Cystic Diseases

Question 1

1. Explain the pathogenesis of cystic kidney disease.

Answer 1

hereditary (genes)
developmental (develops en urtero)
acquired (develops after births)

Question 2

2. Recognize the clinical presentation of cystic kidney disease , especially ADPKD.

Answer 2

in ADPKD cysts grow in many parts of the nephron, in various sizes and cause the stretch of the arteriole system causing hypoxia and cytokine release (sclerosis); results in LARGE kidney

symptoms include: pt. 30+ yo with hematuria, nocturne, HTN, variable polycythemia, flank pain (stones), URTI and intracranial hemorrhage

GI: colonic diverticula, abdominal wall hernia
Liver cysts
Subarachnoid hemorrhage

Question 3

3. Describe the role of diagnostic imaging in cystic kidney diseases.

Answer 3

ultrasound is the gold standard for ADPKD diagnosis

Question 4

4. Identify factors involved in disease progression of ADPKD.

Answer 4

PKD-1 gene mutation
male gender
HTN
UTI, drugs- further kidney damage

Question 5

5. Explain therapeutic principles of dialysis and transplantation related to cystic diseases.

Answer 5

.

Question 6

List the 3 broad categories of hereditary renal disease and examples from each.

Answer 6

Hereditary polycystic kidney disease:
ADPKD
ARPKD

cystic diseases of the renal medulla:
medullary cystic disease and nephronophthisis and medullary sponge kidney

Misc
Tuberous sclerosis
Von Hipel-Lindau Disease

Question 7

Describe the pathogenesis of ADPKD.

Answer 7

ADPKD is due to mutation in PKD-1 (most common) or PKD-2 for protein mutations in polycystin-1 (16) and 2 (4)

polycystin- 1 is associated with cell-cell adhesion and polycystin-2 is important for proliferation and differentiation, acting as a Ca++ voltages channel

mutations in either result in increased apoptosis, proliferation and cyst formation
NOTE polarization of EGF receptor and Na/K ATPase is uttered to maintain growth

Question 8

What criteria exist for dx. of ADPKD?

Answer 8

Family history
UA (moderate proteinuria and hematuria), changes in serum creatinie and anemia/polycythemia

ultra sound imaging the gold standard, confirmatory tests include CT or MRI

rarely genetic testing for equivocal tests in determining donor fitness (expensive)

60yo 8 cysts bilaterally

if no cysts after age 30, no ADPKD-1, very little ADPKD-2

Question 9

What is the treatment options of ADPKD?

Answer 9

no curative tx.

slow progression pre ESRD with control of BP and proteinuria, add ACEI and ARB to limit fibrosis and avoid contact sports
V2 receptor antagonists may be helpful, mTOR inhibitor more helpful than CNI

in ESRD, transplant has excellent outcomes, dialysis and nephrectomy for symptoms

Question 10

Describe the pathogenesis of ARPKD.

Answer 10

mutation in PKHD-1 which codes protein fibrocystin, a gene found expressed in the kidney, liver (portal HTN) and lung; mutation leads to alteration in phosphorylation

note cyst formation is only in the distal tubule

the disease manifests early in childhood and has a high mortality early in life

ideal tx. is transplantation

Question 11

2. Describe the presentation of Nephronophtisis- Medullary Cystic Kidney Disease.

Answer 11

impairment of urinary concentrating ability that progresses to ESRF because of the disruption of tubular basement membranes, end result is tubulointerstitial fibrosis and renal cysts (note the thin cortex)

can be caused by two different mutations to cause distinct but similar disorders.

Question 12

Contrast MCKD and Nephronophthisis medullary cystic disease.

Answer 12

MCKD is AD common in adults resulting hypuricemia and gout and progresses to kidney failure by 20-60y

Nephrophothisis is AR (nephrocystin or inversin) associated with extra-renal manifestations of hepatic fibrosis, retinal disease and bone disease; leads to hypertension and growth retardation

both result in small kidneys, salt and water wasting and treated by dialysis and transplant

Question 13

2. Describe the presentation and pathophysiology of Medullary Sponge Kidney.

Answer 13

common but benign condition that causes cystic dilation of the terminal collecting duct (pericalyceal and renal pyramid regions)

Question 14

2. Describe the presentation and pathology of Tuberous Sclerosis or TS Complex. How would you treat this disease?

Answer 14

AD neurcutaneous disease where tubers are deposited by the body due to mutation in either hamartin or utberin; brain (seizures and mental retardation) and kidneys tumors can lead tuber associated hemorrhage

other associated abnormalities of the kidney include hematuria, HTN, CKD and renal cell carcinoma (pre- cancerous lesion)

imaging with CT and US is used for diagnosis and follow up

Question 15

2. Describe the presentation and pathology of Von Hippel-Lindau Syndrome. How would you treat this disease?

Answer 15

AD disease that follows the “two-hit” model leading to multiple visceral cysts which are considered pre-malignant (40% develop CCRC)

tx. includes surveillance and renal sparing surgical removal, high incidence of malignancy and death

Question 16

Name 3 developmental cystic kidney diseases.

Answer 16

a genesis (lack of kidney)
hypoplastic kidney (20% renal failure in childhood)
renal dysplasia (disordered anatomic and histologic strutter, ie. horseshoe kidney)

Question 17

Name the three ways patients are prone to acquired kidney cystic disease.

Answer 17

aging
CKD
dialysis