Pediatric Fluid & Electrolyte Abnormalities: Board Review Course Summary

1. Metro NY/ NJ Pediatric Board Review CoursePediatric Fluid/ Electrolytes and NephrologyJune 2015 Leonard G. Feld MD PhD Levine Children’s Hospital Charlotte, NC

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

3. Case 1 4 mo old infant with 4-5 day history of fever (38.5oC), numerous watery diarrhea and decreased activity. Child refused to take breast milk or solid foods. Mother substituted non-carbonated soda (Coca-cola, etc ~550-700 mOsm/kg H2O & < 5 mEq/L Na. Over last 12 hrs few episodes of emesis and less wet diapers. EXAM: lethargic, dry mucous membranes, no tears, sunken eyeballs & reduced skin turgor. BP 74/43 mmHg; Temp 38.5oC, RR 36 , HR175 beats WT 6 kg. Weight 7 days ago was 6.6 kg. There were no other significant findings.

4. Electrolyte Composition of Body Fluid Compartments

5. BODY WATER DISTRIBUTION

6. Clinical Assessment

7. Maintenance Requirements

8. Laboratory Sodium 124 mEq/L Chloride 94 mEq/L Potassium 4 mEq/L Bicarbonate (or total CO2) 12 mEq/L Serum creatinine 0.8 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%)

9. 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

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

11. 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 6

12. Causes of SIADH • Neurological conditions • Pulmonary conditions • Tumors • Medications

13. Criteria • Hypotonic hyponatremia. • Inappropriate urine osmolality compared to plasma osm. Patients with medical condition associated with occurrence of SIADH, a urine osmolality > maximal dilution (75-125 mosm/L) and low plasma osm is “inappropriate” to state of water balance. • Absence of thyroid, adrenal, cardiac, or renal disease • Absence of volume contraction • High urinary sodium concentration

14. Additional hints for SIADH • Fluid balance even or positive • CVP > 6 • Urine volume decreased • Uric acid decreased • BUN and Cr decreased • Urine Na > 20 mEq/L

15. Points on Hypernatremic Dehydration

16. Hypernatremia – SLOW and CLOSE Key points: look quiet then irritable on stimulation; may look better than % of dehydration based on weight Fluid selection: 5% dextrose + ¼ isotonic saline (~30-40 mEq/L of Na) + 20 mEq KCl /L (D5W with 1/2/ NS + KCl is also OK). • 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.

17. Case 2 Susan an 8 yr old noted on routine exam to have moderate hematuria on dipstick. Unremarkable past medical hx. Family hx is negative in the parents and siblings for any renal disease. Hx of hematuria is unknown. Repeat urine in 1 wk still positive, urine culture showed no growth.

18. 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 6

19. More on Hematuria • BIG 3 • Repeat a first AM void following restricted activity , perform a microscopic on a fresh urine • Check the family members 3 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

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

21. 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-glomerular hematuria • urine culture, urine Ca/creatinine ratio • possible: hemoglobin electrophoresis, • coagulation studies, isotope scans, • Flat plate, CT, ??IVP, cystoscopy

22. 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.

23. 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.

24. 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

25. Case 3 7 yr old boy developed gross tea colored hematuria after a sore throat and URI. No urinary symptoms but urine output was decreased. Complained of mild diffuse lower abdominal pain. No fever, rash or joint complaints. Past med hx was unremarkable but had intermittent headaches 2 years ago. EXAM Afebrile, BP 95/65 mmHg, no edema, some suprapubic tenderness, red tympanic membranes. Mother thinks that a similar episode occur on vacation a few months ago. Urinalysis - 20 RBCs/hpf, 5-10 WBCs, 100 mg/dL protein, rare cellular and hyaline casts. Serum creatinine is 0.8 mg/dL, C3 100 (normal). .

26. Question 3: The most likely cause of the gross hematuria is: • Myoglobinuria • Urinary tract infection • Obstructive uropathy • IgA nephropathy • Benign familial hematuria 6

27. 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

28. Work of AGN • UA, renal US, 24 hrurine protein/creatinine, spot urine protein and creatinine ratio • Glomerulonephritis – hematuria + one of these four – proteinuria, oliguria, hypertension or abnl renal function active sediment (protein, RBCs, dysmorphic RBCs/or RBC casts), 300 mg - >1 gm/day proteinuria, HTN, + edema • Low complement GN: SLE, SBE, cryoglobulinemia, shunt nephritis; Isolated renal: post-infectious GN, MPGN Normal complement GN: Systemic: HSP, ANCA-associated (Wegener’s, PAN), Goodpasture’s syndrome, hypersensitivity vasculitis Isolated renal: IgA nephropathy, anti-GBM disease, RPGN

29. 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.

30. 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

31. 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

32. 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

33. Acute glomerulonephritis: DD • Acute Poststreptococcal glomerulonephritis (PSAGN) – most common • Acute Postinfectious or nonstreptococcal postinfectious glomlerulonephritis (AIAGN) • 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)

34. 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

35. 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.

36. 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 6

37. What is Orthostatic Proteinuria ? Protein Excretion

38. 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.

39. 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

40. 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)

41. 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

42. 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

43. Nephrotic Syndrome - RX Corticosteroid treatment • Induction therapy: Exclude active infection or other contraindications prior to steroid therapy. • Oral prednisone- 60 mg/m2/d (~2 mg/kg/d) daily for 4 -6 wks. • Oral prednisone at 40 mg/m2 (or ~1.5 mg/kg) given as a single dose on alternate days for 4 -6 wks. • Relapse therapy - For infrequent relapses, • Prednisone 60 mg/m2/d (~2 mg/kg/d) as single AM dose until proteinuria resolved for at least 3 -4 days. • Following remission of proteinuria, prednisone reduced to 40 mg/m2 (or ~1.5 mg/kg) given as a single AM dose on alternate days for 4 weeks. Prednisone may then be discontinued or a tapering regimen. Frequently relapsing nephrotic syndrome is steroid-sensitive nephrotic syndrome with 2 or more relapses within 6 mos or more than 3 relapses within a 12-mo period.

44. Hypertension

45. 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.

46. 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

47. BP Classification

48. 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

49. Evaluation of Hypertension

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