NOVEMBER BOARD REVIEW

Renal: Part I

Test Question

You like having 15 questions during board review instead of 10.

A. True

B. False

Hematuria

Question #1 The mother of a 5-year-old female brings her daughter to

your clinic on Monday morning because when she went potty this morning her urine was red. She is afebrile and has no complaints of dysuria or musculoskeletal pain. Her BP is 94/55 and her urinalysis is negative for blood, protein, nitrites, and leukocyte esterase. Microscopy reveals 1 RBC and no casts. You notice scratches on the girls fingers, and her mother reports that they have just returned from a friends farm and went “berry pickin” over the weekend.

Of the following, the next MOST appropriate step is: A. Reassurance B. Renal U/S C. Creatinine kinase D. BMP E. Urine culture

Hematuria 5 or more RBCs per high-power field in 3

consecutive fresh, centrifuged specimens obtained over the span of several weeks

(+) dipstick for hemeMyoglobinuriaHemoglobinuria

(-) dipstick for hemeDrugs (sulfa, nitrofurantoin, salicylates,

phenazopyridine, phenolphthalein)Toxins (lead, benzene)Food (food coloring, beets, blackberries, rhubarb,

paprika)

Glomerular Bleeding

Discolored urine RBC casts Distorted RBC morphology

Causes

Microscopic Macroscopic (Gross)

Symptomatic

Asymptomatic + proteinuria

Isolated asymptomatic

Gross Hematuria

Underlying cause is found in 56% of cases

Common causes:UTITraumaCoagulopathyCrystalluriaNephrolithiasis

Question #2 The mother of a 3-year-old male comes to clinic for follow-up of

hematuria. The results of today’s UA are: pH 6.0 3 + blood Negative for protein, nitrite, and leukocyte esterase 10 to 20 RBCs/HPF 0 WBCs

These results are similar to the UA you performed 2 weeks ago. The patients BP is 105/58, but otherwise the physical exam is normal. Being the astute clinician that you are, you ask mom about any family history of renal disease. She mentions that both of her older brothers are on dialysis.

Of the following, the MOST likely cause of this patient’s hematuria is: A. Benign familial hematuria B. Polycystic kidney disease C. Alport syndrome D. Sickle cell disease E. Ureteropelvic junction obstruction

Family History is Important! Alport syndrome

X-linked (85%), autosomal recessive, and autosomal dominant

Mutation in Type IV collagen of GBMKidney failure by 2nd or 3rd decade in malesSensorineural hearing loss Anterior lenticonusFemales may only have microhematuria

Family History is Important! Benign familial hematuria

Autosomal dominant○ But many people are unaware

Also mutation in type IV collagen of GBMMicroscopic hematuria with occasional

gross episodic hematuria (<10%)Proteinuria and HTN are unusual

Family History is Important! Sickle cell disease and trait

Occlusion of the vasa recta capillaries result in renal infarct

Hematuria more common in malesUnilateral, left more commonRecurrence in 40% of casesContributing factors

○ Hypoxia○ Acidosis○ High osmolality○ Stasis

Symptomatic Microscopic Hematuria If accompanied by elevated proteinuria on

first morning urine → higher likelihood of underlying renal disease

Clinical manifestationsNonspecific

○ Fever, malaise, weight changeExtrarenal

○ Malar rash, purpura, arthralgia/arthritis, headachesLocalized

○ Dysuria, suprapubic pain, flank pain, edema, oliguria

Question #3 The results of a urinalysis for a 13-year-old male in your

practice reveal: pH 6.0 3+ blood Negative glucose, protein, nitrite, and leukocyte esterase 5 to 10 RBCs/HPF

He has never noticed any changes in his urine, has no complaints, takes no medications, and has no family history of kidney disease.

