New research from NewYork-Presbyterian/Weill Cornell Medicine physicians in collaboration with researchers from various institutions published in Pediatric Nephrology confirms that the progression of chronic kidney disease (CKD) surges in children after puberty, particularly among boys. “People have observed this for a very long time,” says lead study author Hannah S. Kim, MD, a pediatric nephrologist at NewYork-Presbyterian/
The study, a follow-up to two prior studies, aimed to clarify the factors involved in the progression of CKD in children and was significant in several ways. First, puberty was measured by levels of luteinizing hormone (LH), a more objective measure than assessing clinical features, such as the onset of menses or breast development and testicular enlargement (Tanner stage).
LH levels were measured from stored serum obtained at yearly visits. As expected, there was a general upward trend in LH over time after the onset of puberty.
Puberty occurred at a median age of 9.9 years among girls and 10.2 among boys with CKD. This is similar to the population at large.
Multiple measures of kidney function
Also significant, kidney function was assessed with both estimated glomerular filtration rate (eGFR), which relies on measures of creatinine and cystatin C, and measured GFR (mGFR), which focuses on the clearance of iohexol. In the study, eGFR measures were taken annually; mGFR tests were conducted every other year.
“A unique thing about this study and the previous study was that we used many different markers to estimate kidney function,” says Dr. Kim. “Creatinine is the most ubiquitous biomarker we use, but it's a muscle mass breakdown product, meaning if you have more muscle mass, that number will be higher. It’s sometimes hard to interpret in someone who's growing because their creatinine may increase because their muscle mass is increasing, but also because their kidney disease is progressing.”
A unique thing about this study and the previous study was that we used many different markers to estimate kidney function. Creatinine is the most ubiquitous biomarker we use, but it's a muscle mass breakdown product, meaning if you have more muscle mass, that number will be higher. It’s sometimes hard to interpret in someone who's growing because their creatine may increase because their muscle mass is increasing, but also because their kidney disease is progressing.
— Dr. Hannah S. Kim
The results were consistent across measures, however, says Dr. Kim, suggesting that perhaps growth alone was not responsible for the worsening of disease. Adding credence to the theory, in the team’s previous study, the decline in GFR remained significant after adjusting for participant’s BMI. And in the present study, Dr. Kim and the study team observed a faster decline in GFR after the onset of hormonal puberty in boys, which occurs prior to the growth spurt associated with puberty. “There might be something more to this than just them growing,” says Dr. Kim.
Could sex hormones play a role?
Sex hormones could be a missing factor. “We think there may be a hormonal component to this,” Dr. Kim says. “That's a hypothesis, which we haven't really shown with this paper, but it's a launching point for more studies.”
Animal studies have shown that androgens have a negative effect on the progression of kidney disease, the authors wrote. And in studies of women taking estrogen as part of hormone replacement therapy, a higher cumulative dose of the hormone was linked to a greater decline in eGFR. However, no pediatric study has explored this issue.
CKD from congenital anomalies can be silent in some children until it's at a very severe stage,” says Dr. Kim. “If patients haven't seen a nephrologist for some time, this might be a time where you want to check in and make sure they're getting any follow-up that they need. This might be a time when they progress.
— Dr. Hannah S. Kim
The group has received funding from the Pediatric Nephrology Research Consortium to study the role of testosterone in CKD progression at puberty. “[Kidney decline] appears to be accelerating after puberty,” Dr. Kim says. “The question is, ‘Is there an effect from hormones that are upregulated during puberty?’” Answering such questions should help improve the outcomes of CKD patients on the cusp of adulthood.”
A robust network of experts
Dr. Kim says that NewYork-Presbyterian’s robust network of experts that collaborate closely really benefits patients with CKD. “When you work here, your patient may not realize it, but they're probably getting information from not just one physician, because we tend to talk with a lot of other physicians,” says Dr. Kim. “We’re a very connected institution, and that is probably to the patient's advantage.”
Her advice to other clinicians with pediatric kidney patients is to pay close attention to them around the time of puberty. “CKD from congenital anomalies can be silent in some children until it's at a very severe stage,” says Dr. Kim. “If patients haven't seen a nephrologist for some time, this might be a time where you want to check in and make sure they're getting any follow-up that they need. This might be a time when they progress.”
