Kidney Condundrums: A Case-Based Approach to Common Issues in Pediatric Nephrology. Disclosures. Hot Off the Press! Learning Objectives

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Kidney Condundrums: A Case-Based Approach to Common Issues in Pediatric Nephrology Darcy Weidemann MD MHS Children s Mercy Hospital Clinical Advances in Pediatrics September 26, 2018 Disclosures No

1 Kidney Condundrums: A Case-Based Approach to Common Issues in Pediatric Nephrology Darcy Weidemann MD MHS Children s Mercy Hospital Clinical Advances in Pediatrics September 26, 2018 Disclosures No conflicts of interest relevant to discussion to disclose. The Children's Mercy Hospital, Learning Objectives Hot Off the Press! 1. Distinguish between primary nocturnal enuresis and secondary etiologies of enuresis which may require further diagnostic evaluation 2. Implement a learning framework for appropriate initial evaluation of asymptomatic hematuria and/or proteinuria and identify red flags which require subspecialty consultation 3 4 Case 1 What is Next Appropriate Step? 7 year old boy presents to clinic for evaluation of nocturnal enuresis Has never been dry at night, potty-trained ~age 3, is wet on average 7 out of 7 nights/week PMH includes ADHD, well-controlled on methylphenidate A. More H&P B. Urinalysis C. Abdominal X-Ray D. Renal Ultrasound E. BMP F. Urodynamics 5 6 1

History is Key! History is Key! Walle JV et al. Practical consensus guidelines for the management of enuresis. Eur J Pediatr 2012; 171:971-983.

tract infections Occasional daytime frequency/urgency FH + for father with enuresis until age 9 PE: BP 96/58, HR 85, Ht (50%ile), Wt (75%ile) Unremarkable PE other than small amount of palpable stool

2 History is Key! History is Key! Walle JV et al. Practical consensus guidelines for the management of enuresis. Eur J Pediatr 2012; 171: Case 1 Further History Case 1 Cont d Described as deep sleeper by parents No history of daytime accidents, voids 4-5x/day Stools daily to every other day, Bristol 3 Denies history of urinary tract infections Occasional daytime frequency/urgency FH + for father with enuresis until age 9 PE: BP 96/58, HR 85, Ht (50%ile), Wt (75%ile) Unremarkable PE other than small amount of palpable stool in LLQ, normal external GU exam UA: SG 1.015, ph 6.5, neg LE, neg nitrite, neg glucose neg blood, neg protein 9 10 Primary Monosymptomatic Enuresis What Should Be Considered Next? ICCS recently developed standardized terminology Enuresis: discrete episodes of urinary incontinence during sleep in children 5yo Monosymptomatic: no other LUT symptoms Primary: have never achieved satisfactory period of nighttime dryness < 6 months A. Behavioral Interventions B. Moisture Alarm C. Stool Softeners D. DDAVP E. Oxybutynin F. Imipramine Franco et al, Evaluation and treatment of nonmonosymptomatic nocturnal enuresis: A Standardization document from the International Children s Continence Society. J Pediatr Urol 2013;

Pathophysiology of Enuresis Pathophysiology of Enuresis Poor arousal from sleep Nocturnal Polyuria Moisture Alarm Poor arousal from sleep Nocturnal Polyuria DDAVP Small bladder storage capacity Small

fluid intake prior to bed Eliminate potential bladder irritants (4C s: caffeine, carbonation, citrus, vitamin C; articial food dyes) Aggressive constipation management Most effective therapy ~2/3

