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Evaluation of Proteinuria in the Pediatric Patient

Evaluation of Proteinuria in the Pediatric Patient. Alicia M. Neu, M.D. Division of Pediatric Nephrology. Definition of Abnormal Proteinuria. Adults: >150 mg/24 hours Children: >4 mg/m 2 /hour. Sources of “Normal” Proteinuria. Plasma proteins filtered at the glomerulus

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Evaluation of Proteinuria in the Pediatric Patient

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  1. Evaluation of Proteinuria in the Pediatric Patient Alicia M. Neu, M.D. Division of Pediatric Nephrology

  2. Definition of Abnormal Proteinuria • Adults: >150 mg/24 hours • Children: >4 mg/m2/hour

  3. Sources of “Normal” Proteinuria • Plasma proteins filtered at the glomerulus • Proteins excreted by renal tubular cells • Proteins secreted by the lining of the bladder and urethra

  4. Mechanisms of Abnormal Proteinuria • Overflow proteinuria • Increased glomerular permeability • Tubular proteinuria • Tissue proteinuria • Altered renal hemodynamics

  5. Evaluation of Proteinuria • Qualitative testing- the urine dipstick • measures primarily albumin • false positives with alkaline pH • results affected by concentration of urine

  6. Evaluation of Proteinuria • Timed urine collection for total protein and creatinine • normal < 4 mg/m2/hour • significant 4-40 mg/m2/hour • nephrotic range > 40 mg/m2/hour

  7. Evaluation of Proteinuria Nephrotic range proteinuria may occur with or without the nephrotic syndrome, but almost always signifies glomerular disease.

  8. Evaluation of Proteinuria • Fractionated urine collection 3 separate collections: 8 am-4 pm 4 pm-12 midnight 12 midnight-8 am Separate measurement of urinary total protein and creatinine on each collection Look for increasing proteinuria during the day, but normal overnight

  9. Evaluation of Proteinuria • Random urine protein/creatinine : Age Uprotein/Ucreatinine NORMAL NEPHROTIC <2 y <.492 >1.5 2-13 y <.178 >1.5 >13 y <.178 >1.5

  10. Evaluation of Proteinuria • Urinary microalbumin Typical quantitative tests measure total protein and have lower limit of detection of 5 mg/dl “Urinary microalbumin” tests measure only albumin and lower limit of detection is 3 mg/L (.3 mg/dl) Normal for children 27 mcg/mg creatinine

  11. Evaluation of Proteinuria • Microscopic urinalysis: rbc, wbc, casts • H&P: attention to clues for underlying systemic disease, chronic renal disease, risk factors for HIV, Hepatitis • Other labs: CBC, CMP, PO4, C3, C4, ANA, HIV, Hepatitis B, C • Consider renal ultrasound

  12. Indications for Referral • Abnormal renal function • Abnormal serologies • Significant proteinuria that does not “fractionate” • + Nephrotic syndrome, especially atypical

  13. Indications for Renal Biopsy • Significant or nephrotic range proteinuria without the nephrotic syndrome (in adolescent patient confirm that urine does not “fractionate”)

  14. Indications for Renal Biopsy • Nephrotic range proteinuria with the nephrotic syndrome and any of the following: • gross hematuria • age < 2y, > 12 y • abnormal renal function, serologies

  15. CASE PRESENTATIONS

  16. Case I MN is a 14 yo BM noted on a sports PE to have 4+ proteinuria. PMH neg, ROS neg. Plays lacrosse and soccer.

  17. Case I PE WT 55 kg; SA 1.1m2 BP 118/70. PE wnl U/A: S.G 1.015, pH 5.5, 4+ protein, - heme, - glucose Microanalysis- neg

  18. What would you do next ? • Monitor without further w/u or therapy ? • Perform “screening” laboratory studies ? • Treat empirically with steroids ?

  19. Case I 24 hour urine: 481 mg protein (18 mg/m2/h) Na 136, K 3.9, Cl 108, HCO3 24, BUN 19, Cr 0.7, TP 7.0, Alb 3.9, Chol 112 C3 99, C4 18, ANA neg HIV neg Hep B neg Renal ultrasound normal

  20. What would you do next ? • Monitor without further w/u or therapy ? • Perform further laboratory studies ? • Treat empirically with steroids ?

