metro new york / new jersey pediatric board review course pediatric nephrology june 2013

Metro New York / New Jersey Pediatric Board Review Course

Pediatric NephrologyJune 2013Leonard G. Feld MD PhD

Levine Children’s HospitalCharlotte, NC

March 17, 2005

For the ExamFluid and Electrolyte MetabolismA. 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

For the ExamRenal DisordersA. Normal function, proteinuria, hematuria, persistent microscopic hematuria, causes of

gross and microscopic hematuria, nonhematogenous etiology of red urine,dysuria, B. Incontinence - Nocturnal, functional, daytime incontinence, C. Congenital - Renal dysplasia, unilateral multicystic dysplastic kidney, autosomal

dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, Juvenile nephronophthisis, Renal agenesis

D. Abnormalities of the collecting system, kidney, and bladder – Hydronephrosis, Hydroureter and megaureter, Ureterocele, Vesicoureteral reflux,

E. Abnormalities of the urethra - Posterior urethral valves, Urethral strictureF. Hereditary nephropathy - Familial nephritis, Congenital nephrotic syndromeG. Acquired - Infection of the urinary tract (Pyelonephritis, Cystitis), acute

glomerulonephritis, Nephrotic syndrome, Hemolytic-uremic syndrome, Henoch-Schoenlein purpura,IgA nephropathy

H. Renal failure - Prerenal failure, Intrinsic renal failure , chronic renal failure, I. Other - Trauma, renal injuries, Urethral injury, Toxins, Renal stones, Renal tubular

acidosis, Hereditary conditions with renal manifestations, Nephrogenic diabetes, insipidus, Cystinosis

J. Hypertension – General, Renal, Vascular, Adrenal, Pheochromocytoma, Cushing syndrome, Miscellaneous causes, Essential hypertension, Administration of drugs, Traction on legs

ANSWERS TO THE CONTENT SPECIFICATIONS

• Fluid and electrolyte

• Nephrology

[email protected]

SUBJECT LINE: NYNJ PEDS

mailto:[email protected]

Outline• Fluid and Electrolyte abnormalities

– Dehydration

• Renal– Hematuria– Proteinuria– Hypertension– Urinary tract infections– Glomerulonephritis

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.

March 17, 2005

Electrolyte Composition of Body Fluid Compartments

BODY WATER DISTRIBUTION

TOTAL BODY WATER (TBW)0.6 x Body Weight (BW)

EXTRACELLULAR FLUID (ECF)

0.2 x BW

INTRACELLULAR FLUID (ICF)0.4 x BW

Interstitial Fluid Plasma ¾ of ECF ¼ of ECF

Clinical AssessmentFluid

Deficit

Clinical

Status

Clinical

Assessment

Mild

( 5%)

50 cc/kg Compensated Thirsty, HR, Normal BP tears, slightly dry mucosa, alert/restless, [urine]

Moderate

(10%)

100 cc/kg Decompensated Very dry mucosa, < skin turgor, sunken eyes, deep resp, weak pulses, cool extremities, oliguria

Severe

(15%)

150 cc/kg Shock Intense thirst, BP, cap refill > 3 sec, weak pulses, apnea/rapid breathing, coma, anuria

Maintenance RequirementsBody wt 0-10 kg 10-20 kg 20 kg

TBW 100 ml/kg 1000 ml +

50 ml/kg for each kg > 10kg

1500 +

20 ml/kg for each kg > 20kg

Na+ 3 mEq/kg 3 mEq/kg 3 mEq/kg

K+ 2 mEq/kg 2 mEq/kg 2 mEq/kg

Cl- 5 mEq/kg 5 mEq/kg 5 mEq/kg

Deficit

Type of Dehydrationbased on serum [Na] in

mEq/L

Water (mL/kg)

Sodium (mEq/kg)

Potassium (mEq/kg)

Isonatremic [Na] 130-150 100-120 8-10 8-10

Hyponatremic [Na] < 130 100-120 10-12 8-10

Hypernatremic [Na] > 150 100-120 2-4 0-4

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%);

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

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

35 Na 64 K

15 Na55 K

10 Na

15 Na54 K

10 Na

280

0

280

0

280

0

258

0

200

0

258

0

0.25 Liters 0.40 Liters



NORMAL

AFTER LOSS

AFTER OSMOTIC ADJUSTMENT

NORMAL ECF NORMAL ICF

mOsm/L

400

0

Loss0.10 LIters

10 K10 Na

Question 1: What is the appropriate parenteral solution

A. 5% dextrose + 0.45% isotonic saline + 40 mEq KCl /L

B. 0.45% isotonic saline + 40 mEq KCl /L

C. 0.9% isotonic saline + 40 mEq KCl /L

D. 5% dextrose + 40 mEq KCl /L

E. 5% dextrose + 0.2% isotonic saline

5% dextrose

+ 0.45% isot..

