Aquifer - Renal

Question 1

What is nephrotic syndrome?

Answer 1

Results when there is an increase in the permeability to negatively charged proteins of the glomerular filtration barrier in the kidney. This increased permeability leads to the four major characteristics used in diagnosing nephrotic syndrome.

Question 2

4 characteristics of nephrotic syndrome?

Answer 2

1. Nephrotic range proteinuria
2. Hypoalbuminemia
3. Edema
4. Hyperlipidemia

Question 3

Describe the pathophysiology of nephrotic syndrome.

Answer 3

Increased protein permeability of the glomerular filtration barrier leads to a loss of protein in the urine (proteinuria), including alubmin (hypoalbuminemia)

Decreased serum oncotic pressure from hypoalbuminemia results in interstitial fluid accumulation and resultant edema

Upregulation of albumin and other circulating proteins -> increased synthetic function of the liver resulting in hyperlipidemia

Question 4

Age/sex of nephrotic syndrome in children?

Answer 4

Can affect children of any age, from infancy to adolescent

More common in pre-school and school age children

M>F (2:1), but this fails to persist in adolescence

Question 5

Most common cause of primary nephrotic syndrome in children?

Answer 5

Minimal change disease (90% of cases under age 10)

Question 6

Characteristic histologic finding in minimal change disease?

Answer 6

Diffuse effacement of the epithelial cell foot processes on EM with otherwise normal findings (normal on light microscopy)

Question 7

Clinical findings of nephrotic syndrome?

Answer 7

Edema (most prominent symptom)
Periorbital edema that improves when the child is upright (gravity dependent edema)
Pitting edema, ascites, weight gain
Nonspecific symptoms of increased tiredness and decreased appetite due to interstitial fluid accumulation

Question 8

Nephrotic range protein:creatinine ratio?

Answer 8

> 2.0 mg protein/mg creatinine

Question 9

Evaluation of generalized edema?

Answer 9

1. Electrolytes, BUN, creatinine (indication of renal function)
2. AST, ALT, cholesterol, albumin, triglycerides (hepatic inflammation/impaired hepatic synthetic function)
3. C3 and C4 complement levels (associated with several GN - membranoproliferative, post-strep, SLE)
4. Streptozyme - antibodies to strep antigens, + in the setting of PSGN

Question 10

Pathogenesis of proteinuria in nephrotic syndrome?

Answer 10

Increased filtration of moderately sized proteins (predominantly albumin and IgG) through the glomerular capillary wall, resulting in proteinuria

Specifically, this is caused by loss of the polyanion charge characteristic of the normal glomerular capillary wall. Normally, all layers of the glomerular filtration surface have a negative surface charge due to proteoglycans such as heparin sulfate. Loss or reduction of this charge may permit moderately sized negatively charged proteins like albumin to leak through the membrane.

Question 11

Rx of primary nephrotic syndrome?

Answer 11

Children between 1-10 years without signs of nephritis (gross hematuria, HTN, elevatd Cr) may receive an empiric trial of corticsteroids (2 mg/kg/day of prednisone or prednisolone)

Treat for at least 12 weeks (6 full dose, 6 week taper); shorter courses associated with increased relapse risk

Sodium restriction to 1500-2000 mg/day

Combined IV furosemide and albumin (25%) - only for children with symptomatic edema (dyspnea, scrotal edema, etc.)

Question 12

Why is IV furosemide not recommended in primary nephrotic syndrome?

Answer 12

Circulating volume is already low because of hypoalbuminemia, so furosemide without concurrent albumin administration may lead to dangerously low volume states and an increased risk for venous thrombosis

Question 13

Why is albumin treatment alone not recommended?

Answer 13

May lead to redistribution of the interstitial fluid volume, which may cause CHF and pulmonary edema if it expands too rapidly

Question 14

Types of response to steroids?

Answer 14

1. Steroid responsive
2. Relapsing/steroid-dependent (long-term prognosis is excellent, no long-term damage)
3. Steroid-resistant

Question 15

Define steroid-resistant primary nephrotic syndrome and next steps.

Answer 15

Those who do not respond to steroids with elimination of proteinuria after 8 weeks of therapy

Renal biopsy

Question 16

Indications for renal biopsy in patients with nephrotic syndrome?

Answer 16

1. Steroid-resistant
2. Hematuria, HTN, and/or elevated creatinine suggestive of another etiology of nephrotic syndrome or GN (excluding those dx with post-infectious)
3. Children >10 years of age (if dx is not a drug reaction or postinfectious GN)

Question 17

During a nephrotic syndrome relapse with steroid use, patients are at high risk for infection - why?

Answer 17

Decreased Ig levels
Edema fluid acting as a culture medium
Protein deficiency
Decreased leukocyte bactericidal activity
Immunosuppression from steroids
Decreased splenic perfusion due to hypovolemia
Urinary loss of a complement factor (properdin factor B) that opsonizes certain bacteria

Question 18

Common infectious complications of nephrotic syndrome?

Answer 18

Spontaneous peritonitis (insidious presentation of fever and minimal other findings)
Pneumonia
Cellulitis
UTI

Question 19

Most common pathogen causing peritonitis in nephrotic syndrome?

Answer 19

S. penuoniae

Question 20

When in remission, patients should receive ___ to prevent complications from nephrotic syndrome.

Answer 20

Polyvalent pneumococcal vaccine
2 doses varicella vaccine (if not already immunized)
Annual influenza vaccine