Polycystic Kidney Disease

Polycystic kidney disease is an inherited disorder characterized by progressive development of multiple fluid filled cysts within the renal parenchyma. The kidneys enlarge over time, and most affected individuals develop chronic and eventually end stage kidney disease.

Autosomal dominant polycystic kidney disease is by far the more common form in adult practice. It is caused predominantly by mutations in PKD1 (associated with a more severe phenotype and earlier progression to end stage renal disease) or PKD2 (generally a milder course with later onset renal failure).

It typically presents in adulthood, though cysts may be detectable earlier on imaging in at risk individuals.

Autosomal recessive polycystic kidney disease is much rarer and more severe. It typically presents in infancy or childhood and is associated with significant hepatic fibrosis in addition to the renal involvement. It carries a substantially worse prognosis than the autosomal dominant form.

Many patients with autosomal dominant polycystic kidney disease are asymptomatic for years. The condition is identified incidentally on imaging performed for another reason, or through family screening once a relative is diagnosed.

Flank or abdominal pain is common as cysts enlarge. It results from the mass effect of the enlarging kidneys and from episodes of cyst hemorrhage or infection, either of which can cause a more acute exacerbation of pain. Visible or microscopic hematuria may occur, typically from cyst rupture into the collecting system.

Hypertension develops in the majority of patients, often preceding any significant decline in renal function. It reflects activation of the renin angiotensin system by the distorted, cystic renal architecture.

Extrarenal manifestations are a defining feature of the condition and should be actively assessed for.

• Hepatic cysts are extremely common, generally without significant impact on liver function even when extensive.
• Intracranial berry aneurysms occur with increased frequency compared to the general population.
• Mitral valve prolapse and other cardiac valvular abnormalities occur with increased frequency.
• Colonic diverticulosis is also more common in this population.

Most patients do not require routine screening for intracranial berry aneurysms. Screening is recommended for those with a family history of aneurysm or subarachnoid hemorrhage. It is also recommended for those in high risk occupations where a bleed would be particularly catastrophic, given the risk of subarachnoid hemorrhage if an aneurysm ruptures.

Progressive renal impairment develops over years to decades. A majority of patients with autosomal dominant polycystic kidney disease progress to end stage renal disease, typically in mid to later adulthood. The rate of progression varies considerably, including by genotype.

Renal ultrasound is the standard initial diagnostic tool. Diagnostic criteria for at risk individuals (those with an affected first degree relative) are based on the number of cysts present relative to age, because cyst number and size increase progressively over the course of the disease.

CT or MRI provides more detailed characterization where ultrasound findings are equivocal. It also allows more precise assessment of total kidney volume, which is increasingly used in specialist practice as a marker of disease severity and progression risk.

Genetic testing for PKD1 and PKD2 mutations is available and can be useful in specific circumstances: diagnostic uncertainty, family planning discussions, or evaluation of a potential living related kidney donor within an affected family. It is not required for diagnosis in the majority of cases, given the reliability of imaging based criteria in an at risk individual.

Blood pressure should be assessed regularly given the high prevalence of hypertension. Renal function should be monitored over time to track disease progression.

Differentials:

• Simple renal cysts: common, generally few in number and without the family history or extrarenal features associated with polycystic kidney disease.
• Acquired cystic kidney disease: occurs in the context of long standing dialysis, without a hereditary basis.
• Other less common hereditary cystic kidney conditions such as tuberous sclerosis, which can also cause multiple renal cysts alongside its other characteristic features.

Blood pressure control is a central component of management. Hypertension is highly prevalent in this population, and more intensive blood pressure control may slow the rate of renal function decline. ACE inhibitors or ARBs are generally used as first line antihypertensive agents given their additional renoprotective properties.

Tolvaptan, a vasopressin V2 receptor antagonist, is used in selected patients with rapidly progressing disease to slow the rate of cyst growth and decline in renal function. Its use requires careful monitoring because of the risk of hepatotoxicity. Polyuria and thirst are an on target effect of the mechanism and add a practical burden.

General measures:

• Maintain good hydration.
• Avoid nephrotoxic medications where possible.
• Treat cyst infection or urinary tract infection promptly with antibiotics. Where cyst infection is suspected, choose antibiotics with good cyst penetration, since not all achieve adequate concentrations within cyst fluid.

Genetic counseling should be offered to affected individuals and their families, given the autosomal dominant inheritance pattern with a 50% risk to offspring of an affected parent. Screening of at risk relatives is generally offered from adulthood. The timing and extent of imaging based screening are individualized to the family's circumstances and the individual's preferences.

Management of extrarenal manifestations follows their own specific pathways, including monitoring and, where indicated by risk factors, screening for intracranial aneurysm.

Progressive chronic kidney disease is managed following the general principles applicable to any cause of chronic kidney disease. Plan renal replacement therapy in a timely fashion as the disease approaches its later stages.

Referral: nephrology for all confirmed cases, for ongoing monitoring of renal function, blood pressure management, and planning for eventual renal replacement therapy. Genetic counseling services for affected individuals and at risk family members.