Kidney News September 2017 9#9 : Page 1

September 2017 | Vol. 9, Number 9 New Hints on Preeclampsia Mechanism Revealed By Bridget M. Kuehn pressure and protein in the urine during pregnancy (Mistry HD, et al. J Lipid Re-search 2017; 58:1186–1195). It also adds to emerging evidence linking cardiovascu-lar disease risk to malfunctioning in the body’s cholesterol flushing system. University of Nottingham’s School of Medi-cine. “If we understand the mechanism, we can do something to prevent it.” Already, scientists know that the placenta plays an important role in preeclampsia. For example, a previous study by Mistry and his colleagues revealed signs of atherosclerosis in blood vessels in the placentas of women who had preeclampsia (Hentschke MR, et al. J Lipid Research 2013; 54:2658–2664). This is the same kind of narrowing and hardening caused by a buildup of cholester-ol seen in the arteries of people with heart disease. Atherosclerosis constricts blood flow and in people with heart disease may lead to heart attack, stroke, or death. In the placenta, this narrowing might compromise the flow of nutrients from the mother to the developing fetus and the flow of waste from the fetus to the mother. Such a constric-tion might explain why some babies born to mothers who had preeclampsia are smaller than expected. “We know the placenta is involved,” Mistry said. Continued on page 2 Inside Nephrology and Palliative Care Our in-depth look at conservative care in kidney disease spans prognostication, depression and anxiety, and integration of palliative care into existing care delivery. More to come next month. Placenta problems? Better understanding of this complex condition is critically important be-cause it occurs in about 3%–5% of pregnancies in the United States, ac-cording to the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It also accounts for about half of maternal deaths in the developed world, according to NICHD. Women who experience preec-lampsia and survive have an elevated risk of cardiovascular disease and kidney disease. Their children also face a higher risk of heart disease later in life. “We’re still trying to work out what happens during preeclampsia and what causes it,” said Hiten Mistry, PhD, a sen-ior research fellow in the Division of Child Health, Obstetrics & Gynecology at the Policy Update ASN pushes for adjustments to Quality Payment Program Findings HbA1c underestimates glucose in African Americans with type 1 diabetes T he system that regulates blood cholesterol goes into overdrive in women who are experiencing preeclampsia, according to results of a re-cent study. Published in the Journal of Lipid Re-search , the study provides the latest clue into what may cause preeclampsia, a condition in which women experience elevated blood Infections in Dialysis Eliminating preventable infections in the dialysis unit ANCA Disease What’s in a name? CKD–Mineral and Bone Disorder KDIGO releases new guidelines Diabetes Prevalence Data Herald High Rates of Kidney Disease in Years Ahead By Timothy O’Brien Industry Spotlight Fresenius acquires NxStage; American Renal Associates announces 2017 second quarter results A recently released report on dia-betes prevalence underscores the need for determined efforts to contain the burden of diabetes and diabetic complications in the years ahead. The Centers for Disease Control and Prevention’s (CDC) 2017 National Dia-betes Statistic Report highlights the devas-tating impact of diabetes in the US, with estimates suggesting that 30 million Ameri-cans have diabetes and another 70 million meet criteria for prediabetes. “More than a third of US adults have prediabetes, and the majority don’t know it,” said CDC Director Brenda Fitzgerald, MD. “Now, more than ever, we must step up our efforts to reduce the burden of this serious disease.” The aging US population and sky-high percentage of Americans with prediabetes mean diabetes-related complications will continue to be a concern moving forward. Based on a US Renal Data System report, more than 52,000 Americans developed ESRD with diabetes as the primary cause during 2014. Adjusted for age, sex, and race/ethnicity, the rate of diabetes-related Continued on page 6

New Hints On Preeclampsia Mechanism Revealed

Bridget M. Kuehn

The system that regulates blood cholesterol goes into overdrive in women who are experiencing preeclampsia, according to results of a recent study.

Published in the Journal of Lipid Research, the study provides the latest clue into what may cause preeclampsia, a condition in which women experience elevated blood pressure and protein in the urine during pregnancy (Mistry HD, et al. J Lipid Research 2017; 58:1186–1195). It also adds to emerging evidence linking cardiovascular disease risk to malfunctioning in the body’s cholesterol flushing system.

Placenta problems?

Better understanding of this complex condition is critically important because it occurs in about 3%–5% of pregnancies in the United States, according to the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It also accounts for about half of maternal deaths in the developed world, according to NICHD. Women who experience preeclampsia and survive have an elevated risk of cardiovascular disease and kidney disease. Their children also face a higher risk of heart disease later in life.

