

Treatment issue in NS
2. treatment of proteinuria
 Steroid for steroid sensitive causes(e.g MCD)
Decreasing intraglomerrular pressure
A. Drug that increase afferent arteriolar tone
NSAIDS,cyclosporine
B. Drugs that decrease efferent arteriolar tone
ACEI, dypridamole
C. Resistant and refractory proteinuria
3. Treating complications
Hypoproteinemia
Adequate diet should be ensured
Hypercoagulabilty
Risk increases as serum alb decreases to <2.5g/dl
Prophylactic low dose heparin
 Relative immobilization
 Low serum albumin 2-2.5g/d.

Full dose anticoagulation

 Serum alb<2g/dl
 Documented throboembolism
Nephritic syndrome
Post streptococcal
glomerulonephrtis
Pathogensis
Treatment
Prognosis
Memberanoproliferative GN –

ass with hep c

n
Endocarditis- ass. GN
Lupus nephritis
Acute GN and RPGN
 Often present with acute onset of manifestation of nephritis:
 Azotemia, oliguria, edema, HTN, proteinuria and hematuria with
active urinary sediments (RBC casts, pigmented casts and cellular
debris)
 RPGN-leads to ≥ 50% loss of kidney function with in weeks to months.
 Pathologic processes that often lead to ~ are inflammatory glomerular
lesions.
The two most aggressive forms of GN are
anti-GBM cresentic GN and
ANCA cresentic GN
RPGN: Cresentic GN
Structurally the most sever form of active GN is Ceresentic GN
 New onset kidney disease with nephritic sediment, serum Cr- >3mg/dl,
and Crescent.
Cresents
 Proliferation of cells with in the BC –both phagocytes and glomerular
epithelial cells.
 A response to glomerular rupture and is a marker of sever glomerular
injury.
 Usually > 50% of glomeruli needs to be involved to label cresentic.
 Also % involved imp’t for prognosis in same category.
RPGN: Cresentic GN
Types of Cresentic GN
 Type I – Anti-GBM Ab disease
 Type II- Immune complex RPGN
 nature of the immune deposit not diagnostic of a specific disorder
 Most cases: Ix point underlying systemic disease. Eg. Anti strept Ab and
subepith humps in post infectious GN; ANA and subendothelial deposits in
LN…
 Type III- Pauci- immune
 Necrotizing GN but few or no immune deposits by IF or EM.
 Majority with renal limited vasculitis- ANCA +
 Type IV- double antibody positive disease
 Has features of both types I and III
RPGN…
Clinical Presentation: RPGN
 May be similar to sever PSGN- acute onset of macroscopic hematuria,
decreased urine output and edema
 Insidious onset- common : with fatigue or edema
 Renal insuficiency present at Dx in almost all cases. Cr- > 3gm/dl
 UA- nephritic feature
 NS unusual, most likely to occur in pt’s with less severe renal
insufficiency
 Systemic compliants common in Type III
 Pulmonary h’ge and hemoptysis – in anti- GBM ab disease
RPGN:- Goodpasture’s
Autoimmune
Commonly 2nd-3rd decade and second peak in 60+ age
group
Some present with renal involvement (Goodpasture’s ds )
Some present with pulmonary haemorrhage and GN
(Goodpasture’s syndrome)
Rarely some present with only
pulmonary involvement
RPGN:- Goodpasture’s
 Classic – haemoptysis after URTI, history of smoking or hydrocarbon exposure is
common
 have nephritic urinary sediment
 CXR – pulmonary haemorrhage
 Lab- Anaemia(IDA) & renal dysfunction, circulating anti-GBM antibodies
 Kidney biopsy crescentic GN with linear staining IgG & C3 along the GBM
 Treatment
 High dose IV steroids (methyl pred 500mg daily for 3 days) followed by oral
prednisolone and cyclophosphamide
 Plasma exchange every other day until anti-GBM Ab titire is negative
 Px guarded (if present with oliguria and elevated creatinine, or severe
scarring – unlikely to recover renal function)
RPGN: Evaluation and Diagnosis
Medical emergency
Immediate hospitalisation
U/A: ‘full house’ nephritic urinary sediment
Accurate and urgent Dx essential
Renal biopsy and serology
Serology: ANCA, anti GBM Abs, Complement assay, ANA,
others as indicated from the biopsy results.
Treatment: RPGN
Untreated- typically progresses to ESRD over a period of
weeks to a few months
Pts with fewer crescents- more protracted course.
Early methyl prednisolone followed by daily oral
prednisolone, oral or IV cyclophosphamide and in some
settings plasmapheresis
Early Dx with renal biopsy and serologic testing and early
initiation of appropriate treatment is essential to minimize
the degree of irreversible renal injury.
Treatment: RPGN
Empiric treatment:
Severe disease, renal biopsy or interpretation delayed
Consists of :
 IV pulse methylprednisolone (500-1000mg/dx3)
 oral or IV cyclophosphamide
 Plasmapheresis- if hemoptysis

