NEPHROTIC SYNDROME TEAM 4 - PowerPoint Presentation

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NEPHROTIC SYNDROME

TEAM 4

ANITA TSADO

MIRACLE OGBONNA

BRIDGET EBIRERI

Slide2

Nephritic syndromeNephrotic syndrome

Types of glomerulonephritis

Treatment

CONTENTS

Slide3

Nephritic Syndrome

Nephritic syndrome—due to GBM disruption. Inflammation of the glomerulus.

Acute

poststreptococcal

glomerulonephritis •

Rapidly progressive glomerulonephritis

IgA nephropathy (Berger disease)

s

Alport

syndrome

Membranoproliferative glomerulonephritis.

Slide4

Nephritic Sympthoms

Hematuria

Azotemia

RBCS Cast in urine

Hypertension

Oliguria

Proteinuria (< 3.5 g/day)

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Nephrotic Disease

Due to increased glomerular permeability.

Nephrotic syndrome—

podocyte

disruption → charge barrier impaired.

Slide6

Types of Nephrotic Diseases

May be 1° (

eg

, direct

podocyte

damage

)\

O

r

2° (

podocyte

damage from systemic process [

eg

, diabetes]). •

Focal

segmental glomerulosclerosis (1° or 2°) ) (35%)

•

Minimal change disease (1° or 2°)

%) is

the most common cause in

children

(75% of cases

•

Membranous nephropathy (1° or 2

°)

nephropathy is most common in adults (40% of cases),

• Amyloidosis (2°)

•Diabetic

glomerulonephropathy (2

°)

Lupus Nephritis

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Nephritic-nephrotic syndrome

S

evere nephritic syndrome with profound GBM damage that damages the glomerular filtration charge barrier → nephrotic-range proteinuria (> 3.5 g/day) and concomitant features of nephrotic syndrome. Can occur with any form of nephritic syndrome, but is most commonly seen with:

Diffuse proliferative glomerulonephritis

Membranoproliferative glomerulonephritis

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Diagnosis of Nephrotic Syndrome

1. Urine dipstick test (read color changes)

2. Urinalysis

Initial test once proteinuria is detected by dipstick test

Fatty casts

suggest nephrotic syndrome (

lipiduria

3 .24 hour urine collection for creatinine and albumin

4. Test for microalbuminuria

Corresponds to albumin excretion of

30

to

300mg/day

. Other tests to determine etiology (may or may not be necessary depending on case) a. Cr clearance—best test of renal function b. Serum BUN and Cr c. CBC—to detect anemia due to renal failure

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SYSTEMIC CAUSES OF NEPHROTIC

Systemic causes:

one-third

Sickle cell anemia (papillary damage due to sickling in hyperosmotic medullary

interstitium

).

Diabetic glomerulopathies (diffuse glomerulosclerosis, nodular glomerulosclerosis).

Multiple myeloma (

Bence

Jones proteinuria from immunoglobulin light chains or their breakdown

.

SLE

amyloidosis.

Drugs/toxins—captopril, heroin, heavy

metals, NSAIDs, Penicillamine

.

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Minimal Change disease

The most common cause of nephrotic syndrome in children. Idiopathic etiology

;

2° causes include NSAIDs and hematologic

malignancies

.

Light microscopy appears normal; electron microscopy shows fusion of epithelial foot processes with lipid-laden renal cortices.

Steroids; excellent prognosis.

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Treatment

Dietary : reduce salt intake, but not fluid, normal protein diet

Bed rest

Avoid deep

venipuncture

, and intravascular volume depletion

i.e

Diuretics: use judiciously because of likely complications(thromboembolism)

-use low ceiling diuretics initially e.g.

Chlorothiazide

10mg/kg/dose q

12hrly

-can

use Furosemide 1-2mg/kg/dose q 12hrly

-intravenous albumin(0.5g/kg/12hr) can be combined with loop diuretics

Pneumococcal vaccine should be given in remission and not in steroids.

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Treatment

For MCD, Age between 1-8yr start steroid therapy if

mantoux

is negative

Prednisolone 60mg/m

2

/day or 2mg/kg/day (max daily dose 80mg) daily for 4wks consecutively. Tapering should be slow over many weeks 80-90% will respond

Monitor daily weight

Monitor daily urinalysis

Remission if urine trace or negative for protein for 3 consecutive days

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Treatment

After 4-6wks, reduce steroid to 40mg/m

2

/day or 1.5mg/kg/day to be given every other day as a single morning dose

Continue to taper the dose and discontinue over the next 2-3months

Alkylating agents

Cyclophosphamide is effective in Steroid –dependent, frequent

relapsers

, Steroid resistant patients and steroids intolerance. Dose is 2-3mg/kg/day as a single dose for 8-12wks

Monitor WBC

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Treatment

another option is high-dose pulse Methylprednisolone at 30mg/kg bolus

Cyclosporine-

when steroids

is contraindicated

Dose 3-6mg/kg/day – monitor for side effects

e.g

,

gingival hyperplasia, hirsutism

ACE-Inhibitors may be helpful as adjunct therapy to reduce proteinuria in steroid-resistant patients

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TERMS/DEFINTION

Steroid–resistant Nephrotic Syndrome: failure to respond to steroid therapy after 6

wks

of treatment

Steroid –dependent Nephrotic Syndrome: relapse occurring during the alternate day steroid therapy

Frequent

relapsers

: relapse occurring twice in a 6month period

All are candidates for second line of treatment

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Focal segmental glomerulosclerosis

Idiopathic, IV drug use, HIV infection, obesity

10 per cause of nephrotic syndrome in children

The typical patient is a young African-American male with uncontrolled hypertension.

Leads to hypertension and chronic renal failure

Microscopic hematuria; biopsy shows sclerosis in capillary tufts

Prednisone, cytotoxic therapy, ACEIs/ARBs to ↓ proteinuria

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Treatment

Prednisolone 1mg/kg or 60-80mg/day for 2-6months

Remission is 200-300mg/d of protein

If refractory

Reduce steroid dose and add cyclophosphamide 2.5mg/kg

Cyclosporine 5-10mg.kg.d

Mycophenate

mofetil

750-1000mg twice daily

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Accounts for about 30% of nephrotic syndrome in adults and is the most common cause in Caucasians. More commonly found in males with a 2:1 ratio and peak age of incidence is the fourth and fifth decade of life, except when due to

s

econdary causes.

Disease is due to

subepithelial

immune complex deposition and could be idiopathic (antigens are unknown but recently found to be associated with

antiphospholipase

A2 receptor antibody) or secondary to infections (hepatitis B, HCV, syphilis, malaria), drugs (NSAIDs, gold, captopril, lithium), neoplasm (leukemia, lymphoma, carcinoma, melanoma) and autoimmune diseases.

MEMBRANOUS NEPHROPATHY

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Onset is insidiousSome patients present with asymptomatic proteinuria but about 80% describe edema.

Hypertension may be present but is not specific for disease in early stage.

Patients may have systemic symptoms like anorexia, malaise and fatigue.

Clinical manifestation

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Spike and dome appearance due to granular deposit of IgG and C3 at basement membrane.

Histology

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Low salt diet to reduce edema. Protein restriction may or may not be helpful.

Diuretics and antihypertensive for edema and hypertension.

Treat underlying causePrednisone and cytotoxic agents for severe disease. Do not treat asymptomatic patients with immunosuppressive agents.

Renal transplant in end stage renal disease, though there is risk of recurrence.

Treatment

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Clinical syndrome characterized by persistent albuminuria confirmed on at least 2 occasions 3-6months apart, progressive decline in glomerular filtration rate and elevated arterial blood pressure.

It is a microvascular complication of diabetes mellitus and starts as microalbuminuria (30-300mg/day) then to clinical proteinuria without appropriate glycemic control.

Has 2 characteristic forms:

Diffuse hyalinization - also seen in hypertension

Nodular

glomerulosclerosis

(

Kimmelstiel

-Wilson lesions)- pathognomonic for diabetes.

Diabetic nephropathy

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There are 3 major histologic changes:

Nonenzymatic

glycosylation of efferent arterioles→ ↑GFR→ mesangial expansion from

hyperfiltration

injury

Nonenzymatic

glycosylation of glomerular basement membrane→↑permeability of membrane → hyaline thickening of membrane

Glomerular sclerosis due to

intraglomerular

hypertension from dilatation or narrowing of artery.

Pathophysiology

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Patients generally have long standing, poorly controlled diabetes with evidence of retinopathy or neuropathy.

Appropriate glycemic control

ACEIs or ARBs to decrease disease progression

Aggressively treat HTN if present because it increases risk of progression to ESRD.

Microalbuminuria is the screening test

Clinical manifestation and treatment

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Classified as WHO types I–V. Both

nephrotic

and nephritic. The severity of renal disease often determines overall prognosis.

Lupus nephritis

Slide27

Proteinuria or RBCs on UA may be found during evaluation of SLE patients.

Mesangial

proliferation;

subendothelial

and/or

subepithelial

immune complex deposition.

Laboratory

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Prednisone and cytotoxic

therapy may slow disease progression.

Treatment

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1° (plasma cell dyscrasia

) and 2° (infectious or inflammatory) are the most common.

Patients may have multiple myeloma or a chronic inflammatory disease (

eg

,

rheumatoid arthritis, TB).

Rena

l

amyloidosis

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Nodular glomerulosclerosis

; EM

amyloid fibrils;

apple-green birefringence

with Congo red stain.

Slide31

Prednisone and melphalan

. Bone marrow transplantation may be used for multiple myeloma.

Treatment

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Associated with HBV, HCV,

cryoglobulinemia

, SLE, and subacute bacterial

endocarditis

.

“Tram-track,” double layered

basement membrane.

Subendothelial

and

mesangial

deposits.

Low serum C3.

Corticosteroids and

cytotoxic

agents may help.

Membranoproliferative (type 1)

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Often idiopathic.

Intramembranous

dense deposits. Occurs by way of C3 nephritic factor.Same.

type2

Slide34

Robbins Basic pathology (8

th

edition). Saunders/Elsevier.Medscape.com

Steven S and Elizabeth D

Agabegi

. “Step up to medicine” (4

th

edition)

IE courtesy of the armed forces institute of

pathology,Bethseda

.

Tao Le et al, first aid for the USMLE step 2ck, 8

th

edition

kaplan

internal medicine course review book for the USMLE step 2ck.

Kasper,

Fauci

, Hauser “Harrison’s principles of internal medicine”(19

th

edition).

Ian B. Wilkinson “Oxford handbook of clinical medicine” (10

th

edition)

First aid for medicine clerkship

References