Nephrotic Syndrome
Three common forms of nephrotic syndrome.
What are...?
1. Idiopathic (MCD and FSGS)
2. Secondary (Membranous, FSGS)
3. Congenital/Infantile
Distinguishing feature of congenital versus infantile nephrotic syndrome.
What is the age of presentation of renal features including pathologic proteinuria?
1. Congenital: within first 3 months of life
2. Infantile: 3 months to 1 year of age.
This is detectable when fluid retention is >3-5% of body weight in patients with nephrotic syndrome.
What is edema/anasarca?
POE, ascites, lower extremity, scrotal
What are treatment options?
Four features of acute glomerulonephritis.
What are macroscopic and microscopic hematuria, proteinuria, HTN, and edema?
Bonus: Examples of diseases that commonly have macroscopic hematuria include...
12 year old male with PMH of Celiac disease and visible hematuria last winter that lasted 2 days without recurrence. At WCC, BP: 119/78, PE: normal, labs: electrolytes normal, creatinine 0.8 mg/dl, and UA: large hematuria, 100 mg/dl proteinuria, no pyuria, dysmorphic RBCs.
What is IgA Nephropathy?
Most common cause hematuria worldwide. Recurrent macroscopic hematuria only, persistent hematuria, proteinuria (variable), NS, RPGN. Diagnosis: Biopsy. Treatment: Depends on MEST-C score on biopsy. BP control.
Bonus: Should you draw an IgA level?
Define the 4 features of nephrotic syndrome.
What are...?
1. Nephrotic range proteinuria
2. Hypoalbuminemia (albumin <3 g/dl)
3. Edema
4. Hyperlipidemia
Renal disease name and 3 classic features associated with a mutation in WT1.
What is Denys Drash Syndrome?
1. Infantile NS with diffuse mesangial sclerosis.
2. Male pseudohermaphroditism
3. Wilms tumor
Types of infections and common disease-causing microorganisms associated with uncontrolled nephrotic syndrome.
What are UTIs, peritonitis, pneumonia, enteritis, empyema, sepsis, cellulitis, and menigiitis, and what are S. pneumoniae, E. coli, and Varicella?
Three pediatric renal diseases with hypocomplementemia.
What are post-infectious glomerulonephritis, systemic lupus erythematosus, and membranoproliferative glomerulonephritis?
14 yo obese AA male with allergic rhinitis (Zyrtec) with bilateral foot pain. PE: BP 132/83, POE, 3+ LE edema. UA: small heme, >300 mg/dl proteinuria, no pyuria. Labs: Sodium 132, BUN 22, creatinine 1.3 mg/dl, albumin 2.8 g/dl. Diagnosis? Prognosis? Treatment? Genetic testing?
FSGS (primary versus secondary FSGS)
Prognosis based on treatment response and biopsy
Treatment: ACEI, ? diuretics, BP meds, prednisone, tacrolimus
Genetic testing: Podocin/actinin, APOL1 in AA
Renal biopsy electron microscopy findings in patients with nephrotic syndrome.
What are segmental and diffuse podocyte foot process effacement (GBM)?
Genetic defect and clinical features associated with congenital nephrotic syndrome - Finnish type.
What is NPHS1 mutation (nephrin) and elevated AFP, prematurity, fetal distress, severe anasarca, profound hypoalbuminemia, poor growth, high infection and thromboembolic event rates, treatment resistant, early onset of ESKD?
(NPHS2: Podocin protein in GBM, familial FSGS)
Lipid panel abnormalities in nephrotic syndrome.
What are increased cholesterol synthesis, increased LDL generation, decreased LDL and VLDL clearance, increased hepatic production of fatty acids and triglycerides, and increased lipoprotein A synthesis?
Common acute and chronic renal complication of glomerulonephritis.
What are acute kidney injury (AKI) and chronic kidney disease (CKD)?
