Metro New York / New Jersey Pediatric Board Review Course Pediatric Nephrology June, 2009

1. Metro New York / New Jersey Pediatric Board Review CoursePediatric NephrologyJune, 2009 Leonard G. Feld MD PhD Levine Children’s Hospital Charlotte, NC

2. For the Exam Fluid and Electrolyte Metabolism A. Composition of body fluids -Intracellular, extracellular, Electrolytes (sodium, potassium, chloride), Protein B. Acid-base physiology -Normal mechanisms and regulation, Acidosis, alkalosis C. Electrolyte abnormalities - Sodium – Hypernatremia; Hyponatremia; Potassium Hyperkalemia; Hypokalemia; Chloride imbalance D. Disease states, specific therapy - Pyloric stenosis, gastroenteritis, acute renal failure, shock, SIADH, Cystic fibrosis, Dehydration, Hyperosmolar non-ketotic coma

3. For the Exam Renal Disorders • Normal function, proteinuria, hematuria, persistent microscopic hematuria, causes of gross and microscopic hematuria, nonhematogenous etiology of red urine,dysuria, • Incontinence - Nocturnal, functional, daytime incontinence, • Congenital - Renal dysplasia, unilateral multicystic dysplastic kidney, autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, Juvenile nephronophthisis, Renal agenesis • Abnormalities of the collecting system, kidney, and bladder – Hydronephrosis, Hydroureter and megaureter, Ureterocele, Vesicoureteral reflux, • Abnormalities of the urethra - Posterior urethral valves, Urethral stricture • Hereditary nephropathy - Familial nephritis, Congenital nephrotic syndrome • Acquired - Infection of the urinary tract (Pyelonephritis, Cystitis), acute glomerulonephritis, Nephrotic syndrome, Hemolytic-uremic syndrome, Henoch-Schoenlein purpura,IgA nephropathy • Renal failure - Prerenal failure, Intrinsic renal failure , chronic renal failure, • Other - Trauma, renal injuries, Urethral injury, Toxins, Renal stones, Renal tubular acidosis, Hereditary conditions with renal manifestations, Nephrogenic diabetes, insipidus, Cystinosis • Hypertension – General, Renal, Vascular, Adrenal, Pheochromocytoma, Cushing syndrome, Miscellaneous causes, Essential hypertension, Administration of drugs, Traction on legs

4. Outline • Fluid and Electrolyte abnormalities • Dehydration • Renal • Hematuria • Proteinuria • Hypertension • Urinary tract infections • Glomerulonephritis

5. Case 1: Dehydration A 4 mo old infant presents with a four to five day history of low grade fever (38-38.5oC), numerous watery diarrhea and decreased activity. Since the child refused to take her usual breast milk volume or solid foods, the mother and grandmother substituted non-carbonated soda (Coca-cola, ginger ale, apple juice or orange juice will have ~550-700 mOsm/kg H2O) with less than 5 mEq/L of sodium), and “sweet” (sugar added) iced tea. Over the last 12 hours there were a few episodes of emesis and there were less wet diapers. On examination the child was lethargic, dry mucous membranes, no tears, sunken eyeballs, and reduced skin turgor. Vitals signs were the following: Blood pressure 74/43 mmHg; Temperature of 38oC, respiratory rate of 36 per minute and pulse of 175 beats per minute. The weight was 6 kg. Weight at the time of her immunization 7 days ago was 6.6 kg. There were no other significant findings.

6. Electrolyte Composition of Body Fluid Compartments

7. BODY WATER DISTRIBUTION

8. Clinical Assessment

9. Maintenance Requirements

10. Deficit

11. Laboratory Sodium 124 mEq/L, chloride 94 mEq/L normal 98 -118 mEq/L), potassium 4 mEq/L (normal 4.1-5.3 mEq/L), bicarbonate (or total CO2) was 12 mEq/L (normal 20-28 mEq/L or mmol/L), serum creatinine 0.8 mg/dL (normal ~0.3-0.5 mg/dL), blood urea nitrogen 40 mg/dL, blood glucose 70 mg/dL; complete blood count was normal except for a hemocrit of 38% (normal ~ 36%);

12. Hyponatremia • Serum [Na+] < 130 mEq/L • Water shifts into cells – lower ECF volume • <125 mEq/L – nausea and malaise • < 120 mEq/L – headache, lethargy, • <115 mEq/L – seizure and coma

13. Loss of hypertonic Fluid and Sodium from the ECF secondary to Dehydration

14. Question 1: What is the appropriate parenteral solution • 5% dextrose + 0.45% isotonic saline + 40 mEq KCl /L • 0.45% isotonic saline + 40 mEq KCl /L • 0.9% isotonic saline + 40 mEq KCl /L • 5% dextrose + 40 mEq KCl /L • 5% dextrose + 0.2% isotonic saline