“We’re still trying to work out what happens during preeclampsia and what causes it,” said Hiten Mistry, PhD, a senior research fellow in the Division of Child Health, Obstetrics & Gynecology at the University of Nottingham’s School of Medicine. “If we understand the mechanism, we can do something to prevent it.”

Already, scientists know that the placenta plays an important role in preeclampsia. For example, a previous study by Mistry and his colleagues revealed signs of atherosclerosis in blood vessels in the placentas of women who had preeclampsia (Hentschke MR, et al. J Lipid Research 2013; 54:2658–2664).

This is the same kind of narrowing and hardening caused by a buildup of cholesterol seen in the arteries of people with heart disease. Atherosclerosis constricts blood flow and in people with heart disease may lead to heart attack, stroke, or death. In the placenta, this narrowing might compromise the flow of nutrients from the mother to the developing fetus and the flow of waste from the fetus to the mother. Such a constriction might explain why some babies born to mothers who had preeclampsia are smaller than expected.

“We know the placenta is involved,” Mistry said.

Cholesterol implicated

Appropriate levels of cholesterol are necessary for both healthy adults and developing fetuses. It is used to build new cells for growth and repair, to protect nerves, and to make important hormones. But too much so-called bad cholesterol or low-density lipoprotein (LDL) cholesterol has been linked to heart disease and preeclampsia (Spracklen CN, et al. Am J Epidemiol 2014; 180:346–358).

Sufficient levels of a type of cholesterol called high-density lipoprotein (HDL) on the other hand have been found to be important for good heart health.

Low levels of HDL are associated with insulin resistance and other factors that may contribute to heart disease, so it has been hard to tease out HDL’s role, noted Anand Rohatgi, MD, an associate professor and preventive cardiologist at the University of Texas Southwestern Medical Center in Dallas. One reason HDL may be helpful is that it helps the body remove LDL cholesterol and transport it to the liver where it can be eliminated. The first step in that process is called efflux.

Rohatgi and his colleagues found that people who are better at removing LDL cholesterol this way have a lower risk of having a heart attack, stroke, or other serious heart disease–related event (Rohatgi A, et al. N Engl J Med 2014; 371:2383–2393).

That study led Mistry to wonder whether this cholesterol flushing system also might play a role in preeclampsia.

Pregnant mothers need to supply their fetuses with cholesterol for development and they need it to aid their recovery after delivery, Mistry explained.

“It’s getting the balance right,” he said.

He and his colleagues suspected pregnant women with preeclampsia wouldn’t clear cholesterol as efficiently as pregnant women without the condition. So they compared cholesterol efflux in pregnant women with and without preeclampsia. But they found that efflux is turned up in women with preeclampsia and in their fetuses. This may help the women try to mitigate the potentially harmful effects of elevated cholesterol.

“This study showed this is a compensatory mechanism for damage limitation,” Mistry said.

The findings add some much needed information about efflux during pregnancy, said Rohatgi, but more studies are needed to understand whether efflux is a cause of preeclampsia or merely an indicator.

“I think this is provocative,” Rohatgi said. “Because it is case controlled you get a link to efflux at the time of preeclampsia, but you don’t know if it is causing preeclampsia.”

In fact, the role of efflux in cardiovascular disease more generally is still being worked out. Some phase 2 trials are currently underway to test whether treatments that boost efflux would improve patient’s cardiovascular disease outcomes.

“What has been established pretty well is that as a cardiovascular risk prediction marker efflux does work,” Rohatgi said. “We still don’t know what drives efflux—what makes it go up or down.”

Emphasis on prevention

The findings may have important implications for protecting the long-term cardiovascular and renal health of mothers who experience preeclampsia, as well as the health of their children.

Women who have elevated cardiovascular risk are at higher risk of preeclampsia. After preeclampsia, a woman’s cardiovascular risk is elevated substantially, noted study co-author Markus Mohaupt, MD, a nephrologist and head of internal medicine at Lindenhofgruppe, a foundation based in Bern, Switzerland, that supports research. Understanding these relationships may aid prevention and possibly treatment efforts.

“Is it a disorder that preexists the development of preeclampsia or a disorder that develops after [that contributes to the elevated cardiovascular risk]?” asked Mohaupt, who is also a professor at the University of Bern. “It could be either or both.”

In addition to having an elevated risk of heart disease over the long term, women who experience preeclampsia are also more likely to undergo a renal biopsy, develop chronic kidney disease, and require treatment for kidney disease, Mohaupt said.

To help prevent such poor outcomes, Mohaupt recommended that clinicians monitor lipid levels in women with a history of preeclampsia, especially after menopause.

Rohatgi agreed that long-term monitoring for signs of cardiovascular disease is warranted. He also emphasized the importance of good prenatal care and managing conditions like high blood pressure or gestational diabetes that increase the risk of preeclampsia. “The low hanging fruit is simple prenatal care,” he said.

