Transcript Nephrotic Syndrome - Selam Higher Clinic

Nephrotic & Nephritic Syndromes
By:Dawit Ayele
MD,Internist
objectives
• Understand the difference between
nephrotic and nephritic syndrome
• Understand the biology of the glomerular
filtration barrier
• Differentiate primary from secondary
nephrotic syndromes
• Approach to management of nephrotic
syndromes
• WHAT MAKES THESE
DISORDERS DIFFERENT?
Normal glomerular BM
• Arteriolar lumen containsAlbumin –negatively
charged,small
Immunoglobulins positively charged,large
*Endothelial fenestrae –
Negatively charged
*Basement membrane –
Negatively charged
*podocyte- -Bowman’s space- - - -
How do we make a diagnosis?
• Clinically, at the
bed side?
• Investigations?
Nephrotic syndrome
• Proteinuria > 3g/day (adult)
• Proteinuria >40mg/h/m2 (child)
• Hypoalbuminemia
• Edema
• Hyperlipidemia
• Lipiduria
Nephrotic syndrome
• Diagnose type by renal
biopsy
• Histologic hallmark of
proteinuric states
– simplification/ effacement of
visceral podocyte foot
processes
• Classically non-inflammatory
• Lack of inflammation is
consistent with:
– Absence of “active” urine
(casts and cells)
– Creatinine may not be very
elevated
Proteinuria
Depends on charge and size of molecules
• Small negatively charged molecules e.g..
albumin are repelled by negatively charged
capillary wall
• Loss of charge but no overt structural injury can
cause→ albuminuria (minimal change disease)
• Immunoglobulins are positively charged but too
big to get through unless structural injury
Urine Protein
• A normal person has 7200g
(180Lx 40g/L albumin) pass
through the glomerulus every day
(not filtered)
• Normal excretion of < 20mg/day =
fractional excretion of
0.00028%!!!!!!!!!!!!!!!!!!!!!!!!!
• Even a nephrotic patient excreting
3g a day = 0.42%
Diagnosing Proteinuria
• Dipstick positive:
– Likely > 150 – 300 mg/24h
– Measure protein: creatinine ratio (PCR)
24h Urine Protein ≈PCR
• Dipstick negative:
– Cannot exclude proteinuria, especially in DM
and HT
– Send albumin : creatinine ratio (ACR) if
available (expensive)
Categories of nephrotic syndrome
• Primary renal:
– Minimal change disease
– Focal Segmental Glomerulosclerosis
– Membranous
• Secondary
– Diabetes
– Amyloid
– HIV
– Drug associated: NSAIDS, gold, pamidronate
– Etc…
Diagnoses made clinically and on
biopsy
Age prevalences of nephrotic
syndromes
Minimal change disease (MCD)
• 90% of nephrotic syndrome in children
• 20% of nephrotic syndrome in adults
• May not need biopsy
• Trial of steroids is part of diagnosis
• May be beginning of spectrum ranging to FSGS
especially in black children
• Secondary forms may be associated with
allergies, drugs (NSAIDS!!!), hematologic
malignancies, viral infections
Minimal Change Disease
• Light microscopy normal
• Normal immunostaining
• • Electron microscopy
shows fusion of podocyte
foot processes
• There is loss of negative
charge
Specific treatment of 1° MCD
• 90% respond to steroids with 4-6 weeks
– Taper over 6 weeks
– Proteinuria resolves before albumin improves
• Implies not only decreased oncotic pressure
driving edema…
• 25 % long term remission
• 25-30% infrequent relapses
• 20% chronically relapse – steroid dependent
• 5% don’t respond – steroid resistant
Membranous Nephropathy
• Most common cause of 1°nephrotic syndrome in
adults (25%)
• Peak incidence in 4-5th decade (adult: child
26:1)
• 2-3:1 male predominance at ESRD