Of the following, the MOST likely associated urinary finding is: A. Bacteriuria B. Hypercalciuria C. Hemoglobinuria D. Protein-to-creatinine ratio 1.0 E. Myoglobinuria

Isolated Asymptomatic Hematuria Rarely have significant renal disease 25% normalize within 5 years Rarely have gross hematuria Get good family history! Monitor for HTN and proteinuria Hypercalciuria

Risk for urolithiasisUrinary Ca/Cr > 0.2 or 24 hour urinary calcium

excretion > 4 mg/kg/dayMostly idiopathic

○ Consider immobilization, diuretics, vit D intoxication, hyperparathyroidism, and sarcoidosis

Question #4

A 14-year-old female has 3+ blood, 2+ protein, and 10 to 20 RBCs/HPF on urinalysis. She has no symptoms.

Of the following, the BEST next step is:A. Refer to nephrologyB. Renal U/SC. Urine cultureD. Urinary calcium-to-creatinine ratioE. Repeat UA with first morning urine

Asymptomatic hematuria + proteinuria In most cases, resolution of one or both

features Determine if proteinuria is orthostatic

First morning urine Persistent proteinuria is more indicative

of a glomerular process Refer to nephrology

Diagnostic Evaluation

Diagnostic Evaluation First stage

BP, UA +/- urine culture Second stage

Search for underlying disease especially if edema, HTN, systemic symptoms, etc.○ BMP○ ASO○ Complement○ ANA○ Hepatitis panel○ HIV○ CBC○ Hgb electrophoresis

Renal U/S, biopsy, cystoscopy when indicated Refer to nephrology unless the cause is clear (UTI, postinfectious)

Question #5 An 8 yo M presents to the ED with c/o “dark urine” for

the past 24 hours. Per Mom, this has never happened before. He is a very healthy boy, with the exception of being treated with antibiotics for a sore throat 2 weeks ago. On exam, his BP was found to be 130/82, and there was some mild periorbital edema bilaterally. Of the following, the most likely set of laboratory findings in this patient is:A. Normal complement levels; 3+ protein, no blood on UAB. Elevated complement levels; 1+ protein, 1+ blood on UAC. Low complement levels; trace protein, 3+ blood on UAD. Low complement levels; 3+ protein, no blood on UAE. Normal complement levels; no blood or protein on UA

Acute poststreptococcal glomerulonephritis (PSGN)

Pathophysiology Caused by a reaction to a nephritogenic

strain of group A beta-hemolytic Streptococcus

Multiple pathogenic mechanisms inflammation of the glomeruliDeposition of Ag-Ab complexes in the glomeruliIn situ deposition of nephritogenic Ag with

formation of immune complexesDirect activation of complement by the

nephritogenic Ag within the glomeruli

Presentation

Timeline10-14 days after pharyngitis3-6 weeks after pyoderma

Clinical featuresClassic nephritic syndrome

○ Gross hematuria○ Edema (fluid overload can pulmonary

edema)○ HTN○ Renal insufficiency

Laboratory Findings Low C3 UA

Hematuria*ProteinuriaRBC casts

BMPMild renal insufficiency

Evidence of past streptococcal infectionStreptozymeAnti-DNAase B

Question #6 Of the following, which most accurately

describes the natural course of PSGN:A. Renal function improves within 3 weeks,

complement values normalize within 8-12 weeksB. Renal function improves within 6-24 months,

complement values normalize within 8-12 weeksC. Renal function improves within 3 weeks,

complement values remain low indefinitelyD. Renal function continues to deteriorate,

complement levels remain low indefinitelyE. Renal function improves within 3 weeks,

complement values normalize within 2-4 weeks

Treatment and Prognosis

Supportive managementAntibiotics (Rx Strep infection)For Fluid overload:

○ Fluid/ Na restriction○ Diuretic therapy

Monitor electrolytes and renal functionAnti-hypertensives

Treatment and Prognosis Prognosis is excellent!

