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Autosomal Dominant Polycystic Kidney Disease
Aka: Autosomal Dominant Polycystic Kidney Disease, Polycystic Kidney Disease, ADPKD
- Epidemiology
- Prevalence: 300,000 to 600,000 patients in United States
- Symptom onset most often after age 30 years
- Responsible for 4.7% of End Stage Renal Disease in the United States
- Pathophysiology
- Formation of cysts in multiple organ systems, most notably in the Kidneys
- PKD1 and PKD2 gene mutations result in signal dysregulation
- Increased cyclic Adenosine monophosphate and increased cytogenesis
- Cysts form, expand and gradually result in nephron loss
- Initial compensation via hyperfiltration by remaining renal tubules
- Ultimately is overcome and Renal Failure progresses
- Once GFR starts to decline, it does so at a rate of 4.4 to 5.9 ml/minute/year
- Inheritance in Autosomal Dominant pattern
- A child has a 50% chance of inheriting ADPKD from an affected parent
- Spontaneous mutation is responsible for 5% of cases
- Types
- PKD1 Gene: (86% of cases, 95% of cases in Caucasians)
- ADPKD1 gene on short arm of Chromosome 16
- PKD1 encodes integral membrane protein Polycystin-1
- End-stage renal disease average age of onset: 57
- Associated with a higher risk of progression to end-stage renal disease than for the PKD2 gene mutation
- PKD2 Gene: (14% of cases)
- ADPKD2 gene on Chromosome 4
- PKD2 encodes integral membrane protein Polycystin-2
- End-stage renal disease average age of onset: 69
- Symptoms
- Symptom onset is delayed until patients are in their 30-40s
- Flank or Abdominal Pain (60%) causes
- Renal Cyst rupture
- Enlarged Kidney compression of regional structures
- Nephrolithiasis
- Urinary Tract Infection
- Gross Hematuria
- Urinary Tract Infection symptoms
- Signs
- Hypertension
- With advanced renal or hepatic disease, cyst-related mass effect may be palpable
- Labs
- Renal Function test monitoring
- Urinalysis
- Urinary Tract Infection
- Hematuria
- Proteinuria
- Genetic screening indications
- Not routinely indicated
- Young, at risk asymptomatic patients with normal Ultrasound screening
- Large Kidneys with Renal Cysts and no known Family History of ADPKD
- Kidney transplant potential donor who is at risk of ADPKD
- Imaging
- First-Line
- Renal Ultrasound (effective, lower cost, no radiation)
- Alternative screening (if non-diagnostic Ultrasound or large body habitus)
- Abdominal CT
- Abdominal MRI
- Diagnosis
- Ultrasound criteria for those at risk of ADPKD Type 1
- Age <30 years: 2 or more cysts in one or both Kidneys
- Age 30 to 59 years: 2 or more cysts in each Kidneys
- Age >60 years: 4 or more cysts in each Kidneys
- Ultrasound criteria for those at risk of ADPKD with unknown Genotype
- Age 15 to 39 years: 2 or more cysts in one or both Kidneys
- Age 40 to 59 years: 2 or more cysts in each Kidneys
- Age >60 years: 4 or more cysts in each Kidneys
- MRI criteria for those at risk of ADPKD
- Age <30 years: 5 or more cysts in each Kidneys
- Age 30 to 44 years: 6 or more cysts in each Kidneys
- Age 45 to 59 years (males): 6 or more cysts in each Kidneys
- Age 45 to 59 years (females): 9 or more cysts in each Kidneys
- References
- Pei (2009) J Am Soc Nephrol 20(1): 205-12 [PubMed]
- Complications
- Renal Failure (at least 45% of cases)
- Accounts for 5-10% of End Stage Renal Disease (ESRD)
- By age 70 years old, 80% have end-stage renal disease or have died of other cause
- Gabow (1993) N Engl J Med 329(5): 332-42 [PubMed]
- Hypertension
- Children: 30%
- Adults: 60%
- End Stage Renal Disease: 80%
- Extra-Renal Cysts
- Extra-Renal Cysts most commonly occur in the liver (34-78%)
- Cysts also occur in the ovaries, Seminal Vessicles, Pancreas, Spleen and Central Nervous System
- Left Ventricular Hypertrophy
- Mitral Valve Prolapse (26%)
- Aortic Insufficiency (due to aortic root dilitation)
- Gross Hematuria (associated with Renal Cyst rupture)
- Recurrent Urinary Tract Infection
- Nephrolithiasis (20%)
- Renal Cell Carcinoma
- Cerebral Aneurysm (5-10%)
- At least twice as likely as in the general population
