Tarif Bakdash, a pediatric neurologist and Assistant Professor of Bioethicis at Damascus University, Syria, argues that “poor people should have the right to exercise their autonomy by selling their organs.”

The argument that we should protect the poor from being exploited by banning them from selling their organs is a myth, says Dr Bakdash. “The poor are always exploited from the day they are born,” he says, “and in all avenues of life. The only thing of value left for some of them is their bodies.” Dr Bakdash believes that the sale of organs should be legalized and regulated.

But Nancy Scheper-Hughes, Professor of Medical Anthropology at the University of California, Berkeley, and Director of Organs Watch, argues that “dividing the world into organ buyers and sellers is a medical, social, and moral tragedy.”

Research done by Professor Schepher Hughes and colleagues found that among hundreds of kidney sellers in Moldova, Romania, Turkey, the Philippines, and Brazil, many suffer post-operatively from chronic pain, social isolation, stigma, and severe psychological problems. “While many individuals have benefited from the ability to get the organs they need through illegal circuits,” she says, “the violence associated with kidney selling gives reason to pause.”

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Citation: Bakdash T, Scheper-Hughes N (2006) Is it ethical for patients with renal disease to purchase kidneys from the world’s poor? PLoS Med 3(10): e349.

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The researchers also found that published trials provide no information on renal function in participants or the effect of interventions on participants with renal disease. This results in poor information on how to treat cardiovascular disease in CKD patients.

“Inclusion and reporting of kidney disease patients in cardiovascular trials must improve,” said senior investigator Chirag Parikh, M.D., assistant professor in the Section of Nephrology at the Yale School of Medicine. “Alternatively, we need to design separate trials for cardiovascular treatment exclusively in CKD patients.”

Parikh and Steven Coca, renal fellow at Yale, reviewed 153 clinical trials for treatment of cardiovascular disease from 11 major medical and subspecialty journals published from 1985 through 2005. Patients with kidney disease were excluded from 56 percent of the trials and were also more likely to be excluded from multi-center trials. Only five percent of original articles reported the proportion of enrolled patients with renal disease and only 10 percent reported mean baseline renal function.

Cardiovascular death remains the leading cause of death in patients with CKD and over nine million people in the U.S. have CKD.

Parikh and Coca, who are also affiliated with the Clinical Epidemiology Research Center at the VA Connecticut Healthcare System, said there are many biological reasons cardiovascular disease in patients with CKD may be different from that in general population and interfere with effectiveness of existing therapies and prognosis. Patients with CKD have abnormally high levels of protein in their urine, elevated homocysteine levels, and a higher burden of hypertension, anemia and inflammatory factors.

“We strongly urge researchers to universally adopt standards for reporting of renal disease in cardiovascular studies,” said Parikh. “Funding agencies should make these studies a priority to gather information in this increasingly important subgroup of patients.”

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Citation: JAMA, Vol. 296, No. 11 (September 20, 2006)

These awards, which were presented during AAKP’s 32nd Annual Convention in Las Vegas, are designed to honor a patient and physician who have performed extraordinary service on behalf of those with CKD.

The AAKP Spirit of Service Award was established to honor a kidney patient who raises awareness of CKD in his or her community.

This year’s recipient, Jenna Lynne Smith of Iowa City, Iowa, is an inspiring example to fellow patients. An end-stage renal disease (ESRD) patient, she has used peritoneal dialysis, received a living-related kidney transplant, and currently uses hemodialysis to treat her kidneys.

She volunteers for numerous organizations, such as Kidneeds, an organization started by her family to support research to find a cure for membranoproliferative glomerulonephritis type II, known as MPGNII. She makes jewelry, which can be found in jewelry stores throughout Iowa, as well as greeting cards to raise money for kidney research. She is also a regular participant in Habitat for Humanity.

In addition, she received an award by the 2005 Iowa Medical Society Alliance to recognize her community service endeavors, as well as the Peterson Scholarship through the University of Iowa Foundation for her scholastic achievements.

The AAKP Visionary Award was created to pay tribute to a physician for his or her outstanding performance in CKD education.

This year’s recipient, Jay Wish, MD, of Cleveland, has made a positive impact on kidney patients throughout the country.

He was selected for his exemplary efforts in patient education. Dr. Wish is a member of the AAKP Medical Advisory Board and regularly contributes to AAKP’s patient publications, including Kidney Beginnings: The Magazine. He has also participated in important, renal organizations, such as Be Active, the American Society of Nephrology, the International Society of Nephrology, the Renal Physicians Association, and the National Kidney Foundation. In addition, he has worked with ESRD Networks throughout the country for more than 20 years.

Each of these individuals spends countless hours ensuring that kidney patients, especially those with CKD, understand their disease and live life to the fullest. Both recipients have helped increase awareness of CKD among patients, family members and the general public.

It is estimated that CKD – a condition affecting the kidneys that may progress to kidney failure – affects more than 12 million Americans. The most common causes of CKD are diabetes and hypertension (high blood pressure). AAKP would like to thank Ortho Biotech Products, L.P., for its generous sponsorship of the CKD awards presentation.

The study, which drew its findings from patient information gathered by the North American Pediatric Renal Transplant Cooperative Studies, revealed that age, race, the cause of the kidney failure and the amount of residual kidney function were associated with short stature in children with renal kidney disease.

The data of 5,615 child patients registered in a chronic renal failure registry between 1994 and 2004 was reviewed by Dr. Verna Yiu, an associate professor of pediatrics at the University of Alberta in Edmonton, Canada and fellow researchers from the University of Texas Southwestern Medical Centre, the Children’s Medical Centre of Dallas, University of North Carolina and the EMMES Corporation.

The results were published recently in Pediatric Nephrology.

Of the more than 5,600 patients studied, 36.9 per cent had impaired height growth. Of those, 44.4 per cent were Hispanic, 36.1 per cent were Caucasian and 31.9 per cent were black. Younger children aged zero to 12 years also had lower height growth than children 12 and older. As well, children with congenital renal disease, as opposed to those who acquired the disease, had the lowest rate of height growth. Overall, more than one-third of children with kidney disease met the criteria for short stature.

The researchers are unsure as to why growth is delayed for the first two years of life in children with kidney disease, but believe nutrition and the body’s losses of electrolytes play roles.

Ethnicity also appeared to play a role, though standardized norms for height may not take into account natural height differences among ethnic groups, Yiu said. The majority of children in the study with acquired renal disease appeared to be black (39 per cent) versus 17 per cent for the remainder of the registry’s ethnicity.

Another factor which affects height is congenital kidney disease. “Children who have kidney disease from birth will have more long-term effects on growth, versus an older child who attains normal height prior to becoming ill,” Dr. Yiu said. As well, the more severe the renal failure is, the more a child’s growth is hampered by the worsening effects of kidney disease, she noted.

Despite recent advances in managing children with chronic kidney disease, growth remains suboptimal, so it’s important determine what factors play a role, said Dr. Yiu.

“By identifying the factors that contribute to short stature in these children, we hope to be able to address the issues early on so that the growth failure can be treated and corrected in appropriate ways such as intensive nutritional programs and therapies such as growth hormone,” Dr. Yiu said.

“Our study shows a 38 percent increased risk of progressive chronic kidney disease in hypertensive African-Americans classified as having the metabolic syndrome,” comments Dr. J. P. Lea of Emory University, lead author of the new study. “This has important public health implications, as treatments are available to reduce the severity of the metabolic syndrome and may have an impact on reducing the rate of progressive kidney disease.”

Dr. Lea and her fellow researchers analyzed data from a large study of treatment for hypertension (high blood pressure) in African-Americans. Twenty-five percent of the patients had metabolic syndrome, meeting at least three of the five diagnostic criteria: high blood sugar, low high-density lipoprotein (“good”) cholesterol, high triglycerides, and obesity, and high blood pressure. (All patients automatically had one of the criteria, because all were hypertensive.)

Sometimes called insulin resistance syndrome or “syndrome X,” metabolic syndrome is a known risk factor for diabetes, cardiovascular disease, and chronic kidney disease (CKD). Patients with CKD have gradual, irreversible loss of kidney function. Over time, CKD can lead to end-stage renal disease (ESRD)-permanent loss of kidney function requiring dialysis or kidney transplantation.