15. Approach For this 6.6 kg infant Maintenance requirements for 24 hours Water 100 mL / kg x 6.6 kg = 660 mL Sodium 3 mEq / 100 mL x 660 mL = 20 mEq Potassium 2 mEq / 100 mL x 660 mL = 13 mEq For this 6 kg infant with hyponatremic dehydration at 10% Deficits for 24 hours Water Pre-illness weight – Illness weight = 6.6 – 6 kg = 0.6 kg = 600 mL Sodium 10 mEq x 6.6 kg = 66 mEq Potassium 8 mEq x 6.6 kg = 53 mEq

16. Points on Hypernatremic Dehydration

17. Hypernatremia – SLOW and CLOSE Key points: look quiet then irritable on stimulation; may look better than % of dehydration based on weightd Fluid selection: 5% dextrose + ¼ isotonic saline (~30-40 mEq/L of Na) + 20 mEq KCl /L • 1st 24 hrs: 24 hrs of Maintenance + ½ deficit • 2nd 24 hrs: 24 hrs of Maintenance + ½ deficit • Close monitoring of serum sodium every 2-3 hours. Some have suggested using a higher [sodium] – 0.45% isotonic saline or even isotonic saline to restore ECF volume then moving to a lower • sodium containing solution to restore the water deficit. This approach may also reduce the possibility of dropping the serum sodium too quickly and preventing neurological problems.

18. 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.

19. Question 2: Which of the following test is the next step in the evaluation? • VCUG and urine culture • Renal sonogram and urine calcium to creatinine ratio • Urology referral • CBC and Direct Coombs • Recheck in two years

20. More on Hematuria • 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. However a renal sonogram and urine calcium to creatinine ratio • Caveat - Family anxiety because of the connotation of blood and cancer in adults.

21. 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

22. Initial evaluation of the patient with hematuria • All patients: BUN, creatinine, kidney and bladder ultrasound, urine calcium to creatinine ratio • 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 • Probable glomerular hematuria • C3, ASO titer • possible: hepatitis, HIV, SLE serology , SSD • renal biopsy – not for persistent microscopic without proteinuria, decreased renal function, and/or hypertension • Probable non-glomeurlar hematuria • urine culture, urine Ca/creatinine ratio • possible: hemoglobin electrophoresis, • coagulation studies, isotope scans, • Flat plate, CT, ??IVP, cystoscopy

23. Pearls for Hematuria • Hematuria may be 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.

24. 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.

25. 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 includes hypercalciuria or SS trait • Cysto is rarely helpful

26. Case 3 • 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 (afebrile) with a BP of 95/65 mHg, no edema, some suprapubic tenderness and red tympanic membranes. The mother thinks that a similar episode occur on vacation a few months ago. • Urinalysis shows 20 RBCs/hpf, 5-10 WBCs, 100 mg/dL of protein, rare cellular and hyaline casts. Serum creatinine is 0.8 mg/dL, C3 100 (normal).

27. Question 3: The most likely cause of the gross hematuria is: • Myoglobinuria • Urinary tract infection • Obstructive uropathy • IgA nephropathy • Benign familial hematuria

28. IgA • 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

31. Red or Tea colored/ Brown Urine Fresh Centrifuged Urine Sample Sediment Red with Red Cells Supernatant Red without Red Cells Hemoglobinuria* Myoglobinuria Hematuria * Hemoglobinuria will have a red or pink hue to the serum NOTE: If there is no red sediment, no RBCs and a clear supernatant, consider other causes such as urates, bile pigments, beets, porphyria, some medications, etc.

32. Question 4 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 renal ultrasound • Obtain a voiding cystourethrogram • Perform a CBC in the office • Order an ASO titer and C3

33. Question 5 An 8-year-old boy presents with tea colored urine. He has very mild edema. History of strep infection about 2 weeks ago. The work-up should include all the following except. • Complement studies • Serum creatinine • Urinalysis for protein • Monitor blood pressure and urine output • Obtain a renal ultrasound

34. Acute glomerulonephritis: clinical • May be clinically asymptomatic (? 90%) with low C3 and hematuria • Usually within 3 weeks after strep infection – mean about 10 days • Periorbital, peripheral edema • Hematuria - coke-colored, tea-colored, reddish/brown • Nonspecific findings such as abdominal pain, malaise, anorexia, headaches, pallor

