Chapter 527: Nephrotic Syndrome Flashcards
Definition of Nephrotic Syndrome
Clinical manifestation of glomerular diseases, associated with:
1 - Heavy ( nephrotic range) proteinuria
2 - Hypoalbumineamia ( <2.5g/dl)
3 - edema
4 - hyperlipidemia ( cholesterol >200mg/dL)
definition of nephrotic range proteinuria?
1 - Proteinuria > 3.5g/24 hours OR
2 - Urine protein : creatinine ratio > 2
Urine protein : creatinine ratio measurement
- it is the measurement of untimed ( spot) urine specimen.
- It is calculated by dividing urine protein concentration (mg/dL) by urine creatinine concentration (mg/dL)
- It should be ideally performed on first morning voided urine specimen to eliminate possibility of orthostatic proteinuria
- Normal protein excretion is when ratio is <0.5 in children <2 years and < 0.2 in children >2 years.
- Ratio > 2 suggests nephrotic range proteinuria
- between 0.2 to 2 means proteinuria but not in nephrotic range
Timed ( 24 hour) urinary protein
- Urinary protein excretion in a normal child is <100mg/m2/day or a total of 150mg/ day
- In neonates, normal protein excretion is higher, up to 300mg/m2 –> because of reduced reabsorption of filtered proteins
- Reasonable upper limit of protein excretion for a healthy children is 150mg/24hr
- more specifically:
- Normal protein excretion in children is defined as less than or equal to 4mg/m2/hr
- Abnormal proteinuria is defined as 4 -40mg/m2/hr
- Nephrotic range proteinuria is > 40mg/m2/hr
- Test can be influenced by fluid intake, the volume of urine output and importance of including a complete collection without missed voids.
Causes of childhood nephrotic syndrome
1 - idiopathic
2 - Genetic disorders associated with proteinuria or nephrotic syndrome
3 - SEcondary causes of nephrotic syndrome
Secondary causes of nephrotic syndrome (IDIAMG)
Infections, drugs, immunologic, allergic, malignancy, glomerular hyperfiltration ( IDIAMG)
1 - Infections
- Endocarditis
- Hepatitis B and C
- HIV -1
- Infectious mononucleaosis
- Malaria
- Syphilis ( congenital and secondary)
- Toxoplasmosis
- Schistosomiasis
- Filariasis
2 - Drugs
- Captopril
- Penicillamine
- Gold
- NSAIDs
- Pamidronate
- Interferon
- Mercury
- Heroin
- Lithium
3 - Immunologic or Allergic disorders
- Vasculitis syndrome ( SLE, HSP)
- Castleman disease
- Kimura disease
- Beesting
- Food allergens
- Serum sickness
4 - Associated with malignant disease
- Lymphoma
- Leukemia
- solid tumors
5 - Glomerular Hyperfiltration
- Oligomeganephronia
- Morbid obesity
- Adaptation to nephron reduction
Definition of Relapse of Nephrotic Syndrome
Urine protein : creatinine ratio of > 2 OR > or equal to 3+ protein in urine dipstick testing for 3 consecutive days.
Definition of steroid resistance
failure to achieve remission after 8 weeks of corticosteroid therapy .
Complications of nephrotic syndrome
1 - Infection: Spontaneous bacterial peritonitis is most frequent type of infection. Bacterial sepsis, Cellulitis, pneumonia, UTI, 2 - Flare up of tuberculosis 3 - Venous and arterial thromboembolism 4 - Acute renal failure : Severe hypovolemis leads to acute renal failure especially when complicated with AGE and other infections 5 - Hypertension 6 - Tetany ( due to hypocalcemia) 7 - Risk of collagen vascular disease 8 - Hormonal and mineral alteration 9 - Abnormal growth 10 - cataract, steroid facies
Children with nephrotic syndrome are especially susceptible to infections ( such as cellulitis, SBP, bacteremia). WHY?
1 - due to Hypoglobulinemia due to urinary loss of immunoglobulin G.
2 - Defects in complement cascade from urinary loss of complement factor ( especially C3 and C5) +
3 - Altered pathway factors B and D => leads to impaired opsonization of microorganisms.
** factor B is important for integrity of alternative pathway of complement activation, which is crucial in phagocytosis of encapsulated bacteria such S pneumoniae.
4 - Large fluid collection is prone to get infected
5 - Severe edema causes extreme stretching of skin, which may break spontaneously or after trauma and allow bacterial entry.
hypercoagulability state of nephrotic syndrome results from what?
How does DVT occur in nephrotic syndrome?
1 - Vascular stasis from hemoconcentration and intravascular volume depletion
2 - increased platelet number and aggregability
3 - changes in coagulation factor levels.
*** there is an increase in hepatic production of fibrinogen along with urinary losses of antithrombotic factors such as anti thrombin 3 and protein S
4 - alteration in lipid profile including increased cholesterol, triglycerides, low density lipoprotein LDH, and very low density lipoprotein VLDL ==> increase cardiovascular risk ratio although less severe than adults.
mechanism of edema formation in nephrotic syndrome?
Underfill hypothesis and overfill hypothesis
1 - Underfill hypothesis ==> nephrotic range proteinuria leads to fall in plasma protein level, decreasing plasma oncotic pressure. this leads to leakage of plasma water to interstitial space causing edema.
As a result of reduced intravascular volume, there is increased production of vasopressin, atrial natriuretic factor which along with aldosterone ==> cause increased sodium and water retention by tubules. sodium and water retention occur as a consequence of intravascular volume depletion.
2 - Overfill hypothesis ==> it says nephrotic syndrome is associated with primary sodium retention, with subsequent volume expansion and leakage of excess fluid into interstitium. the epithelial sodium channel in distal tubule may play a key role in sodium reabsorption in nephrotic syndrome.
side effects of Cyclophosphamide?
1 - neutropenia 2 - disseminated varicella 3 - hemorrhagic cystitis 4 - alopecia 5 - sterility 6 - risk of future malignancy
Causes of reduced C3 level?
1- Renal ==> 1 - APSGN
2 - membranoproliferative GN
2 - Systemic ==>
1 - lupus nephritis
2 - subacute bacterial endocarditis
3 - shunt nephritis
4 - essential mixed cryoglobulinemia
5 - visceral abscess