More specific therapy can be given once the Dx is

established
Treatment: Pauci-Immune
Treatment two components:
 Remission induction with initial immunosuppressive Rx
 Maintenance treatment- prevent relapse
Remission induction
 Defn: absence of active disease
 Drugs: cyclophosphamide/rituximab and
glucocorticoid
Treatment: Pauci-Immune
Regimens :
 Cyclophosphamide
 Daily oral Vs. Monthly IV pulses

 Similar rate of remission induction

 Duration- until stable remission induced (usually 3-6 months)
 Glucocorticoid
 Pulse methylprednisolone x 3 days flowed d by 1 mg/kg/d x 2-4

wks, if significant improvement observed tapper slowly

 Duration- 6-9 months
Glomerular Disease can Present as
Chronic

GN
Most glomerular disease progress to chronic GN.
 Exceptions- uncomplicated MCD and thin BM nephropathy
 Third leading cause of ESRD in US after DM and HTN.
 Some glomerular diseases have high risk of rapid progression to ESRD
unless treated . Eg. Anti-GBM and ANCA cresentic GN.
 Others- indolent but persistent Eg . IgA N, FSGS
 Some initially severe nephritis but usually resolve completely with little
risk for progression to ESRD. Eg. PSGN
 Unpredictable course Eg. MGN
 may remit spontaneously
 Produce persistent nephrosis for decades without a decline in RFT
or
 progress over several years to ESRD.
Chronic GN…
Pathology
Glomerular scarring , cortical tubular atrophy , interstitial
fibrosis , interstitial infiltration by chronic inflammatory cells
and arteriolosclerosis
Worsening of sclerosis
Histologic evaluation of the kidney can’t reveal the initial causes for
the kidney injury
Pathologic Dx-ESRD
CF- at ESRD- Uremia
Little success in Rx of Chronic GN
Diagnosis of Glomerular Diseases
Diagnosis
 The diagnosis of glomerular injury can be delayed bcecause patients will
not realize they have microscopic hematuria,& only rarely with the
exception of IgA nephropathy & sickle cell disease is gross hematuria
present

