Tag Archive for: Clauss

Handrawn illustration of human Kidneys

Children’s National Nephrology team presents virtually at IPTA’s 11th Congress

Handrawn illustration of human KidneysThe International Pediatric Transplant Association (IPTA) is hosting their 11th Congress meeting March 26-29, 2022, and many Children’s National Hospital providers will be presenting throughout the conference. We hope you will join us!

Diversity, inequity and inclusivity in the practice of pediatric transplantation in the U.S.

Presenter: Marva Moxey-Mims, M.D., division chief, Nephrology

Dr. Moxey-Mims will review the trends in pediatric kidney transplantation over the past decade, focusing on differences by race and ethnicity, whether the gaps have narrowed over that time and steps that can be taken to increase equity.

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study

Presenter: Asha Moudgil, M.D., medical director, Kidney Transplant

Mycophenolate mofetil (MMF) is a common maintenance immunosuppressant in children receiving kidney transplants but is often discontinued for various reasons. In this multi-center Pediatric Nephrology Research Consortium study, researchers sought to determine the prevalence and reasons for MMF discontinuation and its association with patient and allograft outcomes. They will be discussing their methodology and results from this study.

Additional Children’s National staff involved in the study include:

Changes in diastolic function and cardiac geometry after pediatric kidney transplantation: A longitudinal study

Presenter: Kristen Sgambat, Ph.D., clinical assistant professor

Children with end stage kidney disease are at high risk for cardiovascular morbidities. Indicators of systolic function, such as ejection fraction and fractional shortening, are often preserved and may not reveal cardiac dysfunction until it is severe. Longitudinal changes in diastolic function and cardiac geometry have not been well studied.

Additional Children’s National staff involved in the study include:

  • Asha Moudgil, M.D., medical director, Kidney Transplant
  • Sarah Clauss, M.D., cardiologist

COVID19 in pediatric kidney transplant recipients: Incidence, outcomes, and response to vaccine

Presenter: Asha Moudgil, M.D., medical director, Kidney Transplant

At the start of the pandemic, no information was available on the outcomes of pediatric kidney transplant recipients with COVID-19. When the COVID-19 vaccine became available, response of immunosuppressed children to the vaccine was not known. While more information has become available in adult transplant recipients, information on pediatric transplant recipients remains limited.

The team will discuss their methodology of collecting information and their results and conclusions.

Additional Children’s National staff involved in the study include:

Poster presentation: Psychological functioning and adaptive behavior in pediatric patients awaiting renal transplantation.

Presenter: Kaushal Amatya, Ph.D., psychologist

Psychosocial functioning of children with chronic kidney disease (CKD) at pretransplant evaluation is associated with transplant readiness and post-transplant outcomes. Higher prevalence of emotional/behavioral issues is noted in children with CKD compared to healthy counterparts. Although issues with functional impairment is often reported, research on adaptive functioning using a validated measure is lacking. The study aimed to explore psychological and adaptive functioning in pediatric pre-transplant patients to identify areas in need of intervention.

Additional Children’s National staff involved in the study include:

  • Asha Moudgil, M.D., medical director, Kidney Transplant
  • Paige Johnson, Psychology resident

 

close up of an IV bag

Carnitine may improve heart function in children receiving CRRT

close up of an IV bag

A first-of-its-kind study demonstrated that IV carnitine supplementation is associated with improvement in myocardial strain and repletion of plasma total and free carnitine in children with AKI receiving CRRT.

Supplementation of a special nutrient could help improve heart function in children receiving continuous dialysis in critical care units. The nutrient carnitine plays an essential role in producing energy for use by heart and skeletal muscles. Critically ill children with acute kidney dysfunction often need a continuous dialysis therapy (also known as CRRT, continuous renal replacement therapy) to help remove toxins while kidneys are not working. An unintended consequence of this CRRT is removal of carnitine. Often these critically ill children are unable to eat by mouth and therefore can’t receive carnitine unless it is supplemented. Children’s National Hospital researchers have proven that intravenous carnitine supplementation is associated with repletion of the body’s carnitine supply and may cause improvement in heart function as shown by heart strain analysis (which detects subclinical cardiac dysfunction that may not be apparent by traditional echocardiography).

In a first-of-its-kind study, the Children’s National researchers, Asha Moudgil, M.D., Kristen Sgambat, M.D., and Sarah Clauss, M.D., investigated carnitine deficiency in children receiving CRRT. They demonstrated for the first time that these children become severely deficient in carnitine after being on CRRT for >1 week, and that carnitine supplementation is associated with carnitine repletion and improved heart function. This knowledge can help to guide clinical care, as carnitine can be easily added to the IV nutritional formulations that are typically given to these patients.

Although little was previously known about carnitine status in patients with acute kidney injury (AKI) receiving CRRT, iatrogenic carnitine deficiency related to chronic hemodialysis (HD) in patients with end stage renal disease is a well-known phenomenon. It was theorized that given the continuous removal of solutes by CRRT in combination with lack of dietary intake and impaired production of endogenous carnitine by the kidney in critically ill children with AKI, carnitine would be rapidly depleted.

The latest controlled pilot study (NCT01941823) of 48 children hypothesized that carnitine supplementation would improve left ventricular function in children receiving CRRT. Children ages 1-21 years with AKI requiring CRRT, who were admitted to the pediatric intensive care unit at Children’s National Hospital from 2015 to 2018 were eligible to prospectively enroll in the “CRRT Intervention group,” if they were total parenteral nutrition (TPN)-dependent and not receiving any enteral or IV carnitine prior to enrollment.