.

0.45% isoto

nic sa

line + 4...

0.9% isoto

nic sa

line + 40...

5% dextrose

+ 40 mEq KCl /

L

5% dextrose

+ 0.2% isoto

n..

20% 20% 20%20%20%

6

ApproachFor this 6.6 kg infant Maintenance requirements for 24 hours

Water 100 mL / kg x 6.6 kg = 660 mLSodium 3 mEq / 100 mL x 660 mL = 20 mEqPotassium 2 mEq / 100 mL x 660 mL = 13 mEq

For this 6 kg infant with hyponatremic dehydration at 10%Deficits for 24 hoursWater Pre-illness weight – Illness weight =

6.6 – 6 kg = 0.6 kg = 600 mLSodium 10 mEq x 6.6 kg = 66 mEqPotassium 8 mEq x 6.6 kg = 53 mEq

Points on Hypernatremic Dehydration

35 Na 64 K

31 Na

62 K2 Na

37 Na62 K2 Na

280

0

280

0

280

0

318

0


0.15 Liters

0.40 Liters


NORMAL

AFTER LOSS

AFTER OSMOTIC ADJUSTMENT

NORMAL ECF NORMAL ICF

mOsm/L

80

0

Loss0.10 LIters

2 K2 Na

413

0

318

0

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.

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.

Question 2: Which of the following test is the next step in the evaluation?

A. VCUG and urine culture

B. Renal sonogram and urine calcium to creatinine ratio

C. Urology referralD. CBC and Direct

CoombsE. Recheck in two

years

VCUG and urine cu

lture

Renal sonogram

and uri..

Urology r

eferral

CBC and Dire

ct Coombs

Recheck

in tw

o years

20% 20% 20%20%20%

6

• 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.

More on Hematuria

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

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

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.

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.

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

March 17, 2005Trying to think about pediatric kidney disease - nephWHAT

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).

Question 3: The most likely cause of the gross hematuria is:

A. Myoglobinuria

B. Urinary tract infection

C. Obstructive uropathy

D. IgA nephropathy

E. Benign familial hematuria M

yoglobinuria

Urinary tr

act infecti

on

Obstructi

ve uro

pathy

IgA nephropath

y

Benign fa

milial h

ematuria

20% 20% 20%20%20%

6

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

Acute Glomerulonephritis

Low Complement Normal Complement

Systemic diseasesSLE

Subacute Bact EndocarditisShunt nephritis

Essential mixed cryoglobulinemiaVisceral abscess

Systemic diseasesPolyarteritis nodsa

Hypersensitivity vasculitisWegener’s

HSPGoodpasture’s

Renal diseasesAcute proliferative GN

Membranoproliferative GN

Renal diseasesIGA

RPGN -Anti-GBM, immune complex GN

Serologic evidence of antecedent strep infection(ASO, anti-Dnase B, streptozyme

PSAGNStrep endocarditis

LupusEssential mixed cryoglobulinemia

Shunt nephritisVisceral abscess

MPGNNon-strep infection

Clinical evidence to support endocarditis

Blood culturesEchocardiogram Treat PSAGN

Positive Negative

Glomerular Non-glomerular

Urinalysis Dysmorphic RBCCellular castsBrown/tea colorBright redClotsCrystalsProtein

++

+++--+

--+

++++-

History Family Hx of ESRDSystemic diseaseNephrolithiasisTraumaSymptomatic vomiting

++---

--+++

Physical HypertensionSystemic signsEdemaAbdominal massGenital bruising

++++--

+--++

Red or Tea colored/ Brown Urine

Fresh Centrifuged Urine Sample

Sediment Red withRed Cells

Supernatant Red withoutRed Cells

Hematuria

NOTE: If there is no red sediment, no RBCsand a clear supernatant, consider other causes such as urates, bile pigments,beets, porphyria, some medications, etc.

Hemoglobinuria*

Myoglobinuria

* Hemoglobinuria will havea red or pink hue to the serum

On routine physical examination, an 8-year-old boy is found to have microscopic hematuria. The first step in your evaluation should be.

A. Examine the urine sedimentB. Order an renal ultrasoundC. Obtain a voiding cystourethrogramD. Perform a CBC in the officeE. Order an ASO titer and C3

Question 4

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.