After four years’ follow-up, the patients with metabolic syndrome had significantly higher rates of progressive CKD, defined as continued declines in kidney function, ESRD, or death. The risk of progressive CKD was about 40 percent higher for patients with metabolic syndrome, even after adjustment for other factors known to affect kidney disease outcomes-such as age, sex, obesity, and initial level of kidney function.

On their own, none of the individual metabolic syndrome risk factors was related to progressive CKD. The increased risk associated with metabolic syndrome was also unaffected by which blood pressure treatment the patients received.

Although previous studies have linked metabolic syndrome to an increased risk of CKD, it has been unclear whether metabolic syndrome contributes to progression of established CKD. Once CKD is present, African-Americans have higher rates of progression to ESRD.

“Diabetes and hypertension are the leading causes of kidney failure, which disproportionately affects African-Americans,” says Dr. Lea. “Despite good treatments for diabetes and hypertension, there is still a continued rise in the rates of kidney disease. More studies are needed to determine why some patients with CKD progress more rapidly to ESRD-that is, to dialysis-than others.”

This study of African-Americans with high blood pressure finds that metabolic syndrome is a significant risk factor for progressive CKD. “Metabolic syndrome can contribute to worsening kidney disease,” adds Dr. Lea. “That’s important, because if we can reduce the severity of metabolic syndrome through diet and medication, it may help to reduce the rate of progressive kidney disease-and thus delay ESRD and the need for dialysis therapy, which is very costly and debilitating.”

Medical doctor and researcher Bjoern Egil Vikse from the Department of Medicine at University of Bergeb is the first author of an upcoming article in the March issue of the Journal of the American Society of Nephrology.

Vikse explains that there were two reasons for becoming involved in this work. The first was that a collegaue had previously found a strong correlation between pre-eclampsia and a later incidence of cardiovascular disease. The second is that UiB researchers have a unique research tool. They have access to two large databases: one is a birth registry; the other is a kidney biopsy registry. This enables them to use large, well-documented data pools in their work.

The Birth Registry provided Vikse with data from 1967 and the Kidney Biopsy Registry dates from 1988.

Unexpectedly strong correlation

Vikse and his colleagues first compared data from the two registries to see if there was a correlation between the children of mothers who had experienced pre-eclampsia and incidence of kidney disease in these children. They found no correlation.

They then compared the two databases for a possible correlation between the incidence of pre-eclampsia and later incidence of kidney disease in the mothers and found an unexpectedly strong result.

“We were amazed that the correlation was so strong,” says Vikse. The data showed that pre-eclampsia alone was responsible for the mothers having a 3.3% increased risk of developing kidney disease later. If, in addition, the child had a low birth weight, the risk increased to a 4.8% increased risk with low birth-weight and a dramatic17% increased risk with very low birth-weight.

Another unexpected finding was that the increased risk was not associated with any particular kidney disease: all kidney diseases had a similar increased risk.

“You would expect the risk increase to be linked to a particular disease,” explains Vikse. “It was most unusual to find that this was not the case.”

Future directions

Vikse explains that the researchers will now try to characterise the correlation further as well as checking for correlations with other medical conditions such as kidney failure. Studies into the development of both pre-eclampsia and kidney disease are also needed to see if there are any similarities between the mechanisms by which both medical conditions develop.

According to Vikse, there are also more far-reaching consequences as well. This result suggests that information about having experienced a pregnancy with pre-eclampsia should be included in a woman’s medical history record. Such women need to be followed up for the rest of their lives because of their increased risk of cardiovascular and kidney disease.

Researchers studied 92 children with mild to moderate kidney disease and found that increases in the amount of protein in the urine (proteinuria) corresponded directly to loss of kidney function. The relationship between proteinuria and loss of kidney function is well-established in adults, but had not been studied in children, particularly in those born with kidney disease.

“These results are quite encouraging because this test is fast, cheap and simple and is a really handy tool to help us track disease progression in children with kidney disease,” says Susan Furth, M.D., Ph.D., of the Johns Hopkins Children’s Center.

The current standard for tracking kidney function is GFR (glomerular filtration rate), a test conducted by injecting a contrast agent into the bloodstream and measuring how fast the kidneys remove it. By using both GFR and the urine tests, Furth and colleagues showed that, as proteinuria increased, GFR proportionately decreased.