Renal function improves within 3 weeksComplement values normalize within 8-12

weeksMicroscopic hematuria may persist 6-24 months

Indications for renal biopsy:Renal function or BP abnormal for >4wksProteinuria present for >6mosSerum complement concentrations remain low

for >12wks

Enuresis

Definitions Primary nocturnal enuresis = nighttime wetting in a

child who has never been dry on consecutive nights for longer than 6 monthsDryness is expected to be achieved by 5 years of age10 to 15% of 7-year-olds still have bedwetting99% of children are dry by 15 years

Incontinence = uncontrollable leakage of urine that may be intermittent or continuous and occurs after continence should have been achieved Leakage that occurs during the day is daytime

incontinence Dysfunctional voiding = inappropriate muscle

contraction during voiding

Question #7 A 7-year-old boy has nighttime bedwetting. No one

else in the family wet the bed, but his mother his concerned about his weight and that he is constantly tired during the day. Other than being overweight, his physical exam and screening UA are normal.

The MOST likely cause of his nocturnal enuresis is:A. Genetic predispositionB. Bladder dysfunctionC. He is a “deep” sleeperD. Occult spinal dysraphismE. Obstructive sleep apnea

Causes of Nocturnal Enuresis No data to support “deep”

sleep theory

Obstructive sleep apnea↑ atrial natriuretic factor leads to increased

diuresisT & A has been shown to cure enuresis

Abnormal circadian release of ADH

Causes of Nocturnal Enuresis Bladder dysfunction

Smaller-than-normal functional bladder capacity at night

Higher bladder instability

Daytime + Nighttime = higher degree of abnormalities and treatment failure

Causes of Nocturnal Enuresis Genetics

1 parent with enuresis = 44% chance of child affected

2 parents with enuresis = 77% chance of child affected

Psychological factors30% greater chance of enuresis in kids with

ADHD Maturational delay

Fine and gross motor clumsiness, perceptual dysfunction, speech defects co-exist

Secondary Enuresis

New-onset nighttime wetting on consecutive nights after a 6-month or greater period of dryness

Usually not related to an organic cause Stressful events can be the source

Birth of a sibling, move, death in the family

EvaluationHistory Physical Labs

Nights/week Distended bladder Urinalysis +/- Urine cx

Episodes/night Fecal impaction

Fluid intake Phallus and meatus

Caffiene Labial adhesions

Polyuria, polydipsia Muscle tone

Urgency, frequency, dysuria

Reflexes and sensation

Abnormal urine stream Skin over spine (tuft of hair or sacral dimple)

History of UTIs

Constant wetness

Bowel complaints

Sleep apnea

Neuro/dev history

Question #8

An 8-year-old female is diagnosed with primary nocturnal enuresis. The parents are interested in therapy.

The MOST effective treatment for ending the enuresis is:A. DesmopressinB. Alarm therapyC. ImipramineD. AnticholinergicsE. Limiting dairy products before bed

Treatment of Nocturnal Enuresis

Behavioral Medical

Limit nighttime fluid intake Desmopressin

Limiting dairy products 4 hours before bed

Anticholinergics

Voiding before bed Imipramine

Alarm therapy Combination therapy

Alarm Therapy Most effective

Success rates as high as 66 to 70%

Most difficult to employ Must be used every

night Requires 3 to 4 months

for results Parents may need to

wake up child if the child does not wake to alarm

Offers a real cure No adverse effects

Daytime Wetting

Can be caused by stressful eventsDivorce, death in the family, abuse

Children with daytime wetting may have a difficult temperamentIncreased risk for constipation and

encopresis

Classification of Daytime Wetting Storage problem

Neurologically normal who cannot fill and storeNeurologically abnormal who have high pressure

bladderHypersensitive bladderInadequate sphincter tone

Emptying problemFailure to empty completely with little residual

urineMay be neurologic, anatomic, muscular, or

fucntional

Question #9

A 7-year-old female patient has nighttime and daytime wetting. You order a UA and urine culture. Her physical exam is normal.

