Download INHERITED RENAL DISORDERS

INHERITED RENAL
DISORDERS
AUTOSOMAL DOMINANT
POLYCYSTIC KIDNEY DISEASE
• Prevalence: 1:300 to 1:1000
• 90% of cases are inherited, 10% are
sporadic
• Only1 to 5% nephrons developed cysts
• Cysts are in medulla and cortex
• ADPKD causes symptoms in third or
fourth decade
• 50% of patients developing ESRD by age
60
RENAL Symptoms of ADPKD
• Chronic flank pain
• Acute pain indicates:
infection (pyelonephritis- pyocyst)
urinary tract obstruction
sudden hemorrhage into cysts
• Hematuria
• Impaired renal concentrating ability
• Nephrolitiasis in 15%to 20%
• Hypertension in 75% adults
Diagnostic Criteria- Ultrasound
• Age 15-29 ………..2 cysts in one or both
kidneys
• Age 30 to 59 …….2 cysts in each kidney
• Age >60 ………….4 cysts in each kidney
EXTRARENAL SYMPTOMS
• CYSTS in: Liver
Spleen
Pancreas
Ovaries
• Intracranial aneurism
• Colonic diverticular disease
• Mitral valve prolapse
Factors affecting progression to
End Stage Renal Failure
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Hypertension
Recurrent Haematuria
UTI (in men)
Massive Liver cystic Disease (mostly
women)
• More than 3 pregnancies
• Age at symptomatic diagnosis
• Sickle Cell Trait
Autosomal recessive (infantile) polycystic
kidney disease
• Infants, adolescents, young adults
• 1 in 20,000 affected
• 1 in 10,000 in Finland
• Up to 50% livebirths die within hours of birth
• Those that survive neonatal period – 50% alive
at 10 yo
• Most severe forms early in life
• Less severe forms present later
– Always bilateral
– Always congenital hepatic fibrosis
• AR – 1 in 4 chance – neither parent shows signs
• Ch. 6 identified in all forms
Clinical features
• Renal and liver pathology inversely related
• Oligohydramnios
• Potter’s facies
• Respiratory distress –pulmonary
hypoplasia
Histopathology
• Retain fetal lobulation
• Subcapsular cysts
• Radial cortical cysts –
dilated tubules
Evaluation
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In utero US
– Oligohydramnios, enlarged
kidneys
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IVP
– Medullary streaking (Sunburst
pattern) – due to dilated
collecting tubules
– Dense nephrogram
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US – microcysts
• Liver biopsy if necessary
• Detailed family history
• Genetic counselling
MEDULARY SPONGE KIDNEY
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0.5 to 1% of all IVP
Male and female affected equally
Dilatation in collecting ducts
In 70% bilateral renal involvement
It presents in third or fourth decade with:
kidney stone
infection
hematuria
• Diagnosis with: IVP
• Renal function is normally preserved
• Relatively common and benign, present at
birth and not usually dx’d until age 40-60
• Characterized by widening and cystic
dilatation of distal collecting tubules
• 70% bilateral, maybe affecting all papillae
• Infection and calculi occasionally seen as
result of urinary stasis in the tubules
• Pts present with:
– Hematuria
– Recurrent UTIs
– Nephrolithiasis
• UA may show decreased urinary
concentrating ability (due to tubule
damage)
• Treatment
– No known therapy
– Increase fluids to prevent stone formation
– Treatment directed toward complications
• Pyelonephritis
• Renal calculi
• Only small percentage of pts develop
complications…overall prognosis is good
Medullary Cystic Disease
• A rare, familial dz that may become
symptomatic during adolescence
• Manifested by many small cysts scattered
through the renal medulla
• Pts may present with pallor, polyuria, and
lethargy
• May later develop HTN
Labs •
– UA shows inability to concentrate urine
– CBC to confirm anemia
– Chem panel to check phosphate, sodium,
BUN, creatinine levels
• Rad
– US and CT scan to dx
• Tx
– No current medical therapy to prevent
progression to ESRD
– Adequate water and salt replacement
essential to replenish renal losses
– Renal transplantation
Liddle syndrome
• Rare autosomal dominant disorder
• Presented with:
hypertension
hypokalemia
metabolic alkalosis
• Renin and aldostrone are suppressed
• Caused by activating mutations in
amiloride-sensetive sodium channel
Bartter’s syndrome
• Bartter’s syndrome is usually diagnosed in
childhood, sometimes associated with
growth and mental retardation. The defect
is impaired NaCl reabsorption in the loop
of Henle. Findings are similar to
administration of a loop acting diuretic:
– Salt loss leading to volume depletion and
activation of the renin-angiotensin system
– Increased urinary calcium
Bartter’s syndrome
• Presented with:
normal blood pressure
hypokalemia
metabolic alkalosis
• Renin and aldostrone are activated
• Caused by mutation in frusomide sensitive
channel
• Weakness, muscle cramp, polyuria
• 3 or 4 types of Bartter’s have been
identified:
• Defects in the luminal Na-K-Cl transporter
• Defects in the luminal potassium channel
• Defects in the basolateral chloride channel
Gitelman’s syndrome
• Like Bartter’s an autosomal recessive disorder,
but not usually diagnosed early in life.
• Findings mimic administration of a thiazide
diuretic: the defect is in the Na-Cl transporter.
• Patients may complain of polyuria, cramps.
• They do not have hypercalciuria, but typically
have low serum magnesium levels.
• Diagnosis is made by history as well as
lab findings. Lab findings are
indistinguishable from thiazide use:
– Hypokalemia, hypomagnesemia, increased
renin and aldosterone levels, decreased
urinary calcium.
– Genetic screening?
Gitelman’s syndrome: treatment
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Potassium
Magnesium
Aldactone or amiloride
ACEI’s
NSAIDS of no benefit
Continues to require very large doses of KCl,
and is on amiloride.
• Magnesium levels have consistently been low or
low normal.
RENAL TUBULAR ACIDOSIS
• Disorder of renal acidification out of
proportion to the reduction in GFR
• Hyperchloremic metabolic acidosis with
normal serum anion gap
• There are multiple forms of RTA
ALPORT SYNDROME
• The most common inherited nephritis
• X-linked
• Defect in the gene for the a5 chain of type
IV collagen (major component of GBM)
• EM: fragmentation and lamellation in GBM
• Deafness in 30 to 50%
• Ocular lesion in 15 to 30%
Thin
segment
Thick
segment
Note the abnormal appearance of the glomerular
basement membrane (GBM) typical of Alport's syndrome,
including irregular contours, areas of thinning, and
marked thickening and splitting with inclusion of
electron-dense granules in electron-lucent areas
BLADDER CANCER
• Cancers occurred 90% in bladder, 8% in pelvic, 2% in
ureter & urethra
• Male/female=4/1
• Withes/ blacks=2/1
• Risk factors are: smoking
aniline dyes
drugs
radiation
infection
• Symptoms: gross hematuria, irritative symptoms
• Diagnosis: urine cytology, CT scan, IVP
RENAL CELL CARCINOMA
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90% Kidney cancer
Male/Female=2/1
Incidence peaks between the ages of 50 to 70
Risk factors: smoking
obesity
acquired cyst in ESRD
tuberous sclerosis
VHL
• SYMPTOMS: Hematuria
abdominal pain
abdominal mass
fever
Weight loss
anemia
varicocele