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GR 11 NEPHROTIC AND NEPHRITIC SYNDROME.pptx
1. NEPHROTIC AND NEPHRITIC SYNDROME
PEDIATRIC AND CHILD HEALTH
GROUP 11
CHARLES BENEDICT NOAH
ZAINAB I KOROMA
ALPHA MADU BAH
ABUBAKARR MARRAH
KADAY SENESIE
SCHOOL OF CLINICAL SCIENCES
MAKENI
LECTURER: DR. JALLOH
2. OUTLINE/Objectives
• What is Nephrotic Syndrome?
• What is the pathophysiology?
• What are the identified causes?
• How does it present/complications?
• How is it diagnosed?
• What is the treatment?
• Take home message/contributions
3. Introduction
• Nephrotic syndrome – kidney disorder characterized by
massive proteinuria, leading to hypoalbuminemia,
hyperlipidemia and varying degrees of oedema
• Viewed as a manifestation of glomerular disease – may be
intrinsic (primary) or extrinsic (secondary)
• Podocytopathy – more specifically
10. Pathophysiology – oedema
• Two theories –
• Under-fill theory – hypoalbuminemia produces a reduced oncotic
pressure – oedema, and potentially intravascular contraction and poor
perfusion
• Over-fill theory – there is a primary renal defect causing sodium and
water retention – oedema, and potentially hypertension and resolution
of oedema during remission even with hypoalbuminemia
• There seems to be a balance of some sort
15. Clinical features
• Oedema –
• usually generalized
• First noticed in the face – periorbital, then the legs, and the
abdomen. Resolution tends to follow same order
• Scrotum and labia may also be involved
• Embarrasing oedema
19. Diagnosis
• Classification of Nephrotic Syndrome –
• According to age –
• Congenital NS – 0-3months of life, usually due to genetic causes
• Infantile NS – 4-11months
• Childhood NS – 1yr and above
• Due to disease intrinsic or extrinsic to the kidneys –
• Primary (idiopathic) NS – most common (90%), commoner between 1-
10yrs
• Secondary NS – due to a systemic or extra-renal disease, more
common as children get older
20. Diagnosis
• Classification contd. –
• Histology –
• Minimal change disease – commonest type; >90% are steroid
sensitive
• Focal segmental glomerulosclerosis (FSGS) – second commonest
type, also most commonly found in steroid-resistant types; only about
20-30% are steroid sensitive
• Membranoproliferative GN
• Mesangioproliferative GN
• Membranous nephropathy – rare in childhood, 100% steroid resistant
23. Laboratory Investigations
Required to make a diagnosis
(a) dipstick urinalysis ≥3+
(b)serum protein-creatinine ratio >2
(c)serum protein and albumin – albumin <2.5g/dl
(d) serum cholesterol and lipids – elevated
32. Take home message
• Nephrotic syndrome is defined by massive proteinuria leading to
hypoalbuminemia, with other consequences
• It is a podocytopathy
• Most cases in childhood are idiopathic, other extrinsic causes are SCD,
HIV disease, hepatitis, SLE
• Most cases in children are MCD and steroid sensitive
• Treatment requires monitoring and frequent clinic visits – watch for
response, complications of the disease and side effects of
medications
34. OUTLINE
• INTRODUCTION
• EPIDEMIOLOGY
• ANATOMY OF THE KIDNEY – the Glomerulus
• PATHOPHYSIOLOGY
• CLINICAL PRESENTATION
• DIFFERENTIAL DIAGNOSIS
• INVESTIGATIONS
• TREATMENT
• PROGNOSIS
• PREVENTION
35. INTRODUCTION
• Acute Nephritic syndrome –
• Hematuria – persistent presence of >5 red blood cells (RBCs)/high
power field (HPF) in uncentrifuged urine.
• Significant haematuria >50RBCs/HPF
• Oedema – almost always involving the face, but can be generalized.
• Hypertension – blood pressure (BP) >95th percentile for age, sex and
height, or BP >130/80mmHg for adolescents ≥13years of age
• Renal dysfunction – varying degrees
• Proteinuria
• Elevated serum creatinine
36. INTRODUCTION
• APSGN can follow streptococcal skin infection (pyoderma,
infected scabies) or streptococcal pharyngitis.