 Can be difficult to distinguish between Glomerular disease and tubulo-

interstitial disease

 Patients age& characteristics of the urine sediment can allow narrowing

of the ddx options prior to biopsy
Diagnosis…
Evaluation of patients with Glomerular Diseases
 Clinical evaluation
 Lab Studies
 Imaging tests and
 Renal biopsy
Diagnosis…Clinical evaluation
History, P/E, Ix
 Exclude non-glomerular diseases
 Associated multisystem disease(2nd ry GN)
 Establish renal function
General Workup: History
Multisystem diseases ass’d with glomerular disease:
 DM, HTN, amyloid, lupus and vasculitis
Specific questions may reveal
 Edema , HTN, foamy urine or urinary abnormalities during prior
routine testing
Family history of kidney disease and hearing trouble (Alport’s syndrome)
Medications that can damage the kidney (NSAID’s, ACEI, penicillamine,
gold, mercury in some skin lightening creams)
Recent throat infection - ? Strep- PSGN or viral – Wegener's
granulomatosis, IgA
Cancer – solid tumour(MGN)s, Hodgkin’s (minimal change) or NHL
(MPGN)
Physical exam
HTN, edema
White bands on nails- hypoalbuminemia
Xanthelasma- hyperlipidemia ass’d with NS
Pulmonary signs
Palpable purpura
 Vasculitis ,
 SLE,
 cryoglobulinemia,
 endocarditis
Lab Studies
RFT
U/A- urine protein, dysmorphic RBC and casts
Serologic tests-
 ANA, Anti DNA
 Cryoglobulins and RF- cryoglobulinemia
 Anti- GBM abs, ANCA, ASO
Serum or urine electrophoresis
Ongoing infection- blood culture, HBV,HCV,HIV
C3, C4 level
Laboratory Work
Specific serology
 For a nephrotic type picture
 HIV, HCV, HBV, ANA, serum cryoglobulins, anti DNA ab,
complements
 For a nephritic type picture
 Blood cultures, ASOT, AntiDNAse B, ANA, Anti DNA ab,
anti GBM ab, ANCA, complements
Imaging Studies
 An ultrasound of the kidney is frequently recommended if
glomerular disease is suspected, primarily to rule out
other causes of blood in the urine and/or decreased
kidney function.

The ultrasound can also measure the size of the kidneys,

which can provide a clue as to the duration of the kidney
disease.
Plain X-ray
CT
Renal Biopsy
 Diagnosis , define cause, prognosis, data research
 Indications, percutaneous biopsy:
 Cause can’t be determined or adequately predicted by less invasive
procedures
 Parenchymal disease suspected
 Ddx with different treatment and Px.
 Clinical circumstances
 NS in adults
 Steroid resistant NS in children
 GN in adults other than clear cut PSGN
 ARF of unknown cause
Contraindication and Precuations
 Uncooperative patient
 Complications- infrequent
 Solitary kidney
 Small perirenal hematomas
 Hemorrhagic diathesis
 Gross hematuria(10%)
 Uncontrolled sever HTN
 Hemorrhage requiring surgery
 Cystic kidney
< 1%
 Hydronephrosis  death<0.1%
 Multiple renal aa aneurysms  Specimen sent for
 Acute PN/perinephric abscess  LM
 Renal neoplasms  IF
 ESRD  EM
Renal Pathology (type of lesions)
A renal biopsy in the setting of glomerulonephritis quickly identifies the
type of glomerular injury and often suggests a course of treatment.
 Proliferative GN
 show increased cellularity
 endocapillary
 Extracapillary

 Synechiae and crescents

 Sclerotic glomeruli
Treatement of Glomerular Disease
General principles
Confirm the disease is primary or secondary
Supportive measures:
 BP, hypoproteinemia
 Control of edema
 Avoid nephrotoxic drugs
 Address other metabolic consequences
• Treatment of the underlying cause
Treatement of Glomerular Disease
Hypertension
 Life style modification, regular exercise, smoking cessation
 High dose diuretics with moderate dietary salt restriction
 ACE I/ ARBs , non- dihydropyridine CCB
Proteinuria
 Prevents progressive loss of renal function if <o.5g/d
 ACE I/ARBs
 Reduce proteinuria by about 40-50%
 Low protein diet
Hyperlipidemia
 Statins needed
 Dietary modification alone not effective in NS
Disease specific treatment
Immunosuppressive :
 steroid
 Cyclophosphamide
 azathioprine
Antimicrobials- infection eg. SBE, HCV
Little success in Rx of Chronic GN.
Thank You
Treatment issue in NS
Differentiation b/n Nephrotic and Nephritic Syndrome
Evaluation of Isolated Asymptomatic Protienuria
Asymptomatic Proteinuria & Nephrotic Syndrome
Proteinuria- hallmark of GD
Normal urine- protein<150mg/24hr, 20-30mg alb)
Microalbuminuria- 30-300mg/d
Non- nephrotic proteinuria
<3.5g/24hr or <3g/g
Non-parenchymal, urinary tract conditions