Metropolitan New York / New Jersey Pediatric Board Review Course Pediatric Nephrology May, 2008

1. Metropolitan New York / New Jersey Pediatric Board Review CoursePediatric NephrologyMay, 2008 Leonard G. Feld MD PhD Levine Children’s Hospital Charlotte, NC Howard Trachtman MD Schneider Children’s Hospital New Hyde Park, NY

2. Materials • Consider all other material to help you achieve a passing score • American Academy of Pediatrics – Pediatrics Review and Education Program (PREP), Pediatrics in Review.

3. Renal / Urology • General • Normal function • Proteinuria • Hematuria • Persistent microscopic hematuria • Causes of gross and microscopic hematuria • Dysuria / Incontinence • Congenital • Renal dysplasia • Abnormalities of the collecting system, kidney, bladder

4. Renal / Urology • Acquired • Infection of the urinary tract • Acute glomerulonephritis • Nephrotic syndrome • Hemolytic uremic syndrome • Henoch-Schoenlein purpura • IgA nephropathy • Other • Renal Failure,Trauma, renal stones, RTA

5. Renal / Urology • Hypertension • Nephrogenic diabetes insipidus • Cystinosis

6. Outline – Part 1 • Hematuria • Proteinuria • Hypertension • Urinary tract infections • Glomerulonephritis

7. A 3-week-old male infant presents with a history of irritability, low grade fever, emesis and diarrhea. Prenatal and family history is non-contributory. On examination the infant is irritable, temp of of 39.0°C, has mottled skin and a capillary refill of 4 sec. The systolic blood pressure is normal and the pulse is 185 beats/min. The anterior fontanelle is full. Hemoglobin 14 g/dl White cell count 30,000 Platelets 110,000 What studies would you like to perform. What is your initial therapy? What is your initial diagnosis (es)?

8. Answers • Blood culture, urine, CXR, and LP • Fluid resuscitation + broad spectrum antibiotics • Late onset neonatal sepsis / meningitis

9. From Consensus in Pediatrics Fever In Infants and Children, Feld LG, Hyams J eds. Mead Johnson Nutritionals, 2007.

10. PEARL – No question on the < 28 day old febrile infant

11. Hematuria Case: Susan is an 8 year old noted on routine exam to have moderate hematuria on dipstick. She has an unremarkable past medical history. Family history is negative in the parents and siblings for any renal disease. History of hematuria is unknown. A repeat urine in one week is still positive and a urine culture showed no growth. • What is the next step? What would be a major consideration for a referral to a pediatric nephrologist?

12. Repeat a first AM void following restricted activity , perform a microscopic on a fresh urine • Check the family members • If there is still blood without protein, casts, crystals, normal BP with or without a strong family history, no further work-up is generally required. • Caveat - Family anxiety because of the connotation of blood and cancer in adults.

13. Classification of Hematuria • Microscopic (vast majority of the cases) • Transient • Persistent • Macroscopic (urologic / renal disorders) • Transient • Persistent (> 2 weeks) • Persistent microscopic/ Transient macroscopic • IgA or Berger’s; benign recurrent hematuria

14. Glomerular v. Non-glomerular bleeding • Glomerular • oliguria, edema, hypertension, proteinuria, anemia • Non-glomerular • dysuria, frequency, polyuria, pain or colic, hx exercise • crystals on microscopic • mass on exam • medication history - sulfas, aspirin, diuretics

15. Who should be worked up? • Presence of proteinuria and/or hypertension • History consistent with infectious history, HSP, systemic symptoms, medication use or abuse, strong family history of stones or renal disease/failure. • Persistent gross hematuria • Family anxiety - limit evaluation

16. Initial evaluation of the patient with hematuria • All patients: BUN, creatinine, CBC, kidney and bladder ultrasound • Probable glomerular hematuria • C3, ASO titer • possible: hepatitis, HIV, SLE serology • renal biopsy • Probable non-glomeurlar hematuria • urine culture, urine Ca/creatinine ratio • possible: hemoglobin electrophoresis, • coagulation studies, isotope scans, • Flat plate, CT, ??IVP, cystoscopy

17. Pearls for Hematuria • Hematuria is an important sign of renal or bladder disease • Proteinuria (as we will discuss) is the more important diagnostic and prognostic finding. • Hematuria almost never is a cause of anemia • The vast majority of children with isolated microscopic hematuria do not have a treatable or serious cause for the hematuria, and do not require an extensive evaluation. So a VCUG, cysto and biopsy are not indicated.