• The nephritogenic strains observed in Sub-sahara Africa –
• Skin infection – 49 (most common), 2, 55, 57, 59, 60
• Pharyngitis – 12 (most common), 1, 3, 4, 18, 25
• Latent period between antecedent infection and
manifestation of kidney disease –
• Skin infection – 3-6weeks
• Pharyngitis – 1-2weeks
37. EPIDEMIOLOGY
• 97% of cases currently seen in developing countries
• Poor hygienic conditions
• Near eradication of streptococcal pyoderma in developed countries
• A causal seasonal variation seen in temperate regions – post pharyngitis
in cold seasons and post pyoderma in warmer seasons.
• In the tropics – pyoderma accounts for most APSGN all year long
• Epidemics are not common; clusters have been reported in homes and
camps (military)
• Typically affects age 4-12 years. Uncommon in children <3years
• Male:female is 1:1
• Post pharyngitic cases male:female is 2:1
41. PATHOPHYSIOLOGY
• Following a poorly treated streptococcal infection by
nephritogenic strains, and after the latent phase:
• Circulating antibodies elicited by streptococcal antigens react with
normal glomerular antigens (molecular mimicry)
• There is in-situ deposition of streptococcal antigens on the
glomerular cells, which are bound to antibodies, forming immune
complexes and stimulating the inflammatory process
• Direct Complement activation by streptococcal antigens in the
glomerulus
• The processes activate several mediator pathways –
especially the complement pathway
42. PATHOPHYSIOLOGY
• The classic pathway activated by antigen-antibody immune
complexes
• The alternate (properdin pathway) activated by the
endotoxins
• Both meet at C3
• Major end products of the complement activation are
• Anaphylatoxin – stimulates contractile proteins within vascular
walls increasing vascular permeability
• Chemotactic factors (C5a) which attract neutrophils and
macrophages to the site, leading to damage to vascular cells and
GBM
43. PATHOPHYSIOLOGY
• The pathologic changes in the glomerulus following immunologic
injury – glomerular proliferation involving the epithelial and
mesangial cells and matrix
44. CLINICAL PRESENTATION
• History –
• Typical age is 5-12 years
• Complaints can vary – varying degrees of body swelling (with
facial puffiness, worse in the morning), coke coloured urine
and/or reduced urine volume
• Associated complaints of headache, double vision, nose bleeds,
fast breathing and orthopnea are suggestive of severe
hypertension
• History of antecedent pharyngitis (1-2weeks before presentation)
or skin infection (3-6weeks ago) should be sought
45. CLINICAL PRESENTATION
• History –
• Trauma, recurrence of symptoms, known chronic
conditions like SCD can help to exclude differentials
• Careful drug history will help exclude other causes of
red urine, or implicate possible nephrotoxic agents
• Family history should be carefully ascertained to
exclude familial causes of glomerulonephritis
• Social history – overcrowding, low socio economic
status, unhygienic living conditions will support APSGN
46. CLINICAL PRESENTATION
• Physical Examination –
• Vital signs –
• BP – after child has rested at least 5minutes;
appropriate cuff size; grade of HTN ascertained and
management instituted
• Tachycardia and tachypnea may suggest heart failure
• General exam – obvious respiratory distress, orthopnea
and cough may suggest heart failure and pulmonary
oedema; facial puffiness and varying degrees of
peripheral oedema often seen
47. CLINICAL PRESENTATION
• Systemic examination –
• CVS – raised JVP, displaced apex beat, S3, hepatomegally
suggests heart failure
• Respiratory – bibasal crepitations in ambulant children
suggest pulmonary oedema
• CNS – altered mental status, new seizures, epistaxis suggest
hypertensive emergency
• Abdomen – ascites may be present; kidneys are not typically
ballotable, renal angle tenderness suggests severe disease
or other differentials
48. CLINICAL FEATURES
Typical picture is infection of the skin or the pharynx; followed by a latent
period of about 10/7(1-3wks) for pharyngitis associated AGN and 3-6wks for
pyoderma associated AGN before appearance of features of AGN:
A. Oedema – milder than in Nephrotic syndrome
Facial, limbs, worse on waking up,
disappears later in the day/with ambulation
B. Hypertension – which falls with recovery
49. C. Haematuria – gross in 30-70% of pts.
(Brownish, coca-cola, tea or agbo coloured due→
to degradation of Hb to acid heamatin)
Microscopic haematuria in all
D. Signs of circulatory overload
- Pulm oedema →resp. distress, crepts
- Heart failure →tachycardia, tachypnoea, gallop rhythm,
tender hepatomegaly
E. Severe pallor → dilutional anaemia
F. Evidence of pharyngitis or pyodema. Siblings may
have evidence of AGN.