“Now that we know that the urine tests accurately parallel what’s going on with kidney function, we’ll take the next step, which is to learn just how good the test is,” Furth says. “The hope is that eventually, we will be able to say with precision that ‘X’ amount of protein in the urine corresponds to a risk of ‘Y’ amount of kidney function loss.”

In an analysis of 677 patient records from a national registry, the Hopkins team found 71 percent of the white males, but only 59 percent of black males, had healthy levels of hemoglobin, the iron-rich oxygen transporters in red blood cells. Seventy-four percent of white girls had healthy levels, compared to 51 percent of black girls.

“Racial disparities are well-established among adult patients with kidney disease, but our findings show the same worrisome picture for children,” says Meredith Atkinson, M.D., a third-year nephrology fellow at the Children’s Center. “The next step is to figure out what combination of factors, such as differences in biology or access to health care, are responsible for the disparities.”

Patients with uncontrolled anemia, a well-known complication of kidney disease, generally have worse outcomes and worse quality of life than patients whose anemia is under control.

Identifying the mutant gene is important to scientists because PLCE1 affects the development of podocytes – specialized cells that play a vital role in the kidney’s ability to remove waste products from blood, while retaining important blood proteins.

To parents of infants with inherited PLCE1 mutations, the study is especially significant because it provides the first evidence that some types of a kidney disease called nephrotic syndrome, if diagnosed early in infancy, may be treated successfully in children.

“This is the first report of infants with two mutations in a recessive gene for steroid-resistant nephrotic syndrome who nevertheless responded to steroid treatment,” says Friedhelm Hildebrandt, M.D., the U-M’s Frederick G L Huetwell Professor for the Cure and Prevention of Birth Defects. “The early onset form of the disease is severe and infants often go into end-stage renal disease within the first year of life. So, until now, most physicians believed there was no point in trying treatment.”

The study will be published Nov. 5 in Nature Genetics as an Advance Online Publication, and will be printed in the journal’s December 2006 issue.

There are many types and many causes of nephrotic syndrome, but basically it is a disease of the glomerulus, the kidney’s main blood filtration unit. There are about one million of these filtration units in each human kidney. As blood flows through a network of tiny capillaries in the glomerulus, excess water, salts and toxic molecules are removed and flushed out in urine, while important blood proteins like albumin are retained in the bloodstream. If the kidney’s filtering units don’t work properly, nephrotic syndrome develops. Proteins leaking out from the glomerulus are excreted in urine, and body tissues retain too much water, which causes swelling around the eyes and throughout the body.

Some types of nephrotic syndrome can be treated with steroids or other drugs, but steroid-resistant forms of the disease as a rule do not respond to treatment. Untreated nephrotic syndrome often causes severe scarring and a condition called focal segmental glomerulosclerosis (FSGS), which progresses about 50 percent of the time to end-stage kidney disease and renal failure.

PLCE1 is the seventh gene scientists have found to be involved in different types of steroid-resistant nephrotic syndrome, and the second gene that is expressed in podocytes – specialized cells with octopus-like tentacles surrounding the glomerulus.

Podocytes are currently under intensive study, because scientists believe they play a vital role in the blood filtration process. Identifying genes and proteins that are active in podocytes will help scientists understand how they work.

“We found that PLCE1 is expressed in developing and mature podocytes,” says Hildebrandt. “Most of the PLCE1 mutations we identified apparently prevented podocytes from developing normally in the embryo, so defects were present at birth. A milder mutation seemed to interfere with repair mechanisms in the glomerulus, so defects didn’t show up until later in life.”

U-M scientists used DNA microarrays to analyze blood samples from 26 families around the world who had children diagnosed with steroid-resistant nephrotic syndrome. After eliminating known mutations, the study team was left with DNA from 12 children with the disease. All 12 had inherited recessive mutations in PLCE1 from both parents. None of the seven different PLCE1 mutations were present in the 138 control subjects in the study.

All 12 children developed symptoms of nephrotic syndrome before age four. Five children progressed to end-stage renal disease before age 5. But surprisingly, two children who received early treatment with steroids or cyclosporin A were still alive and healthy, with no symptoms of the disease.