18. More Pearls • Urethrorrhagia – boys with bloody spots in the underwear • Presentation – prepuberal ~ 10 yrs • It is painless • Almost 50% will resolve in 6 months and > 90% at 1 year; it may persist for 2 yrs • Treatment – watchful waiting in most cases • Painful gross hematuria – usually infection, calculi, or urological problems; glomerular causes of hematuria are painless.

19. More Pearls – gross hematuria • Gross hematuria is often a presentation of Wilms’ tumor • All patients with gross hematuria require an imaging study. • If a cause of gross hematuria is not evident by history, PE or preliminary studies, the differential is hypercalciuria, SS trait, or thin basement membrane disease. • Cysto is rarely helpful

20. 7 year old boy developed gross tea colored hematuria after a sore throat and upper respiratory infection. No urinary symptoms but urine output was decreased. He complained of mild diffuse lower abdominal pain. There is no fever, rash or joint complaints. Past med history was unremarkable but had intermittent headaches for two years. On exam he was well with a BP of 95/65, no edema, some suprapubic tenderness and red tympanic membranes. The mother thinks that a similar episode occur on vacation a few months ago. WHAT WOULD YOU LIKE TO DO?

21. Tests • Normal electrolytes • Creatinine 0.5 mg/dl • Urinalysis – large blood, no protein • Urine culture – no growth

22. More to the story • She calls with a recurrent episode of gross hematuria with a URI three months later • So what do you do ?

23. Other tests • ANA, ANCA, ASO, Family screening • Complement – C3NF

24. Now what • IGA nephropathy • Boys > girls • Mostly normotensive, with persistent microscopic hematuria • Chronic glomerulonephrits – up to 40% of primary glomerulonephritis • Complement studies are nl, some inc IgA • Prognosis – not so good if > 10 yrs of age, proteinuria, reduced GFR, hypertension and no macrohematuria

27. A four-year boy presents with a 5-day history of swollen eyes and “larger ankles”. On exam he has periorbital and pretibial edema. The most appropriate tests include all the following except. • a. Urinalysis • b. Blood tests for total protein and albumin • c. Serum creatinine • d. Sedimentation rate • e. Serum complement (C3)

28. On routine physical examination, an 8-year-old boy is found to have microscopic hematuria. The first step in your evaluation should be. • Examine the urine sediment • Order an intravenous pyelogram • Obtain a voiding cystourethrogram • Perform a CBC in the office • Order an ASO titer

29. An 8-year-old boy presents with tea colored urine. He has very mild edema. The work-up should include all the following except. • Complement studies • Serum creatinine • Urinalysis for protein • Monitor blood pressure and urine output • Obtain an intravenous pyelogram and VCUG

30. Proteinuria John is an 12 year old noted on a basketball team physical to have 2+ protein on dipstick. He has an unremarkable past medical history. Family history is negative in the parents and siblings for any renal disease. A repeat urine in one week in his PMD’s office is still positive. What is the next step? Should you refer?

31. Repeat a first AM void following restricted activity, perform a microscopic on a fresh urine; also an alkaline pH may give a false positive result • If there is still protein perform a more formal orthostatic test. If orthostatic, no further work-up is generally required, although no indemnification from subsequent renal disease. • Caveat - Family anxiety because of the connotation of protein and friends told them about kidney failure.

