ANSWER 26
This patient has autosomal dominant polycystic kidney disease(ADPKD). She has macro-
scopic haematuria, hypertension and impaired renal function. The palpable abdominal
masses in both flanks have the characteristic features of enlarged kidneys. They are ballot-
table and resonant to percussion because of overlying bowel. The other principal causes for
palpable kidneys are renal cell carcinoma and massive hydronephrosis. Rest is the best
management for cyst bleeding. Gross haematuria rarely lasts for more than a week.
ADPKD is the most common inherited renal disease, occurring in approximately 1:600 to
1:1000 individuals. Although the name ‘ADPKD’ is derived from renal manifestations of
cyst growth leading to enlarged kidneys and renal failure, this is a systemic disorder mani-
fested by the presence of hepatic cysts, diverticular disease, inguinal hernias, mitral valve
prolapse, intracranial aneurysms and hypertension. Flank pain is the most common symp-
tom, and may be caused by cyst rupture, cyst infection or renal calculi. Macroscopic
haematuria due to cyst haemorrhage occurs commonly and usually resolves spontaneously.
Renal calculi occur in approximately 20 per cent of ADPKD patients (most commonly uric
acid stones). Hypertension occurs early in the course of this disease affecting 60 per cent
of patients with normal renal function. Approximately 50 per cent of ADPKD patients will
develop end-stage renal failure.
Although it is not known if this patient’s father had renal disease, it is highly likely that
he had ADPKD and an associated ruptured berry aneurysm as the cause for his subarach-
noid haemorrhage. The patient’s uncle required a renal transplant. The pattern of inher-
itance in this family is consistent with an autosomal dominant trait.
Ultrasound is the preferred initial screening technique as it is cheap, non-invasive and rapid.
It detects cysts as small as 0.5 cm. For a certain diagnosis, there should be at least three renal
cysts with at least one cyst in each kidney. Computed tomography (CT) and magnetic reson-
ance imaging (MRI) are more sensitive techniques for detecting smaller cysts. Ultrasound in
this patient shows the typical appearance of multiple cysts (black areas) surrounded by
thickened walls (Fig. 26.1). She should be referred to a nephrologist for long-term follow-up
of her renal failure, and plans should be made for renal replacement therapy. She needs to
have effective blood pressure control with diastolic pressure!85 mmHg to retard the pro-
gression of her renal failure. Clinical trials are starting of vasopressin receptor antagonists
which show promise at inhibiting cyst growth.
She should have MRI angiography to exclude an intracranial aneurysm. This is not advo-
cated for all ADPKD patients, but is indicated for those patients with a positive family his-
tory of aneurysm rupture. The patient’s children should have their blood pressure checked
and later be screened by ultrasound. By age 30 years, 90 per cent of ADPKD patients will
have cysts detectable by ultrasound.
Ninety per cent of ADPKD patients have mutations in the ADPKD1gene. This gene encodes
for the protein polycystin which is a membrane glycoprotein that probably mediates
cell–cell and/or cell–matrix interactions. Most remaining patients have mutations in the
ADPKD2gene which codes for polycystin-2, which has structural homology to polycystin
and to calcium channels. ADPKD1 patients generally have an earlier age of onset of hyper-
tension and development of renal failure as compared to ADPKD2 patients.