Which of the following should also be included in your initial evaluation?A. Post-void residualB. VCUGC. UrodynamicsD. MRI of the spineE. Cystoscopy

EvaluationHistory Physical Labs

Age of toilet training Meatal stenosis UA

Pattern of wetting Hypospadias Urine culture

Volume of wetting Tight phimosis Postvoid residual

Times/day Female epispadias

Time of day (during play)

Labial adhesions

History of UTIs Intralabial masses

Nighttime wetting Back and sacrum

Bowel function (“skid marks”)

Rectal exam

Social history

Ectopic Ureter Females No history of day- or

nighttime dryness “Constant dribbling” Evaluate with MR

urography, CT, or IVP

Refer to pediatric urology

Manifestations of Storage Problems Urge incontinence

Frequent attacks of a strong desire to urinate countered by hold maneuvers such as squatting, dancing, and curtseying

Uninhibited bladder contractions

Dampness rather than soaking

Functional bladder capacity is usually small

Storage Problems

Overflow incontinenceInfrequent and incomplete voidingOvertime decreased sensation of the need to voidUsually large wetness

Daytime incontinenceInfrequent or delayed voiding, especially

associated with distraction or playSmall to large urine lossAssociated with behavior problemsDevelopment after continence should prompt

referral

Storage Problems

Urinary frequencySudden need to urinate very frequently,

sometime up to 30 times per dayAges 3 to 8Self-limitedRelated to psychological stressors

Manifestations of Emptying Problems Lazy bladder syndrome

Void 3 or fewer times a day Must strain abdominal muscles to void Intermittent stream and cannot empty bladder completely Recurrent UTIs Constipation

Detrusor sphincter dyssynergia (DSD) Inappropriate contraction of the

external urethral sphincter during bladder

contraction Staccato type of voiding Post-void residual “spinning-top urethra”

Emptying Problems

Hinman syndromeNonneurogenic neurogenic bladderLongstanding DSD leads to detruser

decompensationCan lead to renal insufficiency and failure

Other Types of Daytime Wetting

Giggle incontinenceComplete bladder emptying with extreme

laughterFemales age 10 to 20No associated voiding abnormalitiesCataplectic phenomenon that exists in

patients with narcolepsy

Question #10 The mother of a 5-year-old female complains that

her daughter’s underwear is always damp, even just after urinating. The girl states that she feels dribbling soon after she goes pee-pee. The patient is overweight, and sometimes has trouble balancing on the toilet.

The MOST likely cause of her symptoms is:A. ConstipationB. Vaginal refluxC. Urinary tract infectionD. Lazy bladder syndromeE. Daytime incontinence

Other Types of Daytime Wetting

Vaginal refluxDribbling associated with urine being trapped in

the vaginal introitus after voiding and leaking out when the child walks away

Often seen in overweight and young girlsAlso seen with vaginal adhesionsUnderwear is “always damp”Diagnose by postvoid vaginal exam with Valsalva

eliciting urine from the introitusTreat by having patient sit backward on toilet and

keep thighs separated

Therapy Behavioral therapy

Encourage voiding q 2 hoursAvoid bladder irritants (caffiene, carbonated

drinks, citrus-content beverages, red dyes)Sit on the toilet 30 minutes after a large meal

with feet supported for 10 min (pelvic floor relaxation)

Bowel programMost patients have some form of constipationHigh-fiber dietMedications (polyethylene glycol)

Therapy

Anticholinergic agents for urinary frequency

Biofeedback for emptying problems (DSD, etc)

Alpha-blocking drugs for emptying problems

Nephrotic syndrome

Nephrotic Syndrome

Heavy proteinuria and hypoalbuminemia Edema Hyperlipidemia

Pathophysiology of Proteinuria

Edema

Pathophysiology of Edema Classic theory:

Decrease in plasma oncotic pressure secondary to hypoalbuminemia water extravasation into the interstitial space decrease in intravascular volume activation of the RAA system aldosterone increases reabsorption of Na edema

