Adult polycystic kidney disease
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Transcript of Adult polycystic kidney disease
Adult polycystic kidney disease
BY DR.K.PRATHYUSHA
UNIT-M2
PKD : multisystemic; progressive hereditary disorder characterized by cyst formation and enlargement in the kidney & other organs (eg, liver, pancreas, spleen).
Potter classification : type 1- ARPKD; type 2- multicystic dysplastic kidney disease; type 3- ADPKD
ADPKD-Genetic disorder mediated by mutations in 2 different genes
Incidence:
Autosomal dominant 1:500-1000 live births PKD1(85%)>PKD2(15%)
Autosomal recessive 1:6000-40000 live births
Genes : mutation
Gene Protein Chromosome
ADPKD1 polycystin 1 short arm 16
ADPKD2 polycystin 2 long arm 4
ARPKD fibrocystin/polyductin 6
Severity -PKD1 >PKD2 ARPKD>ADPKD
Median age of ESRD
PKD1-50 yrs
PKD2-70yrs
If atleast 1family member developed ESRD <55yrs then highly predictive of PKD1
If ESRD<75yrs then predictive of PKD2
Etiology & Pathogenesis
Disordered function of polycystins-defects in primary cilia- is basis for cyst formation
Polycystin 1 may regulate tubular epithelial cell adhesion and
differentiation; polycystin 2 may function as an ion
channel, with mutations causing fluid secretion into cysts.
Mutations in these proteins may alter the function of renal
cilia, which enable tubular cells to sense flow rates.
Cystogenesis
leading hypothesis -tubular cell proliferation & differentiation
are linked to flow rate & that ciliary dysfunction leads to
cystic transformation.
Early -tubules dilate & slowly fill with glomerular filtrate.
Eventually, the tubules separate from functioning nephron
& fill with secreted rather than filtered fluid, forming cysts.
In general
How cysts develop - is not known
Due to disruption of signalling pathways regulated by primary cilium like intracellular Ca2+ ; cAMP ; planar cell polarity Cysts arise from nephrons & collecting tubules - they communicate ; normal parenchyma exists b/w cysts
cAMP - cyst growth & overall enlargement
transepithelial secretion of Cl through apical CFTR channels - Fluid secretion into cyst
Cystogenesis
Signs & symptoms
1. Most common symp - pain in back & sides
pain can be due to:
Enlargement of one or more cystsBleeding: confined inside the cyst or lead to gross hematuria
with passage of clots or a perinephric hematoma
UTI (eg, acute pyelonephritis, infected cysts, perinephric abscess)
Nephrolithiasis and renal colicRarely, a coincidental hypernephromaDull aching pain due to cysts in liver
abdominal pain in patients with ADPKD may be a diagnostic challenge.
2. Other physical symptoms seen in early-stage ADPKD : fatigue, breathlessness, weakness, and malaise
3.Hematuriafrequently the presenting manifestation and usually is self-
limited, lasting 1 week or less.
Polycystic kidneys are unusually susceptible to traumatic injury, with hemorrhage occurring in approximately 60% of individuals.
Mild trauma can lead to intrarenal hemorrhage or bleeding into the retroperitoneal space accompanied by intense pain that often requires narcotics for relief.
On Examination:
Hypertension: common early manifestation in which increased DBP is the rule; Palpable, bilateral flank masses: In advanced ADPKDNodular hepatomegaly: In severe polycystic liver diseaseRarely, symptoms related to renal failure (eg, pallor, uremic
fetor, dry skin, edema)Clinical course - severe early then little less as renal
insufficiency progresses
Complications
Both renal & extrarenal
Renal include :
1. HTN
2. Hematuria & infection
3. Nephrolithiasis
4. Renal failure
HTN
Extrarenal include :
1. Hepatic & pancreatic cysts
2. Cardiac valve defects - MVP; TR; AR
3. Intracranial aneurysms-saccular “berry”
4. Azotemia - seminal vesicle cysts
5. Hernias
Liver/GI complications
Liver cysts -94% common mostly asymptomatic
Marked hepatomegaly results in heaviness , pain
Hepatic cyst infection more serious than renal cyst
CA 19-9 marker for hepatic cyst infection
Intracranial aneurysms
90% in ant.circulation
10% in post.circulation(great risk of rupture)
Mean age of rupture is less in adpkd compared to general
Diagnosis
1. Routine lab tests
2. Genetic testing
3. Imaging studies(gold standard) : includes
USG
X-RAY
CT & MRI
Ultrasound
Technique of choice
Screening of family members
Exploring extrarenal features like hepatic cysts
Ultrasonographic diagnostic criteria for ADPKD1
At least 2 cysts in 1 kidney or 1 cyst in each kidney in an at-risk patient younger than 30 years
At least 2 cysts in each kidney in an at-risk patient aged 30-59 years
At least 4 cysts in each kidney for an at-risk patient aged 60 years or older
USG diagnostic criteria for ADPKD in patients with a family history but unknown genotype are as follows
Three or more (unilateral or bilateral) renal cysts in patients aged 15-39 years
Two or more cysts in each kidney in patients aged 30-59 years
Fewer than 2 renal cysts in the findings provides a negative predictive value of 100% and can be considered sufficient for ruling out disease in at-risk individuals older than 40 years.
