Polycystic Kidney Disease 

A. Characteristics

1. Common hereditary disorder, ~0.2% of population
   1. 90% inherited autosomal dominant
   2. 10% sporadic mutation
2. Usually affects adults >50 years old
3. Gene linked to chromosome 16 (called ADPKD1)
4. Diagnosis requires bilateral renal cysts and enlargement
5. Cause of 8-10% of End Stage Renal Disease (ESRD)

B. Cyst Formation

1. Renal Cysts 100%
2. Renal Adenomas 21%
3. Hepatic Cysts 50%
4. Pancreatic Cysts 10%
5. Colonic Diverticula 80% of patients with ESRD
6. Arachnoid Cysts 5%
7. These are all "ductal" organs

C. Pathogenesis

1. Autosomal Dominant Disease caused by mutations in at least three genes
   1. PKD1 - codes for 4304 amino acid membrane protein called polycystin (chromosome 16)
   2. PKD2 - mapped to chromosome 4
   3. Unidentified third locus
2. Cyst formation in kidneys
3. Abnormality in Na+/K+ ATPase Pump
   1. Cystic epithelium has pump in apical location
   2. Normal renal tubular epithelium has this pump on the basolateral surface
4. Increased programmed cell death (apoptosis) in both dominant and recessive forms [3]
5. Mice with homozygous deletions in the proto-oncogene bcl-2 develop PKD [4]
6. Other mouse models (pcy and cpk) of the disease are now being studied

D. Diagnosis

1. About 60% of patients report a family history
2. Ultrasound slightly less sensitive than CT scan
3. DNA linkage analysis (requires two affected persons)

E. Differential Diagnosis

1. Multiple bilateral cysts on Ultrasound or CT Scan
2. Multiple simple cyst disease
3. Autosomal recessive polycystic kidney disease
   1. Onset in childhood
   2. Often with congenital hepatic fibrosis
4. Tuberous Sclerosis (bilateral cystic, AD type)
5. von Hippel - Lindau Syndrome

F. Symptoms

1. Decline in renal concentrating ability
2. Renin and erythropoietin elevated
3. Hypertension
4. Pain
   1. Acute - pyelonephritis, UTI, stone, cyst infection
   2. Chronic - increase in renal size
5. Extrarenal Manifestations
   1. Cerebral aneurysm
   2. Cardiac valve disease
   3. Colonic diverticula
   4. Hepatic cysts
   5. Umbilical and inguinal hernia
6. ACE inhibitors have little effect on progression of renal dysfunction [5]

G. Complications

1. Hypertension >80% with ESRD
2. Hematuria or hemorrhage 50%
3. Acute and chronic pain 60%
4. UTI's, pyelonephritis Common
5. Renal Stones 20%
6. Renal Failure 45% by age of 60
7. Cyst Infection

H. Treatment 

1. Control of Hypertension
   1. Disease is characterized by high renin activity
   2. ACE inhibition may therefore be highly effective for blood pressure control [6]
   3. Angiotensin II blockers (Losartan, Cozaar®) may also be effective
   4. Careful renal function monitoring must be carried out
2. Cyst Infection
   1. Only a few antibiotics penetrate the cysts
   2. Trimethoprim / Sulfamethoxazole (TMP/SFX)
   3. Ciprofloxacin
   4. Chloramphenicol
3. Renal Transplantation

I. Intracranial Aneurysms [2] 

1. Incidence of intracranial aneurysms (asymptomatic) is increased in PKD vs. normals 
2.    2.     Increased incidence of morbidity (renal failure) with cerebral angiography in PKD patients
3. Recommendations are therefore NOT to screen for such aneurysms in PKD patients

 

References

1. Gabow PA. 1993. NEJM. 329(5):332
2. NEJM. 1992.327(13):916
3. Woo D. 1995. NEJM. 333(1):18
4. Nakayama K, Nakayma K, Negishi I, et al. 1994. Proc Natl Acad Sci USA. 91:3700
5. Maschio G, Alberti D, Janin G, et al. 1996. NEJM. 334(15):939
6. Giatras I, Lau J, Levey AS. 1997. NEJM. 127(5):337

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