Not fully supported by clinical evidencePlasma volume decreased only in some childrenStudies have failed to demonstrate elevations in

the RAA hormones

Pathophysiology of Hyperlipidemia Increased VLDL, IDL, and LDL

secondary to:Overproduction in the liver due to low

plasma albumin concentrationLow oncotic pressure and impaired

catabolism of apolipoprotein B and VLDL chylomicrons

Epidemiology Incidence: 2.7 new cases/ 100,000 children per

year Sex predilection: 2:1 (males:females) in

childhood; sex difference wanes by adolescence

Increased familial incidence (siblings) Mean age of onset 3.4 yrs (Asians) and 4.2 yrs

(Europeans) African American and Hispanic children have

greater incidence of nephrotic syndrome, a more severe form and poorer prognosis

Differential Diagnosis

ClassificationPrimary Secondary

Minimal change nephrotic syndrome (MCNS) 85% of cases

Focal segmental glomerulosclerosis (FSGS) 10-15% of cases

Membranous nephropathy (MN) 4% of cases

Question #11

Which of the following is the best prognostic indicator in children with nephrotic syndrome?A. Age< 10 yo at time of diagnosisB. UPr/Ucr <4.0C. Steroid responsivenessD. Serum creatinine <1.1E. Serum albumin>2.0

Further Classification…

Steriod-sensitive nephrotic syndromeMCNS

Steriod-resistant nephrotic syndromeCongenital nephrotic syndromeFSGSMN

Minimal Change Nephrotic Syndrome

Histopathology

Light microscopy glomeruli normal Electron microscopy fusion of the

epithelial foot processes

Clinical Features

Additional symptoms:AnorexiaIrritabilityFatigueAbdominal discomfortDiarrhea

Respiratory tract infection preceding onset common (not likely pathogenic)

History of allergy is reported in 50% of children with MCNS

Question #12 A 4 yo M presents to your office with a 3 day h/o

diarrhea, irritability, and poor PO intake. His eyelids have also been swollen for 2 days, which Mom attributed to “pink eye.” This morning, she noticed that his scrotum appeared very swollen and became concerned. You suspect nephrotic syndrome. A urine protein to creatinine ratio greater than what value would confirm your suspicion?A. 0.2B. 0.5C. 1.0D. 2.0E. 3.0

Laboratory Features

Plasma protein markedly reducedAlbumin <2.5

ProteinuriaEstimation by dipstickConfirmation by quantitative measurement

○ 12 or 24 hour timed urine collection>50mg/kg/d or 40mg/m2 indicative of nephrotic

syndrome

○ UPr/UcrNormal: Age >2 yo= <0.2, Age 6mos-2 yrs= <0.5Nephrotic syndrome: >3.0

Laboratory Features

Elevated cholesterol, TG, and lipoproteins

Low NaHyperlipidemiaRetention of water (increased ADH)

Low CaHypoalbuminemia

Question #13 A 4 yo F presents with a 2 day h/o worsening

periorbital and labial swelling. Her BP is normal and PE unremarkable except for the above noted edema. Her UA shows 3+ protein and trace blood with 0-2 RBC/hpf. BUN and Cr are normal along with C3. Albumin is 2.1 and LDL 165. Of the following, which is the next best step in her management? A. Renal biopsy B. Prednisone therapy C. Dialysis D. Bilateral nephrectomy E. Cyclosporine therapy

Question #14 What anticipatory guidance should you give the

patient’s family regarding the course and prognosis of MCNS?A. Your daughter will likely go on to develop ESRDB. After one course of steroids, your daughter will likely not

need anymore treatment for this illnessC. Your daughter will likely respond to the steroids; however,

there is a strong probability that she will eventually relapseD. Your daughter will not likely to respond to the steroids

and will need a renal biopsyE. Your daughter will likely be admitted to the hospital

several times in the next month from complications of this illness

Treatment and Course

Indications for Renal Biopsy

Congenital Nephrotic Syndrome (CNS)

