Nephrotic Syndrome powerpoint presentation

Nephrotic Syndrome

1. Nephrotic
Syndrome/Primary
Glomerulopathies
Prof. Joshua K. Kayima

2. Glomerular Diseases
1.Various diseases affect the glomerulus
they could be inflammatory or non-
inflammatory
2.Diseases lead to alterations glomerular
permiability [Proteinuria] ; structure
[Histology] ; and function [GRF].

3. [Contd.] Glomerular Disease
Glomerular disease can be primary [restricted in
clinical manifestation to the kidney, with unknown
cause]
Or secondary (secondary to known primary
conditions or part of a multisystem disease)
E.g. systemic lupus
Vasculitis
HIV / HBV / HCV
Diabetes mellitus

4. Disease expression.
The hallmark of glomerular disease is the
excretion of protein in urine
Presentations
Asymptomatic urinary abnormalities
Acute glomerulonephritis
Rapidly progressive glomerulonephritis
Chronic glomerulonephritis
Nephrotic syndrome
(Overlap syndromes)

5. Nephrotic Syndrome
Key component = PROTEINURIA (severe/heavy)
Def.: > 3.5g/1.73m
2
/24 hrs
Practice: > 2.5 – 3g/24 hrs
Other components of the syndrome and metabolic
complications are all 2
°
to proteinuria

6. (cont.) Other Components of
Syndrome
Hypoalbuminemia
Oedema
Dyslipidaemia (Hyperlipidemia)
Lipiduria
Hypercoagulability

7. Pathology
Nephrotic syndrome can complicate any disease that
Perturbes
negative electrostatic charge or
architecture of:
a) GBM and
b) Podocytes and
c) their slit diaphragms
Molecules mediating GBM – Podocyte – slit diaphragm
interactions
nephrin, podocin
alpha-actin-4
Interest in mechanism of disease

8. Causes of Nephrotic Syndrome
Idiopathic
Post infectious
Viruses [Hepatitis B, C, HIV, measles, EBV]
Bacteria [streptococcal, syphilis]
Parasites [plasmodiam malarie, schistosoma]
Vasculitis /Collagen [SLE, Wegener’s, Henoch-
Schönlein purpura PAN, Good pasture’s]

9. Causes of Nephrotic Syndrome
[Contd.]
Systemic diseases [Diabetes Mellitus,
amyloidosis]
Drugs/chemicals [Penicillamine, captopril,
gold, Mg]
Allergy [Drugs, vaccines, stings]
Malignancies – [colon, prostate, lung, breast]

10. Investigations
1.Diagnosis:- urinalysis, protein estimation
- serum protein, albumin
- lipid profile
2.Ancillary:- protein c, s, transferrin
- TBC, Renal ultrasound, C-xray
- U/E/Cr
3.Renal biopsy

11. Investigations [Contd.]
4.Cause a) clinical examination
b) ASOT, Anti-DNAse, VDRL,
HBs Ag, HCVAb, HIV Elisa, B/S-
MPs, stool, urine micro Blood
sugar, C
3 – levels, ANA ,anti -
GBM, ANCA, Anti PLA 2R Ab
Culture (throat, discharges,
skin, blood urine)

12. Histologic entities [Common]
Minimal change disease (MCD)
Mesangial proliferative GN
Focal and segmental glomerulosclerosis (FSGS)
Membranous glomerulopathy
Membranoproliferative glomerulonephritis (MPGN)
Diabetic nephropathy
Amyloidosis

13. Renal Biopsy
Valuable- Adults
Probably even paediatrics locally
30 – 45% minimal change disease (MCD)
Definitive diagnosis
Guiding therapy
Assessing prognosis

14. Pathogenesis
Some Nephrotic patients may have expanded
plasma volume
RAA – axis suppressed
Yet with oedema
1
o
renal salt/H
2O retention may be responsible
for oedema ? GN

15. Hypoalbuminaemia
↑ Urinary loss
↓ Synthesis – Liver
↑ Catabolism - Renal

16. Dyslipidemia (Hyper-)
2
o
to:
i) ↑ hepatic lipoprotein synthesis due to
↓ oncotic pressure
ii) ↑ urinary loss of proteins (regulate
lipid homeostasis)
iii) Defective lipid catabolism
↑ LDL-c, ↑ Total Chol – usual
↑ TG, ↑ VLDL-c – late
Effects - Accelerate artherosclerosis
- Progression of CKD

