the kidney in bardet-biedl syndrome robert haws, m.d. pediatric nephrology marshfield, wisconsin

The Kidney in Bardet-Biedl Syndrome

Robert Haws, M.D.Pediatric Nephrology

Marshfield, Wisconsin

Bardet-Biedl Syndrome

Everything important that I have learned about Bardet-Biedl syndrome I have learned from my friends- the children and their families that allow me to be their doctor

Diagnostic Criteria

Primary Features

Rod-cone dystrophyPost-axial polydachtylyTruncal obesityLearning disabilitiesHypogonadismRenal anomalies

Secondary Features

Speech delay/disorderBehavioral abnormalitiesEye abnormalitiesBrachydactyly/syndactyllyAtaxia/poor coordination/imbalanceMild hypertoniaDiabetes mellitusOrodental abnormaltiesCardiovascular anomaliesHepatic InvolvementCraniofacial dysmorphismsHirschsprung diseaseAnosmia

Diagnosis of BBS based on four primary features or three primary features plus two secondary features

Based on the pioneering work of Dr Philip Beales

Bardet-Biedl syndrome and the kidney


Electron micrograph courtesy of Dr John A. Sayre, University of Newcastle upon Tyne

From Pediatr Nephrol (2006) 21: 1369–1376Lisa M. Guay-Woodford

So how does the BBS affect kidney health?

Structure (anatomy) Size of Kidneys Drainage of urine Filters and Tubes Cysts

Function

Urine VolumeRemoval of waste products Blood pressure control

Bardet-Biedl syndrome and urine output

•Impaired ability of the kidney to concentrate urine • Polyuria & Polydipsia• May be present in the absence of

impaired kidney function• Fluid restriction is not a valid

recommendation• Importance of extra fluid on “sick

days”• Enuresis

• Avoidance of DDAVP• Need to evaluate for posterior urethral

valves and meatal stenosis in boys and detrusor instability of the bladder

From Harnett et al. NEJM 319(10); 616

From Putoux A, et al. Pediatric Nephrology (2012) 27:7-15

Bardet-Biedl syndrome and kidney function

• Impaired kidney function is highly variable

• Differences between family members

• Complex genotype/phenotype relationship?

• 10% reach CKD stage 5* in pediatric years

• 25% reach CKD stage 5* by 48 years (O’Dea et al.)

• May not be recognized in a timely manner

• Little things can make a difference* CKD stage 5 (person promptly needs dialysis or

kidney transplant)Imhoff, O. et al. Clin J Am Soc Nephrol 6:22-29, 2011

Bardet-Biedl syndrome and kidney function

•“Typical” Chronic kidney disease• Hypertension• Proteinuria (protein in urine)• Hematuria (blood in urine)• Anorexia (lack of appetite)• Fatigue• Anemia (low blood count)• Declining urine output and often

complete loss of urination after dialysis is started

•Chronic kidney disease in BBS• Hypertension is present but

usually not severe• Proteinuria usually mild• Hematuria uncommon• Anorexia does not develop• Symptoms of fatigue are often

absent• Anemia often milder• Decline of kidney function is

usually gradual and urine output remains present even on dialysis

Common sense ways to preserve kidney function in Bardet-Biedl Syndrome

• Avoid non-steroidal anti-inflammatory medications (NSAIDS)

• Avoid dehydration• Potential benefit of

increased hydration

• Treat UTI promptly• Control blood sugar &

cholesterol• Monitor blood pressure

and treat if needed

• NSAIDS (partial list)• Ibuprofen• Advil, Motrin,

Pediaprofen• Naproxen• Aleve, Anaprox

• Aspirin• Bayer, Bufferin

• Celecoxib• Celebrex

• Ketorolac• Toradol

The kidneys and high blood pressure in BBS

• Kidney disease and high blood pressure (hypertension) go hand in hand

• Hypertension is common in BBS even in childhood

Imhoff, O. et al. Clin J Am Soc Nephrol 6:22-29, 2011

Why is hypertension common in BBS?Potential explanations

• Kidney disease (hypertension is common in other cystic kidney diseases such as PKD)