50. Severe cases – present with complications of the
dx.
1.Hypertensive encephalopathy - Convulsions, impaired
consciousness, paresis.
2.Oliguric acute renal failure
3.Pulmonary oedema
4.Heart failure
5.Nephrotic syndrome
• -Massive oedema + proteinuria
• A rare cause of Nephrotic syndrome in our environment
6.Retinopathies
7.RPGN → renal failure
51. Evaluation to Document Likelihood of
Typical Poststreptococcal Acute
Glomerulonephritis
-Typical presentation with no findings
suggestive of other systemic disease.
• Evidence of prior streptococcal infection.
• Throat or skin lesion culture positive for
Streptococci
• Elevated antibody titers using panel (acute and
convalescent titers must be done)
• Complement abnormalities typical
• Decreased CH50 and C3 during acute phase.
• C4 usually normal
• Levels rise toward normal by 6-8 weeks
52. • Beginning recovery in 1 week
• Diuresis
• Blood pressure normalizes
• BUN, creatinine begin to fall.
• Normalization of urine sediment
• Resolution of gross hematuria by 2-3
weeks
• Resolution of proteinuria by 3-6 months
• Resolution of microscopic hematuria by 1
year
53. Investigations contd.
• Urinalysis – (part of the examinations in the
side room)
• -Colour, blood, protein (+ or ++),
-Microscopy→rbc +++, wbc casts – esp rbc
casts.
{Casts are proteins filtered but not reabsorbed
which form moulds at the tubules rbcs
attached
-Rbc casts
Granular casts etc (when rbc degenerate),
Hyaline casts.}
54. • Serum electrolyte
- Na = (N)
- Cl = (N)
- ↑K+
- ↓ HCO3
-
- Urea, creatinine
- Serum protein- (N)
• Serum C3 estimation
-Complement system is activated in post
streptococcal AGN
-Serum C3 is elevated for 6-8/52 before
returning to normal; Serum C4,(N)
-If not normal by 8-12 wks, review diagnosis.
55. • Serum cholesterol- to R/o N. syndrome
• 24hour urine for protein and creatinine
clearance
• Blood film for mp
• Chest X-ray-if heart failure or Pulmonary
oedema present
• Renal ultrasound
57. Additional indications for renal biopsy in a child
presenting with Acute nephritic syndrome
• Features suggestive of a diagnosis other
than APSGN:
-Family hx of glomerular dx
-Age under 4yrs and over 15yrs
-Previous hx of similar symptoms
-Evidence of extrarenal dx
-Evidence of acute or chronic non-
streptococcal infection
-Atypical investigation results- Low C4,
Positive ANCA, ANA, anti-dsDNA, anti-GBM
antibodies
GFR < 50% of N for age
58. Confirmatory tests:
a. culture streptococcus – throat swab or skin swab
b. serology (indirect):
(i) Antistreptolysin 0 titre (ASO titre)
- starts to rise in the 1st 10days
- reaches a peak in 4/52
- and tails off in 6/52
- ASOT > 333 Todds Unit markedly raised, <166
normal
- More raised in pharyngitis - related AGN
(ii)Anti-hyaluronidase – higher in Pyoderma than
pharyngitis associated AGN
(iii) Anti-deoxy ribonuclease B - raised in both but more
in pyoderma
If (i) to (iii) elevated, sure of diagnosis
(iv) +ve Streptozyme test – a slide agglutination test
that incorporates the above. Uses a mixture of
extracellular products of the streptococcus.
59. •DIFFERENTIALS
•1. Post infectious AGN
Bacteria- Staph, other Strept, Typhoid,
Secondary Syphilis, Meningococcaemia etc
Mycoplasma
Post viral AGN – Echovirus, Coxsackie,
Varicella, Mumps, Influenza, Hepatitis
B&C, Parvovirus etc.
