Nephrotic syndrome

1. Nephrotic syndrome
Dr Velmurugan
Assistant Professor
Department of Medicine

5. What is Nephrotic syndrome?
The term "nephrotic syndrome" refers to a
distinct constellation of clinical and laboratory
features of renal disease.

6. COMPONENTS
 Heavy proteinuria (protein excretion greater
than 3.5 g/24hours/1.73m2
Hypoalbuminemia (less than 3 g/dL)
 Peripheral edema
 Hyperlipidemia
 Thrombosis
Minimal hematuria and sometimes
Hypertension

7. Pathophysiology

9. General Clinical Aspects

10. Identify ?

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13. Identify?

15. Identify?

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19. MINIMAL CHANGE DISEASE

20. • Also called as lipoid nephrosis or
foot process disease.
• It comprises 20% nephrotic cases in
adults.
• While 80% of nephrotic cases in
children.

21.  Idiopathic (majority)
 In association with systemic disease or drugs.
- Drug induced interstitial nephritis induced by
NSAIDs, rifampin, interferon alpha.
- Hodgkin’s disease and other lymphoproliferative
malignancy.
- HIV infection.
MAJOR CAUSES OF MCD

22. LAB PARAMETERS
• Microscopic hematuria present in 20-30%
• Hypertension and renal failure are very rare.
• In children urine contains albumin principally
• In adults proteinuria is typically non
selective.

23. PATHOLOGY
• Light microscopy - no changes.
• Immuno-fluorescence - typically negative for
immunoglobulin and C3.
• Electron microscopy – diffuse effacement of
the foot processes of visceral epithelial cell.

25. Identify

27. Histopathology of MCD

28. IMMUNOFLUORESCNCE

29. ELECTRON MICROSCOPY

31. TREATMENT

32. • MCD is highly steroid responsive and carries an excellent
prognosis.
• Approximately 90% children and 50% of adults enter
remission following 8 week of high dose oral glucocorticoid.

33. • Adults – 1-1.5 mg/kg body weight
(prednisone) per day for 4 weeks, followed
by 1 mg/kg/day on alternate day for 4
weeks.
• Up to 90% of adults enter remission if
therapy extended for 20-24 weeks.

34. • Steroid dependent – relapse occur whenever dose
is reduced or within two weeks of discontinuation
of steroid.
• Steroid responder – absence of protein in urine for
three consecutive days.
• In frequent relapse - <3 relapse in a year.
• Frequent relapse - > 3 relapse in a year.
• Steroid resistance – no response to treatment after
6 month of therapy

35. Treatment of relapse and steroid dependent MCD
• Cyclophosphamide – induction of remission with
Predinisone followed by institution of
cylcophosphamide (2 mg/kg) for 8-12 weeks.
• Chlorembucil - 0.1 to 2.0 mg/kg/day
Side effect – higher incidence of malignancy

36. Treatment of storied resistant MCD
• Pulse methylprednisolone
- May induce remission in some corticosteroid resistant
children
• Cyclosporine- 5mg/kg/day
• Levamisole – 2.5mg/kg/day on alternate day.
- It is an antihelmenthic drug (Immunomodulating role)
- Transient cytopenia may occurs in 2/3rd patients.

37. MEMBRANOUS
GLOMERULOPATHY

38. • Leading cause of idiopathic nephrotic syndrome in adults (30
to 40%) with male to female ratio of 2 :1
• Proteinuria is usually non selective
• Microscopic hematuria is present in up to 50% of cases
• Hypertension in only 10-30% of patients

39. • Idiopathic (majority)
• In association with systemic diseases or drugs
CONDITIONS ASSODATED WITH MEMBRANOUS
GLOMERALOPATHY

40. INFECTIONS
 Syphilis
 Malaria
 Leprosy
 Hydatid disease
 Filariasis
 Enterococcal endocarditis

41. Systemic auto immune diseases
 SLE
 Rheumatoid arthritis
 Sjogren's syndrome
 Hashimoto's disease
 Grave’s disease
 Primary biliary cirrhosis
 Ankylosing spondylitis
 Myasthenia gravis

