Approach to Hematuria and Proteinuria in Children

Approach to Hematuria and Proteinuria in Children Adi Alherbish Objectives To be able to define and recognize hematuria and proteinuria To be able to generate a differential diagnosis of the commonest and most serious causes of hematuria and proteinuria To have a clinical approach to both conditions.

Case 1 14 year old boy presenting with red urine since last night. Otherwise healthy. Normal BP, no flank pain, no ankle edema. Whats the next step? Case 1 Urine dipstick: negative Case 2

5 year old boy presenting with pallor, and shortness of breath. Urine dip: SG 1.015, Hg 2+, Prot neg, Urinalysis: RBC 0, WBC 0 Case 2 CBC: Hg 80, WBC 5, Plt 180 Retics: 3% Hemolytic Anemia Send blood for: Hg electrophoresis,

peripheral smear, Coombs test, G6PD Case 3 14 year old girl, healthy Regular check up: Urine dip: SG 1.035, Hg 2+, Prot trace Urinalysis: RBC 5- 10 /HPF WBC 0- 5 / HPF Case 3 Repeat urinalysis after drinking a bottle of

water: Urine SG: 1.015 RBC: 1- 5 /HPF WBC: 0- 5 / HPF HPF= x 400 Case 5 9 year old girl, presenting with fever, rash, coryza, conjuctivitis, and dark urine. Urine dip: SG 1.015, Hg +3, Prot trace

Urinalysis: RBC > 100/ HPF WBC 10- 25/ HPF Case 5 Urine positive for adenovirus Case 6 14 year old girl, presenting with intermittent, sudden onset left flank pain and dark urine. Urine SG: 1.015, Hg 3+, Prot neg

Urinalysis: RBC 100/ HPF, WBC 0 Crystals present Case 6 In clinic: send urine for Ca/ Cr ratio, citrate, oxalate, uric acid, cystine Case 7 14 year old girl, with hypertension, left knee arthritis, dark urine, malar rash Urine dip: SG 1.010, Hg 2+, Prot 2+

Urinalysis: RBC 10- 25/ HPF WBC 0 RBC casts Case 7 Send blood for: C3, C4, ANA, anti-ds DNA Hematuria Presence of > 5 RBC/ HPF, on more than two occasions, in the context of a normal

urine specific gravity The 3 Vital Questions 1 2 3 Is it true hematuria? Is it serious (urgent)? What is the cause?

Is it serious? Nephritis Hematuria Hypertension Oliguria

Increased Cr Nephrosis Edema Nephrotic range proteinuria Low albumin Hypercholestrolemia Rapidly Progressive

Glomerulonephritis (RPGN) RPGN Immune Complex Post- strep GN IgA nephropathy

Lupus HSP Pauci- immune Wegners granulomatosis Microscopic

polyangiitis Polyartritis nodosa Anti- GBM Goodpastures disease RPGN Immune Complex

Post- strep GN IgA nephropathy HSP Lupus ASO, anti-DNase Immunoglobulins

ANA, anti-ds DNA, C3, C4 Pauci- immune Wegners granulomatosis Microscopic

polyangiitis Polyartritis nodosa ANCA Anti- GBM Goodpastures disease Anti- GBM

Post strep Glomerulonephritis Strep pharyngitis, or strep skin infection, followed 10 to 14 days by microscopic hematuria, nephritis, or nephrosis Diagnosis: positive ASO low C3 which normalize in 8 weeks Management: supportive Prognosis: Excellent (Vog et. Al: 137 cohortESRD: none, high Cr 10%) IgA nephropathy

Typical presentation: intermittent gross hematuria that happen during colds Other: gross hematuria microscopic hematuria nephritis nephrotic syndrome ESRD IgA nephropathy Diagnosis: clinical suspicion IgA level 20% sensitivity!

Kidney biopsy- IgA in Immunoflorecence Treatment: supportive in mild cases ACEI in proteinuria Steroids Henoch Schonlein Purpura (HSP) Pathology: IgA nephropathy Clinical: - purpuric rash - arthritis

- intestinal edema (intussusception) - hematuria/ nephritis/ nephrosis Hemolytic Uremic Syndrome Pathogenesis: - typical (d+): E. coli O157:H7 shiga toxin 1 induced vascular injury - atypical (d-): alternative complement pathway defect

Clinical: triad of microangiopathic hemolytic anemia, thrombocytopenia, ARF Alport Syndrome (Hereditary Nephritis) Homozygous mutation in genes encoding type IV collagen in basement membrane Genetics: 80% X-linked AR, AD

Clinical: persistent microscopic hematuria, hearing loss, lenticonus Benign familial hematuria (thin basment membrane nephropathy)

