Nephrotic syndrome

1
Nephrotic syndrome GN

• Ebadur Rahman
• FRCP (Edin),FASN, Specialty Certificate in
  Nephrology(UK)
• MRCP(UK),DIM(UK),DNeph(UK),MmedSciNephrology(UK).
• Consultant clinical tutor
• Department of Nephrology
• Riyadh Armed Forces Hospital

2
Nephrotic syndrome

• This is characterized by proteinuria
  (Typically gt 3.5g/24h),
• hypoalbuminemia ( less than 30g/dL ) and
  edema.
• Hyperlipidaemia.
• nephrotic range nephrotic proteinuria

3
Presentation

• New-onset oedema
• Initially periorbital or peripheral
• Later genitals, ascites, anasarca
• Frothy urine
• Generalised symptoms lethargy, fatigue, reduced
  appetite

4
(No Transcript)
5
Figure 1. Nephrotic edema.
6
(No Transcript)
7
Heavy proteinuria (albuminuria)
8
(No Transcript)
9
Further possible presentations...

• Oedema
• BP
• Leukonychia
• Breathlessness
• Pleural effusion, fluid overload, AKI,PE,MI.
• DVT
• Eruptive xanthomata/ xanthalosmata

10
(No Transcript)
11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14

• Hemoconcentration
• Immobility, especially in patients with anasarca
• thrombocytosis, increased platelet activation,
• decreased levels of
• antithrombin,
• free protein S,
• and plasminogen (due to urinary losses),

15
NEPHROTIC SYNDROME

• Secondary
• Primary glomerular disease

16
Primary glomerular disease
17
PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease- commonest in children
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy- commonest in adult
• Membranoproliferative Glomerulonephritis(MPGN)
• Iga nephropathy RARE to cause nephrotic syndrome
  but commonest GN

18
(No Transcript)
19
(No Transcript)
20
For exam

• Minimal change gn
• Membranous gn
• Amiloidosis
• SLE
• DM

21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
Urine dipstick

•  The urine sediment (or direct counting of RBC
  per mL of uncentrifuged urine) is the gold
  standard for the detection of microscopic
  hematuria.
• Dipsticks for heme detect 1 to 2 RBCs per high
  power field

25
false positive tests due to the following

• Semen is present in the urine after ejaculation
  and may cause a positive heme reaction on the
  dipstick
• urine pH greater than 9 or contamination with
  oxidizing agents used to clean the perineum
• The presence of myoglobinuria

26
False negative tests

• have been reported in patients ingesting large
  amounts of vitamin C

27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
(No Transcript)
31
Isolated glomerular hematuria

• Renal biopsy is not usually performed
• there is no specific therapy for these conditions
• renal prognosis is excellent
• management of these patients is not usually
  affected by the biopsy
• When renal biopsy is performed in such patients,
  the most common findings-are a normal biopsy
• IgA nephropathy,
• Thin basement membrane disease (benign familial
  hematuria),
• mild nonspecific glomerular abnormalities,
• Alport syndrome

32

•  All patients should have a urine culture to
  exclude infection prior to evaluation of
  hematuria.

33
Hyperlipidemia

• total cholesterol and low-density lipoprotein
  (LDL)
• Lipoprotein (a) Lp(a)
• high-density lipoprotein (HDL) cholesterol .

34
Renal biopsy

• Nephrotic syndrome
• Nephritic syndrome
• Unexplained renal impairement
• Vasculitis where kidneys are commonly involved
• Renal allograft dysfunction

35
Percutaneous renal biopsy is generally
contraindicated in the following settings

• Uncorrectable bleeding diathesis
• Small kidneys which are generally indicative of
  chronic irreversible disease
• Severe hypertension, which cannot be controlled
  with antihypertensive medications
• Multiple, bilateral cysts or a renal tumor
• Hydronephrosis
• Active renal or perirenal infection
• An uncooperative patient