A. Complement studiesB. Serum creatinineC. Urinalysis for proteinD. Monitor blood pressure and urine outputE. Obtain a renal ultrasound

Question 5

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

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)

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

SO you

call this

urinary

frequency

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.

Question 6: Which of the following is the best approach?

A. Obtain a 1st AM urine for protein

B. Perform a complete biochemical profile

C. Obtain a C3, ASO and ANA

D. Refer for a renal biopsy

E. Schedule a renal sonogram and VCUG

Obtain a 1st

AM urin

e fo...

Perform

a complete bi...

Obtain a C3, A

SO and ANA

Refer for a

renal b

iopsy

Schedule a re

nal sonog...

20% 20% 20%20%20%

6

What does Orthostatic Proteinuria mean?

Normal Orthostatic Recumbant

Erect

Threshold of Detection

ProteinExcretion

• 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.

More on Proteinuria

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

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. UrinalysisB. Blood tests for total protein and albuminC. Serum creatinineD. Sedimentation rateE. Serum complement (C3)

Question 7

March 17, 2005

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

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

Nephrotic Syndrome - RXCorticosteroid 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.

Hypertension

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.

Question 8: What is the most appropriate initial testing for this child?

A. Renal mag-3 flow scan

B. Electrolytes, BUN, Creatinine, Bicarbonate

C. Renal Sonogram with doppler

D. Urinary screening for drugs

E. 24 hour urine for catecholamines

BP ClassificationGrade of hypertension Definition Appropriate next step

“White-coat” hypertension BP levels >95th percentile in a physician's office or clinic, but normotensive outside a clinical setting

Readings may be obtained at home with appropriate family training or with the assistance of a school nurse, or with the use of ambulatory BP monitoring (ABPM)

Normal < 90th %ile

Pre-hypertension >120/80 mm Hg should be considered pre-hypertensive or90-95%ile

Additional readings may be obtained at home with appropriate family training or with the assistance of a school nurse

Stage I hypertension 95th -99th %ile + 5 mmHg Organize a diagnostic evaluation in a non-urgent, phased approach

Stage II hypertension Average SBP or DBP that is >5 mm Hg higher than the 99th percentile

Organize a diagnostic evaluation over a short period of time in conjunction with pharmacological treatment

Hypertensive urgency and emergency

Average SBP or DBP that is >5 mm Hg higher than the 95th percentile, along with clinical signs or symptoms

Hospitalization and treatment to lower the blood pressure

Estimate of Hypertension

Estimate without height adjustment1. If systolic BP equals or exceeds

100 + 2 times pt age in yrs

2. If diastolic BP equals or exceeds 70 + pt age in yrs

Estimate with height adjustment1. 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 heightAdd 2 mmHg to the value at the 50th %tile

Historical Information

Physical Examination

Neonatal historyFamily historyDietary history

Risk Factors (smoking, alcohol use, drug use)

Non-specific / specific symtomatologyReview of Systems - sleep and exercise

patterns, etc.

Vital signs(including extremities)

Height/WeightSpecific attention to organ systems -

cardiac, eye, abdominal or other bruits, etc.

Consider ambulatory blood pressure monitor

Evaluation Phase 1

CBC, urinalysis, urine culture, electrolytes, BUN, creatinine, thyroid studies, uric acid

plasma renin, lipid profile, echocardiogram, renal ultrasound with duplex doppler

Evaluation Phase 2 Selected studies based on magnitude of the hypertension and/

or other clinical /laboratory findings

Renal flow scan (MAG 3)CT Angiography (CTA)

MRA (may not provide adequate evaluation for peripheral renal vascular lesions)

Renal arteriography with renal vein samplingPlasma / urine catecholamines and/or steroid concentrations

Evaluation of Hypertension

Indications for Treatment

• Symptomatic hypertension

• Secondary hypertension

• Hypertensive target-organ damage

• Diabetes (types 1 and 2)

• Persistent hypertension despite nonpharmacologic measures

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.

Urinary Tract Infections

59

Case 9

• A 4 mo old girl presents with low grade fever, mid-lower abdominal pain and nighttime-incontinence. She is not eating well. Prior visits she had normal blood pressure, urinalysis and excellent growth. Urinalysis shows hematuria, 30 mg/dL of protein, leukocyte esterase and positive nitrite. Urine culture is obtained.

Question 9: What is the most likely bacterial cause of her urinary tract infection?

