Below is an edited excerpt by Ellen Kuwana of a conversation with pediatric nephrologist Sangeeta Hingorani.
How did you get interested in nephrology?
While I was in medical school on the East Coast, I did an elective in nephrology at Seattle Children’s, and I realized that nephrology offered the right combination for me of inpatient and outpatient, complicated and diverse cases.
So you did your residency here, then a fellowship in nephrology?
Yes, after residency I worked as a general pediatrician for two years in private practice in Kirkland. I always knew I wanted to come back to do the three-year fellowship in nephrology; during that time I also completed the MPH program at the UW. I was able to reverse the order of my fellowship to complete my two research years first and then my clinical year. At the end of my fellowship, I added an extra year to work on my research and apply for grants and jobs. The combination of this training prepared me to care for patients and for success in clinical and translational research.
Which leads us to what research projects you’re doing now.
I have two major research projects going on right now.
The first project is based at Fred Hutchison Cancer Research Center, and it’s a prospective study looking at kidney injury after hematopoietic cell transplant (HCT). Kidney injury is a common complication of HCT, and was thought to be a result primarily of the medicines (e.g., calcineurin inhibitors) patients are on after transplantation. What we have discovered is that graft-versus-host disease (GVHD) has emerged as a major cause of kidney injury in these medically complex patients. The connection between kidney injury and GVHD is controversial. We identified a novel marker of kidney injury, elafin. It had previously been identified as a serum marker of GVHD of the skin. Elevated urinary elafin levels are associated with acute kidney injury and chronic kidney disease. We are continuing to search for other biomarkers, with the aim being to come up with an intervention to prevent both acute and chronic kidney disease in patients who have had hematopoietic cell transplants. The pathology of GVHD in the kidney has not clearly been defined and one of our new projects involves a collaboration with Seattle Children’s pediatric hematologist-oncologist Leslie Kean, to use the kidney tissue from her primate model of GVHD to describe the findings on histology that are present in the kidneys of these animals.
My other major project is in collaboration with neonatologist Sunny Juul. She is the principal investigator for the Premature Epo Neuroprotection Trial (PENUT), a large multicenter trial looking at the neuroprotective effects of erythropoietin for brain injury in extremely preterm infants. I remember her project being announced at a faculty meeting; I emailed her that night, and we started talking—I just knew it was a great opportunity for kidney research, as well.
In my study, Recombinant Erythropoietin for Protection of Infant Kidney Disease (REPAIReD), I am focusing on the search for urinary biomarkers to learn more about the implications of being premature (born at 24 to less than 27 weeks) and acute kidney injury. The REPAIReD study is a collaborative effort with colleagues from Alabama, Ohio and Iowa. We will try to identify biomarkers to predict clinical outcomes, to define acute kidney injury in this patient population and to evaluate the effectiveness of erythropoietin to ameliorate acute kidney injury. Right now there are no FDA-approved treatments for acute kidney injury.
Compared with term infants, premature babies have twice the rates of chronic kidney disease and end-stage kidney disease. PENUT has reached its target enrollment of 940 babies at the 18 sites. Another exciting aspect of this study is that we will have data at their follow-up visit at two years. This time point may well allow for an assessment of potential longer-term complications of prematurity and acute kidney injury such as albuminuria, hypertension and chronic kidney disease. Biomarkers at this time point might also help us to identify those children who are at risk later in life to develop these complications. We hope that our findings can benefit the 50,000 infants who are born before 28 weeks of gestation each year in this country.
And you have research projects currently underway at Seattle Children’s, correct?
Yes, I’m also the site PI for two large prospective studies at Seattle Children’s where we are examining blood and tissue samples, and looking at the genes involved to better understand the mechanisms of nephrotic syndrome (NEPTUNE).
- C-NEPTUNE is collecting long-term observational data to better understand nephrotic syndrome, which is a constellation of symptoms that can result from focal segmental glomerulosclerosis (FSGS), minimal change disease (which is most common in children) and membranous nephropathy. We are enrolling patients within 30 days of initiation of treatment (usually prednisone). The goal of the study is to gather clinical and laboratory information to pinpoint characteristics of patients who will respond compared with those who are resistant to treatment and to identify triggers for relapse. We are also looking longer term at quality of life. An innovative aspect of this study is the use of text messaging to track patients’ compliance, relapses and symptoms—and to send them reminders to check their urine and take their medications. The parent study, NEPTUNE, is enrolling the above patients at the time of biopsy.
- Cure Glomerulonephropathy (CURE-GN) is looking at patients with focal segmental glomerulosclerosis (FSGS), minimal change disease, membranous nephropathy and IgA nephropathy.
And how does the CCTR help you with these large studies?
I use many of the core services, such as grants administration and the research coordinator core, for staffing my projects – it saves me a lot of time to have experienced research staff available.
What do you like best about working at Seattle Children’s?
I appreciate the connections that I’ve made with colleagues within and across divisions – I’ve been here 24 years now! And I have to mention the nursing staff is wonderful.
What do you like to do when you’re not working?
I like to swim in Lake Washington and to ride my bike when I can. I read whenever I get the chance; I’ve been in the same book club since 1994. On the home front, one of my sons is in college, and I have 13-year-old twin boys at home. We love to travel and have been fortunate to be able to take some amazing trips as a family over the years to India, Africa, Europe, Argentina and the Arctic. Our next adventure is a trip my husband and I are planning to Thailand and Vietnam, just the two of us.
– E. Kuwana
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