17. Hypercoagulability
Fibrinolysis
↑ Conc. of Fibrinogen
Factor V, VII, VIII, X
↑ Platelet aggregation
Accelerated thromboplastin generation
Loss of ATIII, protein-C, protein-S
Hypo-volaemia

18. Complication of hypercoagulability
Renal vein thrombosis → renal necrosis
DVT → PTE
Sagittal sinus thrombosis
Arterial thrombosis
→ organ Ischaemia

19. Infections
1 gG loss in urine
↑ Catabolism

20. Infections in Nephrotic Syndrome
1
o
peritonitis
Bacteremia
Septicaemia
Cellulitis – Strep pneumoniae
β- hemolytic strptococci
E. coli
Klebsiella
↓ Immune function
predispose to viral infections
e.g. measles (varicella)

21. “Transport – Proteins” Loss
Transferrin- microcytic anaemia
Cholecalciferol- binding protein
- Vit D deficiency,
- Hypo Ca++
- 2
o
hyperparathyroidism
Thyroxine- binding globulin
- depressed thyroxine levels
Protein-bound drugs
changed pharmaco-kinetics

22. Anaemia Risk
Urinary Iron loss
loss of trasfernin (transport protein)
Impaired biosynthesis of Erythropoietin
Concurrent ACE inhibitor therapy

23. Growth & Development Delay with
Active nephrotic

24. Hypovolaemia
→ Oliguria, ARF
↑ BUN
↑ Risk of thrombosis

25. Untreated Nephrotic Syndrome
Numerous complications:
Hypovolaemia
Hypertension
Hyperlipidemia
Hypercoagulability
Growth and
developmental days
Anaemia
Risk of severe
infections

26. Ascites – (untreated)
Associated with:
Venous Dilation – of abdominal wall
Umbilical hernia
Rectal prolapse
↑ Respiratory difficulty
Scrotal/labial pain
Anasarca

27. Glomerular
Injury
Proteinuria
Transport
Protein
Albuminuria
Immunoglobulin
1gG
ATTIII, Protein-C,
Protein-S
Infections
Hypoalbuminuria
↓ oncotic pressure
Hypovolaemia
Osmotic
pressure
Oedema
Liver
RAAS
Aldosterone
AVP
• Skin sepsis
• DVT
↑ Synthesis of fibrinogen
Lipoproteins
HypelipidaemiaRenal salt % water retention
• Failure of growth &
development
• Malnutrition
• Bone disease
• Transferrin
• Hormones
• Drugs
• Ca++

28. Treatment Goal
Induce prompt remission
Minimize complications and subsequent
mortality

29. Approach to Solving Problems for
the Nephrotic Patient
Search, identify, deal with:
Glomerular injury.
Corticosteroids,(prednisone) immunosuppressive
agents,
(cyclophosphamide,cyclosporine,tacrolimus,azathio
prine) monoclonal Ab
Associated hypertension
Stage of CKD

30. Approach to Solving Problems for the
Nephrotic Patient
2.Oedema – Symptomatic
Care for intravascular volume
Loop diuretic? Spironolactone?, thiazides?,
bed rest?
?Albumin infusion

31. Approach to Solving Problems for the
Nephrotic Patient
3.Infections
Care –(aseptic technique)
Search for (septic screen)
Antibiotics
? Immunisations ( influenza, pneumococcal, HBV,
varicella)
Immunoglobulins (with exposure)
Isolation (epidemics)

32. Approach to Solving Problems for the
Nephrotic Patient
4.Hyperlipidaemia
“Statins” – lipid lowering agents
(HMGCoA reductase inhibitors)
5.Hypercoagulable State
Anticoagulants
- Heparin
- Warfarin

33. Approach to Solving Problems for the
Nephrotic Patient
6.Malnutrition
High protein diet
7.Bone Disease
Vit D, Ca++ suppl
Bisphosphonates (osteoporosis)

34. Approach to Solving Problems for the
Nephrotic Patient
8.Proteinuria
Angiotensin Converting Enzyme (ACE)
inhibitors
Angiotensin
2
Receptor blocker (ARB)
Sodium-Glucose Cotransporter-2 (SGLT-2)
inhibitors
Mineralocorticoid Receptor Antagonists (MRA)