You explain to the patient that ADPKD is a genetic disease and that he and his siblings each had a certain chance of inheriting it. Although different presentations may occur (“congenital” polycystic kidney disease, hypertension, or obesity), they all must undergo ultrasonographic screening for ADPKD. You add that although ADPKD is a genetic disease, it can also be diagnosed in different members of the same family at different ages.
TREATMENT
The goal of treatment for the patient with ADPKD is to slow cyst development and the natural course of the disease. If this can be achieved, the need for dialysis or kidney transplantation may be postponed for a number of years. Because cyst growth causes an elevation in renin and activates the angiotensin II renin system26 (see figure,24), an ACE inhibitor is the most effective treatment to lower blood pressure and thus slow the progression of ADPKD. Most patients with ADPKD are started on an ACE inhibitor at an early age to slow the rate of disease progression.27,28 Several studies are under way to determine the best antihypertensive medication and the optimal age for initiating treatment.29,30
Lipid screening and treatment for dyslipidemia are important23 because ADPKD can lead to a reduction in kidney function, resulting in chronic kidney disease (CKD). CKD is considered a coronary heart disease risk equivalent, and most professionals will treat the patient with ADPKD for hyperlipidemia.23,31 While there are no data showing that statin use will reduce the incidence of ESRD or delay the need for dialysis or kidney transplantation in patients with ADPKD, the beneficial effects of good renal blood flow and endothelial function have been noted.32,33
One of the most common and significant complications in ADPKD is intracranial hemorrhage resulting from a ruptured cerebral aneurysm. In the younger adult, the incidence of cerebral aneurysm is 4%, but incidence increases to 10% in patients older than 65.34-36 Family clusters of aneurysms have been reported.37 If an intracranial aneurysm is found in the family history, the risk of an aneurysm in another family member increases to 22%.38
Since rupture of an intracranial hemorrhage is associated with a 30-day mortality rate of 50% and 80% morbidity,5,38 standard of care for patients with ADPKD includes CT or magnetic resonance angiographic (MRA) screening in the asymptomatic patient with a positive family history.34,38 If an aneurysm is found, the lifetime chance of rupture is 50%, although the risk is greater in the case of an aneurysm larger than 10 mm.5
As in all patients with kidney disease, left ventricular hypertrophy is common among patients with ADPKD.23,28,39
The Case Patient
The patient is started on an ACE inhibitor, scheduled for fasting lipid screening, and referred to a nephrology practice for disease management. As research and investigation of possible treatment options for ADPKD are ongoing, the patient may benefit from participating in a new research protocol.
Because the patient’s family has no history of cerebral aneurysm, CT/MRA screening is not required. A discussion of the pros and cons of genetic testing for the entire family, including nieces and nephews, is initiated. The patient and his family are referred to a genetic counselor to decide whether the benefit of early treatment for hypertension outweighs the risk of carrying a diagnosis of ADPKD for his younger relatives, who may later seek health insurance coverage.
NATURAL PROGRESSION OF ADPKD
Hypertension and cyst formation will continue as the patient ages. The natural progression of ADPKD is to renal failure with renal replacement therapy (dialysis or organ transplantation) as treatment options. If the progression of ADPKD can be slowed through pharmacotherapy, the patient may live for many years without needing dialysis. This ideal can be accomplished only through aggressive hypertension control, which should be started in the teenage years.23,30,31
Suggestions to increase fluid consumption and to limit the use of NSAIDs, contrast dye, and MRI with gadolinium are appropriate. It is rare for hypertension to be diagnosed before some organ damage has already occurred.12 Often the patient’s renal function, as determined by measuring the GFR, remains stable until the patient reaches his or her 40s.40 However, kidney damage often begins before any detectable change in GFR. Once the GFR does start to decline, the average decrease is 4.4 to 5.9 mL/min/1.73m2 each year.41
MANAGEMENT CONSIDERATIONS
For ESRD Organ Transplantation
Kidney transplantation—the only curative treatment for ADPKD—can be offered to patients once the GFR falls below 20 mL/min. However, the patient with ADPKD can experience kidney enlargement to such an extent that introducing a third kidney into the limited abdominal space becomes technically difficult. Although nephrectomy is avoided whenever possible, there are cases in which there is no alternative.42