3 Pathophysiology of Enuresis Pathophysiology of Enuresis Poor arousal from sleep Nocturnal Polyuria Moisture Alarm Poor arousal from sleep Nocturnal Polyuria DDAVP Small bladder storage capacity Small bladder storage capacity Behavioral interventions, stool softeners Behavioral Interventions Moisture Alarm Increased hydration during daytime hours with timed / double voiding q2-3 hours Limit fluid intake prior to bed Eliminate potential bladder irritants (4C s: caffeine, carbonation, citrus, vitamin C; articial food dyes) Aggressive constipation management Most effective therapy ~2/3 will show improvement Works via feedback mechanism May take 8-12 weeks to see effect Desmopressin (DDAVP) Indications for Referral Works best for children with nocturnal polyuria and normal functional capacity Effective in ~ 60-70% Relapse rate high after discontinuation Can titrate to 0.6 mg (3 tabs) Small risk of hyponatremia Vast majority of primary nocturnal monosymptomatic enuresis could be managed in primary care setting Resource, time limitations Coexistence of daytime symptoms, evidence of red flags for pathology, or treatment failure should prompt referral 3+ months of alarm and/or DDAVP (0.4mg)

4 Case 1 Con td Alternative Reality Back to Case yo male cc: primary nocturnal enuresis Denies daytime symptoms, wet 7/7 nights PE: BP 120/68 (confirmed on manual), growth chart shows he s dropped 2 percentile curves for length UA: SG 1.005, neg LE, neg nitrite, neg glucose, neg blood, 1+ protein 20 What is Next Appropriate Step? Case 1 A. More H&P B. Urinalysis C. Abdominal X-Ray D. Renal Ultrasound E. BMP F. Urodynamics History notable for urosepsis at 3.5 months Bilateral hydroureteronephrosis, VCUG with no VUR, MAG3 consistent with primary nonobstructing megaureters Subsequently lost to followup Repeat imaging showed worsening bilateral hydroureteronephrosis, cystic kidneys Labs with stage 3 CKD (creatinine of 1.5 corresponding to egfr of 39.4 ml/min/1.73m 2 ) History is Key! Onset Acute or subacute onset is this a presentation of a systemic illness? (diabetes mellitus, CKD) Co-morbid emotional, behavioral, or physical triggers? Primary vs Secondary previously dry at night > 6 months? Presence of daytime symptoms polyuria, recurrent UTI, straining or poor urinary stream Fluid intake (restrictions in fluid intake, caffeine, polydipsia) Bowel habits (constipation, fecal soiling) + family history of bedwetting or kidney disease 23 Requisite Physical Exam Components Height, weight, blood pressure poor growth, weight loss, hypertension Abdomen distended bladder, fecal mass Inspection of external genitalia Lower back/spine exclude occult spinal dysraphism or tethered cord (asymmetric gluteal fold) Assessment of lower extremity spinal reflexes 24 4

When to Refer to Specialist Transition Slide History of UTIs (consider renal ultrasound) Suspected neurological disorder MRI lumbar spine to assess for tethered spinal cord Dysfunctional voiding or

10yo football player presents for preparticipation sports physical A. More H&P D. BMP Urine Dipstick: SG 1.030 ph 7.0 1+ blood Neg protein Neg glucose Neg nitrite/le 27 B. Repeat in 1-2 weeks C.

5 When to Refer to Specialist Transition Slide History of UTIs (consider renal ultrasound) Suspected neurological disorder MRI lumbar spine to assess for tethered spinal cord Dysfunctional voiding or history of urinary tract malformations Suspected diabetes mellitus or chronic kidney disease (CKD) 25 Need picture or funny meme 26 Case 2 What is Next Appropriate Step? 10yo football player presents for preparticipation sports physical A. More H&P D. BMP Urine Dipstick: SG ph blood Neg protein Neg glucose Neg nitrite/le 27 B. Repeat in 1-2 weeks C. Urine Microscopy E. Renal Ultrasound F. Refer to Nephrology 28 Case 2 Choosing Wisely # 1 Denies symptoms no dysuria, abdominal pain, edema, fatigue/weight loss, headaches Unremarkable PE, BP 95/58 Follow-up urinalysis one week later (not after football practice) showed resolution of the hematuria 29 Don t order routine screening urine analyses (UA) in healthy, asymptomatic pediatric patients as part of routine well child care 30 5

hypertension, active systemic disease, prematurity, IUGR, or family history of genetic renal disease 31 The 3 Most Important Questions You Must Ask 1. Is it real? 2. Is it serious? 3. What is the cause?

