Nephrotic Syndrome Flashcards
Nephrotic-range proteinuria is defined as
> 3.5g/24hr or UPCr >2g/g
Triad of clinical findings associated with nephrotic syndrome arise from
Large urinary losses of protein
Triad of clinical findings associated with nephrotic syndrome
1) Hypoalbuminemia (less than 2.5g/dL) 2) Edema 3) Hyperlipidemia (cholesterol >200mg/dL)
Without treatment, nephrotic syndrome is associated with a high risk of death, most commonly from
Infections
___% of children with nephrotic syndrome respond to corticosteroid therapy
80
MC glomerular lesion associated with idiopathic nephrotic syndrome
Minimal change disease
Underlying abnormality in nephrotic syndrome
Increased permeability of the glomerular capillary wall
A highly differentiated epithelial cell located on the outside of the glomerular capillary loop
Podocyte
Functions of the podocyte
1) Structural support of the capillary loop 2) Major component of the glomerular filtration barrier to proteins 3) Involved in the synthesis and repair of the GBM
MC presenting symptom of children with nephrotic syndrome
Edema
Postulates that nephrotic syndrome is associated with primary sodium retention, with subsequent volume expansion and leakage of excess fluid into the interstitium
Overfill hypothesis
Postulates that sodium and water retention therefore occur as a consequence of intravascular volume depletion.
Underfill hypothesis
Goal of nephrotic syndrome therapy
Gradual reduction of edema with 1) Judicious use of diuretics 2) Sodium restriction 3) Cautious use of albumin infusions
Why are children with nephrotic syndrome especially susceptible to infections
1) Hypoglobulinemia as a result of the urinary losses of immunoglobulin (Ig) G 2) Impaired opsonization from urinary loss of complement factors (predominantly C3 and C5)
Children with nephrotic syndrome are at significantly increased risk for infection with what kind of bacteria
Encapsulated, particularly pneumococcal
Most frequent cause of peritonitis
Pneumococcus
Peritoneal leukocyte counts of ____ are highly suggestive of SBP
> 250
Nephrotic syndrome us a hypercoagulable state resulting from
1) Vascular stasis from hemoconcentration and intravascular depletion 2) Increased platelet number and aggregability 3) Changes in coagulation factor levels (increased production of fibrinogen, urinary losses of antithrombotic factors ATIII and protein S)
Clinical risk of hypercoagulable state in children is
2-5%, low compared to adults
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Most commonly presents as nephrotic syndrome
MCNS
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Least hematuria
MCNS
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Asymptomatic proteinuria
MPGN
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Most hypertensive
MPGN
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Does not progress to renal failure
MCNS
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Associated with HIV and heroin use
FSGS
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Associated with sickle cell disease
FSGS
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Associated with RVT
MN
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Associated with partial lipodystrophy
MPGN II
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Associated with reflux nephropathy
FSGS
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Low complement levels
MPGN I
Primary Renal Disease That Manifest as Idiopathic Nephrotic Syndrome: Steroid resistant
MN, MPGN
Approx ___% of children with nephrotic syndrome have idiopathic nephrotic syndrome
90
Approx 85% of total cases of nephrotic syndrome in children is ___ in pathology
MCNS
___% of children with MCD respond to corticosteroid therapy
85
FSGS: LM findings
Mesangial cell proliferation and segmental scarring
FSGS: IF findings
Positive for IgM and C3
FSGS: EM findings
Segmental scarring of the glomerular tuft with obliteration of the glomerular capillary lumen
Only ___% of patients with FSGS respond to prednisone
20
Idiopathic nephrotic syndrome is more common in what gender
Males
Idiopathic nephrotic syndrome appears between the ages of
2 and 6 years
MC cause of idiopathic nephrotic syndrome in children less than 6 y/o
MCNS
MC cause of idiopathic nephrotic syndrome in adolescents
FSGS
Nephrotic syndrome can initially be misdiagnosed as ___ because of the periorbital swelling that decreases throughout the day
Allergic disorder
Important features of minimal change idiopathic nephrotic syndrome
Absence of hypertension and gross hematuria
Diagnosis of nephrotic syndrome is confirmed by
1) Urinalysis with first morning urine protein:creatinine ratio 2) Serum electrolytes, BUN, Crea, albumin, cholesterol
Evaluation to rule out secondary forms of nephrotic syndrome (children >/10 yr)
C3, ANA, dsDNA, Hepatitis B and C, HIV
Evaluation for children >/12 yr with idiopathic nephrotic syndrome, who are less likely to have MCNS
Kidney biopsy
Nephrotic syndrome: UA protein
3+ or 4+
Microscopic hematuria is present in ___% of children with nephrotic syndrome
20%
Nephrotic syndrome: Spot urine protein:crea ratio
> 2
Nephrotic syndrome: Serum albumin level
Less than 2.5g/dL
Nephrotic syndrome: Serum complement
Normal
Idiopathic nephrotic syndrome is less likely to be MCNS if it occurs at what ages
Less than 1 year or >12 years old
Mainstay of therapy of MCNS
Corticosteroids
Response to steroids is defined as
Attainment of remission within the initial 4 weeks of corticosteroid therapy
MCNS: Remission consists of
UPCr <0.2 or <1+ protein on dipstick for 3 consecutive days
