Test for Kidney Transplant Management Cleared by FDA

The U.S. Food and Drug Administration today announced that it has cleared a test to help manage potential organ rejection in kidney transplant patients. The test, called QMS Everolimus Immunoassay, monitors the blood level of everolimus, a drug that helps prevent rejection in kidney transplants

Everolimus, marketed under the trade name Zortress, was approved by FDA in April 2010 for use in adult kidney transplant patients who are at low-to-moderate immunologic risk.. [Read more…]

Undiagnosed Diabetes Patients May Also Have Undiagnosed Kidney Disease

Millions of Americans may have chronic kidney disease (CKD) and not know it, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN).

“Our research indicates that much of the CKD burden in the United States is in persons with prediabetes and undiagnosed diabetes, who are not being screened for CKD,” comments Laura C. Plantinga, ScM (University of California, San Francisco). The researchers believe that broader screening may be needed to detect patients with these two “relatively silent yet harmful diseases.”

In a study funded by the Centers for Disease Control and Prevention, Plantinga and colleagues analyzed a nationally representative sample of about 8,200 Americans from the National Health and Nutrition Examination Survey. Standard laboratory tests were used to assess the rate of CKD, focusing on people with undiagnosed diabetes or prediabetes (sometimes called “borderline” diabetes).

Based on lab tests, 42 percent of subjects with undiagnosed diabetes had CKD—similar to the 40 percent rate in those with diagnosed diabetes. “Only a small percentage of participants were aware of the diagnosis of CKD,” says Plantinga.

In addition, CKD was present in nearly 18 percent of subjects with prediabetes. Among participants without diabetes or prediabetes, the rate of CKD was about 11 percent.

“Based on these results, there may be a substantial number of individuals in the United States—up to 13 million—who have undiagnosed diabetes or prediabetes and who already have signs of kidney damage and/or reduced kidney function,” says Plantinga. Such patients would be at high risk for worsening kidney disease and diabetes, and for the poor outcomes associated with both conditions—including cardiovascular disease and death.

Diabetes is the most important risk factor for kidney disease, but the new results suggest that harmful effects on the kidneys may be occurring even before diabetes is diagnosed. “Persons at risk for diabetes and their health care providers should be aware that earlier screening for both diabetes and kidney disease may be warranted,” says Plantinga. “Earlier screening would allow for appropriate, timely medical care to prevent further progression and poor outcomes.”

In an accompanying editorial, Gary C. Curhan, MD, ScD (Brigham and Women’s Hospital, Boston, MA) calls for CKD screening to be extended to patients with prediabetes. Curhan also suggests that it may be time to consider the concept of “pre-CKD”—identifying patients at a very early stage of CKD when the disease may still be preventable or reversible.

Although the study shows an association, it cannot determine whether the development of CKD followed the development of diabetes, or whether CKD was actually caused by diabetes. There is also likely some misclassification of both diseases, although the association remained significant when tested under a range of different assumptions.

Study co-authors include Deidra C. Crews, Josef Coresh, Edgar R. Miller III (Johns Hopkins University, Baltimore, MD), Rajiv Saran, Elizabeth Hedgeman (University of Michigan, Ann Arbor), Jerry Yee (Henry Ford Hospital, Detroit, MI), Meda Pavkov, Mark S. Eberhardt, Desmond E. Williams (Centers for Disease Control and Prevention, Atlanta, GA), and Neil R. Powe (University of California, San Francisco) on behalf of the Centers for Disease Control and Prevention Chronic Kidney Disease Surveillance Team.

Disclosures: The authors reported no financial disclosures.

Source: Clinical Journal of the American Society Nephrology (CJASN), “Prevalence of Chronic Kidney Disease in US Adults with Undiagnosed Diabetes or Prediabetes,” (doi 10.2215/CJN.07891109) and the accompanying editorial,” Pre-Diabetes, Pre-Hypertension…is it time for Pre-CKD?” (doi 10.2215/CJN.01650210)

Avosentan Reduces Urinary Protein Loss but May Cause Serious Side Effects, Says Study

The drug avosentan substantially reduces urinary protein loss in people with type 2 diabetes and kidney disease, but the drug causes serious side effects, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The results suggest that lower doses of avosentan may have a more favorable risk/benefit ratio for patients.

Despite aggressive treatments, individuals with kidney disease often experience proteinuria, or excessive loss of protein in the urine, which increases kidney damage. A key factor in the development of proteinuria is endothelin, which by constricting blood vessels and raising blood pressure, causes the kidney’s filtering function to deteriorate. Researchers suspect that blocking the endothelin peptide could be a promising new treatment strategy for patients who develop proteinuria. Endothelin antagonists such as oral avosentan are already available and are prescribed for patients with cardiovascular conditions.