l? Must distinguish dipstick vs. microscopic vs gross hem

6 Should Anyone Get Screening UA s? We recommend limiting screening UA to patients at high risk for CKD patients with a personal history of CKD, acute kidney injury (AKI), congenital anomalies of the urinary tract, acute nephritis, hypertension, active systemic disease, prematurity, IUGR, or family history of genetic renal disease 31 The 3 Most Important Questions You Must Ask 1. Is it real? 2. Is it serious? 3. What is the cause? Is It Real? Must distinguish dipstick vs. microscopic vs gross hematuria Gold standard: > 5 RBC/hpf (40x magnification) False positive with myoglobin (i.e. rhabdomyolysis) due to heme peroxidase activity 33 Non-hematuria Causes of Red or Brown Urine Drugs Toxins Foods Misc Sulfonamides Lead Beets Urate crystals Nitrofurantoin Benzene Blackberries Food coloring Salicylates Rhubarb Bile pigments Phenazopyridine Paprika Homogentisic acid Phenolphthalein Rifampin Chloroquine Iron Sorbitol Melanin Methemoglobin Porphyrin Tyrosine 34 Transient Choosing Wisely #2 Common in healthy children up to 4% of the population of healthy school-age children in at least 1 out of 4 serial measurements Of those + UA, only 6% positive in 4/4 samples Recommend testing 3 specimens at least 1 week apart (well, no exercise) Do not initiate a workup for hematuria or proteinuria before repeating abnormal urine dipstick analysis (UA) Dodge WF et al. Proteinuria and hematuria in schoolchildren. J Pediatr 1976;88(2):

7 2. Is It Serious? What Is The Cause? History is Key! Hypertension Proteinuria (Pr/Cr > 0.2 on first-am sample) Persistent gross hematuria Evidence of volume overload Pain (dysuria, flank pain) Abdominal mass History of trauma Recent trauma, exercise Urinary symptoms of incontinence, dysuria, frequency, urgency? UTI, bowel and bladder dysfunction, hypercalciuria Unilateral flank pain radiating to groin renal calculus Flank pain, +/- fever pyelonephritis Recent pharyngitis (post-streptococcal: 2-3 weeks; IgA nephropathy 1-2 days preceding) Sickle cell disease/trait, coagulopathy Hearing loss/deafness in self or first degree relative Family history of end stage renal disease Recent medication exposure (NSAIDS) Suggested Approach Persistent Asymptomatic Microscopic Choosing Wisely #3 Resolves Follow-up as needed Repeat UA weekly x 2 (no exercise/illness) Red Flags Noted* Persistent microscopic hematuria (>5 RBC/hpf) Urgent subspecialty consultation / referral Urine culture Urine calciumcreatinine Follow every 3-6 months with H&P, UA Treat for infection if positive Treat with diet and lifestyle if elevated (>0.2 if > 6yo, >0.4 if 2-6) persists after 1 year Recheck UA after infection clears Recheck UA after 3 months Renal ultrasound Test parents UA Labs (BMP, HgEP) Refer to nephrology Avoid ordering followup urine cultures after treatment for uncomplicated UTI in patients that show clinical resolution Adapted from Patel HP, Bissler JJ et al. Pediatr Clin North Amer 2001; 48: What Is the Cause? Suggested Approach Gross 80% 37% 16% 22% 25% More likely to identify etiology for gross vs microscopic hematuria Hypercalciuria is most common identifiable cause of microscopic hematuria Glomerulonephritis more likely with gross hematuria (IgA nephropathy 16%, post-strep GN 9%) Bergstein et al, JAMA Pediatrics Symptomatic hematuria Trauma S/sx UTI? S/sx perineal/ meatal irritation? S/sx nephrolithiasis? S/sx glomerular disease? No obvious clues on Hx CT Abd/Pelvis Urine culture Reassurance, Urine Ca/Cr Renal / bladder US BMP, CBC, albumin, C3/C4, UPr/Cr, consider ASO, ANA, Renal/bladder US Consider: urine culture, urine Ca/Cr, HgbEP, test parents, renal/bladder US Repeat UA after antibiotic treatment Repeat UA 1-3 months Urology consultation if + Referral to pediatric nephrology 42 7