A. Proteus mirabilis

B. E. coli

C. Coagulase positive Staphlococus

D. Alpha hemolytic Streptococcus

E. Klebsiella pneumoniae

61

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%

62

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

63

Diagnosis

• Leukocyte test and nitrite test

• Urine culture > 40-50,000 CFU/mL

• Pyuria - not on recurrent UTIs

64

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

65

Radiological Evaluation

• Renal ultrasound - anatomy, size, location, echogenicity

• DMSA (2nd choice glucoheptanate - SGH) - cortical integrity, photopenic regions, differential function, abscess

• CT scan - abscess• VCUG – not the current standard for first

UTI; radionuclide for follow-up or siblings

• IVP - NO WAY

AAP SEPT 2011Practice guidelines

• DX: Urinalysis with pyruria and culture with 50,000 col/ml single organism by SPA or cath

• Treat for 7-14 days• Ultrasound for all with febrile UTI• VCUG only with abnl Ultrasound, or other

findings to suggest atypical or complex issues• VCUG – after 2nd febrile UTI• No Abx prophylaxis unless VUR grade V

67

Grades of Reflux

68

Reflux Recommendations“the simple way”

• GRADES I - III Antibiotics

• GRADES IV - V Surgery

• Although endoscopic approach is gaining favor over open reimplantation

69

Treatment

• Oral– SMX-TMP, Amoxicillin/Clavulanate– Cefuroxime, cefprozil, cefixime, cefprodoxime

• Parenteral– Neoates: Ampicillin / Gentamicin– Older Children:

• Advanced level cephalosporin• Beta lactam + beta lactamase inhibitor• Aminoglycoside (+ ampicillin)

Feld - 10/98 70

Case10: 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 and shows > 100,000 colonies of E. Coli. Antibiotics are given.

Question 10: What is the most appropriate next step?

A. Perform a DMSA renal scan

B. Refer to urology for cystoscopy

C. Perform a renal sonogram and VCUG

D. Perform urodynamics and flow studies

E. Repeat urine culture in 3 months

Glomerulonephritis / Acute renal failure

73

Case 11

• A 3 year old boy was attending summer camp. Five days later he presents with diarrhea, abdominal pain and appear pale. His mother finds out that there was cook out at camp. On examination the child is pale and is unable to void. His laboratory testing in your office shows a WBC of 26,000, hemoglobin of 8 g/dL, platelets 98,000, Serum creatinine of 1 mg/dL, BUN 54 mg/dL, urinalysis with large blood, 100 mg/dL of protein.

Question 11: What is the most likely diagnosis?

A. Henoch Schoenlein Purpura

B. Post streptococcal glomerulonephritis

C. IgA nephropathy

D. Acute pyelonephritis

E. Hemolytic uremic syndrome

Clinical prodrome

• Diarrhea prodrome 1-15 days• Abdominal pain – may be confused with

ulcerative colitis, appendicitis, rectal prolapse, intussusception

• Pallor• Irritability, restlessnes• Edema – after rehydration• Oliguria/anuria

HUS: Clinical manifestations

• Thrombocytopenia

• Hemolytic anemia

• Renal failure

• Neurologic (irritability, seizure, CVA)

• Pancreatitis (IDDM) and colitis

• Hypertension

March 17, 2005

HUS: Pathogenesis

• Endothelial cell damage occurs secondary to toxin injury via binding to glycolipid receptor or lipopolysaccharide absorption.

HUS: Differential diagnosis

• Other forms of acute Glomerulonephritis / renal failure

• Vasculitis

• Urosepsis

• Renal vein thrombosis

• Coagulopathy (DIC)

Conservative management

• Fluid restriction to <insensible losses plus urine output

• Foley catheter – limit to 24-48 hrs

• Blood transfusion / platelets

• Routine use of antibiotics controversial

• Diuretics

• Nutrition

Surgical Complications

• Toxic megacolon

• Rectal prolapse

• Colonic gangrene

• Intussusceptions

• Perforation

• Strictures

• Mimic appendicitis, IBD

BONUS 1John is a very dedicated weight lifter and started to take a creatine supplement. He asks you to explain the physiologic effects of creatine on his body. Which is the best explanations about creatine?

1.Creatine which is synthesized in the liver and kidney, is transported through the blood to be taken up by high energy demand of the brain and skeletal muscle.

2.Creatine supplementation affects hydration status and heat tolerance during exercise leading to muscle cramping and diarrhea

3.Creatine supplementation does improve physiological response to resistance exercise, increasing the maximal force production of muscles in men, not women.

4.Pasteurized cow's milk contains lower levels of creatine than human milk

5.Creatine has been shown to improve cognitive performance in young athletes.

