Nephrotic
Syndrome
Presenter: Dr. Vaibhav Gupta
Guide: Prof. Dr. S. S. Sharma
Introduction
• Richard Bright (1827) “Bright’s disease” - generalized swelling
and albuminuria (protein in the urine) and linked it to kidney
disease .
Definition
• Nephrotic syndrome is defined by presence of pentad
of -
• Proteinuria
• Adult : > 3.5g/ day or urine ACR > 2.2g/day
• Child : > 40mg/h/m2 or >4mg/kg/hr
• Hypoalbuminemia
• Edema
• Hyperlipidemia
• Lipiduria
Common Presentation
• Adult –
• Edema
• Frothy urine
• Subnephrotic Proteinuria (FSGS / MN) (>1g) + Hypoalbuminemia
• Child –
• Swelling on the face
• Followed by Anasarca
Classification
Nephrotic
Syndrome
Primary Secondary
Focal Membranou
Minimal
Segmental s
Change
Glomerulo - Nephropath
Disease
sclerosis y
Primary Genetic
Secondary Nephrotic
Syndrome
• MCC of Secondary Nephrotic Syndrome- Diabetes Mellitus
• Medications and other chemicals
( NSAIDs , Bisphosphonates , COX 2 inhibitors )
• Infections
( HIV , Hepatitis B , Hepatitis C )
• Neoplasms
( Solid tumors, Hodgkin’s disease , Multiple Myeloma )
• Multisystem diseases
( SLE , RA )
• Hereditary familial and metabolic diseases
( DM , Amyloidosis )
• Miscellaneous
( Reflux Nephropathy )
Pathophysiology
Proteinuria
• Glomerular Proteinuria – Albumin
• Cause – Podocyte Injury (mutation – Congenital / autoantibody )
• Other plasma proteins may be lost -
• Immunoglobulins
• Metal Binding Proteins
• Complement
• Coagulation components
Hypoalbuminemia
• Urinary loss
• Liver compensatory
mechanism blunted .
Edema
Jurgen Flora, Marcello Tonelli, Richard J. Johnson , Comprehensive Clinical Nephrology, 7th ed. The United States. Elsvier Inc.
Hypercoagulabilit
y
Jurgen Flora, Marcello Tonelli, Richard J. Johnson ,
Comprehensive Clinical Nephrology, 7th ed. The
United States. Elsvier Inc.
Hyperlipidem
ia
&
Lipiduria
Jurgen Flora, Marcello Tonelli, Richard J.
Johnson , Comprehensive Clinical Nephrology,
7th ed. The United States. Elsvier Inc.
Approach to Nephrotic
Syndrome
• History
• Examination
• Routine investigation
• Urine investigation –
• Urine dipstick (Albumin, RBCs )
• Urine r/m ( Protein , Dysmorphic
RBCs +/- RBC casts , fat bodies or
fatty casts –Maltese cross)
• Urine ACR , 24 hr urine protein
• Ultrasound KUB
• Chest radiogram
• Additional laboratory tests include:
• HbA1C
• ANA and anti dsDNA
• Anti-PLA2R autoantibody
• Age > 50 yr – Serum free light chains and serum
protein electrophoresis with immunofixation
• Serum C3 and C4 complement levels
Renal Biopsy
• Indicated in • Deferred in
• Adults • Adults –
• Children > 8yr • Obvious etiology .
• Amyloidosis suspected .
• Children with Primary
SRNS ( Steroid Resistant • Positive anti-PLA2R autoantibody .
Nephrotic Syndrome)
• Biopsy cannot be performed or is
• Children with atypical refused .
presentation
• Child
• An underlying familial cause .
• A secondary aetiology .
Genetic Testing
• Recommended in – (IPNA)
• All SRNS children .
• Features suggesting hereditary cause .
• Congenital NS (presenting< 3 months) .
• Syndromic features or a strong family history of
NS.
• Not recommended in -
• Initially respond to steroids and subsequently
develop steroid resistance .
• First episode of idiopathic NS, prior to initiation
Mininal Change Disease
• MC Nephrotic Syndrome in Children .
• Presents with Pentad of symptoms .
• Pathophysiology – Effacement of Foot process ( Podocytopathy) .
• Renal Biopsy
• Light Microscopy- Normal
• Immunofloresence – Normal
• Electron Microscopy - Effacement of Foot process
Focal Segmental Glomerulosclerosis
• MC Nephrotic Syndrome in Adults .
• One fourth will be asymptomatic .
• Pathophysiology –Podocytopenia .
• Hematuria , Hypertension and raised creatinine present.
