Approach to Nephrotic & Nephritic Syndromes Academic Half-Day Aug 2, 2012

Nephrology Olympics!

Name two NBA athletes with Nephrotic Syndrome

Proteinuria Some protein in urine is normal (< 4mg/m2/hr or < 100 mg/m2/24h) Non-pathologic Postural (orthostatic) Febrile Exercise-induced Pathologic Tubular Inherited (cystinosis, Wilson ds, Lowe syndrome) Acquired (antibiotic, AIN, ATN, heavy metal poisoning) Glomerular

Hematuria Gross Trauma - perform imaging and cystoscopy Pain - rule out renal stones, mass, UTI Painless - consider stones, mass, HSP, familial (thin BM), hematologic, other glomerular disease, systemic disease Microscopic Symptomatic - symptoms direct investigation Isolated hematuria - rarely have significant renal disease (benign familial hematuria or hypercalciuria) Asymptomatic hematuria and proteinuria - more worrisome, requires thorough evaluation by nephrology.

Edema Differential diagnosis Loss of oncotic pressure decreased protein synthesis increased protein loss Increased capillary permeability viral/bacterial immune mediated mechanical/thermal trauma drugs Increased hydrostatic pressure congestive heart failure lymphatic blockage

What is the term for extreme, generalized edema? ANASARCA

Golmerular Disease Presents in one of 4 ways: Acute Nephritic Syndrome Nephrotic Syndrome Rapidly Progressive Glomeruloneprhitis Asymptomatic

Nephrotic Syndrome Nephrotic range proteinuria 3+ or 4+ > 250 mg/mmol creatinine > 40 mg/m^2/hr Hypoalbuminemia Hyperlipidemia Hypercoagulable

Pathophysiology Glomerular Filtration Barrier

What is this fictional doc’s specialty? NEPHROLOGY AND INFECTIOUS DISEASE!

Etiology Primary or idiopathic Minimal change disease FSGS MPGS Membranous nephropathy

Minimal Change Disease 85% of cases

FSGS 10-15% of cases

Membranous Nephropathy 4% of cases

In what event did this athlete win a bronze medal? 100m freestyle

Etiology Secondary causes Genetic Metabolic Infections Drugs Immunologic/Allergic Malignancy Glomerular hyperfiltration

Idiopathic Nephrotic Syndrome 90% of childhood nephrotic syndrome 85% of all cases due to MCD Consider diagnosis other than MCD in: Children 10 years Family history nephrotic syndrome Extra-renal findings More than minimal hematuria

Idiopathic Nephrotic Syndrome Clinical manifestations: Most common between age 2 and 6. Often follows minor infection. Mild edema progressing to generalized. Ascites Pleural effusions Genital edema Anorexia, abdo pain, diarrhea, irritability common.

What food item is known scientifically as Phaseolus vulgaris?

Diagnosis Laboratory findings Low serum albumin High cholesterol, triglycerides, lipoproteins Low serum sodium Nephrotic range proteinuria Indications for biopsy: Age > 10, gross hematuria, hypertension Renal insufficiency Low C3 complement value Persistent proteinuria following 4 week course of steroids

Treatment Prednisone drug of choice. Dose: 60 mg/m^2 per day divided TID Continue daily for 4 weeks, then 40mg/m^2 as single dose on alternate days for 4 weeks. 90% of MCD is steroid responsive Of those, 60% relapse Frequent relapsers can be treated with cyclophosphamide

Steroid-resistance Up to 10% of all children with NS Poor prognosis Eventually leads to dialysis and renal transplant

Complications of Nephrotic Syndrome Thromboembolic events Loss of antithrombin III and protein S Increase in fibrinogen concentration Infection Loss of factor B, low IgG, impaired Tcell function Most common infection is peritonitis Most common organisms are Strep pneumo or gram- negatives Steroid side effects

Where did this duo rank in badminton at the 2012 Olympics? DISQUALIFIED for CHEATING!

Nephritic Syndrome Results from inflammation within glomerulus Characterized by Hematuria, RBC casts, dysmorphic RBCs Mild to moderate proteinuria Azotemia, oliguria Hypertension

Etiology Low complementNormal complement Primary Postinfectious GN Membranoproliferative GN IgA nephropathy Anti-GBM disease Secondar y SLE Endocarditis Abscess Cryoglobulinemia Polyarteritis nodosa Wegener’s HSP Goodpasture’s

Rapidly Progressive Glomerulonephritis Subset of nephritic syndrome Medical emergency Characterized by renal failure in days or weeks (months) Classfication: Type I - anti-GBM (idiopathic, Goodpasture’s) Type II - immune complex (PIAGN, SLE, HSP) Type III - pauci-immune (idiopathic, Wegener’s, microscopic polyangitis, drugs) Treatment Induction of remission (pulse steroids, cyclophosphamide 3-6 months) Maintenance therapy (azathioprine) Newer agents - Rituximab, MMF

Crescent BAD NEWS.

IgA Nephropathy Most common cause of GN Idiopathic or secondary (HSP, rheumatic ds, HIV, Celiac ds, chronic liver ds) Variable presentation: Asymptomatic hematuria and mild proteinuria Recurrent episodes of gross hematuria Nephrotic range proteinuria or RPGN Hematuria coincident with URTI Treatment depends on prognostic indicators Watch & wait vs. immunosuppressive agents

Poststreptococus glomerulonephritis Prototypic acute nephritic syndrome Occurs 2-3 weeks after pharyngitis or skin infection with GAS (nephritogenic strain) Typical history plus low C3, normal C4, and high ASOT, positive anti- DNase B Self-limited disease - three phases latent phase acute phase recovery phase Supportive management of hypertension and edema Indications for biopsy include normal complement level, failure to document strep infection, GFR < 30ml/min/1.73 m2

How much does the average adult kidney weigh? grams!

References Gordillio, R. and Spitzer, A. The Nephrotic Syndrome. Pediatr Rev, 2009;30: Beck, L. and Salant, D. Glomerular and Interstitial Diseases. Prim Care Clin Office Pract 2008;35: Bergstein, J. A Practical Approach to Proteinuria. Pediatr Nephrol 1999;13: Massengill, S. Hematuria. Pedatr Rev 2008;29: Pais, P. and Avner, E. Nephrotic Syndrome. Nelson’s Textbook of Pediatrics, Ch 52: Eison, T., Ault, B., and Jones, D. Post-streptococcal cute glomerulonephritis in children: clinical features and pathogenesis. Pedatr Nephrol 2011;16: