Archive | Kidney Health

Nondiabetic CKD Patients May Not Really Benefit From Intensive Blood Pressure Control

According to a new study published online in the Journal of Internal Medicine, Intensive blood pressure (BP) control in nondiabetic patients with moderate-to-advanced chronic kidney disease (CKD) may not lower their cardiovascular risks and could increase their risk of acute kidney injury (AKI).

Yoshitsugu Obi, MD, of the University of California Irvine, and colleagues found that intensive BP control did not reduce the risk of fatal and nonfatal cardiovascular events among 891 patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2.  His findings came from a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) which consisted of 445 patients who received standard BP control and 446 who received intensive BP control.

AKI developed in 62 patients (13.9%) in the intensive control arm compared with 38 (8.5%) in the standard control arm. Intensive BP control was associated with a significant 73% increased risk of AKI.

Based on the current findings, Dr Obi and colleagues concluded that eGFR significantly modifies the risk-benefit profile of intensive BP control, which may provide little or no benefit and may be harmful to patients with an eGFR below 45 mL/min/1.73 m2.

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Reprogrammed Kidney Cells Could Make Transplants and Dialysis Obsolete

A recently published article in the Journal of the American Society Nephrology (JASN) indicates that patients’ own kidney cells can be gathered and reprogrammed, which means that in the future, fewer patients with kidney disease would need complicated, expensive procedures that affect their quality of life.

Sharon Ricardo, PhD, from Monash University in Clayton, Austria and her colleagues took cells from an individual’s kidney and reprogrammed them into progenitor cells, allowing the immature cells to form any type in the kidney.  The team inserted several key programming genes into the renal cells that made them capable of forming other cells.

In another study, Miguel Esteban, MD, PhD, of the Chinese Academy of Sciences in Guangzhou, China and his colleagues found that kidney cells collected from the patients’ urine can also be reprogrammed in this way.  The use of urine cells is easy to implement in a clinical setting, and the urine cells can be frozen and later thawed before they are reprogrammed.

If researchers are able to expand the reprogrammed cells, known as induced pluripotent stem cells (iPSCs), and return them to the patient, these IPSCs may restore the kidneys’ health and vitality.  The breakthroughs might help investigators to study the causes of kidney disease and to screen new drugs that could be used to treat them.

Ian Rogers, PhD, from Mount Sinai Hospital in Toronto wrote in an accompanying editorial that the two studies “demonstrate the feasibility of using kidney cells as a source o iPSCs and efficient production of adult iPSCs from urine means that cells can be collected at any time.”

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Study Finds Another Risk of Fall in Blood Pressure During Dialysis

A recent study led by researchers at the Stanford University School of Medicine found that there is an increased risk of blood clotting at the point where the patient’s blood vessels are connected to the dialysis machine known as the point of vascular access.  Researchers from the University of Utah also contributed to the study.  The study was published in the Journal of the American Society of Nephrology. This is yet another diverse consequence associated with a fall in blood pressure during dialysis for patients

Dialysis is a life-extending procedure for patients with kidney failure.  It involves sitting in a chair three or more times a week connected to an artificial kidney machine.  The patient’s blood is cleansed by exchanging fluid and electrolytes across a membrane during each three to four-hour session.

The fistula is one of the most common forms of vascular access.  It is created surgically from the patient’s own blood vessels.  The tubes used to transport blood to and from the body to the dialysis machine are connected to the body at this access point.  Clotting is one of the problems of an access point and can lead to its closure.

This study was based on results from the Hemodialysis study, known as HEMO, a National Institutes of Health-sponsored randomized clinical trial that collected data from 1,846 patients on hemodialysis from 1995 to 2000.  This study included data from 1,426 of these patients.

The team found that patients who had the most frequent episodes of low blood pressure during dialysis were two times more likely to have a clotted fistula than patients with the least episodes.

Roughly $2 billion a year is spent on vascular access in dialysis patients in the United States. Low blood pressure during dialysis occurs in about 25 percent of dialysis sessions.

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Elimination of HLA-B Matching Policy Improves Number of Minority Kidney Transplant Matches

A recent study published in the American Journal of Transplantation reveals that since the elimination of the kidney allocation priority for matching for HLA-B on May 7, 2003, access to kidney transplantation for minorities has improved.  This policy reduced the requirements for tissue matching.  Previously, national kidney allocation rules provided priority to candidates who shared HLA-B antigens with potential decreased donors.

Improvements in medications used to prevent transplant rejection reduced the benefit that previously had been associated with HLA-B matching.  Matching for HLA-B also had the unintended consequence of reducing transplant opportunities for minority candidates.

The study was led by Valarie Ashby, MA, of The University of Michigan Kidney Epidemiology and Cost Center.  The research team reviewed outcomes before and after this change using data from the Scientific Registry of Transplant Recipients. Analyses were based on 108,701 solitary deceased donor kidney recipients during the six years before and after the policy change.  It found that since the change in the kidney allocation policy, minorities are now transplanted in proportion to the percentage by which they are added to the waiting list.  In the six years before and after the policy change, the overall number of deceased donor transplants rose 23%, with a larger increase for minorities (40%) and a smaller increase for non-Hispanic whites (8%).

Ashby emphasizes, “The current policy, which offers no allocation priority for HLA-B similarity and gives only one and two points for matches at HLA-Dr, has improved access to transplantation for all minority groups and has not been associated with a decrease in 2-year graft survival during the first six years following the policy change.”

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IV Fluids Lowers Chances of Kidney Failure in Children

According to researchers at Washington University School of Medicine in St. Louis and other institutions, giving children intravenous fluids early in the course of an E. coli O157:H7 infection seems to lower the chances of developing severe kidney failure.  The results of this study were recently published in the Archives of Pediatric and Adolescent Medicine.

Children with E. coli O157:H7 have a high risk of hemolytic uremic syndrome (HUS), the most common cause of short-term, sudden-onset pediatric kidney failure.  Roughly 15 to 20 percent of children with this type of E. coli infection develop HUS.  Although most children recover and their kidneys heal, the syndrome can be fatal and might cause permanent kidney damage.

The first symptoms of E. coli O157:H7 are diarrhea and severe abdominal pain, and later symptoms include bloody diarrhea.  Kidney failure occurs because this strain of E. coli, called Shinga toxins, which hurt blood vessels. The kidneys are especially susceptible to the reduced blood flow that results from this injury. More than half of children with HUS develop kidney failure severe enough to require dialysis.

E. coli O157:H7 infection can come from eating undercooked hamburger, sprouts, unpasteurized fruit juices, dry-cured salami, lettuce, game meat and unpasteurized milk products, as well as exposure to contaminated water and contact with cattle. In the developed world, E. coli O157:H7 is the most common cause of acute kidney failure in otherwise healthy children.  The research team analyzed 50 children under 18 years old who were treated for diarrhea-associated HUS at 11 pediatric hospitals in the United States (St. Louis; Seattle; Sacramento, Calif.; Albuquerque, N.M.; Little Rock, Ark.; Milwaukee; Cincinnati and Columbus, Ohio; Indianapolis; and Memphis, Tenn.) and in Glasgow, Scotland.

Overall, 68 percent of the children stopped urinating. Of the 25 patients who had received no intravenous fluids in the first four days of illness, 84 percent stopped urinating. But in the other 25 patients who were given IV fluids to keep their kidneys working, only 52 percent stopped urinating.  Christina Ahn Hickey, MD, a third-year pediatrics resident at Washington University School of Medicine in St. Louis and St. Louis Children’s Hospital and the first author on the study, says that intravenous fluids are better for children than oral fluids because most of the children infected with E. coli O157:H7 are vomiting and having frequent bouts of diarrhea, so they cannot stay hydrated.

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Mismatch Could Lead to Rejection in Pediatric Kidney Transplants

Researchers found that antigen incompatibility hurts pediatric transplant outcomes but may often be unavoidable unless changes are made to the organ allocation system.  Peter G. Stock, MD, PhD, of the University of California San Francisco (UCSF), and colleagues found in a retrospective cohort study that one or two mismatches for human leukocyte antigen (HLA)-DRB1 between the donor and pediatric recipient increased risk of rejection by 70%.  In a recent issue of the Archives of Surgery, the team reported that the chances of a perfect match were small under the current local organ-sharing scheme.  The study included 178 patients younger than 21 who had successful kidney transplantation at UCSF with daclizumab (Zenapax) induction therapy from 1997 to 2006.

It is estimated that the chance of finding a donor without any HLA-DRB1 mismatch was also compatible for blood type was less than two per 100 local donors for most patients in the study.  The chances were even lower for Asian minorities.

Stock’s team stated that longer waiting time on dialysis can mean severe growth retardation and greater risk of dying for children who need a kidney.  They recommended moving beyond local boundaries for organ sharing to a regional donor poor to give children a better chance of finding their best HLA-DRB1 match.  The team also recommended calculating the frequency of a donor without any HLA-DRB1 mismatch for each patient on the waiting list.  They suggested that those with a higher probability of a perfect match could benefit from waiting, and those with a very low probability, such as ethnic minorities, should undergo transplantation regardless of HLA-DRB1 mismatch.  One- and five-year rates for graft outcomes were 97% and 82% for graft survival and 35% and 55% for rejection.

The team acknowledged that the study could not control for potential confounding from unmeasured factors like medication adherence, but restricting the sample to those on daclizumab precluded confounding from different immunosuppression regimens.  One of the study’s other limitations was the use of medical record review and examination of available blood samples for diagnosis of rejection and sensitization, which may have underestimated outcomes.

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Dallas Urologist Develops HIdES Technique to Minimize Kidney Surgery Scarring in Children and Young Adults

Patricio Gargollo, M.D., a urologist at UT Southwestern Medical Center in Dallas, has developed a minimally invasive procedure to eliminate scarring in kidney surgeries on his pediatric patients.  This new technique, which is just as effective as more common surgical techniques such as laparoscopy, is called hidden incision endoscopic surgery (HIdES).  A working port, a camera port, and a 5mm assistant port are place below the line of incision, and a second working port is placed close to the bellybutton.  This technique allows patients to hide their scars under a bathing suit and below the bikini line.  HIdES won the Best New Technique Award from the International Robotic Urology Symposium in 2010.

Gargollo has used this procedure for 18 cases in 17 patients between April and July 2010, and none of the patients experienced any complications.  Ages of the patients ranged from 3 to 20 years old, and the average age was 10 years old.

A recent study in the Journal of Urology reported that twelve patients and their parents who were asked to answer three questionnaires were more satisfied with the cosmetic appearance of incision scars left by HIdES than by laparascopic or open surgery.  These results were statistically significant.

Broader implications for this technique are that it may be applied to surgery on other parts of the body, including upper abdominal and some pelvic surgeries.  Gargollo reports the technique as being simple and easier to learn than techniques involving laparascopic surgery, which leads to small but visible scars.

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Johns Hopkins Students Create Device to Improve Kidney Dialysis Process

Bioengineering graduate students at Johns Hopkins University have invented a device that can reduce the risk of infection, clotting, and narrowing of the blood vessels in kidney dialysis patients.

The students discovered the need for such a device last year when they accompanied physicians on hospital rounds as part of their program.  One doctor had to perform a procedure to open a narrowed blood vessel at a kidney patient’s dialysis access site.  The students found out that this narrowing was a common problem among kidney dialysis patients.

These students learned that 350,000 people in the United States and 1.5 million people worldwide experience kidney failure that requires them to undergo hemodialysis to prevent a fatal buildup of toxins in the bloodstream.  They found out that the three most common ways to connect the machine to the patient’s bloodstream only work for a short time because of problems with infection, blood clots and narrowing of the blood vessels.  The students found these current options to be “grossly inadequate” and lead to increased healthcare expenses and sometimes patient deaths.

While the device, the Hemova Port, has not been tested in human patients, it has been used in tests on animals.  The prototype is designed to be implanted under the skin of a patient’s leg, giving technicians easy access to the patient’s bloodstream and reducing the risk of infection and clotting.  The device’s two valves can be easily opened and closed at the beginning and end of a dialysis procedure with a technician’s syringe from outside the skin.  Furthermore, the devise includes a simple cleaning system, which helps prevent infections.

The students’ device won them a $10,000 first prize in the 2011 American Society of Mechanical Engineers (ASME) showcase.  The five biomedical engineering students on the team were enrolled in a one-year master’s degree program at Johns Hopkins University’s Center for Bioengineering Innovation and Design.  Sherri Hall, Peter Li, Shishira Nagesh, Mary O’Grady and Thora Thorgilsdottir all recently graduated, but Li, along with Brandon Doan, has remained in Baltimore to form a company that will continue to test and develop the project.  The other four team members will serve as consultants for the project.  The team has filed for three provisional patents covering their device and applied for grants for further testing.

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Relationship Between Kidney Cancer and Arsenic Found

A new study in the Journal of Urology finds that people with moderately elevated levels of arsenic in their urine may have an increased risk of kidney cancer, especially if they have high blood pressure and kidney disease.  This does not necessarily mean that arsenic leads to kidney cancers.  Researchers report that one possibility is that kidney cancer leads to higher levels of arsenic in the urine.

While high levels of arsenic have been linked to many forms of cancer and some studies have linked moderately elevated levels of arsenic to high blood pressure and type 2 diabetes, the effects of low-level arsenic exposure are not yet fully known.

This new study was conducted in Taipei, Taiwan, where researchers looked at the arsenic levels in the urine of people who live in an area with low arsenic concentrations in the drinking water.  In Taipei, arsenic levels in tap water ranges from undetectable to 4 micrograms per liter, which is below the 10 micrograms per liter allowed by the U.S. Environmental Protection Agency (EPA).  Researchers compared 132 patients with kidney cancer to 260 cancer-free adults of the same age and sex.

In general, there was a relationship between higher arsenic levels in the urine and higher chances of kidney cancer.  This relationship was strongest for people who had high blood pressure or impaired kidney function, which have been established as risk factors for kidney cancer.  Study participants with both of these conditions and relatively high levels of arsenic in their urine were six times more likely than people with none of these risk factors to contract kidney cancer.  Participants with two of these risk factors had a quadruple rate of increase in risk of kidney cancer.

One possibility proposed by both researchers involved with the study and researcher who were not was that arsenic exposure led to high blood pressure or kidney disease in some people, which, in turn, contributed to their kidney cancer.

An estimated 13 million Americans live in areas where the public water supply exceeds the EPA’s limit of 10 micrograms per liter, and water from unregulated private wells may contain too much arsenic.

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New Test Better Predicts Kidney Disease

A recent study conducted by researchers at the San Francisco VA Medical Center and the University of California, San Francisco, revealed that cystatin C, a blood marker of kidney function, proved significantly more accurate than the standard blood marker, creatinine, in predicting serious complications of kidney disease.

Researchers found that only patients with chronic kidney disease who have both high levels of creatinine levels and cystatin C are at high risk for death, cardiovascular disease, heart failure, or kidney failure.  Those patients with only high creatinine but normal cystatin C levels had risks similar to those with normal creatinine levels.

“A small but important segment” of the study population was missed by creatinine but identified by cystatin C as being at significant risk of serious complications, said lead author Carmen A. Peralta, MD, MAS, an SFVAMC researcher and an assistant professor of medicine in residence in the division of nephrology at UCSF.

The study included 11,909 participants and was published on December 16, 2010, in the JASN Express section of the Journal of the American Society of Nephrology.  The Multi-Ethnic Study of Atherosclerosis and the Cardiovascular Health Study provided the patient data for the researchers.

Principal investigator Michael G. Shlipak, MD, MPH, chief of general internal medicine at SFVAMC, explains that the study reveals a clinical use for cystatin C as a method for confirming a diagnosis of chronic kidney disease.  Shlipak has long proclaimed the benefits of identifying cystatin C levels, and believes it to be an alternative, accurate, and reliable marker of kidney function.

Both cystatin C and creatinine are substances made in the body and filtered by the kidneys.  If the body contains high levels of either, then it may mean the kidneys are losing the ability to filter these substances and kidney function has been altered.

“However, creatinine is a byproduct made in muscles, so it is affected by what you eat and especially by how much muscle you have.  Thus, a bodybuilder with healthy kidneys might have an elevated creatinine level because of high muscle mass, whereas a frail elderly person might have normal or even low levels of creatinine, but in fact this person’s kidneys are not working well—it’s just that there’s not much creatinine because there’s not much muscle,” explains Peralta.

On the other hand, cystatin C is a protein made in cells throughout the body.  “In studies so far, it does not seem to be that affected by age or muscle mass or diet,” said Shlipak, who is also a professor in residence of medicine and epidemiology and biostatistics at UCSF.

Cystatin C is a low cost, as little as $17 per test, addition that should be made to the current method for confirming or staging chronic kidney disease, proposes Shlipak.  “It’s vital that we have an accurate diagnostic test, because kidney disease does not show symptoms until it’s too late, when your kidneys have almost failed completely,” he added.

“Being missed by creatinine is an important limitation in our current method of diagnosing kidney disease,” said Peralta.  And being incorrectly diagnosed with kidney disease by using inaccurate test results can also decrease the quality of life for patients.  “There is a fear and psychological stress, particularly in communities of color, where people have a lot of friends and family members who are on dialysis,” noted Peralta.  “You can also be subjected to unnecessary and expensive tests and medications.”

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