Children whose mothers had preeclampsia are also at elevated risk for cardiovascular disease.

“The literature is scarce, but what is available tells us a story where the offspring may share the adverse cardiovascular risk factors with their mothers,” said Ingvild Alsnes, MD, a PhD candidate at the Department of Public Health and General Practice at the Norwegian University of Science and Technology in Trondheim, Norway.

Alsnes and her colleagues recently compared the cardiovascular risk of siblings whose mothers had preeclampsia (Alsnes IV, et al. Hypertension 2017; 69:591–598). It turns out that the siblings have similarly elevated risks of cardiovascular disease regardless of whether their mother had preeclampsia during their own gestation.

“It might suggest that it is not the exposure [to preeclampsia] per se that gives an adverse cardiovascular risk profile, but perhaps genetics or lifestyle,” she suggested.

Unanswered questions

Many unanswered questions remain about preeclampsia itself. Alsnes said it would be important to better understand if the cardiovascular risk profiles of women who had severe or mild preeclampsia are different.

“Perhaps they should not be subgroups, but different entities altogether,” she said. “We also need to know whether cardiovascular disease is preventable in this patient group, and how or if they should be followed up or treated.”

The heart risk may differ among women who have had preeclampsia—some may not have an increased risk—so it will be important to identify markers that distinguish those with an elevated heart risk, Rohatgi said.

“Efflux as a marker might help determine which ones are at risk,” he noted.

Markers of elevated cardiovascular risk in women in general are needed, Rohatgi said. Most current heart risk calculators are geared toward men.

“There is a lot of room for improvement in picking out women who are at higher risk,” Rohatgi said.

Early warning sign?

Mistry and his colleagues plan to monitor cholesterol efflux in women earlier in pregnancy to look at whether efflux is elevated before the condition is diagnosed. If so, it might be an early warning sign. They would also like to examine efflux prior to pregnancy in women with chronic hypertension or signs of kidney dysfunction who are at risk of preeclampsia. Rohatgi agreed that these types of studies will be helpful, as will studies that track the long-term cardiovascular outcomes of women who have had preeclampsia.

In the meantime, Mistry emphasized the importance of routine lipid monitoring during pregnancy. He also expressed optimism that elevated cholesterol efflux during pregnancy might one day prove to be a useful tool for monitoring women’s cardiovascular health.

“In the future, it could be a predictor of heart disease later in life,” he said. “If we know a woman is at higher risk, we can intervene early and prevent it.”

Read the full article at http://onlinedigeditions.com/article/New+Hints+On+Preeclampsia+Mechanism+Revealed/2869968/434604/article.html.

Diabetes Prevalence Data Herald High Rates Of Kidney Disease In Years Ahead

Timothy O’Brien

A recently released report on diabetes prevalence underscores the need for determined efforts to contain the burden of diabetes and diabetic complications in the years ahead.

The Centers for Disease Control and Prevention’s (CDC) 2017 National Diabetes Statistic Report highlights the devastating impact of diabetes in the US, with estimates suggesting that 30 million Americans have diabetes and another 70 million meet criteria for prediabetes.

“More than a third of US adults have prediabetes, and the majority don’t know it,” said CDC Director Brenda Fitzgerald, MD. “Now, more than ever, we must step up our efforts to reduce the burden of this serious disease.”

The aging US population and sky-high percentage of Americans with prediabetes mean diabetes-related complications will continue to be a concern moving forward. Based on a US Renal Data System report, more than 52,000 Americans developed ESRD with diabetes as the primary cause during 2014. Adjusted for age, sex, and race/ethnicity, the rate of diabetes-related ESRD was 154.4 per 1 million persons.

The National Diabetes Statistics Report is a periodic update on diabetes in the US, with estimates drawn from CDC data systems and other sources. The 2017 report estimates that 9.4% of all Americans—and 12% of adults— are affected by diagnosed or undiagnosed diabetes. In the absence of a physician diagnosis, diabetes was defined as a fasting plasma glucose level of 126 mg/dL or higher, or an HbA1c level of 6.5% or higher. Prediabetes was defined as fasting plasma glucose of 100 to 125 mg/dL or HbA1c of 5.7% to 6.4%.

The estimates don’t differentiate between type 1 and type 2 diabetes. “However,” the report states, “because type 2 diabetes accounts for 90% to 95% of all diabetes cases, the data presented are likely to be more characteristic of type 2 diabetes.” Overall prevalence appeared steady—the previous CDC diabetes statistical report, issued in 2014, estimated about 29 million Americans with diabetes, or 9.3% of the population.

In 2015, an estimated 1.5 million US adults received a new diagnosis of diabetes.

