Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Review literature: (Kuehn and Walz, 2007)
Definition of Autosomal Dominant Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease is an inherited cystic renal disease with development of terminal renal failure in adulthood.
- Incidence 1:500 to 1:1000
- 15% of dialysis patients are suffering from ADPKD
Etiology of Autosomal Dominant Polycystic Kidney Disease
Variations in two genes are known to cause aut. dom. polycystic kidney disease. In 85–90% of patients with ADPKD, mutations in PKD1 (chromosome 16, coding for polycystin-1) are responsible for the disease. In 10–15%, mutations of PKD2 (chromosome 4, coding for polycystin-2) are responsible. ADPKD caused by mutations of PKD2 has usually a later onset and slower progression of disease. Autosomal dominant inheritance with almost 100% penetrance is typical, so that 50% of children will inherited the disease from affected patients. The disease occurs in accordance with Knudson's theory of two hits: one diseased gene is inherited, the second copy of the gene is damaged by a spontaneous mutation and explains the long asymptomatic latency in the onset of the disease.
Polycystin-1 and polycystin-2 have important functions in signal transduction and in the formation of the primary cilium of the tubular epithelial cells. The disturbed function of polycystin leads to a proliferation of the tubular epithelium and to the formation of cysts; every part of the nephron may be affected. Similar mechanisms may damage blood vessels and other organ systems.
Autosomal dominant polycystic kidney disease leads to enlarged kidneys with multiple cysts [fig. polycystic kidneys]. The cysts are a few millimeters to a centimeter in size and derive from a tubulus of the nephron. The epithelium of the cyst corresponds to the origin.
Cysts are also formed in other organ systems, see section signs and symptoms [fig. liver cysts].
Polycystic kidneys due to autosomal dominant polycystic kidney disease (ADPKD): both organs are greatly enlarged and show multiple cysts. Figure by Dr. Edwin P. Ewing, Jr. Public Health Image Library, Center for Disease Control and Prevention, USA, www.cdc.gov.
Liver cysts in autosomal dominant polycystic kidney disease (ADPKD). Figure from Dr. Edwin P. Ewing, Jr. Public Health Image Library, Center for Disease Control and Prevention, USA, www.cdc.gov.
Signs and Symptoms
Onset of disease:
Symptoms start with the age of 30 to 50 years. Renal ultrasound and genetic screening lowers the average age of initial diagnosis due to the discovery of the asymptomatic disease. Rarely, the disease begins in infancy.
- Hematuria (50%)
- Flank pain and fever (cyst rupture oder cyst infection)
- Gastrointestinal symptoms due to large kidneys
- Arterial hypertension (80%)
- Renal failure and symptoms of uremia usually not before the age of 40 years
Manifestations in further organs:
- Cysts in the liver, pancreas, spleen and lungs
- Aneurysm of the cerebral arteries
- Colonic diverticula
- Mitral valve prolapse
Diagnostic Work-Up of Autosomal Dominant Polycystic Kidney Disease
covering at least three generations.
Young adults of affected families can be tested with renal ultrasound: the diagnosis of more than two cysts per kidney with the age of 20 years most likely confirms the diagnosis ADPKD. In addition, the liver, pancreas and spleen is examined for cysts.
- Abdominal CT: imaging of renal cysts, e.g. if flank pain has to be evaluated.
- Cranial CT: to estimate the risk of intracranial bleeding due to aneurysms.
Intravenous urography in autosomal dominant polycystic kidney disease (ADPKD): With kind permission of Dr. G. Antes, Kempten.
The risk for children of affected parents is 50%. A genetic evaluation and/or sonography and advice to the children of the patients should be offered.
Treatment of Autosomal Dominant Polycystic Kidney Disease
Management of Flank Pain:
Bleeding of infection of cysts may be responsible for flank pain. If imaging can reveal altered cysts, percutanous management (cyst aspiration and sclerotherapy) or laparoscopic unroofing of cysts may be helpful. Studies show contradictory results.
Treatment of Renal Failure:
- Renal transplantation, often after nephrectomy of enlarged polycystic kidneys
Experimental Treatment Approaches:
The inhibition of the signal transduction of the tubulus cell proliferation has been studied without slowing the progression of renal function [Walz et al, 2010].
Prognosis of Autosomal Dominant Polycystic Kidney Disease (ADPKD):
ADPKD leads to dialysis in 2% by the age of 40, 23% by the age of 50 and 48% by the age of 73.
9% of patients with ADPKD die of subarachnoid hemorrhage (aneurysm hemorrhage). In addition, cerebral hemorrhage due to malignant hypertension is possible.
Overall prognosis has become better due to better treatment options of complications like urinary tract infection, nephrolithiasis, hypertension or renal insufficiency.
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W. Kuhn and G. Walz.
- Autosomal dominante polyzystische nierenerkrankung.
Dtsch Arztebl, 104 (44): 3022–8, 2007.
- Walz, G.; Budde, K.; Mannaa, M.; Nürnberger, J.; Wanner, C.; Sommerer, C.; Kunzendorf, U.; Banas, B.; Hörl, W. H.; Obermüller, N.; Arns, W.; Pavenstädt, H.; Gaedeke, J.; Büchert, M.; May, C.; Gschaidmeier, H.; Kramer, S. & Eckardt, K.
- Everolimus in
patients with autosomal dominant polycystic kidney disease.
J Med, 2010, 363, 830-840