36
Table 4
37
(No Transcript)
38
(No Transcript)
39
(No Transcript)
40
In children- diagnosis of MCD is usually made
based upon the clinical. Almost all children
with MCD respond to a short course of
glucocorticoids. it is considered
steroid-resistant (SR-NS) when no remission is
achieved after about two months of full-dose
steroid therapy. Pediatricians usually restrict
renal biopsy to individuals with SR-NS
The clinical findings at presentation in
adults Proteinuria nephrotic range Hematuria
29 percent Hypertension 43 percent Acute renal
failure 18 percent
41
PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative Glomerulonephritis(MPGN)

42
Figure 6. Light microscopic appearances in
focal segmental glomerulosclerosis. Segmental
scars with capsular adhesions in otherwise normal
glomeruli.
43
Table 5
44
PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Iga nephropathy
• Membranoproliferative Glomerulonephritis(MPGN)

45
Membranous nephropathy (MN) - one-third of biopsy
diagnoses in adult nondiabetics

• diffuse thickening of the glomerular basement
  membrane (GBM) on light microscopy, "spikes" on
  silver stain, diffuse granular IgG and complement
  deposition on immunofluorescence, and
  subepithelial dense deposits on electron
  microscopy
• Antibodies to the M-type phospholipase A2
  receptor (PLA2R ) are found in a high proportion
  of patients with primary (idiopathic) MN.
• Most patients with MN present with the nephrotic
  syndrome with normal or near normal serum
  creatinine.
• 10 associated with malignancy

46
Table 6
47
Figure 7a. Early MN a glomerulus from a
patient with severe nephrotic syndrome and early
MN, exhibiting normal architecture and peripheral
capillary basement membranes of normal thickness
(Silvermethenamine 400).
48
Figure 7b morphologically advanced MN
49
Figure 7c. Morphologically more advanced MN
(same patient as in (b))
50
(No Transcript)
51
(No Transcript)
52
IgA nephropathy

• most common cause of primary glomerulonephritis.
  in Asians and Caucasians.
• There is a 21 male to female predominance
• IgA nephropathy is characterized by prominent,
  globular deposits of IgA in the mesangium on
  immunofluorescence microscopy.
• Electron microscopy shows dense deposits
  primarily in the mesangium
• Most patients with IgA nephropathy present with
  either visible hematuria (single or recurrent),
  usually following an upper respiratory infection,
  or invisible hematuria with or without mild
  proteinuria incidentally detected on a routine
  examination

53

• 40 to 50 percent present with one or recurrent
  episodes of visible hematuria, usually following
  an upper respiratory infection
• Another 30 to 40 percent have microscopic
  hematuria and usually mild proteinuria, and are
  incidentally detected on a routine examination
• Less than 10 percent present with either
  nephrotic syndrome or rapidly progressive
  glomerulonephritis

54

• A kidney biopsy only
• protein excretion above 0.5 to 1 g/day, elevated
  serum creatinine concentration, or hypertension.

55
(No Transcript)
56
(No Transcript)
57
(No Transcript)
58
PRIMARY NEPHROTIC SYNDROME

• Membranoproliferative Glomerulonephritis(MPGN)

59
Figure 8. Pathology of membranoproliferative
glomerulonephritis type I. (a) Light microscopy
shows a hypercellular glomerulus with accentuated
lobular architecture and a small cellular
crescent (methenamine silver).
60
Table 7
61
Diagnosis
62

• fasting blood sugar and glycosylated hemoglobin
• antinuclear antibody test
• serum complement,
• In selected patients, cryoglobulins, hepatitis
  B and C serology,
• anti-neutrophil cytoplasmic antibodies (ANCAS),
• anti GBM antibodies,
• renal biopsy to define the pattern of glomerular
  involvement.

63
Complications

• Infection
• Coagulation disorders
• Protein malnutrition and dyslipidemia
• Acute renal failure

64
Treatment

• General treatment
• Relief edema
• Rx Htn
• 2. Symptomatic treatment
• Treating dyslipidemias,
• anticoagulate treatment,
• 3. Immunosupressive treatment