32. Definitions (Pearl) • Urine protein to creatinine ratio • Normal: < 0.2 (< 0.15 adolescents) • Mild to moderate: 0.2 to 1.0 • Heavy or severe: > 1.0 • Persistent proteinuria: present both in the recumbent and the upright posture; even in this situation, proteinuira is less during recumbency

33. What does Orthostatic Proteinuria mean? Protein Excretion

34. Causes of Proteinuria • Transient • fever, emotional stress, exercise, extreme cold, abdominal surgery, CHF, infusion of epinephrine • Orthostatic • Transient or fixed / reproducible • Persistent • Glomerular disease: MCNS, FSGS, MPGN, MN • Systemic: SLE, HSP, SBE, Shunt infections • Interstitial: reflux nephropathy, AIN, hypoplasia, hydronephrosis, PKD

35. Hypertension

36. Hypertension Case: David is a 10 year old boy first noted to have an elevated blood pressure of 140/85 during a PE for headaches. Pt has a long history of learning and behavioral issues. Headache evaluation was normal (CT, sinus,etc.). Referred for evaluation. Initial evaluation noted a Ht / Wt > 99%tile, BP of 128/86 mmHg, normal ultrasound and renal scan, although a plasma renin of 8 ng/ml/min (nl < 2). Do you perform an angiogram?

37. Definition of HypertensionThe 4th Report on High Blood Pressure in Children and Adolescents • Hypertension—average SBP and/or DBP that is greater than or equal to the 95th percentile for sex, age, and height on 3 or more occasions. • Prehypertension—average SBP or DBP levels that are greater than or equal to the 90th percentile, but less than the 95th percentile. • Adolescents with BP levels greater than or equal to 120/80 mmHg should be considered prehypertensive.

38. Evaluation of Hypertension

39. Therapeutic Lifestyle Changes • Normal Encourage healthy diet, sleep, and physical activity. • Prehypertension Recommend weight management counseling if overweight; introduce physical activity and diet management. • Stage 1 hypertension Recommend weight management counseling if overweight; introduce physical activity and diet management. • Stage 2 hypertension Recommend weight management counseling if overweight; introduce physical activity and diet management.

40. Indications for Treatment • Symptomatic hypertension • Secondary hypertension • Hypertensive target-organ damage • Diabetes (types 1 and 2) • Persistent hypertension despite nonpharmacologic measures

41. Pharmacologic Therapy for Childhood Hypertension • The goal for antihypertensive treatment in children should be reduction of BP to <95th percentile, unless concurrent conditions are present. In that case, BP should be lowered to <90th percentile. • Severe, symptomatic hypertension should be treated with intravenous antihypertensive drugs.

42. Urinary Tract Infections

43. Case History • A 12 mo old girl is diagnosed with the first febrile UTI. She is not eating well. UA shows pyuria and bacteria. Urine culture is obtained. Antibiotics are given (SMX-TMP). • How to proceed? • What are some of your concerns? • Radiographic follow-up • Long-term monitoring

44. Bacteriology /Pathogenesis UTI - 1 • Most Common - E. Coli, coliforms • Virulence Factors • adherence to uroepithelium by P-fimbriae • endotoxin release • Pyelo vs cystitis - 80 to 20%

45. Bacteriology /Pathogenesis UTI 2 • Perineal / urethral factors • uncircumcised - 10-20x risk • ? Urethral caliber (infant girls) • other myths such as bubble bath, wiping techniques • Low Urinary factors • dysfunctional voiding ; constipation • Other - indwelling catheters, congenital anomalies, Vesicoureteral reflux, sexual activity

46. Diagnosis • Leukocyte test and nitrate test • Urine culture > 40-50,000 CFU/mL • Pyuria - not on recurrent UTIs

47. Clinical Issues • Lower tract - frequency, urgency, enuresis, dysuria • Upper tract - fever - nearly all in boys under 1 year of age; females peak in first year but still significant through the first decade • Asymptomatic bacteriuria - low risk

48. Radiological Evaluation • Renal ultrasound - anatomy, size, location, echogenicity • DMSA (2nd choice glucoheptanate - SGH) - cortical integrity, photopenic regions, differential function, abscess • CT scan - abscess • VCUG - standard for first UTI; radionuclide for follow-up or siblings • IVP - NO WAY

49. Grades of Reflux

50. Reflux Recommendations“the simple way” • GRADES I - III Antibiotics • GRADES IV - V Surgery