Transcript Nephrotic and nephritic Syndrome 2014

GLOMERULAR DISEASES:
NEPHROTIC AND NEPHRITIC
SYNDROME
Prof Dr. Gülçin Kantarcı
Yeditepe University, Medical Faculty
Nephrology Department
Aims & objectives
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State the definition of nephritic syndrome.
Identify clinical signs of nephritic syndrome.
Explain the pathophysiology of nephritic
syndrome.
State the definition of nephrotic syndrome.
Identify clinical signs of nephrotic syndrome.
Explain the pathophysiology of nephrotic
syndrome.
REFERENCE
1.
Current Medical Diagnosis and Treatment, Maxine A. Papadakis,
Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. http://Chapter 22.
Glomerular Diseases
2.
Bates' Guide to Physical Examination & History Taking 11th edition,
Bickleys LS, Szilagyi PG; Lippincott Williams and Wilkins¸
3.
Kumar and Clark's Clinical Medicine, 8th edition; Kumar & Clark,
Elsevier
4.
Andreoli and Carpenter's Cecil Essentials of Medicine 8th edition,
Andreoli and Carpenter, Elsevier
PART 11: RENAL AND GENITOURINARY DISEASES 123: Glomerular Disorders
and Nephrotic Syndromes
5. http://www.uptodate.com
-Differential diagnosis and evaluation of glomerular disease
- Overview of heavy proteinuria and the nephrotic syndrome
Glomerulus
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the glomerular capillaries can be injured in a
variety of ways, producing many different lesions
and several unique changes to urinalysis.
There are many forms of glomerular disease with
pathogenesis variably linked to the presence of
genetic mutations, infection, toxin exposure,
autoimmunity, atherosclerosis, hypertension, emboli,
thrombosis, or diabetes mellitus.
Even after careful study, however, the cause often
remains unknown, and the lesion is called idiopathic
or primary.
NEPHROTIC SYNDROME
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The nephrotic syndrome is caused by renal diseases that
increase the permeability across the glomerular
filtration barrier
Two issues are important in the pathogenesis of
nephrotic syndrome: the mechanisms of glomerular
injury and proteinuria.
Components of nephrotic syndrome
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Proteinuria 3.5g/24 hr/1.73m2
Hypoalbum. ( serum alb<3.5 g/d)
Hypercholesterolemia (>200mg/dl)
Peripheral edema ± anasarca
Tendencies of glomerular diseases to
manifest Nephrotic Features
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Minimal change glomerulopathy
Membranous GN
Diabetic GS
Amyloidosis
Focal segmental GS
Fibrilary GN
Common causes of NS
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Primary glomerular disorders
Minimal Change Disease
FSGS
Membranous GN
Orthostatik or postural proteinuria
Idiopatic MPGN
IgA nephropathy
Proliferatif GN
Common causes of NS
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Secondary glomerular disorders
Hereditary-familial: DM, Alport’s Syndrome, Sickle cell
disease
Autoimmun: SLE, Goodpasture’s syndrome, Wegener’s
granulomatosis, PAN, RA
Infectious: postinfectious glomerulonephritis, HIV FSGS
Drug-induced: NSAIDs, Heroin,gold, mercury,
Neoplastic: Hodgkin’s D., Lymphomas, leukemia, MM.
miscellaneous: amyloidosis, preeclampsia-eclampsia,
renovascular HT, intertitial nephritis, fever, exercise
Diabetic nephropathy (1/3 cause in
patient on dialysis)
Nodular Sclerosis in DM
Screening for Diabetic nephropathy
When
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BP each visit
Urinary alb: Type 2:
annually, beginning at
diagnosis
Type 1: annually, 5 years
post diagnosis
Normal Range
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<130/80
<30 mg/day
<20 mic/min
<30 mic/mg creatinine
ADA 2004
Proteinuria
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podocyte
changes to capillary endothelial cells, the glomerular
basement membrane (GBM), or podocytes, which normally
filter serum protein selectively by size and charge.