BONUS 2A 6 year old boy presents with recurrent episodes of brownish urine that developed coincidental with URIs. His urinalysis during the episodes reveals red blood cell casts and small protein. His complement levels are normal. His hepatitis B screen is normal. The MOST likely diagnosis is:

1.Post Strep AGN

2.IgA nephropathy

3.Membranoproliferative glomerulonephritis

4.Membranous nephropathy

5.Wegener’s granulomatosis

SOME QUICKIES

• Unilateral multicystic dysplastic kidney – MOST COMMOM CAUSE OF ABDOMINAL MASS IN NEWBORN

– ULTRASOUND AND VCUG to DETERMINE CONTRALATERAL DISEASE

• Polycystic Kidney Disease

– Autosomal recessive – bilateral enlarged kidneys with microcysts (Potter’s – pulmonary hypoplasia); overtime – liver fibrosis and failure

– Autosomal dominant – MOST COMMON INHERITED KIDNEY DISEASE; bilateral enlarged kidneys with MACROCYSTS; association with cerebral aneurysm

• Hydronephrosis

– Usually obstruction; Ultrasound may show enlarged kidney without hydroureter

• Posterior urethral valves – – MOST COMMON CAUSE of OBSTRUCTIVE UROPATHY IN MALES; remember poor

urinary stream and palpable bladder

• Vesicoureteral reflux– Grades from I to V; VCUG diagnoses REFLUX, Radionuclide

(DMSA) scans detect scars ; Surgery for grades IV to V (in general)• UTIs

– E. coli most common followed by Klebsiella, Proteus. Males over 1 also have E. Coli then Proteus, Staph

– Females > males; greater in uncircumcised; remember constipation may increase incidence of UTIs

– DX – culture, cath or mid stream; UA – positive nitrites and leukocytes

– 1st febrile UTI – ultrasound ; VUCG for girls with more than 2 UTI in 6 months; all males

• Hematuria– Rule out hemoglobin and myoglobin– Brown urine – glomerular – look for red cell casts– Lower tract – gross red (possible at end of stream), no casts,

possible clots– Rule out hypercalciuria – spot ratio– Common diseases

• IgA – gross hematuria with respiratory or GI illness• Post Strep AGN – follows throat or skin infection by 10-21 days,

Low C3 but recovers by 8-12 weeks, maybe increased ASO titer• HUS – E. coli – 0157:H7 – MOST COMMON CAUSE OF

ACUTE RENAL FAILURE; low platelet count and microangiopathic hemolytic anemia (schistocytes; coombs negative)– cause undercooked meat or unpasteurized milk

• Proteinuria– Rule out Orthostatic Proteinuria; urine protein to creatinine ratio –

abnormal above 0.2 from AM specimen– Nephrotic syndrome – ratio greater than 2 or more the 40 mg/m2/hr

of protein• Minimal change – steroid responsive is MOST COMMON• Usually 2- 6 yrs with mean of 4 yrs; remember edema is

dependent - first eyes than later in day to the legs.• Treatment – prednisone – 60 mg/m2/day for 4-6 weeks followed

by alternate day steroids for 4-6 weeks.

• Tubular entities– Diabetes insipidus

• X linked or secondary to ADH resistance• Look for dilute urine in face of hypernatremia • Water deprivation test then give IV or intranasal vasopressin

– Renal tubular acidosis – normal anion gap – hyperchloremic metabolic acidosis

• Proximal or Type II – bicarbonate wasting– Failure to thrive– pH < 5.5– Serum bicarbonate usually less than 18– Remember FANCONI syndrome is RTA = glycosuria,

phosphaturia, and amino aciduria.– Treated with bicarbonate

– Distal or Type I – impaired distal acidification; pH > 5.5; may have hypokalemia and hypercalciuria

– Look for polyuria, vomiting, nephrolithiasis– Treated with bicarbonate – low dose compared to proximal

– Bartter syndrome• Hypochloremic metabolic ALKALOSIS; hypokalemia. • Look for polyuria, failure to thrive, low serum chloride and low

potassium– Kidney Stones

• Imaging of choice – spinal CT.• Most stones are radiopaque since they contain calcium. Non-

radiopaque are uric acid stones.• Cystinuria – increased urinary excretion of dibasic amino acids

• Acute kidney injury (failure)– Evaluation to determine – prerenal (perfusion);

renal (intrinsic) or post renal (obstruction)

• Chronic kidney disease– Key items – anemia, growth failure, renal

osteodystrophy– Options – dialysis and preferred renal

transplantation

March 17, 2005

Outline – Part 2

• Acute renal failure

• Chronic renal failure

• More Fluids & Electrolytes

• Tubular disorders

• Cystic kidney disease

SCENARIOA 6 year boy is diagnosed as having ALL. He is started on chemotherapy and his white blood cell count drops precipitously. The child is discharged and the family is encouraged. However, after two days at home he spikes a temperature to 39 C. The parents contact the heme/ onc fellow who tells them to come to the hospital immediately.