42. NEOPLASIA
• Ca breast,lung, colon, stomach, and
esophagus
• Melanoma
• Renal cell carcinoma
• Neuroblastoma
• Carotid body tumor

43. Drugs
• Gold
• Penicillamine
• Captopril
• NSAIDs
• Probenecid
• Trimethadione
• Mercury

44. Miscellaneous
 Sarcoidosis
 Diabetes mellitus
 Sickle cell disease
 Crohn's disease
 Guillain-Barre syndrome,
 Fanconi's syndrome
 Alpha-1 antitrypsin deficiency

45. Pathology
• Light microscopy – diffuse thickening of GBM
without evidence of inflammation or cellular
proliferation.
• Immunofluorescence – granular deposition
of IgG, C3 and compliments (C5b-9)

48. The deposits are directly visualized by
fluorescent anti-IgG, revealing diffuse granular capillary loop staining

49.  Stage I—sub-epithelial deposits
A few small, flat, electron-dense deposits are seen on the epithelial
surface of the GBM.
 Stage II—'spike' formation
'Spikes' protruding from epithelial surface of GBM become clearly
visible.
The spikes extend between the electron-dense deposits, and are
present in virtually every capillary loop.
 Stage III—incorporation of deposits
Electron-dense deposits become surrounded by and incorporated
into the GBM. This results in an irregular thickening of the GBM.
 Stage IV—disappearing deposits
The deposits incorporated within the GBM lose their electron density.
Areas of the GBM will have a vacuolated or lucent appearance.
 Stage V—reparation stage
During this 'healing' phase, the deposits have become completely
rarified, and the GBM appearance is returning to normal.

50. Poor prognosis
• Male gender
• Older age
• Hypertension
• Severe proteinuria
• Hyperlipidemia
• Impaired renal function

51. TREATMENT
• Nephrotic syndrome remits spontaneously
and completely in up to 40% of patients
• Glucocorticoids have failed to show consistent
improvement
• Cyclophosphamide, chlorambucil, and
cyclosporine, Mycopthenolate mofetil and
rituximab
• Transplantation

52. • The pathognomonic morphologic lesion in FSGS is sclerosis with
hyalinosis involving portions (segmental) of fewer than 50% (focal)
of glomeruli on a tissue section.
FOCAL AND SEGMENTAL
GLOMERULOSCLEROSIS

53. • Nephrotic proteinuria
• Hypertension
• Mild renal insufficiency
• Abnormal urine sediment that contains red
blood cells and leukocytes
• Proteinuria is nonselective in most cases.

54. • Idiopathic (majority)
• In association with systemic diseases or drugs
HIV infection
Diabetes mellitus
Fabry's disease
Sialidosis
Charcot-Marie-Tooth disease
• As consequence of sustained glomerular capillary hypertension
Congenital oligonephropathies
Unilateral renal agenesis
Oligomeganephronia
Acquired nephron loss
Surgical resection
Reflux nephropathy
Glomerulonephritis or tubulointerstitial nephritis
Other adaptive responses
Sickle cell nephropathy
Obesity with sleep apnea syndrome
Familial dysautonomia
Miscellaneous
Heroin use
ETIOLOGY OF FOCAL AND SEGMENTAL
GLOMERULOSCLEROSIS

55. • Light microscopy - Entrapment of amorphous hyaline
material.
• Electron microscopy - evidence of damage to visceral
epithelial cell.