The researchers say that “An exciting collaborative effort between nephrology and cardiology made it possible to use a sophisticated technology known as speckle tracking imaging to study the effects of carnitine on heart in this population.” This technology can identify early changes in heart motion, also known as cardiac strain that may not be detected using standard heart imaging techniques.

This is the first study to demonstrate that IV carnitine supplementation is associated with improvement in myocardial strain and repletion of plasma total and free carnitine in children with AKI receiving CRRT. A cohort of pediatric chronic HD patients demonstrated similar benefits in a prior study conducted by Drs. Moudgil and Sgambat. Compared with chronic HD, carnitine is even more rapidly depleted by CRRT, with losses approximating 80% of intake. The effect of carnitine deficiency and supplementation on cardiovascular function in patients receiving CRRT had not been previously investigated.

The pilot study by Drs. Moudgil, Sgambat, and Clauss was single center and limited by small sample size. The small sample size may have limited the ability to detect significant differences in demographics and clinical characteristics and multivariable analyses could not be performed. However, given that it is a pilot study, the findings provide a solid launching point for future investigations to show how supplementation can be best utilized to optimize cardiac outcomes in children receiving CRRT.

Asha Moudgil examines a young patient

Preventing cardiovascular disease after pediatric kidney transplant

Asha Moudgil examines a young patient

Pediatric nephrologist Asha Moudgil, M.D. examines a kidney transplant patient.

As obesity has continued to rise among children in the U.S., so has a condition called metabolic syndrome – a constellation of factors, including high abdominal fat, insulin resistance, high blood pressure, high triglycerides and low amounts of high-density lipoprotein (“good” cholesterol), that increase future risk of cardiovascular disease.

Although metabolic syndrome is dangerous in otherwise healthy children, it’s particularly so for those who’ve received kidney transplants due to chronic kidney disease, says pediatric nephrologist Asha Moudgil, M.D., medical director of transplant at Children’s National Health System. Dr. Moudgil and Children’s National co-authors, Registered Dietitian Kristen Sgambat, Ph.D., RD, and Cardiologist Sarah Clauss, M.D., published a literature review in the February 2018 Clinical Kidney Journal outlining recent research about the cardiovascular effects of metabolic syndrome after kidney transplantation.

“Simply having this transplant multiplies the risk of cardiovascular disease in this vulnerable population,” Dr. Moudgil says. “Combined with lifestyle factors that are driving up metabolic syndrome in general, it’s a ‘one-two punch’ for these patients.”

Dr. Moudgil explains that chronic kidney disease itself leads to poor growth, resulting in shorter stature that’s a risk factor for developing increased waist-to-height ratio upon becoming overweight. When children with this condition undergo long-awaited transplants, it reverses some factors that were suppressing appetite and keeping weight in check: The chronically high levels of urea in their blood decrease after transplant, improving their appetites; and there’s no need to maintain the restrictive diets they had been required to follow for kidney health prior to transplant.

The pharmaceutical regimen that patients follow post-transplant often includes steroids that independently contribute to weight gain and insulin resistance. Combined with the typical American high-fat, high-sugar, and high-sodium diet and low levels of physical activity, the majority of patients with chronic kidney disease gain significant weight after they receive transplants. The prevalence of obesity doubles the first year after transplantation, from about 15 percent to 30 percent, not only driving up cardiovascular disease risk but endangering the longevity of their transplant.

At the same time, says Sgambat, risk factors before and after transplantation drive up prevalence of other parts of metabolic syndrome. These include hypertension, which affects the majority of patients with chronic kidney disease before transplant and typically worsens due to sodium and water retention from immunosuppressive drugs. Dyslipidemia, or abnormal lipid concentrations in the blood, is also common among pediatric kidney transplant patients. One study included in the review showed that 71 percent of patients had high triglycerides three months post-transplant.

Ethnicity also can drive up risk for metabolic syndrome and cardiovascular disease. For example, the literature review says, individuals of African descent have a higher risk of these two conditions potentially due to genetic factors, such as high risk apolipoprotein L1 gene variants.

Together, these factors spur production of inflammatory molecules that trigger the development of early cardiovascular disease. Many kidney transplant recipients die from cardiovascular complications in early adulthood, Sgambat says, driving the need for early detection.

To that end, Dr. Moudgil says pediatric patients don’t typically show overt abnormalities in standard measures of cardiac functioning, such as echocardiography. As an alternative, she and colleagues cover three tools in the literature review that could offer advanced insight into whether patients have initial signs of cardiovascular disease. One of these is carotid intima-media thickness, a measure of the thickness of the carotid artery that can be obtained noninvasively by ultrasound. Another is myocardial strain imaging by speckle tracking echocardiography, a global measure of how the heart changes shape while beating. Cardiac magnetic resonance imaging (MRI), a relatively new technique, is already showing promise in detecting signs of early cardiovascular dysfunction.

A far simpler way to gauge cardiovascular risk, Sgambat adds, is calculating patients’ waist-to-height ratio. This measure doesn’t require sophisticated tools and can be tracked in any clinic over time, alerting patients to health-altering changes before it’s too late.

“It’s even more important to treat cardiovascular risk factors aggressively in this population,” Sgambat says. “Getting a concrete measure that something is trending in the wrong direction may motivate patients to change their diet or lifestyle in ways that a simple recommendation may not.”