On arrival to the ER, the child is a bit lethargic. His BP is 60/40.

What is the most important first step in the management of this child?What are the most useful diagnostic tests?What are the possible causes of his condition?How should his condition be treated?

Acute Renal Failure (ARF) vs Pre-renal Azotemia

• Key maneuver is restore RBF to distinguish reversible pre-renal state from short-term irreversible

• Options– Bolus infusion of crystalloid solutions– Infusion of albumin– Administration of pressors– Administration of antagonists of clinical

condition as in anaphylaxis

ARF: DiagnosisPre-renal AGN ATN Obstruction

UA Marginal value

Key

RBC casts

RTEC Marginal value

SG >1.020 >1.020 1.008-1.012

1.008-1.012

UNa <20 <20 >40 >40

FENA <1% <1% >1% >1%

Uosm >400 >400 200-400 200-400

March 17, 2005

ARF: Diagnosis

• AGN– PSAGN– HSP– SLE– MPGN– Wegener’s

ARF: Diagnosis

• ATN– Unreversed pre-renal azotemia– Nephrotoxic meds– Contrast agents– High calcium, uric acid, phosphate– Rhabdomyolysis (myoglobin)– Intravascular hemolysis (hemoglobin)

ARF: Diagnosis

• Obstructive uropathy– PUV– Prune belly– Vesicoureteric reflux– Neurogenic bladder (myelomeningocele)– Megacystis/megaureter– Secondary: stones, fibrosis

• Effect of age and gender

ARF: Testing

• Key labs: BUN, creatinine, K

• EKG

• CXRay

• Renal ultrasound

• Specific blood tests based on underlying condition

ARF: Management

• Urgent issues– Potassium

• Calcium• Glucose/insulin• NOT bicarbonate

– Blood pressure: parenteral therapy• Labetalol• Nitroprusside

– ECF volume

ARF: Conservative Management

• Potassium– Diet restriction– Kayexalate

• Blood pressure– IV/PO meds

• ECF volume– Na restriction– Diuretic use – need for furosemide

ARF: Indications for Dialysis

• Refractory hyperkalemia

• Refractory hypertension

• Symptomatic ECF volume overload

• Symptomatic azotemia– Infection– Bleeding– CNS changes

ARF: Pearls

• Pre-renal azotemia and AGN are similar

• ATN and post-renal failure are similar

• Potassium kills first in ARF

SCENARIOA 6 year boy is seen at a routine physical examination. Although he has no specific complaints, his mother says he has been very listless and his appetite is very poor. He has not been playing well with his friends in play group. Although he is toilet trained he seems to be having more accidents during the night.

On examination, he looks a bit pale and tired. His height has fallen from the 50% at his last visit 18 months ago to 10%. His BP is 106/62 mm Hg.

What is the most important first step in the diagnosing this child’s problems?What are the likely causes his condition?How should his condition be treated?

CKD: Diagnosis

• Stages– CKD I: renal injury GFR >90– CKD II: GFR 60-90– CKD III: GFR 30-60– CKD IV:GFR 15-30– CKD V: ESRD

CKD: Common features

• Impact on growth

• Impact on bone: osteodystrophy

• Impact on puberty

• Impact on development – social and cognitive

CKD: Causes

• Non-glomerular– Hypoplasia/dysplasia– Reflux nephropathy– Obstructive uropathy

• PUV• Prune Belly• Neurogenic bladder

CKD: Clinical manifestations• Growth failure

– Dependent on age of onset– Dependent on level of GFR

• UTIs– Pyelonephritis

• Electrolyte abnormalities– Pseudohypoaldosteronism– Nephrogenic DI

• Neurocognitive disability

CKD: Diagnosis

• Structural assessment

• Imaging studies– US– VCUG: dye vs radioisotope– DMSA scan– Retrograde studies, etc

CKD: Diagnosis

ARFYounger child, abd mass, UTI

UAWBC, impaired concentration

US, VCUG, DMSA

Retrograde studiesCystoscopy, urodynamics

SCENARIOA 15 year old girl comes to the clinic because she has not had her period for the last 8 months. She feels tired all the time at home school and is having a hard time concentrating in school.

She is not taking any medications except for occasional NSAIDs for headaches and some vitamins. Her parents are in good health.

On examination, her height and weight are normal. Her BP is 162/98 mm Hg. She is pale and has a mild amount of edema in both legs. She has no rash or arthritis.