Parasitic – Malaria
Toxoplasmosis
60. • 2. Berger,s disease:- (IgA Nephropathy)
(Benign recurrent Haematuria)
- Episodes of haematuria often pptated
by non-specific viral resp. infections or febrile
episodes.
Latent period of 1-2 days , may occur
concomitantly with URI.
- Males are more commonly affected
than females
- Progressive disease develops in about
30% of patients
- Poor prognosis with hypertension,
reduced renal function and severe
proteinuria between episodes
- Immunosuppressives may be
beneficial
61. •3. Henoch Schonlein purpura
- abd symptoms, abdominal
pain, intussuception,
purpuric lesions
- features of G/N
•4. SLE
•5. PAN (Polyarteritis Nodosa)
62. Based on haematuria
• 1.Haemolytic uraemic syndrome
(HUS)
- Renal failure ± oligonuria –
- Microangiopathic haemolytic anaemia
(fragmented red cell seen in blood film)
- Thrombocytopaenia
- Commonest cause of ARF now among young
caucasian children
2. Hereditary or familial disorders
- Hereditary nephritis with deafness
ALPORT Syndrome
- Familial Benign recurrent haematuria
(good prognosis)
- Polycystic kidney dx.
63. TREATMENT
• Medical management –
• Determination of volume – if hypervolemia present, challenge the
kidneys with diuretics (IV frusemide 2-4mg/kg)
• Observe for urine output, if no improvement, discontinue diuretics and
mainstay of fluid management will be fluid restriction.
• Typically 400ml/m2/day + urine output + stool/vomitus/blood lost
• Manage any metabolic derangements, e.g hyperkalemia, metabolic
acidosis, hypocalcemia
64. TREATMENT
• Medical management –
• Management of hypertension –
• Salt and water restriction – sodium intake <1.5g/day (or no added
salt)
• Diuretics
• These two approaches might be adequate to normalize blood pressure in a
few cases
• Medications –
• ACE inhibitors/ARBs are renoprotective (Enalapril or Losartan);
• long acting Calcium channel blockers (Amlodipine 0.1-0.6mg/kg/day in 2dd)
can also be used.
65. TREATMENT
• Medical management –
• Hypertensive urgency/emergency –
• Continuous infusion of
• Nicardipine 0.5-5µg/kg/min
• Sodium nitroprusside 0.5-10µg/kg/min
• Labetalol 0.25-3mg/kg/hr
• Convert to intermittently dosed antihypertensives when more stable
• Antibiotics – oral penicillin for 10days
66. TREATMENT
• Supportive care and monitoring –
• Nutrition –
• in AKI, sodium, phosphate and potassium are typically restricted
• Protein intake moderately restricted
• Maximize caloric intake
• Strict fluid input and output monitoring
• Daily weighing, BP, serum electrolyte/urea/creatinine, urine panel
67. COMPLICATIONS
• Hypertension – 60% of cases, 10% manifest hypertensive
encephalopathy
• Can lead to intracranial bleeding when prolonged
• Heart failure
• Acute renal injury –
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Uraemia
• acidosis
68. PROGNOSIS
• Prognosis is good
• 80% recover completely
• 10% may go into CRF, so follow up for up to adulthood
• Complete recovery is the norm – over 95% of cases
• Mortality in the acute phase can be prevented by prompt
management of hypertension, heart failure and AKI
• Recurrence is extremely rare
• Progression to CRF is rare, <2% of cases
69. PREVENTION
• Level 1 – general health promotion
• On hygiene, avoiding overcrowding, increasing health awareness and health seeking
behaviour
• Level 2 – specific protection
• No vaccines available yet; adequate treatment of pharyngitis and pyoderma
• Level 3 – early diagnosis and prompt treatment
• Early presentation, thorough assessment for CHF, AKI, HTN
• Level 4 – Limitation of complications
• Availability of laboratory facilities, prompt evaluation and treatment of associated
manifestations
• Level 5 – Rehabilitation
• Dialysis, support for the neurologically impaired
70. References
• Nelson’s textbook of Paediatrics, 21st edition
• Lecture notes on Common kidney diseases in children; Dr Chris
Esezobor, Associate Professor, University of Lagos, WACP
membership revision course, August 2022
