Children living outside industrialized nations have limited access to health care, and many children with severe kidney dysfunction do not have access to dialysis. Some developing countries have access to manual peritoneal dialysis, which requires the placement of a catheter into the abdominal cavity every one to two hours, 10 hours per day. But supplies are expensive, and many countries lack the infrastructure needed to get large quantities of dialysis fluid to children’s homes.
Nephrotic syndrome is one of the worst diseases a child can have. It strikes the filtering units of the kidney, structures known as glomeruli. There’s no good treatment: Steroids are the main therapy used, but 20 percent of cases are steroid-resistant. In the syndrome’s most severe form, focal segmental glomerulosclerosis (FSGS), children are forced onto chronic dialysis and often require a kidney transplant—often only to have their disease recur in the new organ.
In 2009, The New England Journal of Medicine reported the case of an otherwise healthy 2-year-old boy in Canada who died after surgery. He had received a codeine dose in the recommended range, but an autopsy revealed that morphine (a product of codeine metabolism) had built up to toxic levels in his blood and likely depressed his breathing. Genetic profiling revealed him to be an “ultrarapid codeine metabolizer,” due to a genetic variation in an enzyme known as CYP2D6, part of the cytochrome P-450 family.
While codeine is no longer used at Boston Children’s Hospital, it’s this kind of genetic profiling that Shannon Manzi, PharmD, would someday like to offer to all patients—before a drug is prescribed.
Not all people respond the same way to drugs. The results of randomized clinical trials—considered the gold standard for drug testing—often produce a dose range that worked for the majority of the patients in the study. They don’t take people’s individuality into account, and that individuality can dramatically affect drug efficacy and toxicity.
Adverse reactions are more common than you might think. …
Part 2 of a two-part series on kidney disease. Part 1 is here.
Friedhelm Hildebrandt, MD, receives around one blood sample in the mail per day from a patient with chronic kidney disease. Over 10 years, he’s collected more than 5,000 samples from patients all over the world—in hopes of finding the genetic mutations that cause them and, ultimately, new treatments.
Consider the mutation in an 8-month-old boy from Turkey, who had fluid collection under his skin and elevated protein in his urine—signs that his kidneys were failing. Doctors identified his disease as a form of nephrotic syndrome, one of the three main types of chronic kidney disease. The disease was proving to be hard to treat: Ten weeks of steroids had produced no result, and an immunosuppressant hadn’t been effective enough to justify its harsh side effects.
Only within the last year, genetic research has revealed that more than 30 percent of childhood chronic kidney diseases—like this child’s—stem from single mutations in single genes. …
Part 1 of a two-part series on kidney disease. Part 2 is here.
In up to 5 percent of all pregnancies, children are born with some degree of kidney dilation or swelling, known as hydronephrosis. Unfortunately, says urologist Richard Lee, MD, of Boston Children’s Hospital, “many of these kids go through a lot of testing after birth and are followed for a long period of time—sometimes unnecessarily.”
Hoping to reduce such testing, Lee and his colleagues are turning to urine. They’ve been collecting comprehensive data on the urinary proteome—all the proteins urine normally contains. With this baseline information, they hope to establish biomarkers that identify kidney damage.
In a recently published study, Lee and his coauthors compared the urinary proteomes of healthy infant boys versus men to find out what happens naturally with age. Through their work, they identified nearly 1,600 protein groups and determined that the healthy male urinary proteome changes over time. …
In my job as a science writer at Children’s, I comb the organization for interesting science and innovation stories that we can push out to various audiences. At the turn of the year, my colleagues ask me to recommend what I see as our top stories. We present this list to funders, industry and physicians who refer patients to us as a way to build our relationships. Today I’m sharing my 2010 list directly with you.
Focal segmental glomerulosclerosis (FSGS) is the second leading cause of kidney failure in children. It ruthlessly attacks the kidney’s filtering system: The glomeruli, tiny clusters of capillaries within each nephron that filter toxins from the blood, scar, harden and stop working. Patients are forced onto chronic dialysis and, all too often, need a kidney transplant.
“To make matters worse, many patients have recurrence of the disease soon after transplant,” says William Harmon, MD, chief of Children’s Division of Nephrology. “First it ruins your native kidney, then it can return instantly in the transplant and ruin that also.” Amazingly, this can sometimes happen within hours of transplantation. …
In polycystic kidney disease, fluid-filled cysts gradually take over the kidneys, forcing patients to go on chronic dialysis — or wait for a kidney transplant. Hopes for a cure were raised when animal models showed promise in drugs inhibiting mTOR, a protein that coordinates cell growth and is over-active in PKD. But recent clinical trials brought disappointing results.
Probing deeper into the biology, Jordan Kreidberg and Shan Qin at Children’s Hospital Boston have opened up a new option. …