• Renal Biopsy
• Light Microscopy- Focal and segmental sclerosis
• Immunofloresence – IgM +/- C3 Focal deposit
• Electron Microscopy - Effacement of Foot process
• Genetic causes –
• AD , adolescent ( alpha actinin 4 , TRPC 6)
• AR, children ( Podocin )
• Adults ( Apo LI)
Membranous Nephropathy
• MC Nephrotic Syndrome in Elderly .
• One third will be asymptomatic .
• MC target antigen – PLA2R receptor ( 85-90%) .
• Pathophysiology – Podocytopenia .
• Hematuria , Hypertension and raised creatinine present.
• Renal Biopsy
• Light Microscopy- Thickening of capillary wall & mesangial
expansion
• Immunofloresence – Capillary IgG +/-C3 ( granular pattern)
• Electron Microscopy - Effacement of foot processes ,
subepithlial deposits , spike pattern
Minimal Change Disease
• Steroids
• Children
Oral Prednisolone
Taper dose over 6
2mg/kg/day or 60
weeks ( or alternate
mg/m2 /day ( max – Stop
day , child –
80mg) daily for 6
40mg/m2/day)
weeks
• Adults
Oral
Remission ->
Prednisolone
start tapering
1mg/kg/day Stop
in 1-2weeks ->
( max – 80mg)
over 16-20wk
daily
• Relapse / Resistant cases
Relapse FRNS / SDNS SRNS
• Repeat • 1st line – Steroids • Cyclosporine,
Corticosteroid Rx until remission f/b Tacrolimus
• With remission • 2nd line- • Toxicity/relapse –
start tapering Cyclosporine, Rituximab
• Over 4 weeks Tacrolimus (CNI) • MMF after
or remission induced
Cyclophosphamid
e or MMF or
Rituximab
Focal Segmental
Glomerulosclerosis
Sub Primary
nephrotic FSGS with
Proteinuria
(good Nephrotic
prognosis) Syndrome
Steroids
RAAS Blockers Full dose Oral
Prednisolone
ACEi or ARBs 1mg/kg/day ( max –
80mg) daily for 12-16
weeks
Remission
Taper over 6
months (after full
dose for 12 weeks)
No Response
Calcineurin
Inhibitors > MMF
Membranous Nephropathy
• Asymptomatic (Sub-nephrotic Proteinuria or Microhematuria )
• Good prognosis
• ACEi and ARBs
• Salt Restriction
• Lipid lowering therapy
• Nephrotic Syndrome
• Modified Ponticelli regimen
• 6 month therapy
• Month 1,3 & 5 –
• 1st 3 days - IV Methylprednisolone 500mg
• Rest days – Oral Prednisolone 0.5mg/kg
• Month 2,4 & 6 –
• Oral Cyclophosphamide 2mg/kg
• No Response/ avoid cytotoxic therapy - Rituximab
• Avoid immunosuppressive therapy if evidence of severe and irreversible kidney
damage or concomitant severe or potentially life-threatening infections present.
Treatment - General
Measures
Edema
• Sodium Restriction- ( < 2g/ day )
• Diuretics-
• Loop diuretics - (monitoring hypovolemia and serum creatinine).
• Loop diuretic-albumin complexes
• Child > adult ( particularly with a reduced effective arterial blood
volume).
• Thiazide diuretic
• inadequate response to loop diuretics
• ENaC inhibitors ( triamterene & amiloride)
• refractory cases
• Loop Diuretics + Acetazolamide
• refractory cases
Proteinuria
• Angiotensin inhibition (ACE inhibitors & ARB)
• A/E –
• Acute decline in glomerular filtration rate
• Hyperkalemia
• A possible benefit is a lesser degree of albuminuria (enhance diuretic
response)
• Lower intraglomerular pressure (decreases protein excretion) .
• SGLT2 inhibitors
• Chronic Kidney Disease and Proteinuria
• May benefit
Hyperlipidemia
• Lipid-lowering therapy only when persistent nephrotic syndrome and
hyperlipidemia despite treatment .
Hypercoagulability
• Preventive measures - prevent stasis and avoid Hemoconcentration.
Role of Albumin
• A definitive recommendation has not been established.
• Factors playing role in diuretic resistance-
• Hypoalbuminemia -> Reduced degree of diuretic protein-binding .
• Some diuretic entering tubular lumen is bound to filtered albumin and
rendered inactive ( ? Uncertain)
*Guidelines for Intravenous Albumin Administration at Stanford Health Care
Jurgen Flora, Marcello Tonelli, Richard J. Johnson , Comprehensive Clinical Nephrology, 7th ed. The United States. Elsvier Inc.
Summary
• Primary Nephrotic Syndrome is most common seen in paediatric
age group.
• Most common causes in adults are Secondary.
• Biopsy is not an emergency .
• Optimal remission and complete course of steroid is important
before tapering .
• Steroid responsiveness is an important factor in prognosis .
• Albumin’s role is limited to Diuretic Resistance.
THANK YOU