The mechanism of damage to these structures is
unknown in primary glomerular disease
The result is urinary loss of macromolecular proteins,
primarily albumin but also opsonins, Ig’s, erythropoietin,
transferrin, hormone-binding proteins, and antithrombin III
in conditions that cause nonselective proteinuria.
Pathophysiology of proteinuria
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Glomerular retention and leakage of protein
molecules
Damage of glomeruler size and charge selectivity
Size:(molecular radius) <17 Å readly pass the glomerular filter,
>44 Å can not pass)
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Albumin 36 Å
Charge: glomerular capillary wall fix negative charge
Normally 1500mg/24 hr Protein filtered, most is reabsorbed
<150 mg of protein excreted each day in the urine
Types of proteinuria
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'Glomerular' proteinuria (more than about 1.5 g
protein/24 h, mostly albumin)
'Tubular' proteinuria (never excretion of more than
1.5 g/24 h )
'Overflow' proteinuria: immunoglobulin light chains
in the urine
Benign proteinuria 'Jogger's nephritis' , orthostatic
proteinuria
Acute Complications of Nephrotic
Syn.
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peripheral edema, ascites, and effusions increased
risk for infection (especially cellulitis and, in 2 to 6%,
spontaneous bacterial peritonitis);
anemia; abnormal thyroid function;
Thromboembolism (especially renal vein thrombosis
and pulmonary embolism in up to 5% of children and
40% of adults).
Thromboembolism may develop not only because of
urinary loss of antithrombin III but also because of
increased hepatic synthesis of clotting factors, platelet
abnormalities, and hyperviscosity from hypovolemia.
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Hypercholesterolaemia is present in 90 per cent of
patients with a urinary protein excretion of over 3
g/24 h
Hyperlipidemia in the NS is the result of both
increased synthesis and decreased catabolism of
lipoproteins.
Chronic complications of NS
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malnutrition in children,
coronary artery disease in adults,
chronic renal failure, and bone disease. Malnutrition
may mimic kwashiorkor, including brittle hair and
nails, alopecia, and stunted growth. Coronary artery
disease develops because NS causes hyperlipidemia,
hypertension, and hypercoagulability.
Chronic complications of NS
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Bone disease develops because of vitamin D
deficiency and corticosteroid use.
hypothyroidism from loss of thyroid-binding globulin
proximal tubular dysfunction causing glucosuria,
aminoaciduria, K depletion, phosphaturia, and renal
tubular acidosis
Symptoms and Signs
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anorexia, malaise, and frothy urine caused by high
concentrations of protein.
Edema may cause dyspnea (pleural effusion or
laryngeal edema), chest discomfort (pericardial
effusion),
arthralgia (hydrarthrosis),
abdominal pain (ascites or, in children, mesenteric
edema).
Edema may obscure signs of muscle wasting and
cause parallel white lines in fingernail beds
(Muehrcke's lines).
Diagnosis
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suspected in patients with edema and proteinuria on
urinalysis and confirmed by 24-h measurement of
urinary protein. The cause may be suggested by
history (eg, cancer); when the cause is unclear,
serologic testing and renal biopsy are indicated.
Besides proteinuria, urinalysis may demonstrate RBCs
and casts (hyaline, granular, fatty, waxy, RBC, or
epithelial cell).
Lipiduria, the presence of free lipid or lipid within
tubular cells (oval fat bodies), within casts (fatty
casts), or as free globules
Oval Fat Body
Evaluation for secondary causes
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serum glucose or glycosylated hemoglobin
(HbA1c),
antinuclear antibodies,
hepatitis B and C serologic tests,
Renal Bx
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In adults, a renal biopsy is indicated to diagnose
the underlying cause of idiopathic NS.
Idiopathic NS in children is most likely minimal
change disease and is usually presumed without
biopsy unless the patient fails to improve on a trial
of corticosteroids.
NEPHRITIC SYNDROME
Defined by hematuria and RBC casts on microscopic
examination of urinary sediment.
