HALT PKD Treatment Breakthrough
In 2014, two PKD treatment trials concluded. Below are the findings:
Paraphrased from www.haltpkd.org:
The Polycystic Kidney Disease Treatment Network (PKD-TN) USA developed the HALT PKD clinical trials to evaluate certain FDA approved drugs believed to be potentially effective in slowing kidney growth in persons with PKD. Seven centers across the United States participated in the two trials.
The studies recruited both male and female participants between the ages of 15 and 64. The trials targeted different levels of kidney function. Study A: early disease defined by GFR >60 mL/min/1.73 m2 and Study B: moderately advanced disease defined by GFR 25-60 mL/min/1.73 m2.
Primary Outcome Measures:
- Study A: Change in total kidney volume, as assessed by abdominal MR at baseline, 2 years, and 4 years follow-up.
- Study B: Time to the 50% reduction of baseline eGFR, ESRD (initiation of dialysis or preemptive transplant), or death.
Paraphrased from http://www.pkdcure.org/news/halt-study-results-released
HALT-PKD Study Finds Rigorous Blood-Pressure Control Could Slow Cyst Growth in ADPKD
Saturday, Nov. 15, 2014
A presentation regarding the results of the HALT-PKD clinical trial was shared this morning at the American Society of Nephrology (ASN) Kidney Week meeting.
The HALT study is important to the PKD community because neither the optimal blood pressure target levels, nor the best medications for control of blood pressure in ADPKD, were known when the study was started in 2006 (the study was completed in June 2014). Currently, the complications of hypertension, including stroke and heart attack, affect many more individuals with ADPKD than ADPKD-specific complications such as liver cysts or brain aneurysms.
According to the New England Journal of Medicine: “These two studies provide important guidance for the care of patients with ADPKD. They show that blood pressure can be controlled with ACE inhibitors, drugs that have an acceptable safety profile. They suggest that rigorous blood-pressure control, early in the disease process, may slow cyst growth…”
From ASN’s Press Release:
In a study of 558 patients with ADPKD, rigorous blood pressure control conferred benefits over standard blood pressure control related to a reduced rate of increase in total kidney volume and greater declines in measures of heart and kidney problems.
“Hypertension was very well controlled in both treatment groups. The results emphasize the potential importance of early detection and aggressive treatment of hypertension in ADPKD,” said lead author Arlene Chapman, M.D.
Also in a study of 486 ADPKD patients with stage 3 chronic kidney disease, treatment with an angiotensin-converting enzyme inhibitor (ACE-1) was safe and by itself sufficient to achieve blood pressure control in the majority of patients.
“Both studies showed that ACE inhibitors alone or in combination with angiotensin receptor blockers are safe and well tolerated and achieve excellent blood pressure control in the majority of patients with ADPKD,” said lead author Vincente Torres, M.D., Ph.D. “However, both failed to demonstrate any superiority of dual blockage with an ACE inhibitor and an angiotensin receptor blocker compared to an ACE inhibitor alone.”
For current PKD patients this means that no matter what stage of the disease you are at, you MUST have your blood pressure regularly monitored by your GP. If your GP doesn’t appreciate the importance of doing so, and of early intervention at the first sign of high blood pressure (hypertension), then you MUST show them the information above. You can even self-monitor your blood pressure, if you wish, as monitors are available for purchase from most pharmacies. Carefully follow the instructions that come with the unit.
If your blood pressure is increasing your GP should prescribe ACE inhibitor medication. These are used to control blood pressure in a range of conditions.
Paraphrased from http://www.patient.co.uk/health/ace-inhibitors:
“ACE inhibitors prevent the body from creating a hormone known as angiotensin II. They do this by blocking (inhibiting) a chemical called angiotensin-converting enzyme. This has a variety of effects but essentially relaxes blood vessels and helps to reduce the amount of water re-absorbed by the kidneys. These actions help to decrease blood pressure, as explained below.
Your body has a number of different ways of maintaining your blood pressure, but there are two main elements. One of the major factors is the resistance of the body’s blood vessels. If the blood vessels tighten (constrict), resistance increases. If the blood vessels relax (dilate), the resistance is lower. If you have the same amount of fluid travelling in one vessel, the pressure will be higher when the vessel is constricted than when it is relaxed.
The other major factor influencing blood pressure is how much blood is pumped out of the heart. In a healthy person this depends on your heart rate (pulse) and the amount of blood that enters and leaves the heart’s chambers. This is known as cardiac output.
Your blood pressure is the result of combining these two factors. It will be high if your vessels are constricted and there is lots of blood circulating through the heart. It will be lower if your vessels are dilated and there is less blood circulating through the heart. ACE inhibitors work by targeting both of these systems.
Blood is not just made up of red blood cells but also contains a large amount of fluid called plasma. Your kidneys control how much fluid you keep in your blood and how much you lose as urine. By retaining (re-absorbing) water that would otherwise become urine, the kidneys increase the amount of fluid in the blood. This increases blood volume.
In good health you have an intricate system set up to maintain your blood pressure. When your kidneys sense that your blood pressure has dropped, a substance called renin is released into the bloodstream. Renin works on another chemical to form angiotensin I. Then the angiotensin-converting enzyme changes angiotensin I to angiotensin II.
Angiotensin II is the active hormone. It has three main effects:
- Constriction of blood vessels.
- Re-absorption of water by the kidneys.
- Release of the hormone aldosterone which also causes water re-absorption by the kidneys.
Increasing the volume of the blood by adding more water and constricting your blood vessels increases blood pressure.
ACE inhibitors stop angiotensin I from becoming angiotensin II. This reduces the amount of angiotensin II which causes blood vessels to dilate. The amount of water put back into the blood by the kidneys decreases. These actions reduce blood pressure.
- In high blood pressure (hypertension), ACE inhibitors should help to reduce the blood pressure.
- In heart failure, there may be too much circulating fluid in the blood vessels. ACE inhibitors help to reduce this. They appear to have a protective effect on the heart and slow the progression of the heart failure” and kidney disease.