SIADH

Polycystic kidney disease refers to an inherited disorder characterized by the progressive development of multiple fluid filled cysts within the renal parenchyma, leading over time to progressive renal enlargement and, ultimately, in most affected individuals, chronic and eventually end stage kidney disease.

Autosomal dominant polycystic kidney disease is by far the more common form encountered in adult practice, 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 a much rarer, more severe condition typically presenting in infancy or childhood, associated with significant hepatic fibrosis in addition to the renal involvement, and carries a substantially worse prognosis than the autosomal dominant form.

Many patients with autosomal dominant polycystic kidney disease are asymptomatic for years, with the condition 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, from a combination of the sheer mass effect of the enlarging kidneys and 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, and 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, and, while most patients do not require routine screening, screening is recommended for those with a family history of aneurysm or subarachnoid hemorrhage, or those in high risk occupations where a bleed would be particularly catastrophic, given the risk of subarachnoid hemorrhage if an aneurysm ruptures. Mitral valve prolapse and other cardiac valvular abnormalities occur with increased frequency. Colonic diverticulosis is also more common in this population.

Progressive renal impairment develops over years to decades, ultimately progressing to end stage renal disease in a majority of patients with autosomal dominant polycystic kidney disease, typically in mid to later adulthood, though the rate of progression varies considerably, including by genotype as noted above.

Renal ultrasound is the standard initial diagnostic tool, with diagnostic criteria for at risk individuals (those with an affected first degree relative) based on the number of cysts present relative to age, reflecting the fact that cyst number and size increase progressively over the course of the disease. CT or MRI provides more detailed characterization where ultrasound findings are equivocal, or for more precise assessment of total kidney volume, which is increasingly used as a marker of disease severity and progression risk in specialist practice.

Genetic testing for PKD1 and PKD2 mutations is available and can be useful in specific circumstances, such as diagnostic uncertainty, family planning discussions, or evaluation of a potential living related kidney donor within an affected family, though 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, and renal function monitored over time to track disease progression.

Differentials include 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 (occurring in the context of long standing dialysis, without a hereditary basis), and 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, given both the high prevalence of hypertension in this population and evidence that more intensive blood pressure control may slow the rate of renal function decline, with ACE inhibitors or ARBs 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, though its use requires careful monitoring given a risk of hepatotoxicity and the practical burden of the resulting polyuria and thirst it causes as an on target effect of the mechanism.

General measures include maintaining good hydration, avoiding nephrotoxic medications where possible, and prompt treatment of cyst infection or urinary tract infection with antibiotics, chosen with attention to good cyst penetration where cyst infection specifically is suspected, since not all antibiotics 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, and screening of at risk relatives is generally offered from adulthood, with the timing and extent of any imaging based screening individualized to the family's specific 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 as above.

Progressive chronic kidney disease is managed following the general principles applicable to any cause of chronic kidney disease, with renal replacement therapy planning initiated in a timely fashion as the disease approaches its later stages (see Indications for Dialysis entry).

Referral: nephrology for all confirmed cases, given the need 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.