Page 258 - Medicine and Surgery

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254 Chapter 6: Genitourinary system

Chronic Hyperuricaemic Nephropathy Renal cystic disease
There is still a debate as to whether patients who have

hyperuricaemia,goutytophi,andchronicrenalfailure Adult polycystic kidney disease
havegoutynephropathyasthecausefortheirrenalim-
Definition
pairment. Renal failure leads to raised uric acid levels
Adult polycystic kidney disease is an autosomal dom-
and in some cases there may have been another cause
inant inherited condition characterised by gradual re-
for their renal failure. It is thought that urate crys-
placement of renal and occasionally other tissue by cysts.
tals deposit in the renal interstitium, causing chronic
inflammation, interstitial fibrosis and hence the de-
Incidence/prevalence
velopment of chronic renal failure.
1in1000.Accountsfor10%ofchronicrenalfailurecases.
There is a distinct autosomal dominant disorder of

uric acid metabolism which is associated with early Age
onset renal failure and hypertension. This is called Presents at any age.
familial juvenile gouty nephropathy, although it is still
unclear whether uric acid deposition is the primary Sex
cause. Allopurinol may improve renal function, but M=F
rarely completely prevents deterioration.
Aetiology
Autosomal dominant; 90% of cases associated with
Acute hyperuricaemic nephropathy
PKD1 gene on chromosome 16, and 5–10% of cases with
This occurs when there is an acute rise in uric acid as

PKD2 on chromosome 4. PKD1 patients tend to develop
in patients who have haematological malignancies or
renal failure earlier.
polycythaemia rubra vera. Prior to treatments such as
PKD1 encodes a protein called polycystin-1, which is
chemotherapyorradiationwhichcauseacutecelllysis,
found in plasma membranes of renal tubular epithelial
prophylactic treatment may be required. Acute hyper-
cells, hepatic bile duct cells and pancreatic duct cells.
uricaemia may also occur in conjunction with tumour
Renal, liver and pancreatic cysts all occur in APKD. Ab-
lysis syndrome (i.e. with hyperkalaemia, hyperphos-
normal polycystin-1 protein may affect cell adhesion,
phataemiaandhypocalcaemia).Uricacidcrystalspre-
leading to inappropriate cell growth. This gene is closely
cipitateinthecollectingducts,renalpelvisandureters,
related to the tuberous sclerosis gene in which renal cysts
causing obstruction.
can also occur.
Patients present with acute oligoanuric renal failure,

PKD2 encodes polycystin-2 protein, which is ex-
sometimes with loin pain or colic. There are very high
pressed in the distal tubules, collecting duct and thick
uric acid levels and uric acid crystals may be seen on
ascending limb of Henle and appears to be involved in
urine microscopy unless there is little or no urine pro-
calcium signalling.
duction.
The mechanism of cyst formation is not yet under-
This complication is prevented by pretreatment with

stood, although it appears that there may need to be a
high doses of allopurinol or rasburicase prior to
second somatic mutation, because the disease variably
chemotherapy or radiation, and giving intravenous
affects tubules and individuals. There is evidence that
fluids to lower the concentration of uric acid in the
the cysts arise from one progenitor cell (monoclonal).
urine. Despite this, some patients still develop ARF in
There also appear to be environmental effects, for ex-
which case fluid and diuretics are given to try to flush
ample liver cysts are more common in women, which is
out the crystals. Haemodialysis may be used to remove
thought to be an effect of oestrogen.
circulating uric acid.
Pathophysiology
Cysts develop in both kidneys, progressing in size and
Uric acid stones
number over the years. They gradually compress the
See page 270. renal parenchyma. There is also evidence of vascular