What is the most important first step in diagnosing this adolescent’s problem?What are the most likely causes?How should her condition be treated?

CKD: Causes

• Glomerular– FSGS– HUS– SLE– Membranoproliferative MPGN)– Alport– IgA Nephropathy– Membranous nephropathy– NOT diabetic or hypertensive nephropathy

CKD: Clinical manifestations• Growth failure

– Dependent on age of onset

• Hypertension– Role of ECF volume and PRA

• Electrolyte abnormalities– Acute– Hyperkalemia

• Edema

• Signs of underlying disease

CKD: Diagnosis

• Low value of radiology tests

• Blood tests– C3, C4, CH50– ASLO– ANA, dsDNA, Ro, La, Sm– ANCA– Anti-GBM– Renal biopsy

CRF: Management

• Nutritional supplementations– CHO deficiency

• Protein restriction– Impact on growth– Effect in more advanced CKD

• BP control– Disease progression– ACEI/ARB

CRF: Management

• Interference with renin-angiotensin aldosterone axis– Safety of ACEI even with advanced CKD– Role of combined ACEI/ARB– Effect of aldosterone antagonists

• Safety issues– Hyperkalemia– Reduction in GFR

CRF: Management

• Endocrine treatments– rhGH

• Doubles growth velocity• Minimal risk of progression

– Erythropoietin• Nearly always effective• Antibody induced pure red cell aplasia

– Calcitriol• IV route• More selective agents

CRF: Pearls

• Chronic glomerular diseases have oliguria vs chronic tubular diseases which can have polyuria and sodium loss– Nocturia and enuresis may indicate CRF

• Severity of growth failure and neurocognitive deficits are inversely related to age of onset of CRF

CRF: More pearls

• Most important feature of nutritional support is to correct low caloric intake

• Medication doses need to be adjusted as GFR declines

• Almost no form of CRF is a contraindication to transplant

SCENARIOA 10-day 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 is 38°C, has mottled skin and a capillary refill of 4 sec. The systolic blood pressure is barely palpable and the pulse is 195 beats/min. The anterior fontanelle is flat. Hemoglobin 18 g/dlWhite cell count 30,000Platelets 280,000

What are key features in the history and examination?What studies would you perform?What is your initial therapy?What is your initial diagnosis (es)?

March 17, 2005

Electrolyte Disorders: Sodium

• KEY function of Na+– ECF cation– Maintenance of intravascular compartment

• Disturbances in ECF volume are secondary to disturbances in Na+ balance

• ECF volume assessment is clinical– Reduced – see dehydration above– Increased – pulmonary and/or peripheral

edema

Electrolyte disorders: Sodium

Assess ECF

High ECF Normal ECF Low ECF

Measure serum Na

March 17, 2005

Electrolyte Disorders: Sodium

• History

• Source of Na loss

• Change in body weight

• Renal response to low ECGF volume– Oliguria– Reduced urine Na+– Reduced FENA


0

20

40

60

80

100

120

Normal Hypo Hyper

ICF

ECF


• Hypernatremia– Risk factors

• Breast feeding• Feeding errors• Impaired thirst• Impaired access to water

– Presentation• Irritability, seizures

– Treatment• SLOW• HYPOTONIC FLUIDS – 1/5 NS


• Hyponatremia– Risk factors

• Feeding errors (Keating)• Salmonella diarrhea• Increased extra-renal salt loss • Pain, anesthesia, post-operative picture• Female gender

– Presentation• Lethargy, seizures

– Treatment• ?SLOW• Correction 25 mmol/L OR 130 mmol/L over initial 48 hr


• Bad outcomes• Brain

– Hemorrhage and cerebral edema in hypernatremia

– Osmotic demyelinating syndrome and acute CNS deterioration in Hyponatremia

• DKA– ?Hyponatremia (100 glucose mg/dl 1.6 Na meq/l)– Comparison to hypernatremia

SCENARIOA 4-week old infant presents with a history of irritability, low grade fever and poor feeding. Prenatal and family history is non-contributory. On examination the infant is irritable, temp is 37°C, has dark skin and a capillary refill of 4 sec. The systolic blood pressure is barely palpable and the pulse is 195 beats/min. The anterior fontanelle is sunken. Hemoglobin 18 g/dlWhite cell count 30,000Platelets 280,000


Electrolyte Disorders: Potassium

• KEY function of K+– ICF cation– Transmembrane potential, secretion,

neuromechanical coupling

• Disturbances in K+ reflect sudden changes in serum concentration and transmembrane ratio

