MORNING REPORT

August 26, 2011 Kortni Unger, PGY-2

ITS NOVEMBER AND YOU ARE IN THE ED

12 year old previously healthy female presents with eye swelling x1 week

HPI
Puffy eyes, worse in AM x1 week, thought to be secondary to allergies Two days prior to presentation, noted some ankle swelling and legs felt tight Swelling in legs worsened, started to develop knee pain so brought into ED Denies any fevers, URI symptoms Denies nausea, vomiting, diarrhea, abdominal pain Denies dysuria, hematuria, frequency No known sick contacts

HISTORY

PMHx
y y

Born at 36 weeks without complications

? Small kidneys in utero, resolved on f/u US prenatally

UTI, age 2 y Chronic constipation dx 2 months ago, home bowel clean-out 2 weeks ago

PSHx
y

Excision of left accessory tear duct, age 6 Miralax 8.5g BID

Medications
y

Allergies: NKDA Immunizations: up to date

HISTORY CONTINUED

SHx
y

Lives at home with parents and younger brother. Currently doing well in the 6th grade. Enjoys playing soccer and singing in choir.

FHx
Maternal aunt: UC and hypothyroidism y Paternal uncle and cousin: T1 DM y No hx of cardiac, pulm, renal or autoimmune diseases
y

ROS
Intermittent bilateral knee pain y Mild itchy rash over elbows y Weight gain ~5-6 lbs in past month
y

PHYSICAL EXAM

VS: T 36.4, HR 110, RR 16, BP 126/69, O2 97% RA Weight: 45.6 kg (65 %ile), was 42.8 kg 1 mo ago Height: 155cm (65 %ile) BMI: 19 (62 %ile)

PHYSICAL EXAM CONTINUED

GEN: Alert, awake, interactive, in NAD HEENT: NC/AT, PEERL, EOMI, no conjunctival injection or discharge. Periorbital edema present bilaterally. OP clear. TMs grey bilaterally. MMM NECK: supple without masses or LAD PULM: CTAB without wheezes/crackles. Normal WOB. CV: Mildly tachycardic without murmurs. 2+ pulses bilaterally, CRT <3 seconds. ABD: Soft, non-tender with minimal distention noted. No fluid wave appreciated. No masses or HSM. + BS EXT: 2+ pitting edema of bilateral LE to knees, minimal hand/UE edema noted. SKIN: eczematous rash noted on elbows NEURO: A/O x3, CN II-XII intact. Normal strength, sensation and gait

Laboratory studies were obtained in order to help make the diagnosis. But first..

12 year old female with worsening edema x1 week.

DDx

RENAL: Nephrotic syndrome (minimal change, FSGS, membranous), nephritic syndrome (membranproliferative, lupus, IgA, post-strep), HSP, AKI ID: allergies, hepatitis B/C, toxo, HIV, syphilis, CMV, malaria, allergic rhinitis, cellulitis RHEUM: SLE, dermatomyositis, vasculitis ONC: lymphoma, leukemia, Chemotherapy toxicity TOX: NSAIDs, interferon, heroin, lithium, lead CV: CHF GI: protein losing enteropathy, malnutrition, kwashiorkor ENDO: hyperaldosteronism, hyperthyroidism, Cushings

LABS

2 weeks PTA - in GI clinic

ESR = 27 y CMP notable for Ca 8.5, Prot 6.0, Alb 2.7 y CBC: normal y TSH: 4.66 (mildly elevated), T4: 0.91 (normal)
y

Day of Presentation to ED
y y y y y y y

CMP notable for Na 136, Ca 8.5, Prot 5.6, Alb 2.0, Bun 17, Cr 0.59 CBC: slight left shift with WBC 11.7 UA notable for SG 1.015, 3+ protein, neg blood, 3 WBC, 0 RBC, 3+ bacteria dsDNA: not detected, ANA: not detected C3 = 179 (normal), C4 = 23 (normal) Urine protein:creatinine ratio = 5.3 (normal <0.2) Total cholesterol 200, TG 321, LDL 95