Components of ?Nephritic
Syndrome
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Often one or more elements of mild to
moderate proteinuria, edema, hypertension,
elevated serum creatinine, and oliguria are
also present.
It has both primary and secondary causes.
Diagnosis is based on history, physical
examination, and sometimes renal biopsy.
Treatment and prognosis vary by cause.
•Asymptomatic Hematuria
•Recurrent Gross Hematuria
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Red blood cell/ HP mic >3 cell
Asymptomatic Hematuria prevalence 5-10 %
Tea or Cola colored urine
Proteinuria< 1 g/24 hr
Serum Cr< 1.5 mg/dl
Tendencies of glomerular diseases to
manifest Nephritic Features
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Proliferative GN(SLE)
Acute diffuse proliferative GN (Post
Step. GN)
Crescentic GN(SLE, Wegener, Ig A)
Mesangioproliferative GN(Ig A)
Asymptomatic glomerular hematuria
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No pathologic abnormality (30%)
Thin basement membrane (26%)
Ig A nephropathy (28%)
Alport syndrome ( rare ? Is it really rare in
Turkey ?)
Alport's Syndrome
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Hereditary nephritis is a genetically
heterogenous disorder characterized by
hematuria, impaired renal function, sensorineural
deafness, and ocular abnormalities.
Cause is a gene mutation affecting type IV
collagen. Symptoms and signs are those of
nephritic syndrome with sensorineural deafness
and, less commonly, those of ophthalmologic
diseases. Diagnosis is by family history and
urinalysis.
Alport's Syndrome
Because of X-linked transmission, women
usually are asymptomatic and have little
functional impairment.
 Most men eventually develop renal symptoms
and signs similar to those of acute nephritic
syndrome and progress to renal insufficiency
between ages 20 and 30.
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Alport's Syndrome
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Diagnosis is suggested by personal and family
history and by findings of microscopic
hematuria on urinalysis or recurrent episodes
of gross hematuria, particularly if
abnormalities of hearing or vision are present.
IgA nephropathy
It is the most common form of GN worldwide.
 It occurs at all ages, with a peak onset in the
teens and 20s; affects men 2 to 6 times more
frequently than women; and is more common in
whites and Asians than in blacks.
 Prevalence estimates are 5% in the US, 10 to
20% in southern Europe and Australia, and 30 to
40% in Asia.
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IgA nephropathy
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Deposition of IgA immune complexes in
glomeruli, manifesting as slowly progressive
hematuria, proteinuria, and, often, renal
insufficiency.
Diagnosis is based on urinalysis and renal
biopsy. Prognosis is generally good ?. Treatment
options include ACE inhibitors, corticosteroids,
and ω-3 polyunsaturated fatty acids.
PATHOGENESIS
Cause is unknown,
 pathogenetic mechanisms,
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increased IgA1 production,
defective IgA1 glycosylation causing increased binding to mesangial cells,
decreased IgA1 clearance,
a defective mucosal immune system,
overproduction of cytokines stimulating mesangial cell proliferation.
Familial clustering has also been observed,
suggesting genetic factors at least in some
cases.
Symptoms and Signs
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persistent or recurrent macroscopic hematuria (90%
of involved children) or
asymptomatic microscopic hematuria with mild
proteinuria
Diagnosis
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urinalysis and renal biopsy.
Urinalysis demonstrates microscopic hematuria,
usually with dysmorphic RBCs and RBC casts.
Mild proteinuria (< 1 g/day) is typical and may
occur without hematuria; nephrotic syndrome
develops in ≤ 20%.
Ig A mesangial deposition
granular deposition of IgA and C3 on immunofluorescent staining in
an expanded mesangium with foci of segmental proliferative or necrotizing lesions.
Postinfectious Glomerulonephritis
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most common cause of glomerular disease in
children between 5 and 15 yr; it is rare in
children < 2 yr and in adults > 40 yr.
occurs after infection, usually with a
nephritogenic strain of group A β-hemolytic
streptococcus.