• Affects all races
• Differences in secondary causes may cause
geographic differences in presentation
Membranous
• Thickening of capillary
wall with “spikes”
• Positive
immunoflourescence
• EM shows subepithelial
deposits within newly laid
basement membrane
Immune complexes
are far from blood
side – don’t incite
inflammation
Clinical features
• Usually presents as nephrotic syndrome but 1020% have < 2g/d proteinuria
• HT from 13-55%
• Most have slightly decreased renal function
• Usually progresses slowly → must investigate
abrupt change in renal function
– Crescents 1/3 have anti GBM, some have ANCA
– Renal vein thrombosis (4-52%)
– Drug-induced injury: NSAIDS, diuretics, antibiotics
Clinical features
• Microscopic haematuria in 30-50%
• Impaired renal function at presentation <10%
• C3 and C4 typically normal
• Hyperfibrinogenaemia and decreased
antithrombin 3
– Renal vein thrombosis in 5-63%
– Deep vein thromboses 9-44%
– Consider anticoagulation if albumin < 20g/L
Causes of Membranous Nephropathy
1°
• Idiopathic
2°
• Malignancy (colon, lung, gastrointestinal)
• Autoimmune diseases: SLE, rheumatoid arthritis,
autoimmune thryroiditis
• Drugs: penicillamine, gold
• Infections: Hep B virus, Syphilis (congenital and
secondary), Hep C, Hepatosplenic schistosomiasis
• Chronic transplant rejection
• Rarely sarcoid, captopril
• Other Glomerulonephritides
Treatment of membranous
• Determine whether idiopathic or 2°
• Decision should be based on an
understanding of natural history:
– Spontaneous remission in 5-30%
– Partial remission (Proteinuria<2g/d) in 25-40%
– Relapse rate 30-50% but only 5% → ESRD
– Renal survival:
• 86% at 5 years
• 65% at 10 years
Treatment of membranous
• If poor prognositic factors or progressing
– Hypertension
– Male
– Elevated creatinine
• Steroids chlorambucil or other
immunosuppression, ? Rituximab, ?
mycophenolate
Nonimmunologic therapy of all
nephrotic syndromes
• Treatment of hypertension esp. ACEI, ARB
– Target < 120/75
• Treatment of hypercholesterolemia
– Target LDL < 2.0
• Low sodium diet
• Calcium and vit D to reduce bone loss if steroid
therapy is prolonged
• Bactrim for PCP prophyllaxis if steroids
• INH for TB prophyllaxis if immunosuppressed
• Anticoagulate if high risk
• Treat underlying cause if secondary
Nephritic syndrome
• e.g.. Postinfectious(streptococcal),
lupus, IgA nephropathy
• Immune complexes and
antibodies accumulate in
subendothelial space →
endothelial injury,
recruitment of WBC
→inflammation and injury.
Serum complement = usually
low
Nephritic Syndrome
• Hematuria –
dysmorphic red blood
cells, red blood cell
casts
• Azotemia
• Oliguria
• Hypertension
• Variable proteinuria
(usually < 3 g/day)
Nephrotic
Nephritic
Onset
Slowe r
Ra p id
Edema
++++
a l l o v e r ++
BP
Norma l/ low
increased
JVP
Norma l/ low
increased
Proteinuria
>3g/day
<3g/day
Hematuria
May o c c u r
+++
U r i n e s ediment
Hya l i n e c a s t s, l i p i d
droplets
R b c , wb c , r b c c a s t s , gr
anularcasts
Albumin
↓↓↓
No rma l /mi l d ↓
Cre a t i n i n e
Norma l / i n c r e a s e d
Us u a l l y i n c r e a s e d
Ser u m sodium
Ma y b e ↓ ↓
Ma y b e ≈ ↓
Work up summary
• History and physical exam
– Including meds!!!
• Quantitate urine protein
• Electrolytes, creatinine, albumin, lipids
• Urine dipstick + microscopy
• If necessary:
– C3, C4, SPEP, UPEP, Hep B, ANA, DS DNA,
LFTs, echo etc…
• Renal ultrasound
• ? biopsy
Thanks