Define AKI: Increase sCr > 0.3mg/dl within 48 hrs, or increase sCr > 1.5 X baseline over 7 days, or oligoanuria. Pre-renal, intrinsic, and post-renal.
CKD stage 1: >90 ml/min to Stage 5 <15 ml/min
7 yo healthful female with acute onset of macroscopic hematuria, dysuria, and headache. PE: BP 104/72, no edema, mostly healed LE abrasion. UA: brown, large heme, 100 mg/dl protein, abundant dysmorphic RBCs, 50 WBC, and RBC casts. What labs? Diagnosis? Treatment?
PIGN, an exudative proliferative GN.
Labs: RFP, complement (low C3), ANA now and repeat C3 in 4-8 weeks.
Tx: Supportive. BP meds (diuretics). Biopsy if pathologic proteinuria. Rare recurrence.
Treatment options for minimal change disease and focal segmental glomerulosclerosis.
What are...?
1. Sodium restriction (not fluid restriction)
2. Prednisone (IV versus oral)
3. Mycophenolate mofetil
4. Rituximab
5. Tacrolimus
Disease name and three clinical features of a genetic mutation in the LAMB2 gene.
What is Pierson syndrome and congenital nephrotic syndrome, ocular malformations (microcoria, cataracts), and neurologic symptoms such as hypotonia?
Potential NS complication in a patient with uncontrolled FSGS who has a headache, feels confused, and has no energy.
What is hypertensive emergency?
Discuss hypertensive urgency versus hypertensive emergency.
Reason(s) for acute kidney injury in acute GN.
What is multifactorial including pre-renal, intrinsic, and post-renal causes?
Hypovolemia --> lower GFR --> acute tubular necrosis
Interstitial nephritis (meds, infection)
Obstruction
8 yo healthful male presents to his PCP for POE and given Xyzal. Returned 1 mo later unchanged. UA: mod heme, >300 mg/dl protein. BP: 114/73. Labs: normal except low C3 and low C4. Repeat labs 6 weeks later unchanged.
Diagnosis? Evaluation? Treatment?
MPGN.
Evaluation: Biopsy (different types)
Treatment variable: ACEI, prednisone, rituximab, eculizumab.
Distinguishing features between minimal change disease and FSGS?
What are...?
MCD: Younger age (<6yo), pronounced edema, no other features, relatively normal biopsy
FSGS: Older age, +/- edema, HTN, microscopic hematuria, nl creatinine versus CKD, biopsy findings
Type of nephrotic syndrome associated with autoantibodies to phospholipase A2 receptor. (PLAR2)
What is membranous nephropathy?
PLAR2 receptors are located in glomerular podocytes.
Common sites and reason for thromboembolic events in patients with nephrotic syndrome.
What are..?
1. DVT, PE, RVT, intracranial
2. Increased coagulation, decreased fibrinolysis, increased blood viscosity, and increased platelet aggregation and activation.
*decreased ATIII/Protein S plus increased fibrinogen and Factors V and VIII
Acute nephritis leading to progressive loss of kidney function over a short period of time.
What is RPGN (rapidly progressive glomerulonephritis)?
Symptoms: fatigue, edema, hematuria, oliguria, HTN
Early biopsy: extensive crescent formation
Early treatment: Pred, Cytoxan, Rituximab, pheresis
High risk of ESKD!
17 yo female with PMH Hepatitis B presents for WCC. BP: 102/67. PE: mild POE, mild-moderate LE edema. UA: trace heme, >300 mg/dl protein. Labs: electrolytes normal, creatinine 0.9 mg/dl, albumin 2.5 g/dl.
Diagnosis: Evaluation? Treatment? Complications?
Membranous nephropathy.
Follow RFP, lipid panel, Pr/Cr closely.
Treatment: Supportive to aggressive therapy (ACEI, pred, cytoxan, rituximab). High rate of spontaneous partial/complete remission. High rate of dyslipidemia and thromboembolic events.
Consider PLAR2 antibody evaluation