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

Rituximab and FSGS.

Intermed. mag. Image: Focal segmental glomerulosclerosis - high mag.jpg (Photo credit: Wikipedia)

FSGS or focal and segmental glomerulosclerosis is the most common non diabetic cause of nephrotic syndrome in the world. This is particularly true among African Americans. The treatment of this disorder is frequently complicated by non response to the primary modality of treatment which is steroids. Combine this with the need for high doses to produce an effect, the known toxicity of steroids and we begin to see there is need for a better drug. Unfortunately many of the drugs attempted are also toxic or produce a situation of dependence where the disease may go into remission but it quickly relapses when the drug is discontinued. Rituximab is a drug that has had some success in lupus nephritis and now it is undergoing trials in patients with FSGS. The current study by investigators from spain, looked at a small cohort of 8 patients and found that rituximab was effective only in the minority of patients, only 3 patients had a favourable response to the drug. It is however interesting that in at least one patient that responded there was a durable massive reduction in proteinuria. The fact that this occurred should inspire some hope that the drug may be useful if an effective regimen capable of benefiting more patients can be elucidated.

Related articles

• Steroids and Kidney Disease (allkidney.com)
• New Treatments For FSGS -ASN Conference (allkidney.com)

New Drugs: Pirfenidone a new hope in diabetic kidney disease.

Diabetic nephropathy may be slowed by several means, the standard of care is blood pressure control, prescription of drugs which reduce protein in the urine and dietary changes. However the condition is almost always progressive despite these interventions.

Pirfenidone is not a particularly new drug, it has been known as an antifibrotic agent in that it reduces the formation of the primary constituent of scar tissue. Scar tissue referred to as fibrosis at the microscopic level forms as a consequence of inflammation during the process of healing.

Diabetic kidney disease has been associated with a unique type of scarring which occurs in the portion of the kidney responsible for filtering the blood. Over time this delicate filter is destroyed by fibrosis.

http://www.chemblink.com/products/53179-13-8.htm

The current study found that pirfenidone when given to laboratory mice reduced the damage to their kidneys by reducing the precursors of inflammation that lead to scarring. This is exciting news as pirfenidone directly targets a pathway that was previously not directly influenced by current therapy. This would therefore be a valuable adjunctive medication to be used alongside established treatment should the drug live up to its promise.

New Drugs: Pirfenidone a new hope in diabetic kidney disease.

Diabetic nephropathy may be slowed by several means, the standard of care is blood pressure control, prescription of drugs which reduce protein in the urine and dietary changes. However the condition is almost always progressive despite these interventions.

Pirfenidone is not a particularly new drug, it has been known as an antifibrotic agent in that it reduces the formation of the primary constituent of scar tissue. Scar tissue referred to as fibrosis at the microscopic level forms as a consequence of inflammation during the process of healing.

Diabetic kidney disease has been associated with a unique type of scarring which occurs in the portion of the kidney responsible for filtering the blood. Over time this delicate filter is destroyed by fibrosis.

http://www.chemblink.com/products/53179-13-8.htm

The current study found that pirfenidone when given to laboratory mice reduced the damage to their kidneys by reducing the precursors of inflammation that lead to scarring. This is exciting news as pirfenidone directly targets a pathway that was previously not directly influenced by current therapy. This would therefore be a valuable adjunctive medication to be used alongside established treatment should the drug live up to its promise.