Nephrotic Syndrome & Acute Glomerulonephritis in Childhood Flashcards by Iseoluwa Ojo

Nephrotic syndrome

It is a common kidney problem in childhood:

• It affects both males and female, with a higher (male or female ?)frequency in younger children and similar
prevalence in older children
• _____________ have the highest incidence of childhood nephrotic syndrome while steroid resistant NS is more common in _________ children

male

South Asians

black

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What is Nephrotic Syndrome?
• It is a manifestation of _________ disease
characterized by _________ _________, massive _________, _________ and
_________.

glomerular

generalized oedema ; massive
proteinuria

hypoalbuminaemia ;
hypercholesterolemia.

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_____________ and _______________ must be present to make a diagnosis of nephrotic syndrome

Hypoalbuminaemia & massive proteinuria

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Hence NS is not a disease in itself but a
manifestation of a disease affecting the
_____________ of the ___________ ; this disease may be intrinsic to the kidney or extrinsic to it.

permselectivity

glomeruli

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Oedema
• Usually ___________ .
• First noticed on the ________ (the ________ region) then the _______ and subsequently the ________ (resolution occurs in the same order).
The scrotum or labia may also be swollen

generalized. ; face

periorbital ; legs ;abdomen

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Oedema

Initially the ________ oedema resolves while _________, but as the oedema increases the resolution when upright may no longer be remarkable

facial

upright

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Oedema

Two theories explain the cause of the oedema:
– Underfill theory: the oedema is due to decreased ————— leading to increased __________ of __________ and __________ in the kidneys

– Overfill theory: the oedema is due to primary increased __________ of __________ in the kidneys

oncotic pressure ; absorption

sodium ; water

re-absorption ; sodium

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Proteinuria
• The proteinuria is ________ or _________-range. it is mostly ________.
• On dipstick it is usually ≥______

massive; nephrotic

albumin; 3+

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Massive or nephrotic-range proteinuria is defined as
– >_______mg/m2/24hr or
– >____mg/m2/hr or
– urine protein : creatinine ratio >____

1000

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The proteinuria is due to increased permeability of the glomeruli to albumin:

• The increased permeability may be due to
– (a) an unknown circulating factor induced by a disorder of __________________ (most common reason) or
– (b) _________ abnormality of the __________ due to ________ disorders
– The increased urinary loss of albumin results in hypoalbuminaemia (serum albumin <_____g/dl)

T cell immunity

structural; glomeruli; genetic

2.5

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The _________ is the major determinant of
glomerular permeability

podocyte

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Hypercholesterolemia
• _______________ and _______________ are elevated
• Hypercholesterolemia is serum cholesterol >____mmol/l or >______mg/dl

Both triglycerides

cholesterol

5mmol/l ;?200mg/dl

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The hypercholesterolemia is due to
– Increased _________ of ____________ by the __________
– Decreased activity of __________________

synthesis ; lipoprotein

Liver

lipoprotein lipase

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Increased risk of Infection
• Children with NS are at an increased risk of infection especially from ___________ organisms such as ___________, ___________.

The infections commonly include ———— , _________ and _________

encapsulated

streptococcal pneumoniae ; H. Influenzae.

sepsis ; cellulitis ; peritonitis

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Increased risk of infection

This is due to
– Decreased ____________ from loss of __________ in urine, especially ________
– Functional ________
– Ascites & oedema
– Concomitant use of ___________ such as ___________, cyclophosphamide etc

opsonization ; complements

factor B ; hyposplenism

immunosuppressants ; steroids

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Increased risk of thrombosis
• May manifest as ___________ ,
gangrene, deep vein thrombosis, renal vein
thrombosis or stroke
• The increased thrombosis is due to
– Increased serum levels of _________ : ____,____,____,_____

– Decreased serum levels of _________ such as _______,________ and ________
– Hypovolemia & immobility

pulmonary embolism,

procoagulants: factors II,
V, VII, VIII

anticoagulants
antithrombin III, protein C & S

Increased risk of acute kidney injury
• Commonly due to __________ of the
kidneys but may be due to renal vein
thrombosis, adverse effects of drugs such as ____________ or _________ or a co-manifestation of the underlying disease as a ______,________

hypoperfusion

ACE inhibitors ; ARB

MPGN ; FSGS

Classification of Nephrotic Syndrome
• Age at onset
(a) Congenital NS: occurring between ____________ of life: usually due to genetic disorders
(b) Infantile NS: occurring between ____________
(c) Childhood NS: Occurring from ____________ of life