IMAGING

Abdominal ultrasound 3 months prior to presentation

Kidneys normal in size y No hydronephrosis, masses or cysts
y

NEPHROTIC VS NEPHRITIC SYNDROMES

Nephrotic Nephritic

Proteinuria hypoAlbuminemia hyperLipidemia Edema

Bloody urine Oliguria Azotemia hyperTension

NEPHROTIC SYNDROME

EPIDEMIOLOGY
Incidence = 2.7 new cases/100,000 kids per year Prevalence = 16/100,000 kids 2:1 male to female ratio during childhood Mean age of initial presentation ~4 years of age

Classification
y

90% of cases are primary (idiopathic)

85% minimal change disease 10-15% focal segmental glomerulosclerosis <5% membranous nephropathy

10% of cases are secondary

SYMPTOMS

Proteinuria
y

Urine protein:creatinine >2.0 (normal <0.2)

Edema (typically eyes first, then extremities)

Albumin <2.5 y Hyponatremia, hypocalcemia
y

Hyperlipidemia
y

Increased cholesterol, TG, lipoproteins

Hypertension? Others:

y

Anorexia, irritability, fatigue, abdominal pain, diarrhea

INDICATIONS FOR BIOPSY

Normal

Indications for Renal Biopsy in Nephrotic Syndrome

At Time of Diagnosis - Age >= 12 years - Persistent or gross hematuria - Hypertension - Renal insufficiency - Low C3 complement values

Abnormal
Subsequently: - Persistent proteinuria (at the end of 4 weeks of daily prednisone therapy)

TREATMENT of NEPHROTIC SYNDROME

Prednisone x 6 wks

Prednisone QOD x 6 wks (no taper)

Relapse > 3 months

Prednisone daily until urine protein neg x 3 days

Relapse < 3 months

Prednisone daily until urine protein neg x 3 days

Steroid resistant
Immunosuppresants Steroids ACE-I/ARB Anti-hypertensives Diuretics Na/fluid restriction

Prednisone QOD x 4 weeks

Prednisone QOD x 4 weeks

Prednisone taper x 2 months (12 weeks total)

Steroid dependant
Daily low dose or QOD prednisone

Frequently relapsing
Cyclophosphamide x 12 weeks Cyclosporine, Tacrolimus, Mycophenolate +-steroids

Cyclosporine, Tacrolimus, Mycophenolate

POTENTIAL COMPLICATIONS
Obesity Impaired growth Hypertension Osteopenia Dyslipidemia Infection Thromboembolism Acute kidney injury Progressive kidney injury

Renal failure (rarely)

OUR PATIENT.

Initial Tx:
y

Prednisone, low Na diet, diuresis

3 relapses within 6 months of dx = steroid sensitive frequently relapsing nephrotic syndrome

Started on cyclophosphamide x 12 weeks y Good response with minimal proteinuria y Did have increased IOP on steroids in past seen by ophtho, dxd with steroid induced glaucoma
y

2 more relapses following cyclophosphamide course

Biopsy consistent with minimal change disease y Started on prednisone + mycophenolate y Mycophenolate tapered after 2 years due to great response without any significant proteinuria x1 year
y

SECONDARY CAUSES OF NEPHROTIC SYNDROME

Infections Hepatitis B, C Human immunodeficiency virus Malaria Toxoplasmosis Syphilis Drugs Gold Non-steroidal anti-inflammatory drugs Pamidronate Interferon Heroin Lithium

Malignancies Lymphoma Leukemia Miscellaneous Systemic lupus erythematosus Mesangioproliferative glomerulonephritis Immunoglobulin A nephropathy Diabetes mellitus

REFERENCES

Gipson, D., et al. Management of Childhood Onset Nephrotic Syndrome. Pediatrics 2009; 124; 747-757. Gordillo, R and Spitzer, A. The Nephrotic Syndrome. Pediatrics in Review 2009; 30; 94-105. GRINSELL!! Roth, K., et al. Nephrotic Syndrome: Pathogenesis and Management. Pediatrics in Review 2002; 23; 237-248.