Tag Archive for: Moudgil

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:

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

 

Kristen Sgambat, Ph.D., and Asha Moudgil, M.D.

Kristen Sgambat, Ph.D., R.D. and Asha Moudgil, M.D. receive Editors’ Choice Award

Kristen Sgambat, Ph.D., and Asha Moudgil, M.D.

Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., were presented with the 2021 AJKD Editors’ Choice Award.

The American Journal of Kidney Disease (AJKD) announced the selection of the 2021 AJKD Editors’ Choice Award, recognizing outstanding articles published in their journal this year.

Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., were presented with the 2021 AJKD Editors’ Choice Award for their July 2021 study, Social determinants of cardiovascular health in African American children with chronic kidney disease: An analysis of the chronic kidney disease in children (CKiD).

The study is the first to investigate the relationship between race, socioeconomic factors and cardiovascular health in children with chronic kidney disease. Dr. Sgambat, Dr. Moudgil and their collaborators found that African American children with chronic kidney disease had increased evidence of socioeconomic challenges, including food insecurity, reliance on public insurance, lower household incomes and lower levels of maternal education. These children had worse cardiovascular outcomes than Caucasian children with the same chronic kidney conditions. Notably, the cardiovascular outcomes of the two groups became more alike when statistical analysis was applied to equalize their socioeconomic factors. This suggests that these socioeconomic indicators do play a role in adverse cardiovascular health outcomes observed among African American children with chronic kidney disease.

“The findings of this study are important because they highlight the urgent need to shift the clinical research paradigm to investigate how social, rather than biological, factors contribute to racial differences in health outcomes,” said Dr. Sgambat. “Future studies should focus on the impact of systemic racism on cardiovascular health among children with chronic kidney disease, an area not well-studied so far.”

plate of food

Looking back one year later – Keeping it Renal: Global Cuisine for Kids

plate of food

The cookbook introduces a variety of culturally diverse kidney-friendly recipes that kids of all ages love.

It has been one year since the Children’s National Hospital Department of Nephrology released their cookbook “Keeping it Renal: Global Cuisine for Kids” and we are still receiving requests for this collection of recipes. In order to stay healthy, most children with kidney disease have to limit or avoid foods that are high in certain minerals including sodium, potassium and phosphorus. “Children on dialysis have to give up a lot of what they like to eat. This cookbook introduces a variety of culturally diverse kidney-friendly recipes that kids of all ages love. By learning to cook these recipes, our patients can take an active role in their own healthcare and learn some fun new skills,” said Kristen Sgambat, Ph.D., R.D., and Asha Moudgil, M.D., medical director of transplant.

It is often challenging for children and their families to balance these dietary restrictions with proper nutrition and enjoyable mealtimes. “This cookbook offers novel and exciting recipes that patients and families may not be aware of. Seeing these options can help patients see that a renal diet does not have to be bland or repetitive and thus improve patients’ outlook on treatment and motivate them to adhere to the dietary restrictions,” said Kaushalendra Amatya, Ph.D., pediatric psychologist for Nephrology and Cardiology at Children’s National.

As an innovative way to facilitate adherence to these limitations, our nephrology department collaborated with our patient families to create the cookbook “Keeping it Renal: Global Cuisine for Kids,” a compilation of their favorite kidney-friendly recipes.

Children’s National is one of the top pediatric hospitals in NIH funding, and our nephrology program ranks number 7 in the country, according to U.S. News & World Report. The Kidney Transplantation Program is the only one of its kind in the Washington, D.C., area focused on the needs of children and teens with kidney disease. Committed to providing the best quality care to all of our pediatric dialysis and transplant patients, we are always looking for new ways to support our patient families.

If you would like to receive a copy of the Keeping it Renal: Global Cuisine for Kids cookbook, please send your request to: emorrow@childrensnational.org.

 

Pediatric Transplantation Journal Cover

Special issue of Pediatric Transplantation features Children’s National experts

Pediatric Transplantation Journal Cover

While much has been written about advances in the field of pediatric transplantation, there have been relatively few publications that address the social, psychological and day‐to‐day struggles faced by pediatric transplant recipients and their families. A special February 2021 issue of the journal Pediatric Transplantation, guest edited by Children’s National Hospital nephrologist and medical director of transplant Asha Moudgil, M.D., features a compilation of articles from a diverse group of professionals who share their expertise on topics related to healthy living for pediatric solid organ transplant patients. Among these leaders in their fields are several clinicians from Children’s National, including Jonathan Albert, M.D. (Infectious Diseases fellow), Benjamin Hanisch, M.D. (Transplant Infectious Diseases), Kristen Sgambat, Ph.D., R.D. (Renal Dietician), Melissa R. Meyers, M.D. (Nephrologist) and Kaushalendra Amatya, Ph.D. (Psychologist).

In an editorial co-written with Priya Verghese, M.D., of Ann & Robert H. Lurie Children’s Hospital of Chicago, Dr. Moudgil writes, “It is widely acknowledged by those practicing in the field of transplant medicine that taking care of pediatric transplant recipients is a complex endeavor for all parties involved, including patients, families, and providers. In this compendium, we bring you expertise from a diverse group of professionals — including physicians, psychologists, social workers, and nutritionists. These authors provide a concise summary of the literature and evidence when available, and offer personal insight where there is paucity of literature in topics related to healthy living in pediatric transplantation.”

Dr. Albert, Dr. Hanisch and Sgambat provide their expertise in an article titled “Approaches to safe living and diet after solid organ transplantation,” which reviews the risks that pediatric and adolescent solid organ transplant recipients encounter through exposures such as household contacts, outdoor activities, travel, animal exposures and dietary choices.

Like their peers, transplant recipients go through challenges of sexual development, but are at greater risk for sexually transmitted diseases due to their chronic immunosuppression. To address this need, Dr. Meyers and colleagues provide an introductory sexual preventive care resource for adolescent and young adult solid organ transplant recipients in their article “Promoting safe sexual practices and sexual health maintenance in pediatric and young adult solid organ transplant recipients.”

And, in an article titled “Psychological functioning and psychosocial issues in pediatric kidney transplant recipients,” Dr. Amatya and colleagues analyze psychological and psychosocial factors related to medical outcomes and overall well‐being post‐transplant.

Pediatric Transplantation articles written by experts from Children’s National in the 2021 February issue:

Asha Moudgil examines patient

Social determinants of cardiovascular health in African American children with CKD

Asha Moudgil examines patient

In a recent study, Asha Moudgil, M.D., and colleagues looked at differences in socioeconomic factors and subclinical cardiovascular disease markers by race in chronic kidney disease patients.

Children with chronic kidney disease (CKD) are known to have an increased risk for cardiovascular (CV) disease. African American children with CKD are also disproportionately affected by socioeconomic disadvantages related to systemic racism.

In a recent analysis of 3,103 visits from 628 children enrolled in the Chronic Kidney Disease in Children (CKiD) study, Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., and their colleagues found that African American children with CKD had increased left ventricular mass index, more ambulatory hypertension and differences in lipid profile compared with Caucasian children. After adjusting for socioeconomic factors (public health insurance, household income, maternal education, food insecurity, abnormal birth history), a trend towards attenuation of the differences in these CV markers was observed.

The authors of the study conclude that, “as many social determinants of health were not captured by our study, future research should examine effects of systemic racism on CV health in this population.”

Read the full study in the American Journal of Kidney Diseases.

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.

mitochondria

Treating nephrotic-range proteinuria with tacrolimus in MTP

mitochondria

Mitochondria are the cell’s powerplants and inside them the MTP enzymatic complex catalyzes three steps in beta-oxidation of long-chain fatty acids.

In one family, genetic lightning struck twice. Two sisters were diagnosed with mitochondrial trifunctional protein (MTP) deficiency. This is a rare condition that stops the body from converting fats to energy, which can lead to lactic acidosis, recurrent breakdown of muscle tissue and release into the bloodstream (rhabdomyolysis), enlarged heart (cardiomyopathy) and liver failure.

Mitochondria are the cell’s powerplants and inside them the MTP enzymatic complex catalyzes three steps in beta-oxidation of long-chain fatty acids. MTP deficiency is so rare that fewer than 100 cases have been reported in the literature says Hostensia Beng, M.D., who presented an MTP case study during the American Society of Nephrology’s Kidney Week.

The 7-month-old girl with known MTP deficiency arrived at Children’s National lethargic with poor appetite. Her laboratory results showed a low corrected serum calcium level, elevated CK level and protein in the urine (proteinuria) at a nephrotic range. The infant was treated for primary hypoparathyroidism and rhabdomyolysis.

Even though the rhabdomyolysis got better, the excess protein in the girl’s urine remained at worrisome levels. A renal biopsy showed minimal change disease and foot process fusion. And electron microscopy revealed shrunken, dense mitochondria in visceral epithelial cells and endothelium.

“We gave her tacrolimus, a calcineurin inhibitor that we are well familiar with because we use it after transplants to ensure patient’s bodies don’t reject the donated organ. By eight months after treatment, the girl’s urine protein-to-creatinine (uPCR) ratio was back to normal. At 35 months, that key uPCR measure rose again when tacrolimus was discontinued. When treatment began again, uPCR was restored to normal levels one month later,” Dr. Beng says.

The girl’s older sister also shares the heterozygous deletion in the HADHB gene, which provides instructions for making MTP. That missing section of the genetic how-to guide was predicted to cause truncation and loss of long-chain-3-hydroxyacl CoA dehydrogenase function leading to MTP deficiency.

The older sister was diagnosed with nephrotic syndrome and having scar tissue in the kidney’s filtering unit (focal segmental glomerulosclerosis) when she was 18 months old. By contrast, she developed renal failure and progressed to end stage renal disease at 20 months of age.

“Renal involvement has been reported in only one patient with MTP deficiency to date, the older sister of our patient,” Dr. Beng adds.

Podocytes are specialized cells in the kidneys that provide a barrier, preventing plasma proteins from leaking into the urine. Podocytes, however, need energy to function and are rich in mitochondria.

“The proteinuria in these two sisters may be related to their mitochondrial dysfunction. Calcineurin inhibitors like tacrolimus have been reported to reduce proteinuria by stabilizing the podocyte actin cytoskeleton. Tacrolimus was an effective treatment for our patient, who has maintained normal renal function, unlike her sister,” Dr. Beng says.

American Society of Nephrology’s Kidney Week presentation

  • “Treatment of nephrotic-range proteinuria with tacrolimus in mitochondrial trifunctional protein deficiency

Hostensia Beng, M.D., lead author; Asha Moudgil, M.D., medical director, transplant, and co-author; Sun-Young Ahn, M.D., MS, medical director, nephrology inpatient services, and senior author, all of Children’s National Health System.

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.”

Connecting allied health professionals in pediatric nephrology

With the meeting in Washington this year, Children’s National Health System will be the local host, a distinct honor for an academic medical center that treats hundreds of nephrology patients each year, says pediatric Nephrologist Asha Moudgil, M.D., who directs Children’s kidney transplant service.

Pediatric nephrology is a relatively small specialty worldwide, encompassing just a few hundred doctors in the U.S. For each allied health field that provides collaborative care with these physicians – including nutrition, child-life, psychology and social work – the numbers of providers are even smaller. There are no national meetings for these individual subspecialty fields and no venues to meet new like-minded colleagues or learn about new research or protocols.

Six years ago, the American Society of Pediatric Nephrology (ASPN) aimed to help resolve this dilemma by launching a new multidisciplinary symposium that brings together allied health professionals of all kinds within pediatric nephrology.

Each year, the “ASPN Multidisciplinary Symposium” changes locations, allowing the meeting to target different regional groups of allied health professionals based on geography. With the meeting in Washington this year, Children’s National Health System will be the local host, a distinct honor for an academic medical center that treats hundreds of nephrology patients each year, says pediatric Nephrologist Asha Moudgil, M.D., who directs Children’s kidney transplant service.

There are multiple advantages to having the symposium in Washington, Dr. Moudgil explains. One is access to Children’s experts in this field, who have a wealth of experience in managing issues that affect patients who live in the greater Washington area. For example, the keynote address scheduled for the meeting’s opening night will be delivered by Jennifer Verbesey, M.D., Children’s surgical director of pediatric kidney transplantation, focusing on living donation in minority populations. Living kidney donors and recipients who are minorities have unique issues that can affect organ longevity, explains Dr. Moudgil, which may not be well known by all clinicians.

Children’s speakers also focus prominently in the main session on the second day, including:

  • Angela Boadu, RD, LDN/LD, a registered dietitian, and Kaushalendra Amatya, Ph.D., a psychologist, are giving a talk about nutrition and the psychosocial aspects of obesity
  • Surgeon Evan Nadler, M.D., director of Children’s Bariatric Surgery Program, is speaking about bariatric surgery before and after transplantation
  • Nurse Practitioner Christy Petyak, CPNP-PC, and Social Worker Heidi Colbert, LICSW, CCTSW, NSW-C, are leading breakout sessions about the practical aspects of immunosuppressive therapy and resources for uninsured patients
  • Amatya, the Children’s psychologist, also is leading a breakout session on internalizing psychological disorders in pediatric renal patients and
  • Registered Dietitian Kristen Sgambat, Ph.D., RD, and Dr. Moudgil are co-leading a breakout session on nutritional challenges and enteral supplementation in chronic kidney disease.

Another advantage to holding the meeting in the nation’s capital is its close proximity to government research and federal regulatory agencies, such as the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). Speakers from both agencies will be present, talking about how the FDA approves medicines for pediatric patients and offering details about the NIH’s rare disease program.

Besides the abundance of more formal knowledge-sharing, Dr. Moudgil adds, there will be plenty of opportunities for attendees to network, making connections within and outside their own respective fields.

“This is a platform for making long-term professional relationships,” Dr. Moudgil says. “Even if you’re the sole clinician representing your specialty at your own institution, you’ll be able to connect with other specialists at institutions across the country. You’re not only acquiring new information, you’re acquiring a group of colleagues you can connect with this year and those professional relationships can extend far into the future.”

antibodies-illustration

Detecting and treating dnDSA early preserves allograft function

antibodies-illustration

Monitoring and treating de novo donor-specific antibodies (dnDSA) before they could cause graft damage helped to decrease dnDSA in a majority of pediatric kidney transplant recipients at Children National Health System and prevented graft failure in the first few years.

Development of de novo donor-specific antibodies (dnDSA) is known to cause graft failure. Therefore, a protocol aimed at prospective monitoring and treating dnDSA – before they can cause graft damage – was developed for kidney transplant recipients at Children National Health System. This helped to decrease dnDSA in 76 percent of pediatric patients and prevented graft failure in the first few years, indicates a longitudinal cohort study published online Jan. 22, 2018, in Pediatric Transplantation. However, the benefit of preserving function of transplanted kidneys came at a price: Heightened hospitalization rates for infection.

An estimated 20 percent to 30 percent of children develop dnDSA and many of these patients go on to develop allograft failure after three to six years, write the study authors.

Clinical signs of graft failure due to antibodies appear too late to safeguard long-term graft survival. According to the study authors, developing earlier methods to detect dnDSA offers the opportunity to intervene before irreversible graft injury occurs.

“Children’s National Health System instituted a routine protocol that standardizes monitoring and treatment of dnDSA,” says Asha Moudgil, M.D., FASN, associate chief of the Division of Nephrology at Children’s National and the study’s senior author. “We followed this protocol as we monitored and treated all children younger than 19 who received a kidney transplant at Children’s National from Jan. 1, 2008, to Dec. 31, 2013.”

After transplant, these children were monitored for development of dnDSA at six months and then yearly. Upon detection of DSA, these children underwent kidney biopsy to assess for acute rejection. Additionally, monitoring was intensified to every two months.

“Our patients did not have a statistically significant increase in graft loss or dysfunction, suggesting that early and targeted treatment of dnDSA may benefit patients,” says Asha Moudgil, M.D., FASN.

Sixty-seven of the 72 children who received kidney transplants during that six-year period were included in this retrospective analysis. Their mean age was 14.1 years. Acute cellular rejection was treated according to a prespecified protocol.

  • The team treated de novo DSA with high-dose intravenous immunoglobulin (IVIG) if antibody titers were low and added two doses of rituximab to that treatment regimen if antibody titers were high.
  • If either C1q binding of immunodominant DSA was present or C4d+ were seen on biopsy, six sessions of plasma exchange were added to the above protocol.
  • Kids who were resistant to such treatment approaches received an additional four doses of IVIG monthly.

Nearly 39 percent of the children developed dnDSA within a median of 1.36 years. Ten of these 26 children had increased creatinine, 12 had new onset proteinuria and six had newly diagnosed hypertension at the time the dnDSA was detected. The multivariate analysis found that the coefficient of variance of tacrolimus, which measures adherence to immunosuppressive drugs, was the only statistically significant predictor for developing dnDSA.

DSA-positive patients had a higher rate of admissions (1.23 hospital admissions for infectious- or immunosuppressive-related side effects per patient, compared with 0.59 hospital admissions for the DSA-negative patients), which the study team attributes to aggressive treatment of dnDSA.

“Our patients did not have a statistically significant increase in graft loss or dysfunction, suggesting that early and targeted treatment of dnDSA may benefit patients,” Dr. Moudgil adds. “There was a higher risk of treatment-related complications, however, and this risk must be balanced against the short-term benefit of prolonging allograft function.”

Study co-authors include Olga Charnaya, M.D., a Children’s fellow when the study was designed and the article was drafted, now at Johns Hopkins; and Children’s Nephrologist, Shamir Tuchman, M.D.