PANCE Blueprint Renal System (5%)

8 y/o with three weeks of progressive edema of face, legs, and abdomen

Patient will present as → a 6-year-old boy who is brought to the emergency department by his mother due to swelling around his eyes and legs. The mother reports that the patient recently recovered from an upper respiratory tract infection. Physical exam is significant for periorbital and lower extremity edema. Laboratory testing is significant for hypoalbuminemia and normal complement levels. Urinalysis demonstrates 4+ protein and fatty casts with a "Maltese cross" sign.

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Nephrotic syndrome ⇒ patient has peripheral or periorbital edema, ascites, pleural effusions, and hypertension. Proteinuria is > 3.5 grams per day (on 24-hour urine) and lab tests show hypoalbuminemia and hyperlipidemia

"Compare this to nephritic syndrome which is where there’s peripheral or periorbital edema, hypertension, oliguria, hematuria and proteinuria between 1 and 3 grams per day"

Proteinuria occurs because of changes to capillary endothelial cells, the glomerular basement membrane (GBM), or podocytes, which normally filter serum protein selectively by size and charge.

• The disorder results in urinary loss of macromolecular proteins, primarily albumin (protein) but also opsonins, immunoglobulins, erythropoietin, transferrin, hormone-binding proteins, and antithrombin III.

The most common primary causes are:

Membranous nephropathy: most common in non-diabetic adults associated with malignancies, and infection with hepatitis B virus

• Caused by immune complex formation in the glomerulus - basement membrane becomes damaged
• IgG antibodies target podocyte antigens

Minimal change disease: the most common cause in kids. Assume minimal change disease if a child with idiopathic nephrotic syndrome improves after treatment with corticosteroids

• The cause and pathogenesis of minimal change disease is unclear and it is currently considered idiopathic

Focal segmental glomerulosclerosis (FSGS): obese patients, heroin, and HIV + black males, sickle cell disease

• Podocyte injury or decreased glomerular filtration barrier integrity
• Primary, when no underlying cause is found
• Secondary, when an underlying cause is identified
  • Toxins and drugs such as heroin and pamidronate
  • Familial forms
  • Secondary to nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux, morbid obesity, diabetes mellitus

The most common secondary causes are:

1. Lupus: both nephritic and nephrotic
2. Diabetes: a common cause of nephrotic syndrome and subsequent renal failure
3. Preeclampsia

Diagnosis is suspected in patients with edema and proteinuria on urinalysis and confirmed by random (spot) urine protein and creatinine levels or 24-h measurement of urinary protein. The cause may be suggested by clinical findings (eg, SLE, preeclampsia, cancer); when the cause is unclear, additional (eg, serologic) testing and renal biopsy are indicated.

• A 24-hour protein collection demonstrating proteinuria above 3.5 grams per day (24-h urine collection) is diagnostic
• Serologic testing and renal biopsy is indicated unless the cause is clinically obvious
• Besides proteinuria, urinalysis may demonstrate casts (hyaline, granular, fatty, waxy, or epithelial cell)
  • Lipiduria, the presence of free lipid or lipid within tubular cells (oval fat bodies), within casts (fatty casts), or as free globules, suggests a glomerular disorder causing nephrotic syndrome
• Hypoalbuminemia - serum albumin often is < 3.5 g/dL
• Hyperlipidemia - levels of low-density lipoprotein or LDL above 130 milligrams per deciliter and levels of triglycerides above 150 milligrams per deciliter

Treat the causative disorder and with angiotensin inhibition, Na restriction, and often diuretics and/or statins.

• Minimal change disease: Prednisone 1 mg/kg (up to 80 mg every day) × 4-8 weeks; gradually taper if a response is noted. ACE-Is may also be used as an adjunct to therapy (to reduce proteinuria), or as sole therapy in mild cases.
  • Frequent relapsers: Prolonged treatment with immunosuppressants chlorambucil, cyclosporine, or cyclophosphamide should be considered.
• Membranous nephropathy: Depends on the risk of progression to ESRD; judged by the amount of proteinuria and the degree of renal insufficiency. Patients at moderate to high risk should be treated with a combination of glucocorticoids and cytotoxic therapy (cyclophosphamide). Those at low risk can be treated with ACE-Is. Lipid-lowering agents should be used in cases of persistent nephrotic syndrome.
• Focal segmental glomerulosclerosis: ACE-I should be used for the reduction of proteinuria. Immunosuppression with prednisone is the first-line therapy.
  • Steroid-resistant cases may benefit from the addition of cyclosporine. Relapses require reinitiation of steroids.