Hildebrandt and his research team couldn’t believe children with the most severe form of nephrotic syndrome had been cured of the disease. So they tracked down their physicians – one in Israel and one in Turkey – to confirm that the information was correct.

“These children were very fortunate,” Hildebrandt says. “Their physicians told us they decided there was nothing to lose by trying a course of treatment. Based on this information, we now think that there may be a critical time window during which treatment can overcome the development defects caused by PLCE1′s loss of function.”

The discovery has important implications for pediatric nephrologists and pediatricians who treat infants with nephrotic syndrome, according to Hildebrandt.

“In very early-onset nephrotic syndrome, it’s important to find out if the child has mutations in PLCE1,” says Hildebrandt. “Some infants with PLCE1 mutations might be treated successfully with steroids. It’s not a golden bullet, but there’s a slim chance, if the treatment is given early.

“Unfortunately, mutations in other podocyte genes, like NPHS2 – also referred to as podocin – are more common,” he adds. “Based on all our knowledge so far, there is no effective therapy when nephrotic syndrome develops as a result of podocin mutations.”

In future research, Hildebrandt and colleagues will continue searching for the causes of nephrotic syndrome. Using zebrafish that lack working copies of plce1, they hope to identify drugs that could reverse the damage to podocytes and the glomerulus caused by the disease.

“Because PLCE1 is an enzyme, we have a much better chance of finding ways to modify its activity,” Hildebrandt explains. “Using the zebrafish model, we can do high-throughput screening of many possible drug candidates for this form of nephrotic syndrome.”

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Citation: Nature Genetics: DOI 10.1038/Ng1918

“Our results clearly show that an ACE inhibitor should always be used in patients with high blood pressure and diabetes, even when they have no evidence of renal or cardiovascular disease,” comments the study’s lead author, Dr. Piero Ruggenenti of Mario Negri Institute for Pharmacological Research in Bergamo, Italy.

The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) study included 1,204 patients with type 2 diabetes and high blood pressure. At the beginning of the study, none of the patients had any signs of kidney disease. They were randomly assigned to treatment with an ACE inhibitor, another type of blood pressure drug called a calcium channel blocker, a combination of an ACE inhibitor with a calcium channel blocker, or an inactive placebo. Rates of microalbuminuria-small amounts of the protein albumin in urine, the first sign of diabetic kidney disease-were compared between groups.

After an average of 31⁄2 years, patients who had good blood pressure control-regardless of which treatment they received-had lower rates of microalbuminuria. Patients taking the combination treatment had the greatest reduction in blood pressure and were less likely to require additional drugs to keep their blood pressure under control.

Taking an ACE inhibitor, alone or as part of the combination treatment, provided further protection against diabetic kidney disease. This was also the case for patients whose blood pressure remained high-as long as they were taking an ACE inhibitor, their microalbuminuria risk was similar to that of patients whose blood pressure was well-controlled. Dr. Ruggenenti points out, “Treatment with an ACE inhibitor was particularly important when the blood pressure was poorly controlled-as may happen in most diabetic patients with hypertension, despite the use of two, three, or even more drugs.”

About 30 percent of people with diabetes will go on to develop kidney failure, while even more may be at risk of premature death from cardiovascular disease. Eighty to ninety percent of patients with type 2 diabetes also have hypertension, a major risk factor for diabetic kidney disease. “Optimizing blood pressure control appears extremely important to reduce or prevent the risk of kidney failure or death for these patients,” says Dr. Ruggenenti.

All doctors who treat diabetes need to know about the protective benefits of ACE inhibitor treatment-especially primary care doctors who care for the vast majority of diabetic patients without kidney disease. “Early and effective treatment of hypertension is of paramount importance in people with diabetes, and ACE inhibitors should be the treatment of choice,” Dr. Ruggenenti concludes. “However, in most patients, an ACE inhibitor alone is not enough to achieve good control of arterial blood pressure-less than 130/80 mm Hg. In these patients, the doctor should also use other antihypertensive drugs, including a diuretic, in most cases, to achieve this target. Although using an ACE inhibitor is important, so is achieving the target blood pressure whenever possible.” For patients who can’t take ACE inhibitors, another class of drugs-the angiotensin II receptor antagonists-may be a valid alternative.