It is estimated that more than one million people worldwide suffering from ESRD are treated with some form of dialysis therapy, 10 to 15 percent of whom rely on a flexible daily PD regimen. The study, conducted by leading researchers in Mexico under the auspices of the Mexican health-care authorities , and supported by Baxter Healthcare Corporation and its Mexico affiliate, appears in the May issue (Volume 13, Issue 5) of the peer-reviewed publication, Journal of the American Society of Nephrology (JASN).
"This is a pivotal study for the nephrology community worldwide--for both doctors and patients," said Salim Mujais, M.D., vice president of Global Medical Affairs for Baxter's Renal business, and ADEMEX (Adequacy of Peritoneal Dialysis in Mexico) study author. "The findings challenge existing treatment recommendations for PD, which may allow for greater flexibility in prescribing the therapy and potentially enable more patients to benefit from it."
The ADEMEX study is a multi-center, prospective, randomized, controlled trial of 965 continuous ambulatory PD patients in Mexico who were followed for a minimum of two years. The trial was designed to examine the effect of increasing PD small solute clearances - a common measure of toxin removal and kidney function - on mortality outcomes in patients with ESRD.
Until now, many kidney specialists prescribing PD have believed that increasing small solute clearances would result in better survival. However, ADEMEX researchers found that increases in small solute clearances to the levels recommended by current treatment guidelines did not impact patient survival rates, even in higher-risk patients. Furthermore, body size, transport status (how quickly different solutes move across the peritoneal membrane of a patient) and other factors that have long been believed to impact survival made no measurable difference to patient outcomes in the ADEMEX study.
These results suggest PD may be more flexible and manageable for physicians to prescribe than previously believed by placing less emphasis on achieving the demanding small solute clearance rates currently recommended by some practice guidelines.
This new evidence allows for a better understanding of PD therapy--particularly the relationship between patient survival and the amount of small solute clearance achieved. Increasing small solute clearances can be achieved either by filling higher volumes of fluid into a patient's abdominal cavity or by performing more patient exchanges of fluid each day, which has often been difficult for patients, physicians, and nurses to achieve. This practice, in turn, has resulted in increased treatment cost, generally more complex prescription management, and may also be a contributing factor to higher rates of patient withdrawals from the therapy due to an inability to achieve defined target clearances.
"The ADEMEX study raises questions about the need to achieve currently recommended small solute clearance targets and suggests that minimum targets be better defined. It also challenges us to focus on treating the entire patient to achieve optimal outcomes, including fluid and nutrition management," said Karl D. Nolph, M.D., F.A.C.P, F.R.C.P.S., Curators' Emeritus Professor of Medicine, University of Missouri-Columbia.
Clinical Trial Mirrors Real-World Clinical Practice
Patients were randomized to two study groups: the active control group was prescribed a standard 2L exchange four times a day, which is the usual prescription used in Mexico in non-study patients (average peritoneal creatinine clearance of 45L per week). The treatment group was prescribed a modified dose by increasing fill volume (to 2.5 or 3L) or by increasing the number of exchanges to five daily with 2.5L to achieve a prescription target creatinine clearance of 60L per week.
Patients enrolled in the study were randomly assigned to the treatment or the control groups. At baseline, the study groups were equivalent with respect to demographic characteristics (age and gender), etiology of renal disease and prevalence of co-existing conditions (e.g., diabetes), as well as blood tests and physical examination measures (e.g., blood pressure, weight, height).
The clinical study design was successful in achieving the intended separation in peritoneal creatinine clearance measurements, which were higher in the intervention group, and in sustaining this separation throughout the course of the study. On average, the two groups were separated by a highly significant difference of 11 liters of creatinine clearance with no difference in survival between the two groups. In addition, significant separation was also achieved between the two groups relative to urea Kt/V, another measure of small solute clearance (control group peritoneal Kt/V averaged 1.62 vs. 2.13 for the treatment group), with no resulting difference in survival rates.
Treatment Options for People with Kidney Disease
It is expected that the number of people with ESRD is growing at about 7 to 8 percent annually. Declining kidney function results in higher levels of toxins and waste products in the blood. When the kidneys no longer adequately eliminate toxins from the bloodstream, dialysis helps to remove these unwanted substances from the body.
Two treatment options are available to patients with ESRD: transplantation and dialysis (hemodialysis or peritoneal). Peritoneal dialysis, which is a form of dialysis usually performed in a patient's home, uses the body's own peritoneal membrane, or abdominal lining, as the filter for removing extra fluids and waste. To gain access, a catheter is surgically inserted into the abdomen into which dialysis solution is infused. Through the process of osmosis, toxins and excess fluids move across the membrane into the solution, which is then drained from the abdomen.
The other form of therapy is called hemodialysis (HD), which removes waste products from the blood accessed through a needle inserted into a blood vessel. The blood is then pumped through an artificial kidney machine containing a filtering system called a dialyzer that cleanses the blood and returns the cleansed blood back to the body. Most people undergoing HD receive treatment at a special center, about three times a week for three to five hours a session.
Baxter is a leading provider of renal products and services worldwide. In 1956, the company introduced the first disposable coil dialyzer, a development that greatly enhanced the use and application of hemodialysis. Nearly 20 years later, Baxter was one of the first companies to introduce continuous ambulatory peritoneal dialysis.
Baxter International Inc. (NYSE:BAX) is a global health care company that, through its subsidiaries, provides critical therapies for people with life-threatening conditions. Baxter's bioscience, medication delivery and renal products and services are used to treat some of the most challenging medical conditions including cancer, hemophilia, immune deficiencies, infectious diseases, kidney disease and trauma.