0-3 months

4-11 months

12 months of life

Classification of Nephrotic Syndrome

• Due to disease intrinsic or extrinsic to the kidneys
(a) primary (idiopathic) NS: not due to ____________________.
Most common type of childhood NS; 90% of childhood NS in children aged 1-10 years

(b) Secondary NS: due to a systemic or extra-renal disease such as SLE, henoch-schonlein purpura, HBV, HCV, HIV,
lymphoma, sickle cell disease. They become more common as children get older.

to any systemic disease.

Classification of Nephrotic Syndrome

Histology
(a) Minimal change NS: __________ histologic form in children.
Normal renal histology on both light and immunoflourescent microscopy. On electron microscopy there is __________ of the __________ of the __________
(b) Focal segmental glomerulosclerosis: _________________ histologic form of childhood NS. Only 20-30% of children with FSGS are sensitive to
steroids
(C) __________ GN
(c) __________ glomerulonephritis
(d) __________ __________: _____ in childhood

commonest ; effacement

foot process ; podocytes

second commonest ; Membranoproliferative

Mesangioproliferative

Membranous nephropathy ; rare

Classification of Nephrotic Syndrome

• Response to steroids:
• Steroid __________ NS: most children have SSNS
• Steroid ___________ NS

Steroid sensitive
Steroid resistant

_______________ is the most important way of classifying NS

Response to steroids

_______________ is the most important way of classifying NS

Response to steroids

Minimal Change Nephrotic Syndrome
• Commonest histology on biopsy of children
• >90% of children with MCNS are steroid ————-
• MCNS can be differentiated clinically from other histologic forms of childhood NS by the the following:
– Age between _____
– __________ renal function
– __________ complement
– __________ of hypertension or pulmonary oedema
– __________ of extra-renal disease such as skin rash, joint pains, anaemia
– __________ of family history
– __________ of active urinary sediment e.g. red blood cell
casts

sensitive; 1-10yr

Normal; Normal; Absence; absence; absence; absence

Indications for Kidney Biopsy in Nephrotic Syndrome Kidney biopsy is reserved for children with NS presenting with the following: a. Age outside _________ b. Significant _________ c. Gross _________ d. _________ disease such as SLE, HSP, SCD e. _________tension f. Persistently ______ serum complement levels g. Steroid _________ h. With severe steroid toxicity Generally kidney biopsy is done when it is not likely that the child has MCNS

1 yr to 10 yr renal failure hematuria Systemic disease Hypertension low ; resistance

Differential Diagnosis of NS • ________ ________ syndrome • Acute or chronic ______________ • _______ failure • Other causes of hypoalbuminaemia such as severe ___________________ , _________ enteropathy • Severe ________ disease

Acute nephritic syndrome kidney disease Heart failure protein-energy malnutrition protein losing enteropathy liver disease

Treatment of Children with Idiopathic Childhood NS Definitive Therapy Drug of choice is __________; it is given to all children with idiopathic childhood NS Dose: ____mg/m2 daily for 6 weeks If the child goes into remission during this period then at the end of 6 weeks prednisolone is reduced to _____mg/m2 alternate day for 6 weeks. If the child remains in remission then prednisolone is tapered slowly over the next 4 weeks. Total duration of steroid: ______ weeks Single daily dose is preferred to divided doses because side effects are less

prednisolone; 60mg/m2 40mg/m2 ; 16 weeks

Treatment of children with idiopathic childhood NS Supportive Therapy ___________ antagonist or ___________ inhibitors ___________ & ___________ supplementation, c

H2 receptor antagonist proton pump inhibitors Vitamin D & calcium supplementation, m

Some common definitions •Relapse: urinary protein excretion >______mg/m2/hr; ≥____ by dipstick on ____ consecutive days •Remission: urinary protein excretion <____mg/m2/hr; nil or trace by dipstick for ___consecutive days •Frequent relapses: _____ or more relapses in ________ of initial response; ____ or more relapses in any 12 mo

