Long question as well as short note MCQ topic Approach to Treatment Resistant Minimal Change Disease

1. Dr Ashutosh Ojha
Reader, Internal Medicine
17 Feb2016Dr A Ojha

2.  Clinical complex characterized by a number
of renal and extra renal features.The most
prominent being.
 Proteinuria of > 3.5 g/d
 Hypoalbuminaemia
 Oedema
 Hyperlipidaemia
 Hypercoagulability.
17 Feb2016Dr A Ojha

3.  Key component is proteinuria
◦ Results from altered permeability of glomerular
filtration barrier(GBM,podocytes& their slit
diaphragm) for proteins
◦ All other metabolic complications are secondary to
urine protein loss.
17 Feb2016Dr A Ojha

4. Proteinuria Loss of lipid
metabolism
Sr Albumin regulating
protein
Oncotic pressure Oedema
Hepatic lipoprotein synthesis
Hyperlipdaemia
17 Feb2016Dr A Ojha

5.  Altered level of Urinary loss of
protein C and S Antithrombin III
 Hyperfibrinogenaemia
 Impaired fibrinolysis
  Platelet aggregability
Hypercoagulability
Peripheral arterial and
venous thrombosis
Renal vein thrombosis
Pulmonary embolism
17 Feb2016Dr A Ojha

6.  Other metabolic complications.
◦ Protein malnutrition
◦ Iron resistant microcytic hypochromic anaemia
◦ Hypocalcaemia
◦ Vit D deficiency
◦ Secondary hypoparathyroidism
◦  thyroxin levels
◦  IgG
17 Feb2016Dr A Ojha

7.  Damage to GBM
o  Number & size of pores
Passage of more and larger
proteins
o  in fixed negatively charged
components
( Repel negatively charged protein
molecules )
17 Feb2016Dr A Ojha

8. 17 Feb2016Dr A Ojha

9.  6 entities account for >90% in adults
◦ Minimal change disease(MCD)
◦ Focal & segmental glomerulosclerosis(FSGS)
◦ Membranous glomerulopathy.
◦ Membrnoproliferative GN (MPGN).
◦ Diabetic nephropathy.
◦ Amyloidosis
17 Feb2016Dr A Ojha

10.  Systemic vasculitis eg-SLE
 Drugs
◦ Penicillamine
◦ Captopril
◦ Gold
◦ Cadmium
 Allergic reactions
◦ Pollens
◦ Bee sting
17 Feb2016Dr A Ojha

11.  History.
◦ Frothy urine –heavy proteinuria
◦ Oedema-Periorbital,arms.ascites,genital oedema.
◦  BP in some.
◦ Features of underlying disease viz SLE,DM
◦ Rule out
 Primary cardiac failure
 Chronic liver disease
17 Feb2016Dr A Ojha

12.  Diagnosis established by
◦ 24 hr urinary protein >3.5g/day
◦ Sr Albumin <3g/dl
17 Feb2016Dr A Ojha

13.   Cholesterol,  LDL,  triglycerides
  Urea, Creatinine ---- progressive disease
 Urine microscopy—RBC,RBC casts
 Throat swab Streptococcal infection
 ASO titer
 C3 level-immune complex mediated
 ANA
 HBsAg&HCAntibodies
 Cryoglbulinaemia

17 Feb2016Dr A Ojha

14.  Sr electrophoresis - MM
  Blood glucose.—DM
 Selective proteinuria—MCD,diabetic
nephropathy,amyloidosis.
 Non selective proteinuria—Diffuse
proliferative GN
17 Feb2016Dr A Ojha

15.  Gradual onset of acute renal failure
 No obvious cause of acute renal failure
 Heavy proteinuria
 Significant haematuria
 Clinical evidence or history of systemic
disease
 Prolonged oliguria
17 Feb2016Dr A Ojha

16.  Not required in
◦ Young children with highly selective proteinuria,no
HTN,no red cells or red cell casts in urine
◦ Long standing insulin dependent diabetes mellitus
◦ On drugs like penicillamine.
17 Feb2016Dr A Ojha

17.  Specific treatment of underlying cause.
 Drugs- immunosuppressive therapy.
 General measures to control proteinuria.
 General measures to control complications.
17 Feb2016Dr A Ojha

18.  80% cases < 16yrs, 20% cases in adults.
 Peak incidence 6-8yrs
 Idiopathic.
 Occurrence after URTI, immunization.
  incidence in HLA B12.
 May be associated with interstitial nephritis,
lymphomas.
17 Feb2016Dr A Ojha

19.  High mol wt proteinuria.
 Benign urinary sediment.
 Microscopic haematuria in 20-30% cases.
 HTN & RF -----rare
17 Feb2016Dr A Ojha

20.  Glomerular size & structure – normal in light
microscopy.
 Immunoflorescense studies –neg for Ig & C3
 Electron microscopy
 Diffuse effacement of foot processes of
visceral epithelial cells.
17 Feb2016Dr A Ojha

21. 17 Feb2016Dr A Ojha

22.  Highly steroid responsive .
 Excellent prognosis.
 Spontaneous remission in 30-40% children.
 Remission with 8 wks of high dose
glucocorticoids in 90% of children, 50% of
adults.
17 Feb2016Dr A Ojha

23. Dose
 Children: 60 mg/mt2/day x 4 wks
40 mg/mt2/day x 4 wks
Adults: 1.15mg/kg/day x 4 wks
1mg/kg/day x 4 wks
 50% relapse fallowing withdrawal.
17 Feb2016Dr A Ojha

24.  Relapse during / shortly after withdrawal
 Relapse - >3 / yr
Cyclophosphamide- 2-3 mg/ kg /day 8 –12
wks or
Chlormabucil- 0.1-0.2 mg/ kg /day 8 –12 wks
 Side effects-infertility, cystitis, alopecia,
infections, sec malignancies.
 Cyclosporin can be tried in those resistant to
above .
17 Feb2016Dr A Ojha

25.  Sclerosis with hyalinosis involving portions of
< 50% glomeruli in a tissue section.
 1/3 cases of nephrotic syndrome in males.
 Proteinuria with HTN and mild renal
insufficiency.
17 Feb2016Dr A Ojha

26. 17 Feb2016Dr A Ojha

27.  Spontaneous remission rare.
 Prognosis poor.
 Drug therapy unsatisfactory.
 Renal transplant.
17 Feb2016Dr A Ojha

28.  30-40% of NS in adults.
 Rare in children.
 Peak incidence 30-50 yrs.
 1/3 rd assocition with systemic diseases like
SLE, infections, malignancy, HBV, drugs.
17 Feb2016Dr A Ojha

29. 17 Feb2016Dr A Ojha

30.  Light microscopy- diffuse thickening of GBM
with e/o cellular infiltration.
 Electron microscopy- immune deposits of IgG
& C3
17 Feb2016Dr A Ojha

31.  Proteinuria- non selective
 Microscopic hematuria in 50%.
 RBC casts, leukocytes, macroscopic hematuria
are rare.
 HTN 10-30%.
 40% remit spontaneously, 10-20% slowly
progressive ESRD, others remit & relapse.
17 Feb2016Dr A Ojha

32.  Steroids- unsatisfactory.
 Cytotoxic drugs- some benefit.
17 Feb2016Dr A Ojha

33.  Features
-Thickening of GBM
- proliferative changes.
-diffuse increase in mesangial cells
and matrix.
-immune deposits- C3, IgG, IgM,
IgA.
17 Feb2016Dr A Ojha

34.  In association with
-IE
-HIV
-HBV, HCV
-Cryoglobulinaemia
-Lymphoma
17 Feb2016Dr A Ojha

35.  Heavy proteinuria
 Active urinary sediment
 Normal to mildly impaired renal function.
 Course- benign to ESRD.
 No effective treatment.
17 Feb2016Dr A Ojha

36.  ACE inhibitors- act by ↓ intraglomerular
pressure and prevent hemodynamically
mediated focal segmental glomerulosclerosis.
Specially in DM, FSGS.
 NSAIDS- act by altering glomerular
hemodynamics& permeability.
17 Feb2016Dr A Ojha

37.  Edema- salt restriction 1-2 gms/ day
 Loop diuretics
 Hyperlipidaemia- statins
 Thromboembolism- anticoagulation.
 Malnutrition- ? High protein diet.
 Vitamins D supplements
17 Feb2016Dr A Ojha

38. Thank You
17 Feb2016Dr A Ojha

39.  Contact-9719713786
 ashutosh8116@yahoo.com
 sumitranikentanpatna@gmail.com
17 Feb2016Dr A Ojha