  21. Case I • Fractionated Urine: 8am- 4pm: 16 mg/m2/h 4pm-12am: 22 mg/m2/h 12am-8am: 3 mg/m2/h

  22. Orthostatic Proteinuria • Accounts for 60% of all children with proteinuria, probably higher in adolescents* • Usually < 1 g proteinuria/day, nephrotic range extremely unusual • Best diagnosed with a fractionated 24 hour urine (vs 1st am void) • Should document normal renal function, BP * J Pediatric, 1976

  23. Case II DJ is a 12 yo AA F who presents to your clinic with a 3 d hx of periorbital edema, and lower extremity edema. His PMH is notable only for a URI 2-3 weeks prior to the onset of swelling.

  24. Case II PE: Wt 35 kg SA 1.0 m2 BP 121/82 P 90 RR 18 + periorbital edema, mild abdominal fullness, labial edema, LE edema U/A: SG 1.020, pH 6.0, 3+ protein, - heme, - glucose Microanalysis- neg

  25. What would you do next ? • Monitor without further w/u or therapy ? • Perform “screening” laboratory studies ? • Treat empirically with steroids ?

  26. Case II 24 hour urine: 1300 mg protein 77 mg/m2/h Na 131; Cl 103; K 4.1; BUN 10; Cr 0.6 TP 4.0; Alb 1.5; Chol 375 C3 103; C4 24; ANA neg Hep B S Ag neg, Hep C Ab neg, HIV neg Renal ultrasound normal CXR normal

  27. What would you do next ? • Monitor without further w/u or therapy ? • Perform further laboratory studies ? • Treat empirically with steroids ?

  28. Case II • Treated with 2 mg/kg/day oral steroids • Within 2 weeks, urine protein negative, edema gone • Successfully tapered off of steroids (after 6 weeks of daily and 6 weeks of qod). Has relapse 2-3 times/year • Presumptive Dx: INS

  29. Idiopathic Nephrotic Syndrome • Children 2-6 years, normal renal function, neg serologies • May have a number of underlying pathologic lesions • Response to steroids best predictor of underlying pathology and prognosis • 93 % will respond to steroids. 7% of initial non-responders will eventually respond • Biopsy: non-responder, steroid-dependent, frequent relapser

  30. Case III • KG is an 15 yo previously healthy WM who presents with 3 day history of low grade fever, malaise, myalgias, abdominal discomfort and diarrhea.

  31. Case III • PE- Wt 65 kg, SA 1.1 m2, BP 119/62 Afebrile He is tired appearing, but otherwise in NAD. PE notable only for mild dehydration and mild, diffuse abdominal tenderness without guarding or rebound. UA: SG 1.010, pH 6.0, 4+ protein, small hgb, - glucose, trace ketones Microanalysis-hyaline casts

  32. What would you do next ? • Monitor without further w/u or therapy ? • Perform “screening” laboratory studies ? • Treat empirically with steroids ?

  33. Case III • Diagnosed with viral syndrome, advised to force po fluids and return for follow up in several days. • On f/u- PE wnl, symptoms resolved. • Repeat UA S.G. 1.010, 3+ protein, sm hgb • Follow up UA 2 weeks later- unchanged

  34. What would you do next ? • Monitor without further w/u or therapy ? • Perform “screening” laboratory studies ? • Treat empirically with steroids ?

  35. Case III 24 hour urine: 900 mg protein 47 mg/m2/h Na 138; Cl 103; K 4.1; BUN 80; Cr 2.6 TP 7.0; Alb 4.0, Calcium 8.0, Phosphate 5.5 WBC 12,200, Hgb 8.0, Plt 325,000 C3 103; C4 24; ANA neg Hep B, C neg HIV neg

  36. What would you do next ? • Monitor without further w/u or therapy ? • Perform further laboratory studies ? • Treat empirically with steroids ?

  37. Case III • Renal ultrasound- small kidneys bilaterally with hydronephrosis • VCUG- bilateral grade V reflux

  38. Reflux Nephropathy • Together with obstructive uropathy is leading cause of end-stage renal disease in childhood • Typically presents with febrile urinary tract infection, may be diagnosed in utero • Although UTI felt to contribute to renal injury, there is not a direct correlation between UTI and progression • Genetic factors also involved

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