MCNS: Vast majority of children who respond to prednisone therapy do so within
First 5 weeks of treatment
Nephrotic syndrome: Indication for admission
Severe symptomatic edema (Large pleural eff, ascites, or severe genital edema)
Sodium restriction
<1500mg/day
Management of hyponatremia in children with nephrotic syndrome
Fluid restriction
Management of swollen scrotum in nephrotic syndrome
Elevated with pillows to enhance fluid removal by gravity
Indications for administration of IV albumin in children with nephrotic syndrome
Severe generalized edema with evidence of intravascular volume depletion (hemoconcentration, hypotension, tachycardia, etc)
Nephrotic syndrome: Albumin is administered at what dose
0.5-1.0g/kg) followed by furosemide (1-2mkdose IV)
Potential complications of parenteral albumin therapy
1) Volume overload 2) Hypertension 3) Heart failure 4) Pulmonary edema
Nephrotic syndrome: Management of dyslipidemia
1) Limit dietary fat intake to <30% of calories 2) Limit saturated fat intake to <10% of calories 3) Limit dietary cholesterol intake to <300mg/day
Nephrotic syndrome: Empiric antibiotic therapy should be broad enough to cover
1) Pneumococcus 2) G- bacteria (3rd gen cephalosporin is a common choice)
Nephrotic syndrome: Management of thromboembolism
1) Imaging studies to confirm presence of a clot 2) Studies to delineate a specific underlying hypercoagulable state 3) Heparin, LMWH, or Warfarin
Nephrotic syndrome: Relapse is defined as
1) UPCr >2 or 2) >/3+ protein on urine dipstick testing for 3 consecutive days
Nephrotic syndrome: Relapses are common, especially in younger children and are often triggered by
URTI or GI infections
Nephrotic syndrome: How are relapses treated
Usually in a similar manner to the initial episode except that daily prednisone courses are shortened
Nephrotic syndrome: Steroid resistance is defined as
Failure to achieve remission after 8 weeks of corticosteroid therapy
SRNS further eval includes
1) Kidney biopsy 2) KFT 3) Quantitation of urine protein excretion on top of urine dipstick testing
SRNS is usually caused by
FSGS in 80% of cases, MCNS, or MPGN
SRNS, specifically FSGS, is associated with a ___% risk for end-stage kidney disease within 5 years of diagnosis if patients do not achieve a partial or complete remission
50
Reduces the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome
Cyclophosphamide therapy
Potential side effects of Cyclophosphamide therapy
1) Neutropenia 2) Disseminated varicella 3) Hemorrhagic cystitis 4) Alopecia 5) Sterility 6) Increased risk of future malignancy
During cyclophosphamide therapy, what blood parameter should be monitored weekly?
WBC count, if below 5,000/mm3, withhold drug
Cumulative threshold of Cyclophosphamide above which oligospermia or azoospermia occurs in boys is
> 250mg/kg
Recommended as initial therapy for children with steroid-resistant nephrotic syndrome
Calcineurin inhibitors (cyclosporine or tacrolimus)
Side effects of calcineurin inhibitors
1) Hypertension 2) Nephrotoxicity 3) Hirsutism 4) Gingival hyperplasia
An antihelmintic agent with immunomodulating effects that has been shown to reduce the risk of relapse in comparison to prednisone
Levamisole
Rituximab is a chimeric monoclonal antibody against ___
CD20
___ and ___ may be helpful as adjunct therapy to reduce proteinuria in steroid-resistant patients
Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers
Live vaccination should be deferred until prednisone dose is
Either below 1mkday or 2mkday on alternate days
T/F Live virus vaccines are contraindicated in children receiving corticosteroid- sparing agents such as cyclophosphamide or cyclosporine
T
Guideline for children on immunosuppresives following close contact with varicella infection
VZ immune globulin
T/F Most children with steroid-responsive nephrotic syndrome have repeated relapses
T
T/F Relapses in children with steroid-responsive NS decrease in frequency as the child grows older
T
Children with nephrotic syndrome with these characteristics are likely to follow an infrequently relapsing course
Children who respond rapidly to steroids and those who have no relapses during the first 6 mo after diagnosis
Infectious agents associated with nephrotic syndrome
1) Malaria 2) Schistosomiasis 3) Hepatitis B 4) Hepatitis C 5) Filaria 6) Leprosy 7) HIV
Proposed mechanism of nephrotic syndrome in lymphoma
Lymphoma produces a lymphokine that increases permeability of the glomerular capillary wall
Drugs associated with Membranous glomerulopathy
Penicillamine, captopril, gold, nonsteroidal antiinflammatory drugs, mercury compounds
Drugs associated with MCNS
Probenecid, ethosuximide, methimazole, lithium
Drugs associated with Proliferative GN
Procainamide, chlorpropamide, phenytoin, trimethadione, paramethadione
Congenital nephrotic syndrome is defined as
Nephrotic syndrome manifesting at birth or within the 1st 3 mo of life
Caused by mutations in the WT1 gene, which results in abnormal podocyte function
Denys-Drash syndrome
Manifestations of Denys-Drash syndrome
1) Early-onset nephrotic syndrome 2) Progressive renal insufficiency 3) Ambiguous genitalia 4) Wilms tumor
Syndrome caused by mutation in LAMB2 gene, leading to abnormalities in β2-laminin, a critical component of glomerular and ocular basement membranes.
Pierson syndrome
Congenital nephrotic syndrome presenting with bilateral microcoria (fixed narrowing of the pupil)
Pierson syndrome
T/F Secondary congenital nephrotic syndrome can resolve with treatment of the underlying cause
T
Definitive treatment of congenital nephrotic syndrome
Renal transplantation