Presentation Massive proteinuria that starts during fetal life Elevated AFP with normal US findings Most affected children born preterm (~2500g) Edema and abdominal distension evident

soon after birth Albumin usually <1.0

Also losing many other proteins metabolic disturbances (lipid abnormalities) atherosclerotic changes as early as the first postnatal year

Treatment

InitialSustaining a good nutritional stateControlling edemaPreventing complications

Uni-or bilateral nephrectomyTo control massive loss of protein

Eventual kidney transplantCNS can recur in transplanted kidneys

Focal Segmental Glomerular Sclerosis (FSGS)

Histopathology

Initially, is sclerosis of some of the glomeruli (focal) that involves only part of the glomerular tuft (segmental)

Progresses to

global, extensive

glomerulosclerosis

and tubular atrophy

Causes Heterogeneous

Genetic ○ Small percentage

IdiopathicHeroin-induced

nephropathyAIDSMultiple myelomaAlport syndromeReflux nephropathyDiabetic nephropathyObesity

Clinical Features

Major signs edema and albuminuria, but HEMATURIA more frequent in FSGS than in MSNS

FSGS cannot be diagnosed at presentationMost children are started on prednisone

therapy and lack of response at 4 weeks prompts renal biopsy diagnosis of FSGS

20% are responsive to prednisone

Clinical Features (con’t)

Disease progression variableESRD reached b/t 2-10 yrs In patients who rapidly progress to ESRD,

there is a high likelihood of recurrence in the transplanted kidney

Treatment NO DEFINITIVE EVIDENCE THAT ANY

DRUG IS EFFECTIVE!!Pulse methylprednisolone: minimal benefitAlkylating agents (cyclophosphamide): little

therapeutic effectCyclosporine

○ Induces remission in 25-50% in those with steroid-resistance

○ Patients relapse promptly when the drug is discontinued

○ Serious adverse effects if the drug is continued for long periods

Treatment (con’t)

Recurrence in transplanted kidney is a major problemReported in up to 50% of transplanted

children with FSGSRisk factors:

○ Older than age 6 at onset○ Progression to ESRD in less than 3 years

Treated with cyclosporine +/or plasmapheresis○ Partial or total remission in a minority of cases

Membranous Nephropathy

Histopathology

Diffuse, irregular thickening of the GBM in the absence of any signs of inflammationElectron microscopy: electron-dense

deposits distorting the GBM

Cause Infections

Hepatitis BMalariaSyphilis

AI diseaseSLECrohn disease

TumorsWilms tumorNeuroblastoma

Idiopathic Drugs

Clinical Features Very rare in children but can present at any

age Presentation

Proteinuria or nephrotic syndrome(Hematuria and HTN rare)

TreatmentSteroids and immunosuppressive drugs (not good

results) Clinical course

Spontaneous remission in 25-50%25-30% develop renal insufficiency

Question #15

A 5 yo F with h/o MCNS presents to the ED with a one day h/o fever to 102, chills and mild abdominal pain. What illness must you consider in this patient?A. PneumoniaB. Adenovirus gastroenteritisC. Shigella gastroenteritisD. PeritonitisE. Pancreatitis

Complications of Nephrotic Syndrome ARF Thromboembolic events

Due to loss of antithrombin III and protein S in the urine

Antiphospholipid syndrome Infections

Due to loss of factor B, a decrease in IgG and impaired T-cell function

Most common infection= peritonitis○ Streptococcus pneumoniae (decreasing with

vaccination)

Complications of Nephrotic Syndrome Anasarca and pulmonary edema Stunting of growth

Side effect of prolonged steroid use Reduced bone mineral density

SteroidsVit D deficiency

Ancillary Therapies Diuretics +/- salt-poor albumin

Edema only requires treatment when associated with severe ascites, peritonitis, respiratory distress or heart failure

Albumin usually given when serum albumin <1.5 ACE inhibitors/ ARBs Statins Vaccination

Conjugated pneumococcal vaccine Low Na diet Vitamin D and Ca supplementation