- Higher risk if Family History of Cerebral Aneurysm in addition to ADPKD
- Colonic diverticulum with risk of perforation
- Inguinal Hernia
- Risk Factors: End Stage Renal Disease
- ADPKD1 gene
- Early onset at young age
- Male
- Black race
- Sickle Cell Trait
- Hypertension
- Left Ventricular Hypertrophy
- Gross Hematuria
- Proteinuria
- Large renal volume
- Hepatic Cysts
- Urinary Tract Infections in males
- Three or more pregnancies
- Management
- No specific interventions prevent cyst development
- All management strategies are to evaluate and treat secondary complications and forestall end-stage renal disease
- Hypertension control (Goal Blood Pressure < 140/90)
- ACE Inhibitor
- Angiotensin Receptor Blocker may be used as an alternative if unable to use an ACE Inhibitor
- Diuretic
- Caution when used with ACE Inhibitor
- Calcium Channel Blocker
- Urine changes
- Proteinuria (30%)
- Gross Hematuria
- Exclude Nephrolithiasis, Urinary Tract Infection, Abdominal Trauma, cyst rupture
- Exclude cancer (Renal Cell Carcinoma, Bladder Cancer) if Gross Hematuria persists >1 week or first time episode in age >50 years old
- Gross Hematuria is an independent risk factor for rapid progression of renal dysfunction (especially prior to age 30 years old)
- CT Abdomen and Pelvis will identify Nephrolithiasis, hemorrhagic Renal Cyst, Renal Mass and Traumatic Injury
- Most resolve spontaneously (including hemorrhagic Renal Cysts which resolves after 1 week)
- Maximize hydration
- Correct Coagulopathy if present
- Flank and Abdominal Pain (e.g. cyst expansion related)
- Exclude Nephrolithiasis if acute change
- Analgesics (avoid NSAIDs due to nephrotoxicity)
- Avoid provocative activities (e.g. Contact Sports, heavy lifting)
- Consider pain management Consultation
- Invasive measures
- Percutaneous cyst drainage and Alcohol sclerosis
- Open cyst reduction surgery
- Urinary Tract Infection (and Renal Cyst infections)
- Urinalysis and Urine Culture are typically positive
- However occult Renal Cyst infections may occur in the absence of Urine Culture growth
- Organisms infecting Renal Cysts
- Escherichia coli (74% of cases)
- Staphylococcus aureus, Enterococcus, lactobacillus and Anaerobes account for remainder of Renal Cyst infections
- Antibiotics with best renal parenchyma penetration
- Fluoroquinolones (best Renal Cyst penetration)
- Third Generation Cephalosporins (poor Renal Cyst penetration)
- Trimethoprim-sulfamethoxazole
- Nephrolithiasis
- ADPKD is associated with a two fold increased risk of Nephrolithiasis (and a 20% lifetime Prevalence)
- Evaluate pain suggestive of Nephrolithiasis (e.g. Flank Pain) regardless of presence of Hematuria
- Adult polycystic liver disease (Liver Cysts)
- Liver function is typically preserved (with only a mild increase in Alkaline Phosphatase)
- As with Renal Cysts, Hepatic Cysts may become infected or bleed
- Avoid Estrogen (combination Oral Contraceptives or Estrogen Replacement Therapy) due to the risk of Hepatic Cyst proliferation
- Symptoms if they occur are related to Hepatomegaly (but most often asymptomatic)
- Increased symptoms in pregnancy (due to hyperestrogenic state)
- Shortness of Breath or lower extremity edema
- Early satiety or esophageal reflux
- Right Upper Quadrant Abdominal Pain or Low Back Pain
- Intracranial Aneurysm
- Occur in up to 5-10% of ADPKD patients (see above)
- Screening indications (with non-contrast MRA using time-of-flight or inflow angiography)
- Before major elective surgery
- CNS symptoms (e.g. new or different Headache, Vomiting, lethargy, focal neurologic findings, Transient Ischemic Attack symptoms)
- Family History of Intracranial Aneurysm or Subarachnoid Hemorrhage
- High risk occupation (e.g. airplane pilot)
- Pregnancy
- Higher risk of maternal and fetal complications when ADPKD is accompanied by Hypertension
- Renal Failure
- See Chronic Renal Failure
- References
- Beebe (1996) Am Fam Physician 53(3):925-31 [PubMed]
- Gibson (2002) Practitioner 246:450-3 [PubMed]
- Grantham (2008) N Eng J Med 359(14): 1477-85 [PubMed]
- Srivastava (2014) Am Fam Physician 90(5): 303-7 [PubMed]