• Sleep Apnea• Obesity• Dietary• Family genetics• Metabolic (e.g. high uric acid levels)• Inflammatory factors

Thoughts on treatment of hypertension

• Encourage your doctor to treat the hypertension• Potential benefit to targeting the 50th percentile

• Preferred medications- ACE inhibitors (prils) & ARBs (tans)

• Discourage thiazides, beta blockers and perhaps calcium channel blockers



Function


Bardet-Biedl syndrome and the fetal kidney

•Fetal imaging may show enlarged kidneys that may be mistaken with other disorders• Autosomal Dominant Polycystic

Kidney Disease• Autosomal Recessive Polycystic

Kidney Disease• Meckel Gruber syndrome• “Meckel-like” syndrome without

encephalocele• Joubert syndrome

Bardet-Biedl syndrome and the fetal kidneyThe clinical evolution in one patient

30 Weeks Gestation


Newborn (1 day old)


Same child at 8 years old


•A variety of urinary tract abnormalities have been identified in Bardet-Biedl syndrome• We don’t know how common

urinary tract problems are present in BBS because of incomplete investigation

• Probably 50% or more of patients with BBS will have an identified urinary tract abnormality

• A variety of abnormalities have been reported

Bardet-Biedl syndrome and the kidneyReported structural abnormalities in BBS

• Calyceal diverticulum• Calyceal blunting• Fetal lobulation• Renal cysts• Dysplastic kidneys (malformed

kidney tissue)• Renal agenesis (absent kidney)• Kidney infections• Kidney scars• Horseshoe Kidney (two kidneys

fused together)

• Ectopic Kidney (kidney in abnormal location)

• Vesicoureteral reflux• Bladder outlet obstruction

• Including severe meatal stenosis & posterior urethral valves

• Urogenital sinus• Vesicovaginal fistulae

(connection between bladder and bowel)

• Kidney stones• Kidney cancers


• Should imaging of the urinary tract occur in all individuals with BBS?• Yes, at least a renal ultrasound in everyone with BBS• Additional studies should be considered when urinary tract

infections, bedwetting, blood in the urine or pain or discomfort in the abdomen is present and of course if the kidney function is impaired

Bardet-Biedl syndrome and kidney failure

• At what age does this happen?• Highly variable from infancy to never

• Can the different BBS genes predict kidney failure?• Maybe

• What are my options if my child or I develop kidney failure (CKD stage 5)?

Bardet-Biedl syndrome and kidney functionWhen dialysis is needed

Bardet-Biedl syndrome and renal transplantation

•Transplantation in BBS has some specific issues but it is absolutely possible• Need for comprehensive

evaluation of urogenital system

•Reported complications• Increased risk of UTI• Previously unidentified

urogenital abnormalities• Obesity even in previously non-

obese pretransplant patients• Tacrolimus & Steroid induced

DM• Drug induced mood changes• Hyperlipidemia• Cholelithiasis (gall bladder

stones)

Bardet-Biedl syndrome and renal transplantation

• The pros and cons of steroid free renal transplantation• Pros• Decreased appetite stimulation• Decreased mood alterations• Decreased infection risk• BBS is a non-immune based disorder

• Cons• Increased rejection risk• May need increased doses of other agents including tacrolimus



Function


Questions?

BBS and renal disease in family members

•Beales, et al in his 1999 article in the Journal of Medical Genetics identified in 3 individuals in 180 (1 in 60) family members with renal cell carcinoma•Renal dysgenesis/agenesis in 1.6% of the family members compared to 0.1% in the general population •Croft et al in 1990 in the American Journal of Medical Genetics that there was an increased risk of obesity, hypertension and renal disease.

•Hjortshoj, et al in 2007 in the American Journal of Genetics examined 116 patients with BBS and 428 relatives and found an overall tendency towards fewer cancers than anticipated.•Webb, et al in 2009 in Kidney International reported that there was no increase in hypertension, chronic kidney disease or obesity compared to the general population.

the kidney in bardet-biedl syndrome robert haws, m.d. pediatric nephrology marshfield, wisconsin

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