Nephrotic syndrome is characterized by significant proteinuria, hypoalbuminemia, and various metabolic complications, often resulting from glomerular diseases that may be primary or secondary. The document discusses the causes, diagnostic investigations, common histological entities, clinical manifestations, and treatment strategies aimed at managing complications such as infections, hyperlipidemia, and hypercoagulability. Treatment goals include inducing remission, managing symptoms, and preventing long-term complications.

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/1.73m2
/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, C3 – 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
 1o
renal salt/H2O retention may be responsible
for oedema ? GN

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

16. Dyslipidemia (Hyper-)
 2o
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
 1o
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++
- 2o
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
Hypelipidaemia
Renal 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
 Angiotensin2 Receptor blocker (ARB)
 Sodium-Glucose Cotransporter-2 (SGLT-2)
inhibitors
 Mineralocorticoid Receptor Antagonists (MRA)