Autosomal dominant Hetrozygous mutation in type IV collagen Microscopic hematuria Screen the parents urine Benign course Work up for hematuria (History is important!) 1. Gross hematuria: onset, duration, progression, aggravating, relieving factors, associated

symptoms 2. UTI symptoms: dysuria, frequency, urgency, urge incontinence 3. Food intake: beet 4. Drugs: rifampin, nitrofurantoin, ibuprofen 5. IgA: gross hematuria onset while having colds 6. post strep: history of sore throat, tonsillitis, skin infection 7. HUS: diarrhea, pallor, fatigue, SOB 8. HSP: pupuric skin rash over legs and buttocks (palpable), join swelling/pain, abdominal pain/bloody stools 9. Goodpasture/Wegners: hemoptysis, cough, SOB 10. SLE/ vasculitis: butterfly rash, discoid rash, mouth ulcers, photosensitivity, CNS

seizures/psychosis, join swelling 11. Kidney stones: renal colic, radiation to groins, past history or family history of stones 12. Anatomic: antenatal U/S, single umbilical artery, abdominal swelling 13 Hereditary: family history of deafness, family member with hematuria 14. Bleeding diathesis: hemarthrosis, epistaxis, petechaie, heavy periods in older girls 15. Problems with high blood pressure 16. Family history: nephritis, kidney failure, transplant, deafness, stones, hematuria, consanguinity Work up for hematuria Nephritis: ASO, C3, C4, anti-ds DNA,

ANA, ANCA, anti- GBM Kidney and bladder U/S Stone work up: urine Ca, Cr, oxalate, citrate, cystine, uric acid Urinalysis in both parents Bleeding tendency: PT, PTT, INR Proteinuria (Urine dip)

Negative Trace 1+ 2+ 3+ 4+

< 10 mg/dl 10- 20 mg/dl 30 mg/dl 100 mg/dl 300 mg/dl 1000 mg/dl Proteinuria (Quantitative) Non- nephrotic Nephrotic

Urine prot/cr: > 20 mg/mmol Urine prot/cr > 200 mg/mmol 24 h urine collection: > 100 mg/m2/day > 4 mg/m2/hr

24 h urine collection: > 1 g/m2/ day > 40 mg/m2/hr The 3 Vital Questions 1 2 3 Is it persistent? Is it nephrotic?

What is the cause? Case 1 15 year old, athletic boy Regular check up: Urine dip: Prot 2+ Urine prot/Cr ratio: 50 mg/mmol What next? Case 1 8 am: urine prot/Cr ratio- 10 mg/mmol

4 pm: urine prot/Cr ratio- 50 mg/mmol Orthostatic proteinuria Non Persistant Proteinuria Fever

Strenuous exercise Cold exposure Epinephrine infusion Orthostatic Case 2 1 year old infant with failure to thrive. Both height and weight are below the 3rd percentile. He has sings of rickets in exam. Urine dip: Prot 3+ , Glu 2+

Derakhshan Ali et al. Saudi J Kidney Dis Transpl. 2007 Oct-Dec;18(4):585-9. Fanconi Synrome PCT defect Proximal renal tubular acidosis (type II RTA) Glucosuria Aminoaciduria Phosphaturia hypokalemia

Proteinuria Glomerular Congenital: -Finish- type - TORCH infection Nephritis: - postinfectious GN

- lupus - Wegner - HUS - Goodpasture Nephrotic: - Minimal change - FSGS - MPGN Drugs: captopril

Neoplasia Renal vein throbosis Tubualr absorption

ATN Fanconi Syndrome Cystic/dysplastic Interstial nephritis Pyelonephritis Protein overload

Hemolysis Rhabdomyolysis Light chain Proteinuria Glomerular Congenital: -Finish- type

- TORCH infection Nephritis: - postinfectious GN - lupus - Wegner - HUS - Goodpasture Nephrotic: - Minimal change

- FSGS - MPGN Drugs: captopril Neoplasia Renal vein throbosis Tubualr absorption

ATN Fanconi Syndrome Cystic/dysplastic Interstial nephritis Pyelonephritis Urine electrophoresis:

Glomerular: albumin Tubular: other proteins.. Protein overload Hemolysis Rhabdomyolysis Light chain

Case 3 5 year old boy, presenting with puffy eyes, enlarged tummy, and feet swelling. Exam: normal BP, ascites, pitting edema Urine dip: Prot 4+ Whats the next step? Case 3 Urine prot/cr 1500 mg/mmol Serum albumin 15 g/l

High cholesterol Nephrotic Syndrome Urine Prot/Cr > 200 mg/mmol Serum albumin < 25 g/l Edema

Hyperlipedemia Nephrotic Syndrome Minimal change disease

Focal segmental glomerulosclerosis Membranoproliferative Membranous GN Infection: HIV, hepatits, syphilis Lupus, Ig A, HSP, post strep Initial therapy

Supportive: albumin 25% and lasix prn Salt restriction Fluid restriction while nephrotic Prednisone 60 mg/m2/day for 6 weeks followed by 40 mg/m2/day for 6 weeks then wean.. Indications for biopsy Steroid resistant: fail to enter remission after 8 weeks of therapy

Steroid dependent: intially enter remission, but develping relapse while on therapy, or within 2 weeks of steroid discontinuration Hematuria Increased Cr (when intravasculary repleted) Low complement

Positive lupus serology

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