New and Upcoming Treatments for Polycystic Kidney Disease.

ID#: 861 Description: Gross pathology of polycystic kidneys. Gross pathology of polycystic kidneys. Ureters are visible. Content Providers(s): CDC/Dr. Edwin P. Ewing, Jr. Creation Date: 1972 Copyright Restrictions: None - This image is in the public domain and thus free of any copyright restrictions. As a matter of courtesy we request that the content provider be credited and notified in any public or private usage of this image. (Photo credit: Wikipedia)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease of the kidney. For many years the treatment of this condition has been at a relative standstill when compared to the advances in therapy in other kidney diseases. However exciting new developments are currently in the research pipeline. These may finally allow specific therapies aimed at reducing the progression of the underlying problem, which has always been the unrestricted almost exponential growth of cysts within the kidney leading to kidney failure.

The main approach to the treatment of autosomal dominant polycystic kidney disease has been good control of blood pressure. This has been shown to reduce the rate of progression of the disease to end stage. Patients with ADPKD have been shown to have elevated levels of a hormone known as renin. Renin is important in regulating the balance of fluid and salts within the body and under normal circumstances renin signals the kidney to retain salt and water in order to maintain a normal volume of blood within the body. In ADPKD renin levels are increased, this may be due to the compression of sensitive areas within the kidney by enlarging cysts, compression of these areas may stimulate the production of renin. Renin and other substances directly produced because of high levels of renin result in increased cyst growth in ADPKD. This produces a viscous cycle of events that leads to ESRD.

Aliskerin is a novel drug which is now available, it functions as an inhibitor of renin. This drug has been shown to significantly lower the levels of renin in patients with ADPKD as well as providing better control of hypertension. This may be become a mainstay of the treatment of hypertension in ADPKD and should definitely be a drug to watch.

A very old drug that has been hypothesized to have a preventative role in ADPKD is colchicine. It is better known for its role in the management of gout. It is a potent anti inflammatory agent and has effects which may be useful in delaying cyst growth.

Cyst growth in ADPKD is based on the accumulation of fluids within the cyst by the action of a complex pump known as CFTR which is the same protein which is abnormal in cystic fibrosis. Inhibtors of CFTR have been available for some time. Recently they have been shown to be of efficacy in reducing cyst growth in mouse models of APKD.

The drug sirolimus which has been used for many years for immunosuppression post renal transplant has been shown in mammalian models of ADPKD to reduce the growth of cysts and is now the target of a study which will determine its role in the treatment of ADPKD in humans. The results of this study will be available in 2010.

Deutsch: Schema der beiden Proteine PKD1 und PKD2. Nach einer Vorlage von http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2003/MaloneyH/Polycystins.html (Photo credit: Wikipedia)

The focus thus far has been on possible therapies aimed at reducing the growth of cysts in order to reduce progression to ESRD. However other new therapies are available currently for the treatment of symptoms associated with ADPKD such as recurrent hematuria and pain.

Techniques aimed at reducing the number of existing cysts in the kidney have been shown to reduce symptoms. Options for this kind of therapy range from open surgery with direct decompression and decortication of cysts, laparoscopic procedures to reduce cyst volume and more recently ultrasound guided techniques where substances that destroy the structure of the cysts are injected under guidance. All these techniques have been proved beneficial in terms of symptom relief but have not been shown to delay progression of the kidney disease.

That  particular goal remains elusive but we are closer now than ever before.


photo credit: euthman