X-RAY
Early stages - normal
Enlargement of kidneys -
outline may be lost
Curvilinear and ring like
opacities may be seen
Ct scan
Not routine
Useful in doubtful & complicated cases
MRI
Not routine
Helpful to differentiate b/w rcc from simple cysts
Best tool to monitor kidney size after Rx to assess progress
MRA
Not routine
Preferred for diagnosing intracranial aneurysms
Indications :
1. Family h/o; past h/o of stroke
2. s/s of intracranial aneurysms
Differential diagnosis
1. Multiple simple cysts
2. Infantile PCKD
3. Medullary cystic disease/nephronopthisis
4. Von hippel lindau disease:cerebellar hemangioblastoma+ retinal hemangiomas + occasionally pheochromocytomas
5. Acquired uremic cystic disease
Management : medical
No specific medication
pharmacotherapy is given to for following:
1. Control HTN: ACEIs or ARBs 2. Control abnormalities related to renal failure: Drugs to maintain electrolyte levels (eg, calcium carbonate, calcium acetate, sevelamer, lanthanum carbonate, calcitriol [possibly], diuretics, blood pressure medications)3. Treat UTI: fluoroquinolones,sulfa drugs penetrate cyst
4. Treat cyst infections: Gyrase inhibitors (eg, ciprofloxacin, chloramphenicol, clindamycin, levofloxacin); dihydrofolic acid inhibitors (SMP)5. Treat hematuria: Possibly analgesic plus copious oral hydration6. Reduce abdominal pain produced by enlarged kidney 7. Prevent cardiac valve infection in patients with intrinsic valve disease
Surgical Rx:
includes:
Surgical drainage: Usually in conjunction with usg guided puncture; in cases of infected renal/hepatic cysts not responding to conventional antibiotics
Open-/fiberoptic-guided surgery: For excision/drainage of the outer walls of cysts to ablate symptoms
Nephrectomy: Last resort for pain control in patients with inaccessible cysts in the renal medullae;
bilateral nephrectomy in patients with severe hepatic involvement
Partial hepatectomy: To manage massive hepatomegalyLiver transplantation: In cases of portal hypertension due to
polycystic liver or hepatomegaly with nonresectable areas
Patients with ADPKD who progress to end-stage renal disease may require the following procedures:
HemodialysisPeritoneal dialysisRenal transplantation
New trials : HALT PKD ; TEMPO 3:4
Rx: 1.V2 receptor antagonists (tolvaptan) - slow increase in renal volume & decline in renal fnctn. Due to side effects not yet approved
2.mtor inhibitors(rapamycin) slow increase in renal volume but not decline of function - not routinely used
3.somatostatin
4. Rx of choice in ESRD is transplantation
Key points
Autosomal dominant polycystic kidney disease occurs in about 1/1000 people
About half of patients have no manifestations, but in others symptoms of back
or abdominal pain, hematuria and/or hypertension develop gradually, usually
beginning before age 30; 35 to 45% develop renal failure by age 60.
Extrarenal manifestations are common and include cerebral and coronary artery
aneurysms, cardiac valve disease, and cysts in the liver, pancreas, and
intestines.
Diagnose PKD based on imaging studies and clinical findings, reserving genetic
testing for patients with no family history, with inconclusive results on imaging,
or who are young and in whom the diagnosis will affect management.
Do not routinely screen asymptomatic patients for ADPKD or asymptomatic
patients who have ADPKD for cerebral aneurysms.
Arrange genetic counseling for 1st-degree relatives of patients with ADPKD.
Give ACE inhibitors or angiotensin receptor blockers for hypertension and to help
prevent renal scarring and dysfunction; treat other complications as they
arise, and consider use of tolvaptan.
Thank youReference : CJASN / davidson / harrisons internal medicine / NICE/ NCBI