Johannes Mann, MD (Schwabing General Hospital and KfH Kidney Centre, in Munchen, Germany) and his colleagues examined the effects of avosentan on proteinuria and kidney function in patients with type 2 diabetes and kidney disease through a multicenter, multinational, double-blind, controlled trial. The Avosentan ASCEND study enrolled 1392 patients already being treated for kidney disease and randomized them to receive avosentan 25 mg, avosentan 50 mg, or placebo.

While avosentan at either dose lowered patients’ urinary protein excretion by 40%-50% (compared with less than 10% in patients taking placebo), individuals taking the drug experienced a high incidence of serious, sometimes life-threatening side effects. These included complications of fluid overload such as pulmonary edema, as well as congestive heart failure. In addition, there were more deaths in the groups taking avosentan (21 and 17) than in the group taking placebo (12).

Dr. Mann noted that the findings from the ASCEND trial highlight the risks and potential benefits of endothelin antagonists in kidney disease patients with proteinuria and will help investigators design future studies to test the drugs’ potential. Specifically, lower doses of avosentan may generate more positive results.

Speedel Pharma Ltd, Switzerland, sponsored the study and appointed the contract research organization Quintiles Ltd for study set-up, initiation, management, and analysis. (Disclosures: Susan Kuranoff and Thomas Littke were employees of the sponsor, and all other authors have consulting funds from Speedel Pharma Ltd.

Source: Journal of the American Society Nephrology, “Avosentan for Overt Diabetic Nephropathy,” online ed. (February 18, 2010, doi 10.1681/ASN.2009060593); American Society of Nephrology (ASN).

Robotic Surgery Faster in Repairing Kidney Blockages

A comparison of two types of minimally invasive surgery to repair kidney blockages that prevent urine from draining normally to the bladder found that robot-assisted surgery was faster and resulted in less blood loss and shorter hospital stays.

Reporting in the Canadian Journal of Urology, Ashok Hemal, M.D., a urologic surgeon from Wake Forest University Baptist Medical Center, compared laparoscopic and robot-assisted surgery for repairing the blockage, known as uretero-pelvic junction obstruction. Following the patients for 18 months showed that both options were equally successful, but the robot-assisted technique had several advantages.

On average, robot-assisted surgery was 50 percent faster (98-minute versus 145-minute average), resulted in 60 percent less blood loss (40ml versus 101ml average), and required a two-day hospital stay, versus 3.5 days for laparoscopic surgery.

“This was one of the first studies where a single surgeon at one center performed both types of surgery and compared the results,” said Hemal, director of the Robotic and Minimally Invasive Urologic Surgery Program at Wake Forest Baptist. “It allows for a more accurate comparison of surgical options than multiple physicians performing the surgeries. The results showed that robot-assisted surgery had significant advantages for this condition. It is also generally easier for surgeons to learn.”

All 60 patients had a procedure known as pyeloplasty that involves reconstructing the narrow area where part of the kidney meets the ureter, the tube that carries the urine from the renal pelvis into the bladder. Blockages in this area can be the result of birth defects or, in adults, from injury, previous surgery or disorders that can cause inflammation of the upper urinary tract.

Previously the repair required a large incision. New technology led to minimally invasive approaches that require only small incisions — laparoscopic surgery, in which the surgeon directly manipulates a viewing device and operating instruments inserted into the abdomen, and robot-assisted surgery, in which the surgeon sits at a console and uses hand and finger movements to control centimeter-size instruments while viewing the surgical site on a screen.

Various studies have reported on the results of the options, but this is one of the first studies in which a surgeon with expertise in both options compared them. Hemal treated 30 patients with laparoscopic surgery and 30 with robot-assisted surgery.

“The evolution of laparoscopic surgery in urology has been limited because it is technically challenging and requires the surgeon to be proficient in advanced suturing,” said Hemal. “Robot-assisted surgery offers a way of overcoming some of the major impediments of laparoscopic surgery. This study shows the two options are equally effective and that robot-assisted surgery has several advantages.”

Hemal’s colleagues on the report are Satyadip Mukherjee, M.D., and Kaku Singh, M.D., both with the All India Institute of Medical Sciences in New Delhi, where the surgeries were performed.

Source: Canadian Journal of Uroloygy, Wake Forest University Baptist Medical Center (2/18/2010)