Diagnosis is suggested by history and urinalysis
and confirmed by low complement.
Symptoms and signs
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asymptomatic hematuria (in about 50%) and mild
proteinuria
full-blown nephritis with microscopic or gross
hematuria (cola-colored, brown, smoky, or frankly
bloody), proteinuria, oliguria, edema, hypertension,
and renal insufficiency.
Severe, late disease is a relatively uncommon cause
of nephrotic syndrome. Flank pain may be
attributable to stretching of the renal capsule.
Renal failure that causes fluid overload with heart
failure and urgent or malignant hypertension and
requires dialysis affects 1 to 2% of patients and may
present as a pulmonary-renal syndrome with
hematuria and hemoptysis
Rapidly Progressive Glomerulonephritis
(RPGN)
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Crescentic Glomerulonephritis
RPGN causes microscopic glomerular crescent
formation with progression to renal failure within
weeks to months.
Diagnosis is based on history, urinalysis, serologic
tests, and renal biopsy.
Treatment is with corticosteroids, with or without
cyclophosphamide, and sometimes plasmapheresis.
Classification
of RPGN
Based on
Immunofluore
scence
Microscopy
Anti-glomerular basement membrane (GBM)
antibody disease (type 1 RPGN)
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The combination of GN and alveolar hemorrhage in the
presence of anti-GBM antibodies is called Goodpasture's
syndrome
autoimmune GN and accounts for 10% of RPGN cases.
It may arise when respiratory exposures (eg, cigarette
smoke, viral URI) expose alveolar capillary collagen,
triggering formation of anticollagen antibodies.
The anticollagen antibodies cross-react with GBM,
fixing complement and triggering a cell-mediated
inflammatory response in the kidneys and lungs.
Immunofluorescent staining of renal biopsy tissue
demonstrates linear IgG deposits.
Immune complex RPGN (type 2 RPGN)
complicates numerous infectious and connective
tissue disorders and also occurs with other
primary glomerulopathies.
 Immunofluorescent staining demonstrates
nonspecific granular immune deposits.
 The condition accounts for 40% of RPGN cases.
Pathogenesis is usually unknown.
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Pauci-immune RPGN (type 3 RPGN)
distinguished by the absence of immune
complex or complement deposition on
immunofluorescent staining.
 It constitutes 50% of all RPGN cases.
 Almost all patients have elevated antineutrophil
cytoplasmic antibodies (ANCAs) and systemic
vasculitis
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crescent formation in a patient with
ANCA–associated small vessel vasculitis
Crescentic
Glomerulonephritis
Thin Basement Membrane
Disease
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(Benign Familial Hematuria)
Thin basement membrane disease is
diffuse thinning of the glomerular
basement membrane from a width of 300
to 400 nm in normal subjects to 150 to 225
nm.
Renal disease in patients with
hematuria undergoing renal biyopsy
Prot<1
Cr<1.5
Prot 1-3
Cr 1.5-3
Cr >3
No abnormality
30%
2%
1%
0%
Thin BM
nephropathy
26%
4%
3%
0%
Ig A
Nephropathy
28%
24%
14%
8%
GN without
crescent
9%
26%
37%
23%
GN with crescent 2%
24%
21%
44%
Other renal
disease
5%
20%
24%
25%
Total
100%
100%
100%
100%
N=43
N=123
N=179
N=255
Renal biopsy: Indications
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The cause cannot be determined or adequatly
predicted by less invasive diagnostic
procedures
The sign and symptoms suggest parenchymal
disease that can be diagnosis by pathologic
evaluation
The differential diagnosis includes diseases that
have different treatment, different prognosis, or
both
Renal biopsy: Contraindications
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Solitary kidney
Uncooperative patient
Bleeding disorders
Uncontrolled severe HT
Severe anemia or dehidratation
Cystic kidney
Hydronephrosis
Multiple renal arterial aneurysms
Acute pyelonephritis or perinephric abscess
Renal neoplasm
ESRD