• Assessment is linked to cardiac impact of abnormal K+ concentration

Electrolyte disorders: Potassium

• Regulatory organs– Kidney secretion

• Na+• Urine flow rate

– Adrenal• Aldosterone

– GI tract

• Transmembrane– pH– Osmolality– Beta adrenergics– Insulin

• Diet

Potassium

• Key tests– BUN, Cr, Na, K, bicarbonate – Urine K useless– Urine Na/K ratio– Hormones

• PRA• Aldosterone


• Hyperkalemia– EKG

• Peaked T waves

– Treatment• Calcium infusion• Glucose/insulin• NOT Bicarbonate• Kayexalate• DIALYSIS

Hyperkalemia: differential diagnosis

• No real disease– Increase cells: WBC, polycythemia, thrombocytosis,

crush injury– Transmembrane

• Renal– ARF– CRF– Liddle’s

• Adrenal– Adrenal failure– Congenital adrenal hyperplasia – ambiguous genitalia– Isolated renin abnormalities

Hyperkalemia: Work-up

• BUN, creatinine, Na, K, Bicarbonate

• PRA

• Aldosterone

• Urinary Na/K ratio


• Hypokalemia– EKG

• U waves

– Treatment• Restore ECF volume to 2hyperaldosteronism• PO potassium

– Limitations: tolerance

• IV potassium– Limitation: 0.3 meq/kg/hr– Central vs peripheral IV

Hyperkalemia: differential diagnosis

• Systemic– Malnutrition

• Adrenal– Adrenal overactivity– Congenital adrenal hyperplasia– Primary renin abnormalities

• Renal– DKA– Osmotic diuresis

SCENARIOA 15 month child presents with a history of poor feeding and impaired growth. Prenatal and family history is non-contributory. On examination the infant’s height and weight are below the 5th percentile. The systolic blood pressure is 102 and the pulse is 110. The rest of the examination is normal. Na 138Cl 114Bicarbonate 16


Electrolyte disorders: acid-base

Acid load

AcuteChronic-Kidney

ProximalChronic-Kidney

Distal

RegenerateTitrated bicarbonate

Reclaim filtered bicarbonate

Lung

Large frequent doses

1-3 mmol/kg/day

March 17, 2005

Electrolyte disorders

• Anion gap

• [Na] – {[Cl] + [HCO3]}

• Normal value: 4-12

• Impact of serum albumin

Electrolyte disturbances: RTA

• Metabolic acidosis– Normal anion gap -- hyperchloremic

• Diarrhea• RTA

– High anion gap -- normochloremic• MUDPIES or KUSSMAUL• Key entities:

– DKA

– Lactic acidosis

– Uremia

– Metabolic disease

– Toxins


• Proximal– Low K – Primary– Secondary

• Glycogen storage• Wilson’s, fructose intolerance, tyrosinemiaPTH, Vitamin D• Cystinosis


• Distal– Primary – Secondary

• Transplant rejection• Drugs: amphotericin, cisplatinum• Collagen vascular disease

Electrolyte disorders: RTA

• Assessment– SMAC: Cl-– VBG: Bicarbonate– Urine: calcium, citrate– Urine anion gap: unmeasured cation (NH4+)– Xrays

Electrolyte disturbances: RTA• Treatment

• Proximal– Higher doses of bicarbonate – More frequent dosing– Exacerbation of hypokalemia with Rx

• Distal– 1-3 mmol/kg varying with age and diet – 3 doses– Stabilization of K with Rx

Electrolyte disorders: Fanconi’s

Fanconi’sSyndrome

Complete proximal tubule dysfunction

RTA GlycosuriaPhosphaturia

TRPAmino Aciduria

Electrolyte disorders: metabolic alkalosis

• Extrarenal/GI loss of K– CF

• Vomiting– NG suction– Pyloric stenosis

• Distal GI loss of bicarbonate– Chloride diarrhea

• Renal– Bartter’s– Gitelman’s– Apparent mineralocorticoid excess (AME)/licorice

March 17, 2005

Electrolyte disorders: DI

• Central

• Nephrogenic

• Risk of CNS disease– 1/12 (1/3 X ¼) of loss from ECF– Limited access to water– Altered thirst

Electrolyte disorders: DI

• Central– AVP replacement

• Nephrogenic– Adequate water intake– Low solute diet– Hydrochlorothiazide

Electrolytes: Pearls

There are three pure renal causes of FTT – azotemia, DI, and RTA

RTA causes hyperchloremic acidosis

Bartter’s and Gitelman’s differ in calcium excretion – high in former low in latter

Thank you

GOOD LUCK

metro new york / new jersey pediatric board review course pediatric nephrology june 2013

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