Flashcards in Cystic Diseases Deck (17):
1. Explain the pathogenesis of cystic kidney disease.
developmental (develops en urtero)
acquired (develops after births)
2. Recognize the clinical presentation of cystic kidney disease , especially ADPKD.
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
3. Describe the role of diagnostic imaging in cystic kidney diseases.
ultrasound is the gold standard for ADPKD diagnosis
4. Identify factors involved in disease progression of ADPKD.
PKD-1 gene mutation
UTI, drugs- further kidney damage
5. Explain therapeutic principles of dialysis and transplantation related to cystic diseases.
List the 3 broad categories of hereditary renal disease and examples from each.
Hereditary polycystic kidney disease:
cystic diseases of the renal medulla:
medullary cystic disease and nephronophthisis and medullary sponge kidney
Von Hipel-Lindau Disease
Describe the pathogenesis of ADPKD.
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
What criteria exist for dx. of ADPKD?
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
What is the treatment options of ADPKD?
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
Describe the pathogenesis of ARPKD.
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
2. Describe the presentation of Nephronophtisis- Medullary Cystic Kidney Disease.
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.
Contrast MCKD and Nephronophthisis medullary cystic disease.
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
2. Describe the presentation and pathophysiology of Medullary Sponge Kidney.
common but benign condition that causes cystic dilation of the terminal collecting duct (pericalyceal and renal pyramid regions)
2. Describe the presentation and pathology of Tuberous Sclerosis or TS Complex. How would you treat this disease?
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
2. Describe the presentation and pathology of Von Hippel-Lindau Syndrome. How would you treat this disease?
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
Name 3 developmental cystic kidney diseases.
a genesis (lack of kidney)
hypoplastic kidney (20% renal failure in childhood)
renal dysplasia (disordered anatomic and histologic strutter, ie. horseshoe kidney)