35. Acute glomerulonephritis: DD • Acute Poststreptococcal glomerulonephritis (PSAGN) – most common • Acute Postinfectious or nonstreptococcal postinfectious glomlerulonephritis 9AIAGN) • Bacterial: endocarditis (low C3), shunt nephritis (low C3), pneumococcal pneumonia, etc. • Viral: hepatitis B, infectious mononucleosis, varicella, etc, • Parasites: • Other: SLE (low C3), membranoproliferative GN (low C3), hyperthyroidism, HSP (nl C3)

36. Acute glomerulonephritis: evaluation/ treatment • Evaluation • ASO, C3, C4 • Renal function • Evaluation for hypertension and oliguria • Magnitude of proteinuria • RX – supportive • Admission for hypertension, oliguria, impaired renal function, nephrotic syndrome • Prognosis: C3 normalizes by 12 weeks, hypertension and other abnormalities resolve by 2-3 months, hematuria may persist for 6-24 mo

37. Proteinuria Case 6: John is an 12 year old noted on a basketball team physical to have 2+ protein on dipstick. There are no recent illnesses. He has an unremarkable past medical history and he is not taking any medications. Family history is negative in the parents and siblings for any renal disease.

38. Question 6: Which of the following is the best approach? • Obtain a 1st AM urine for protein • Perform a complete biochemical profile • Obtain a C3, ASO and ANA • Refer for a renal biopsy • Schedule a renal sonogram and VCUG

39. What does Orthostatic Proteinuria mean? Protein Excretion

40. More on Proteinuria • 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.

41. 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

42. Question 7 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. • Urinalysis • Blood tests for total protein and albumin • Serum creatinine • Sedimentation rate • Serum complement (C3)

43. 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

44. Nephrotic Syndrome • Primary Nephrotic Syndrome: • Minimal change disease (~75%) – mean age 4 yrs • No hematuria, nl C3, no hypertension, nl creatinine • Membranoproliferative GN (~ 5-10%) • FSGS (5-10%) • Proliferative GN, Mesangial proliferation • Membranous nephropathy • Secondary Nephrotic Syndrome: • SLE, HSP, diabetes mellitus, HIV, vasculitis, malignancy (lymphoma, leukemia), drugs (heroin, inteferon, lithium), infections (toxo, CMV, syphilis, hepatitis B and C)etc. • Congenital/Infantile Nephrotic Syndrome: • Finnish-type congenital nephrotic syndrome,Denys-Drash syndrome • Diffuse mesangial sclerosis, Nail-patella syndrome

45. Nephrotic Syndrome - RX Corticosteroid treatment • Induction therapy: • Exclude active infection or other contraindications prior to steroid therapy. • Oral prednisone or prednisolone at 60 mg/m2/d (~2 mg/kg/d) daily for 4 weeks. • Maintenance therapy (following above induction therapy) • Oral prednisone or prednisolone at 40 mg/m2 (or ~1.5 mg/kg) given as a single dose on alternate days for 4 weeks. • NOTE: Some nephrologists recommend daily induction steroid treatment for 6 weeks, followed by alternate day maintenance therapy for another 6 weeks. • Relapse therapy • For infrequent relapses, Prednisone 60 mg/m2/d (~2 mg/kg/d) given as a single morning dose until proteinuria has resolved for at least 3days. • Following remission of proteinuria, prednisone is reduced to 40 mg/m2 (or ~1.5 mg/kg) given as a single dose on alternate days for 4 weeks. Prednisone may then be discontinued or a tapering regimen. Frequently relapsing nephrotic syndrome is defined as steroid-sensitive nephrotic syndrome with 2 or more relapses within 6 months or more than 3 relapses within a 12-month period.

46. Hypertension

47. Hypertension Question 8: David is a 10 year old boy first noted to have an elevated blood pressure of 123/85 during a annual physical examination. Pt has a long history of learning and behavioral issues. He has a previous history of headaches that were evaluated with a CT scan of the brain and sinuses. On following evaluation in one week, his BP is126/86 mmHg with a weight > 99%ile for age and a height at ~50th %ile.

48. Question 8: What is the most appropriate initial testing for this child? • Renal mag-3 flow scan • Electrolytes, BUN, Creatinine, Bicarbonate • Renal Sonogram with doppler • Urinary screening for drugs • 24 hour urine for catecholamines

49. BP Classification

50. Estimate of Hypertension Estimate without height adjustment • If systolic BP equals or exceeds 100 + 2 times pt age in yrs • If diastolic BP equals or exceeds 70 + pt age in yrs Estimate with height adjustment • If systolic BP at 95th %tile for age and sex Add 4 mmHg to the value at the 50th %tile 2. If diastolic BP at 95th %tile for height Add 2 mmHg to the value at the 50th %tile