>40mg/m2/hr; ≥3+ ; 3 <4mg/m2/hr; ; 3 consecutive days two ; 6 months 4 or more relapses in any 12 mo

Some common definitions •Steroid dependence: occurrence of _______________________ during steroid therapy or within ____________ of its cessation •Steroid resistance: failure to achieve _________ after ________ of daily therapy with _______________ at a dose of _____mg/m2/day

2 consecutive relapses 2 weeks ; remission 8 weeks ; oral prednisolone 60mg/m2/day

Acute Glomerulonephritis (AGN) • This is defined as a pathologic process characterized by _________ and _________ of glomerular cells(endothelial, mesangial and epithelial) and infiltration by ___________.

inflammation ; proliferation neutrophils.

AGN • The clinical spectrum of AGN may be ————- with or without __________ , __________ syndrome, nephrotic syndrome or rapidly progressing __________ • _____________________ is the most common clinical presentation of AGN

hematuria ; proteinuria acute nephritic syndrome GN ; Acute nephritic syndrome

Causes of AGN Post infective (a)________________________ (b)Other bacteria such as other streptococci, staphylococcus (c)Viruses such as cytomegalovirus, mumps, Epstein-Barr virus, Hepatitis B, Hepatitis C virus Non post infective (a)Connective tissue disroders: ______ (b)Vasculitis: ______________________ , polyarteritis nodosa, wegener’s granulomatosis Primary Kidney Disease Such as _______ nephropathy, ______________ GN, Idiopathic rapidly progressive GN

Group A beta hemolytic streptococcus SLE ; Henoch-Schonlein purpura, IgA nephropathy Membranoproliferative GN,

Post Streptococcal AGN (PSAGN) PSAGN & ________________ are used interchangeably

Acute nephritic syndrome

PSAGN is the (suppurative or non-suppurative?) complication of streptococcal pharyngitis or skin infection • AGN occurs __________ after pharyngitis or skin infection; the longer duration applies to skin infection. •Some strains of streptococci are known to be more nephritogenic: strain ____ (following pharyngitis) strain ——- (following skin infection)

non-suppurative 1-3 weeks strain 12 strain 49

In developing and tropical countries, ___________-associated PSAGN is more common than _________-associated PSAGN • No known racial predilection

pyoderma pharyngitis

Pathogenesis of PSAGN •It is an ____________ reaction following ____________ infection •The immunological reaction may be due to trapping of circulating ____________ in the ____________ or insitu formation of one (the later is more likely). •The antigens in these complexes may be either components of streptococci or the glomeruli itself (___________). •The two major streptococcal proteins now recognized as Ag in PSAGN are _____________________________ (NSAP) and _______________________________ (NAPIr) •These Ag activate complements commonly via the ___________ pathway leading to proliferation of glomerular cells and infiltration by non glomerular cells such as __________ and __________ The proliferation of glomerular cells leads to __________ of the glomeruli leading to reduced glomerular filtration, oedema, hypertension and oliguria. Damage to the _______ leads to hematuria with or without proteinuria

immunological ; streptococcal immune complexes ; glomeruli ; molecular mimicry Nephritis Strain Associated Protein (NSAP) ; Nephritis Associated Plasmin Receptor (NAPIr) alternate; neutrophils and monocytes occlusion ; GBM

Clinical Features of AGN •Most common presentation is acute nephritic syndrome: ________ (85%), ________, ________ (50-90%), ________ (~100%) and ________(PH2O2) The oedema is first noticed on the face, and rarely associated with ________. •The hypertension is due to ________ and may be complicated by ________ and ________ •The hematuria is usually _______scopic giving urine the ________ appearance. • On microscopy there are numerous ______________ casts and ___________ red cells (characteristic) •Acute kidney injury occurs in some children and may be severe enough to require dialysis (rapidly progressive GN) •Other non-specific features include malaise, lethargy, fever, abdominal pain and headache

oedema; oliguria hypertension ; hematuria proteinuria ; ascites water retention ;heart failure ; encephalopathy microscopic ; smoky red cell casts ; dysmorphic red cells

Prognosis • The short term prognosis is _________ . • The long term prognosis may not be as good as previously reported: prevalence of _________ or _________ may be higher in persons with PSAGN followed up for several years

excellent. proteinuria or hematuria