Autosomal Dominant Polycystic Kidney Disease
- Also referred to as Adult polycystic kidney disease, ADPKD, Potter type III
About ADPKD:
- Slow, progressive disease with nearly 100% penetrance and great variation in expressivity
- systemic disease due to a generalised collagen defect
Causes:
- Gene located on short arm of chromosome 16 (PKD1) (in 90%)
- spontaneous mutation on chromosome 4 in 10% (PKD2)
Incidence:
- 1:1000 people carry the mutant gene
- 3rd most prevalent cause of chronic renal failure
- Risk of recurrence: 50%
- Mean age at diagnosis: 43 years
- Symptomatic mean age of 35 years (cysts grow with age)
- M: F: 1:1
Histology:
- Abnormal rate of tubule divisions (Potter type III) with hypoplasia of portions of tubules left behind as the ureteral bud advances
- Cystic dilatation of Bowman capsule, loop of Henle, proximal convoluted tubule, coexisting with normal tissue
Onset of cyst formation:
- 54% in 1st decade
- 72% in 2nd decade
- 86% in 3rd decade
- Morphogenic evidence in all patients by age 80
Criteria in screening exam for cysts:
- 18-29 years ≥ 5 cysts
- 30-44 years ≥6
- 45-59 years ≥ 6 cysts in females, 9 in males
Associated conditions:
1. Cysts in: liver and pancreas
Also, but rare in: lung, spleen, thyroid, ovaries, uterus, testis, seminal vesicles, epididymis, bladder
2. Aneurysm: Saccular “berry” aneurysm of cerebral arteries, aortic aneurysm
The ADPKD genes PKD1 and PKD2 are known to play a role in maintaining the structure of blood vessels
3. Mitral valve prolapse
Speculated cause of high blood pressure, since hypertension causes left ventricular hypertrophy and left ventricular dilatation.
4. Colonic diverticulosis
No known cause to association. Suggestion that gene faults cause bowel wall muscle to be weaker or produces abnormal extracellular matrix
5. Hypertension (50-70%)
Enlarging cysts placing pressure on blood vessels in the kidney, increasing the activity of renin-angiotensin aldosterone system. Renin acts on angiotensin that constricts blood vessels and stimulates production of aldosterone causing retention of salt and loss of potassium, resulting in high blood pressure and as a result left ventricular hypertrophy
Symptoms:
- Azotemia (high nitrogen)
- Hematuria (blood in urine)
- Proteinuria (increased proteins in urine)
- Lumbar/ abdominal pain
Atypically rare presentation:
- unilateral adult PCKD
- segmental adult PCKD
- adult PCKD in utero/ neonatal period
Common Kidney Appearance:
- Bilaterally large kidneys with multifocal round lesions
- Elongated, distorted, attenuated collecting system
- Unilateral enlargement may be the first manifestation of the disease
- Cysts may calcify in curvilinear rim -/ ringlike irregular amorphous fashion
- Kidneys shrink after beginning of renal failure, after renal transplantation, or on chronic haemodialysis
Imaging:
X-Ray:
- No role in diagnosis or surveillance of disease
- Can show enlarged multilobulated renal outlines, displaced bowel loops or calcifications in ring configurations
US:
- Multiple large cysts in cortical region (usually seen in 50% by 10 years of age)
- Diffusely echogenic when cysts are small
- Renal contour poorly demarcated
- Cysts appear anechoic, well-define imperceptible walls, posterior enhancement and lateral shadowing
- If cysts haemorrhage or are infected echogenic material with appear in the cysts with no blood flow; distinction between RCC solid components of thick septa with blood flow
CT:
- ADPKD show as simple cysts that are rounded structures with attenuation close to water ~ 0HU
- Thin, regular and imperceptible cystic wall
- Haemorrhaged or infected cysts will be hyperattenuating, with non-enhancing septations or calcifications
- Complex cysts with solid components and thick septas which enhance are more suspicious of RCC
*See Bosinak classification system*
MRI:
- Appearance same as CT: rounded, well-defined with very thin regular walls
- T1: low signal
- T2: high signal
- T1 C+ (Gd): simple cysts will not have any solid enhancing components, if enhances with a solid component or septa RCC considered
* care must be taken prior to administering gadolinium-based contrast agents due to the risk of nephrogenic systemic fibrosis*
Nuclear Medicine:
- poor renal function on Tc-99m DTPA scan
- multiple areas of diminished activity, cortical activity only in areas of functioning cortex
Outlook
Treatment and Prognosis:
- No treatment towards cure à only pain relief of symptoms
- End stage renal failure à transplant or dialysis
Complications:
1. Death from uremia (60%)
2. Hypertension/Cardiac Complications (mean age of 50)
3. Aortic Dissection
4. Cerebral hemorrhage (SAH) or ruptured aneurysm 13%
5. Renal calculi 20% (mostly Urate)
Cysts blocking tubules (filter of kidney) preventing normal drainage and crystallizing
Decrease in Urine Citrate substance (prevents kidney stone formation)
6. UTI
7. Cyst rupture
8. Cyst hemorrhage 66%
Common cause of acute flank plain
Shows as hyper attenuated cyst content on CT
9. End Stage Renal Failure
10. Renal cell carcinoma
ONLY increased risk if in renal failure and on prolonged dialysis
Differential Diagnosis:
1. Multiple simple cysts (less diffuse, no family history, less enlargement of kidneys)
2. Von Hippel-Lindau disease (cerebellar hemangioblastoma, retinal hemangiomas, occasionally pheochromocytomas)
3. Acquired uremic cystic disease (small kidneys, no renal function, transplant)
4. Infantile PCKD (usually microscopic cysts)
5. Severe hydronephrosis
6. Autosomal Recessive Polycystic Kidney Disease (ARPKD) (enlarged kidneys, small and numerous cysts, loss of corticomedullary differentiation, changes evident in childhood)
References:
Dahnert, W. (2008). Radiology Review Manual (6th Edition). Philadelphia: Lippincott Williams & Wilkins
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