57. TREATMENT
• First - course of corticosteroid treatment
• other drugs (Azathioprine, Cyclosporine,
Tacroliumus, Mycophenolate, Mofetil) when
ineffective.
• High-dose prednisone is clearly more effective
than dosages less than 1 mg/kg/day.
• Third, response of FSGS to corticosteroids is
much slower in adults than in children and that
steroid resistance cannot be pronounced before
a minimum of 4 months of full-dose
corticosteroid treatment

58. • Is characterized by thickening of the GBM and proliferative
changes on light microscopy.
• Two major types : Type I MPGN and type II MPGN.
Type I MPGN
• The hallmark is presence of subendothelial and mesangial
deposits on electron microscopy that contents C3 and IgG
and IgM rarely IgA.
• It is associated with a variety of chronic infection (bacterial
endocarditis, HIV, hepatitis B and C), systemic immune
complex diseases (SLE, cryoglobulinemia), and malignancies
(leukemias, lyphomas).
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS

60. Type II MPGN
• Type II MPGN is an autoimmune disease in
which patients have an IgG autoantibody,
termed C3 nephritic factor, that binds to C3
convertase, the enzyme that metabolizes C3,
and renders it resistant to inactivation and
deposits on GBM.
• Type II MPGN is associated with partial
lipodystrophy.
• Poor prognosis than type I MPGN.

61. Treatment approach
1. Patients with rapidly progressive renal failure-
crescents on histopathology -- pulse
methylprednisolone therapy followed by oral
prednisone and cyclophosphamide.

62. 2. Patients with microscopic haematuria, proteinuria (<3
g), and normal renal function should be followed up
every 3 months. They can be treated with ACE
inhibitors.
3. Patients with chronic renal failure should be managed
conservatively.
4. Patients with HCV-associated MPGN should be treated
with IFN-α and immunosuppressive agents should be
avoided.

63. • Nephropathy complicates 30% of cases of type I DM and
approximately 20% of cases type IIDM.
DIABETIC NEPHROPATHY

64. RISK FACTORS
 hyperglycemia,
systemic hypertension
glomerular hypertension
Hyperfilteration
 proteinuria
 cigarette smoking
 hyperlipidemia
gene polymorphisms affecting the activity of
renin angiotensin aldosteron axis.

65. • Diabetic nephropathy is usually diagnosed on clinical
grounds without a renal biopsy.
• Supportive clues are the presence of normal sized or
enlarged kidney
• Evidence, proliferative diabetic retinopathy, and a bland
urinary sediments
• Retinopathy is found in 90% and 60% of patients with type I
and type II diabetes mellitus respectively, who develop
nephropathy.

66. • The earliest morphologic abnormalities
nephropathy are thickening of the GBM and
expansion mesangium due to accumulation
of extracellular matrix.
• Prominent nodular matrix expansion
(classical Kimmel steil-Wilson lesion) are
often found.

67. Nodular mesangial expansion, so-called Kimmelstiel-Wilson nodules,
with increased mesangial matrix and cellularity, microaneurysm
formation in the glomerulus

68. TREATMENT
• Aim is to control blood sugar, systemic blood pressure and glomerular
capillary blood pressure.
• ACE in inhibitor and ARBs are drugs of choice for both systemic blood
pressure & intraglomerular hypertension.

69. RENAL AMYLOIDOSIS
• Glomeruli are involved in 75 to 90% of patients.
• Hypertension is present in 20-25%.
• Renal size is usually normal or slightly enlarged.
• A minority of patients present with renal failure.
• Rectal biopsy and abdominal fat pad biopsy reveal
amyloid deposits in about 75% of patients and
may obviate the need for renal biopsy.

70. Amyloidosis shows amorphous, acellular expansion of the mesangium, with
material often also infiltrating glomerular basement membranes, vessels, and the
interstitium, with apple-green birefringence by polarized Congo red stain

71. • Renal biopsy earliest pathologic changes are mesangial
expansion by amorphous hyaline material and thickening of
GBM. Further deposition results in large nodular esinophilic
masses.
• When stained with congo red these deposit show apple –
green birefringence under polarized light.
• Electron microscopy reveals non branching extracellular
amyloid fibrils..

72. THANK YOU