Nephrotic

syndrome
Nephrotic syndrome
 Proteinuria>3.5g per 1.73m per 24hr
 Hypoalbuniemia
 Oedema
 Hyperlipidemia
 Hypercoagulability
Hypoalbuminemia
 Altered permeability of the glomerular
filtration barrier
 Barrier comprised of
 GBM
 Podocytes
 Slit diaphragms
Oedema – underfilling
hypothesis
 Hypoalbuminemia -  intravasc oncotic
pressure
 Leads to leakage of ECF
 Intravasc vol falls
 Stim of RAAS and SNS
 Release of vasopressin(ADH)
 Suppression of ANP
 Promote salt and water retension

 Restoration of intravasc vol

 Triggers further leakage of fluid

Hyperlipidemia
 Due to  hepatic Lp synthesis
 Triggered by  oncotic pressure
 Compounded by  urinary losses of prts
 LDL and cholesterol are 
 VLDL and TGs  with severe disease
 Accelaration of atherosclerosis and
progression of renal disease
Hypercoagulability
  urinary losses of :
 AT III
 Protein C/S
 Hyperfibrinogenemia
 Impaired fibrinolysis
  platelet aggregability
  hepatic synthesis
Acute renal vein
thrombosis
 Sudden onset of flank or abd pain
 Gross hematuria
 L-sided varicocoele
  proteinuria
 Acute decline in GFR
 NB: Chronic renal vein thrombosis is
usu asymptomatic
Metabolic complications
 Protein malnutrition
 Iron-resistant hypochromic anemia
 Hypocalcemia
 Depressed thyroxine levels
  susceptibility to infections
 Change in pharmacokinetics of protein-
bound drugs
Etiology
 Primary GN
 Associated with systemic disease
 Associated with infection
 Associated with tumors
 Associated with drugs
Minimal change disease
 80% of NS in children
 20% in adults
 Peak = 6-8 years
 NS and benign urinary sediment
 HPT and renal insufficiency – rare
 Microscopic hematuria – 20-30%
Minimal change disease
 Glomerular size and architecture
 normal by light
 IF – neg for IG and C3
 EM – diffuse effacement of the foot
processes of visceral epithelial cells
 Etiology is unknown and vast majority
of cases are idiopathic
Causes of MCD
 Idiopathic(majority)
 Inassoc with systemic drugs or diseases
 Drug-induced interstitial nephritis
 Hodgkins disease and other
lymphoproliferative disorders
 HIV infection
Treatment - steroid-
responsive
 Highly steroid-responsive
 Excellent prognosis
 Spontaneous remission – 30-40% in
chd
 Relapses in >50% ffg withdrawal of
steroids
 High dose for 4 weeks then taper for ffg
20-24/52
Non-steroid-responsive

 Alkylating agents
 Cyclophosphamide
 Chlorambucil
 Usu started after steroid therapy and cont for
8-12/52
 Cyclosporin may be used
 Relapse is usu with cyclosporin withdrawal
 Renal prognosis is excellent
FSGS
 Sclerosis with hyalinosis
 Segmental
 <50% of glomeruli
 1/3 of cases of NS in adults
 ½ of cases in Blacks
 Idiopathic - incidence 
 Can complicate a number of systemic
diseases
FSGS
 Nephrotic syndrome(66%)
 Subnephrosis(33%)
 Hypertension
 Mild renal insufficiency and abn urine
sediment
 Rbc
 Leucocytes
 Proteinuria is usu nonselective
Etiology of FSGS
 Idiopathic(majority)
 Assoc with systemic diseases and drugs
 As a consequence of sustained
glomerular cap hpt:
 Congenital oligonephropathies
 Acquired nephron loss
 Other adaptive responses
 miscellaneous
Treatment
 Spontaneous remission is rare
 Renal prognosis is poor
 Steroids – proteinuria remits in only 20-
40%
 Cyclosporin and cyclophosphamide
 50-60% of steroid reponsive
 Ineffective in steroid-resistant
Poor prognostic factors
 Hypertension
 Abn renal function
 Black race
 Persistent heavy proteinuria
 Renal transplant – 50% chance of
recurrence of FSGS with 10% chance of
graft loss
Membranous
glomerulopathy
 Rare in childhood
 30-40% of NS in adults
 Peak – 30-50 y.o.
 Male:female = 2:1
 Pathology
 Diffuse thickening of the GBM
 Spikes along the GBM
Membranous
glomerulopathy
 Proteinuria is nonselective
 Microscopic hematuria – 50%
 Hypertension – 10-30% at outset, but is
common later with progressive renal failure
 Serological tests
 ANF
 ANCA
 Anti-GBM Ab
 Complement
Assoc with membranous
glomerulopathy
 Idiopathic(majority)
 Assoc:
 Infection
 AIDX
 Neoplasia
 Drugs
 miscellaneous
Treatment
 40% - NS remits spontaneously completely
 30-40% - repeated relapses and remissions
 10-20% - slow progressive decline in GFR –
ESRD in10-15 years
Poor prognostic factors
 Male gender
 Older age
 Hypertension
 Severe proteinuria & hyperlipidemia
 Impaired renal function
Treatment
 Glucocorticoids – fail to show consistent
improvement in proteinuria or renal
protection
 Cyclophosphamide, chlorambucil,
cyclosporin
 Reduce proteinuria
 Slow decline in GFR
 Transplantation –option for ESRD
Membranoproliferative
 Common features
 Thickening of GBM with proliferative changes
 Lobular pattern of glomerular tuft is exaggerated
 T1 - Subendothelial and mesangial deposits –
which contain C3 and IgG
 T2 – electron-dense deposits within the GBM
– stain for C3 but little or no Ig
T1 MPGN
 Heavy proteinuria
 Active urinary sediment
 Normal or mildly impaired GFR
 C3 usu depressed
 Immune-complex GN
 Benign disease
 75-80% - survive without abn in GFR
T1 MPGN
 Chronic infections
 Bacterial endocarditis
 Hepatitis Band C
 Systemic immune complex diseases
 SLE & cryoglobulinemia
 Malignancies
 Leukhemias and lymphomas
T2 MPGN
 Heavy proteinuria and NS
 Nephritic syndrome
 RPGN
 Recurrent macroscopic hematuria
 AIDx – IgG autoantibody – C3 nephritic
factor
 No effective therapy
Mesangial proliferative GN
 Diffuse  in glomerular cellularity – due to
proliferation of mesangial and endothelial
cells, and infiltration of monocytes
 Prognosis is variable
 Persistent nephrotic-range proteinuria signals
a poor prognosis
 Many progress to ESRD over 10-20 years
Treatment of
complications
 3 principles
 Specific treatment of underlying known
cause
 General measures to control proteinuria
 General measures to control nephrotic
complications
Drugs
 ACEI
 Reduce proteinuria
 slow the rate of progression of renal failure
 by lowering intraglomerular pressure
 Preventing the dev of hemodynamically
mediated FSGS
 NSAIDS
 Alter glom hemodynamics
 Alter GBM permeability characteristics
Other complications
 Oedema
 Moderate salt restriction – 1-2g/day
 Loop diuretics
 Do not remove >1.0kg oedema/day
 Hyperlipidemia
 Use of lipid-lowering drugs
 Prevents accelerated atherosclerosis
 Slows deterioration of GFR
 Anticoagulation
 DVT/PE?Other arterial embolism
 Resistance to heparin due to ATIII def
 Caval filter if embolization while on
anticoagulation
 Diet
 No consensus
 Vit D supplementation