Transcript The Kidney in Bardet-Biedl Syndrome

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 dystrophy
Post-axial polydachtyly
Truncal obesity
Learning disabilities
Hypogonadism
Renal anomalies
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
Secondary Features
Speech delay/disorder
Behavioral abnormalities
Eye abnormalities
Brachydactyly/syndactylly
Ataxia/poor
coordination/imbalance
Mild hypertonia
Diabetes mellitus
Orodental abnormalties
Cardiovascular anomalies
Hepatic Involvement
Craniofacial dysmorphisms
Hirschsprung disease
Anosmia
Bardet-Biedl syndrome and the kidney
Bardet-Biedl syndrome and the kidney
Bardet-Biedl syndrome and the kidney
Electron micrograph courtesy of Dr John A.
Sayre, University of Newcastle upon Tyne
From Pediatr Nephrol (2006) 21: 1369–1376
Lisa M. Guay-Woodford
So how does the BBS
affect kidney health?
Function
Urine Volume
Removal of waste products
Blood pressure control
Structure (anatomy)
Size of Kidneys
Drainage of urine
Filters and Tubes
Cysts
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
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Impaired kidney function is highly
variable
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Differences between family
members
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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
•Chronic kidney disease in BBS
• Hypertension is present but
• Hypertension
• Proteinuria (protein in urine)
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• Hematuria (blood in urine)
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• Anorexia (lack of appetite)
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• Fatigue
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• Anemia (low blood count)
• Declining urine output and often
complete loss of urination after
dialysis is started
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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
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Avoid non-steroidal antiinflammatory
medications (NSAIDS)
Avoid dehydration
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Potential benefit of
increased hydration
Treat UTI promptly
Control blood sugar &
cholesterol
Monitor blood pressure
and treat if needed
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NSAIDS (partial list)
Ibuprofen
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Advil, Motrin,
Pediaprofen
Naproxen
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Aleve, Anaprox
Aspirin
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Bayer, Bufferin
Celecoxib
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Celebrex
Ketorolac
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Toradol
The kidneys and high blood pressure in BBS
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Kidney disease and
high blood pressure
(hypertension) go hand
in hand
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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
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Kidney disease (hypertension is common in other cystic kidney diseases such
as PKD)
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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
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Potential benefit to targeting the 50th percentile
• Preferred medications- ACE inhibitors (prils)
& ARBs (tans)
• Discourage thiazides, beta blockers and
perhaps calcium channel blockers
So how does the BBS
affect kidney health?
Function
Urine Volume
Removal of waste products
Blood pressure control
Structure (anatomy)
Size of Kidneys
Drainage of urine
Filters and Tubes
Cysts
Bardet-Biedl syndrome and the fetal kidney
•Fetal imaging may show
enlarged kidneys that may be
mistaken with other disorders
• Autosomal Dominant Polycystic
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Kidney Disease
Autosomal Recessive Polycystic
Kidney Disease
Meckel Gruber syndrome
“Meckel-like” syndrome without
encephalocele
Joubert syndrome
Bardet-Biedl syndrome and the fetal kidney
The clinical evolution in one patient
30 Weeks Gestation
Bardet-Biedl syndrome and the fetal kidney
The clinical evolution in one patient
Newborn (1 day old)
Bardet-Biedl syndrome and the fetal kidney
The clinical evolution in one patient
Same child at 8 years old
Bardet-Biedl syndrome and the fetal kidney
The clinical evolution in one patient
Bardet-Biedl syndrome and the kidney
•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 kidney
Bardet-Biedl syndrome and the kidney
Bardet-Biedl syndrome and the kidney
Bardet-Biedl syndrome and the kidney
Bardet-Biedl syndrome and the kidney
Bardet-Biedl syndrome and the kidney
Reported structural abnormalities in BBS
• Calyceal diverticulum
• Ectopic Kidney (kidney in
• Calyceal blunting
abnormal location)
• Vesicoureteral reflux
• Bladder outlet obstruction
• Fetal lobulation
• Renal cysts
• Dysplastic kidneys (malformed
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kidney tissue)
Renal agenesis (absent kidney)
Kidney infections
Kidney scars
Horseshoe Kidney (two kidneys
fused together)
• Including severe meatal stenosis &
posterior urethral valves
• Urogenital sinus
• Vesicovaginal fistulae
(connection between bladder
and bowel)
• Kidney stones
• Kidney cancers
Bardet-Biedl syndrome and the kidney
• 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?
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Maybe
• What are my options if my child or I develop
kidney failure (CKD stage 5)?
Bardet-Biedl syndrome and kidney function
When dialysis is needed
Bardet-Biedl syndrome and renal transplantation
•Transplantation in BBS
has some specific issues
but it is absolutely
possible
•Reported complications
• Increased risk of UTI
• Previously unidentified
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• Need for comprehensive
evaluation of urogenital
system
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urogenital abnormalities
Obesity even in previously nonobese 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
So how does the BBS
affect kidney health?
Function
Urine Volume
Removal of waste products
Blood pressure control
Structure (anatomy)
Size of Kidneys
Drainage of urine
Filters and Tubes
Cysts
Questions?
BBS and renal disease in family members
•Beales, et al in his 1999 article in the
•Hjortshoj, et al in 2007 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.
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.