Case 2 Alternative Reality Back to Case 2 10yo boy presents as ER followup for painless gross hematuria 3 days ago seen for dark red/brown painless hematuria SG 1.

Gross hematuria resolved within one day with hydration BP elevated 129/74 (confirmed x3 manual, average), UA with SG 1.010, 1+ blood, 2+ protein, 25-50 RBC/hpf. CaCr 0.11, Pr/Cr 0.

8 Case 2 Alternative Reality Back to Case 2 10yo boy presents as ER followup for painless gross hematuria 3 days ago seen for dark red/brown painless hematuria SG 1.020, 2+ blood, 1+ protein, trace LE, neg nitrites. Micro: RBC/hpf, 1-4 WBC/hpf. Ucx pending. BP 134/82, BMP/CBC unremarkable (creatinine 0.5). Gross hematuria resolved within one day with hydration BP elevated 129/74 (confirmed x3 manual, average), UA with SG 1.010, 1+ blood, 2+ protein, RBC/hpf. CaCr 0.11, Pr/Cr 0.82 Urine culture negative Referred to nephrology Case 2 Cont d Choosing Wisely # 4 Seen one week later in nephrology clinic BP still high 132/70, UA with similar findings Grandmother noted intermittent episodes of painless brown/dark urine over last year Triggers: poor fluid intake, possibly viral URIs ROS + for weight plateau over last 6 months Suspected acute/subacute glomerulonephritis, made plans for biopsy in next 2-4 weeks 45 Do not initiate an outpatient HTN workup in asymptomatic pediatric patients prior to repeating the blood pressure measurement. 46 Case 2 Renal Ultrasound Case 2 CT Scan

9 Case 2 Pearls Summary Ultimately diagnosed with stage 2 Wilm s tumor, favorable histology S/p right nephrectomy, 21 week course of vincristine/dactinomycin Renal ultrasound indicated in ALL patients with gross hematuria Patients don t always read the books! Systematic workup is key 49 Nocturnal enuresis, hematuria in children are common clinical dilemmas Targeted history and physical necessary to determine scope and timing of initial workup, possible subspecialty referral Isolated asymptomatic microscopic hematuria rarely an indicator of significant kidney disease 50 Further Resources - Enuresis Bayne AP, Skoog SJ. Nocturnal Enuresis: An Approach to Assessment and Treatment. Pediatrics in Review. 2014; 35(8): Walle JV, Rittig S, et al. Practical consensus guidelines for the management of enuresis. Eur J Pediatr. 2012; 171: Franco I, Gontard A, et al. Evaluation and treatment of nonmonosymptomatic nocturnal enuresis: A standardization document from the International Children s Continence Society. J Pediatr Urol. 2013; 9: AAP Resources for families excellent patient handouts: Further Resources - Bignall ON, Dixon BP. Management of in Children. Curr Treat Options Peds. 2018; 4: Massengill S,. Pediatrics in Review Oct, 29(10) Bergstein, J Leiser J, Andreoli S, The Clinical Significance of Asymptomatic Gross and Microscopic in Children, Arch Pediatr Adolesc Med 2005; 159: Diven SC, Travis SLB. A practical primary care approach to hematuria in children. Pediatr Nephrol 2000; 14(1)

Pediatric Nephrology Consult and Referral Guidelines

Pediatric Nephrology Consult and Referral Guidelines Introduction We see children and teens from birth to 21 years. The most common reasons patients are referred to pediatric nephrology services include: