Weight Loss in Children and Adolescents with CKD Occurs with Decrease in eGFR

Children with chronic kidney disease (CKD), including end-stage renal disease (ESRD), are at risk for weight loss. Results of prior cross-sectional studies in adults have suggested that weight loss begins to occur at an estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2. However, there are few available data for longitudinal assessments of the timing or degree of weight loss in children with CKD.

Elaine Ku, MD, MAS, and colleagues conducted an observational cohort study to examine the trajectory of weight change as kidney function declines, using data from the CKiD (CKD in Children) Study. CKiD, an observational cohort study, was conducted in North America in children and adolescents with CKD followed up longitudinally since 2005. The current analysis tested the hypothesis that the “weight trajectory would not be linear with the progression of CKD and that weight loss would primarily occur after the onset of the advanced stages of CKD (stage ≥4). The researchers also sought to determine the characteristics of participants in CKiD who lost significant weight with advancing CKD and whether there was an association with weight changes and a higher risk for ESRD. Results of the analysis were reported in the American Journal of Kidney Diseases [2018;71(5):648-656].

Mean age of CKiD participants was 10.8 years and 63% were boys. The trajectory analysis included 854 participants who had available data on body mass index (BMI) and serum creatinine from an average of 3.8 visits per participant. Mean longitudinal follow-up was 3.4 years.

Before eGFRcr of 35 mL/min/1.73 m2, there was an association between every 10–mL/min/1.73 m2 decline in eGFRcr and a mean decline in BMI z score of 0.008 (95% confidence interval [CI], –0.01 to 0.02). After eGFRcr decreased to <35 mL/min/1.73 m2, there was an association between every 10-mL/min/1.73 m2 further decline in eGFRcr and a mean decrease in BMI  z score of 0.13 (95% CI, 0.09-0.17).

There were no significant changes in results after adjusting for demographic characteristics, cause of CKD, and proteinuria: a decline in BMI z score of 0.14 (95% CI, 0.10-0.18) was noted with every 10-mL/min/1.73 m2 decrease in eGFRcr after eGFRcr decreased to <35 mL/min/1.73 m2. The difference in the association between repeated measurements of BMI z score and kidney function before and after an eGFRcr threshold of 35 mL/min/1.73 m2 was statistically significant (P<.001). When the analyses were performed using measurement of BMI z scores from the 840 participants with eGFRcr data available, results were similar.

Among participants with significant weight loss (decline in BMI z score >0.2 per year) following a decrease in eGFR to <35 mL/min/1.73 m2, the odds of ESRD were 3.28 (95% CI, 1.53-7.05) times greater compared with participants with stable BMI z  scores (BMI z score change per year of 0-0.1).

There were two deaths and 130 cases of ESRD among the 268 children and adolescents who had at least two BMI and serum creatinine measurements after eGFRcr decreased to <35 mL/min/1.73 m2. During 2.7 years of follow-up, approximately 25% of participants had significant weight loss; those with significant weight loss were more likely to have a glomerular cause of CKD. Those who gained weight were most likely to have lower BMI z scores at the visit when eGFR first decreased to <35 mL/min/1.73 m2. There were no associations between the prevalence of poor appetite by self-report and weight change categories.

Of the subset of participants with two or more BMI measurements after eGFRcr first decreased to <35 mL/min/1.73 m2, there was a graded association between degree of weight loss and the odds of ESRD; results were similar in both unadjusted and adjusted analyses. There was also an association between weight gain and higher odds of ESRD; those findings did not reach statistical significance, however.

There was an interaction between significant weight loss and BMI z score starting at the time eGFRcr first decreased to <35 mL/min/1.73 m2 (P=.04). The adjusted odds of ESRD among participants with BMI z scores >0.3 (n=122) when eGFRcr first decreased to <35 mL/min/1.73 m2 were 5.8 (95% CI, 1.61-21.0) times higher among those who had significant weight loss compared with the reference group. Conversely, among those with BMI z scores ≤0.3 (n=125), the odds of ESRD when eGFRcr first decreased to <35 mL/min/1.73 m2, there was no statistically significant difference from that of participants who maintained weight (odds ratio, 0.86; 95% CI, 0.18-4.00).

There were some limitations to the study, including the likely underestimation of the degree of nonedematous weight loss that occurred, and the limited number of longitudinal measurements of inflammatory markers such as C-reactive protein and cholesterol to include in the analyses. There may also be limitations in the ability for BMI measurements to distinguish between adiposity versus fluid weight. Finally, the observational nature of the study makes it difficult to rule out the possibility of residual confounding.

“In conclusion, significant weight loss appears to occur primarily after eGFR decreases to <35 mL/min/1.73 m2 in children and adolescents with CKD during longitudinal follow-up. The development of significant weight loss in children and adolescents with CKD was associated with higher risk for ESRD. Careful attention to nutritional parameters starting in CKD stage 3 may be warranted, with earlier and more frequent assessments than currently recommended. Further research is needed to determine reasons behind the association between weight loss and risk for ESRD in children and adolescents,” the researchers said.

Takeaway Points

  1. Utilizing data from the CKD in Children (CKiD) study, researchers aimed to test the hypothesis that the trajectory of change in weight as kidney function declined would not be linear with the progression of CKD and that weight loss would primarily occur after onset of advanced stages of CKD.
  2. Outcomes of interest were repeated measurements of body mass index (BMI) z score in trajectory analysis and end-stage renal disease (ESRD) in logistic regression models.
  3. In this patient population of children and adolescents with CKD, weight loss occurred primarily when eGFR decreased to <35 mL/min/1.73 m2; there was an association between this weight loss and increased risk of ESRD.