The prevalence data suggested that more women had diagnosed diabetes than men, but that differential may not mean much, as more men had undiagnosed diabetes (4.0 million men versus 3.1 million women). Also, most adults with diabetes were of working age: 4.6 million aged 18 to 44 and 14.3 million aged 45 to 64. At age 65 or older, total diabetes prevalence was 25.2%.

Analysis by race/ethnicity found that diabetes prevalence was highest for American Indians/Alaska Natives, 15.1%; followed by non-Hispanic blacks, 12.7%; Hispanics, 12.1%; Asians, 8.0%; and non-Hispanic whites, 7.4%. Within these categories, there were some important differences by subgroup: prevalence was 13.8% among Mexican Americans, 12.0% among Puerto Ricans, and 11.2% in Asian Indians.

Education, an indicator of socioeconomic status, was also related to diabetes prevalence: 12.6% for adults with less than a high school education, 9.5% for those with a high school education, and 7.2% for those with more than a high school education.

Estimates for prediabetes were staggering—33.9% of US adults in 2015, or 84.1 million people. That included nearly half (48.3%) of adults aged 65 or older. The figures were somewhat lower than in the 2014 report, which estimated that 86 million US adults had prediabetes.

Only 11.6% of adults with prediabetes were aware of their condition. In contrast to the situation with diabetes, there was no significant difference in the prevalence of prediabetes by racial/ethnic group.

High burden of complications and death

“Persons with diabetes are at higher risk of developing serious complications, including blindness, lower extremity amputation, and kidney failure,” said Nilka Ríos Burrows, MPH, of the CDC’s Chronic Kidney Disease Initiative, Division of Diabetes Translation. “However, people with diabetes can take steps (e.g., keeping blood sugar and blood pressure levels under control) to manage their diabetes and delay or prevent complications.”

Diabetes was a listed diagnosis in 7.2 million hospital discharges in US adults in 2014, including 1.5 million discharges for cardiovascular disease: a crude rate of 70.4 per 1000 persons with diabetes. These included approximately 400,000 patients with ischemic heart disease and more than 250,000 with stroke. There were 108,000 hospitalizations for lower extremity amputations and 168,000 for ketoacidosis.

Diabetes was listed as any diagnosis in 14.2 million emergency department visits, including 245,000 visits for hypoglycemia and 207,000 for hyperglycemic crisis. Diabetes was the seventh-leading cause of death in the US in 2015, with a crude rate of 24.7 per 100,000 persons.

Total direct and indirect costs of diagnosed diabetes in the US were estimated at $245 billion in 2012, according to research by the American Diabetes Association. With adjustment for age and sex, average medical costs for people with diabetes were 2.34 times higher than for those without diabetes.

For nephrologists, the high prevalence of diabetes and prediabetes heralds high rates of diabetic nephropathy in the years ahead. “More than 30 million people in the United States are living with diabetes, placing them at risk of developing kidney disease,” Ríos Burrows said.

A recent report by the CDC’s Chronic Kidney Disease Surveillance Team estimated that 36.5% of adults with diagnosed diabetes had stage 1 to 4 CKD during 2011–2012. As reported last year in ASN Kidney News, that study found continued increases among African Americans. The authors highlighted the need for continued vigilance to lessen the impact of CKD in the population, including efforts on the part of nephrologists to promote better awareness and care among primary care clinicians.

“Claims data indicate that testing for urine albumin, the earliest marker of kidney disease in diabetes, is done in less than half of patients,” Ríos Burrows said. “Testing for kidney disease among people who are at high risk for developing CKD—those with diabetes or with high blood pressure— has been shown to be a cost-effective tool to identify people with CKD. CDC’s kidney team is currently designing an online tool to help primary care physicians and other health care providers evaluate a patient’s need for and frequency of screening for CKD.” The latest CDC National CKD Fact Sheet can be found at www.cdc.gov/diabetes/ pubs/pdf/kidney_factsheet.pdf.

What are diabetes rates in your area?

The 2017 National Diabetes Statistics report includes age adjusted, county-level data on adult diabetes prevalence, providing a unique snapshot of diagnosed diabetes, based on 2013 data from the US Diabetes Surveillance System.

Median county-level prevalence was 9.4%. Age-adjusted prevalence of diagnosed diabetes varied widely: from 3.8% in Eagle County, Colorado, to 20.8% in Lowndes County, Alabama. The data can be explored in depth at www.cdc.gov/diabetes/atlas/countydata/atlas.html.

Read the full article at http://onlinedigeditions.com/article/Diabetes+Prevalence+Data+Herald+High+Rates+Of+Kidney+Disease+In+Years+Ahead/2869987/434604/article.html.

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