Pediatric CKD Progression Model Identifies Children at Highest Risk for ESRD

A new model could predict which children with chronic kidney disease (CKD) are at highest risk for progressing to end stage renal disease (ESRD) well before they lose renal function. Using existing patient data, the composite scoring system would facilitate early intervention, giving nephrologists the opportunity to slow the disease course. The model, recently published in the Clinical Journal of the American Society of Nephrology, is the first specifically designed to assess the unique characteristics of children with CKD (1). Although further validation in a larger population is needed, the system could be a valuable resource for the pediatric kidney care team.

“Clinicians could easily apply this tool in their practice, since our model uses routinely available clinical and laboratory data, and can predict the long-term risk for renal impairment with accuracy,” said senior author Eduardo Oliveira, PhD. “The variables included in our model have been considered in many studies of risk factors in adult and pediatric patients.”

Oliveira and his coworkers from the Federal University of Minas Gerais in Brazil developed the predictive score using 18 years’ worth of data from their pediatric CKD clinic. Information obtained from 147 children with CKD who received treatment in the clinic’s multidisciplinary setting (comprising pediatric nephrologists, as well as pediatricians, nurses, nutritionists, and social workers) was included in their analysis.

Primary renal disease, ethnicity, age, baseline eGFR, proteinuria, and uncontrolled hypertension were among the numerous patient characteristics assessed in the scale’s development. Progression to stage 5 CKD was designated as a dependent variable, and renal survival defined as the date of dialysis initiation or first eGFR level of less than 15 mL/min/1.73 m2.

After multivariate analysis, three criteria were found to be independent predictors of children progressing to ESRD: baseline eGFR, proteinuria (dichotomized as either severe or absent/mild), and primary renal disease (dichotomized as glomerulonephritis or other renal diseases). Each of the three variables were weighted to construct a 13-point predictive score stratifying patients into low-, medium-, and high-risk groups for developing renal failure (Table 1). The score was tested against long-term follow-up data from their patient cohort (median follow-up 53 months) to determine how closely the forecasted risk matched the observed results.

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At both 2 and 5 years of follow-up, the model closely predicted the observed outcome for all three risk groups. However, more deviation was demonstrated at the 10- and 15-year follow-up points. Oliveira cautioned that “as we pointed out in our paper, it is clear that our model needs to be validated in a large prospective cohort.”

Children are not small adults

“Proteinuria and etiology are key variables in the adult CKD population, and now this has been validated in children, providing a scientific basis for practice,” said Deepa Chand, MD, FASN, chief of pediatric nephrology at Rush University Medical Center in Chicago, IL. “Intuitively, etiologies that have higher proteinuric states are more deleterious and this study provides the data supporting this theory. It is important to note that, unlike adult CKD patients, protein intake is not restricted in pediatric CKD patients but rather optimized so as to prevent protein malnutrition.” Chand added that the inclusion of baseline eGFR in the scale was a curious finding, but that it stresses the need for early referral to a pediatric nephrologist.

Until now, there have been no CKD to ESRD progression models for the pediatric CKD setting. This is due in part to the difficulty in performing pediatric CKD studies given the relatively small volume of patients, said Chand, who was not affiliated with the study. Both pediatric and adult CKD populations share similar characteristics, she noted. Medication adherence in both groups can be challenging and contribute to the rate of renal function progression. However, the etiologies of pediatric CKD differ from those of adults.

“Because anatomic abnormalities are more prevalent, proteinuria is often a later finding in children, which, as the authors have identified, plays a key role in disease progression,” Chand said.

Unlike adults with CKD, children with kidney disease are also undergoing somatic growth and neurocognitive development, which can complicate the process of predicting progression.

“Times of maximal growth velocity can precipitate decline in renal function in children, as the metabolic demands cannot be accommodated by the dysfunctional kidneys,” said Chand. “Somatic growth in children with CKD is often altered because they do not follow typical growth curves. Acidosis, more prevalent in pediatric patients because of the tubular acidification defect from congenital renal disease, alters growth hormone secretion and contributes to growth retardation. Altered taste sensation is also common in children with CKD, making adequate nutritional intake difficult.”

Preventing neurocognitive delays is a major goal in children with CKD and a key difference in the management of pediatric versus adult CKD patients, Chand emphasized. “A variety of factors, including acidosis, anemia, and uremia, contribute to this delay. It is imperative that these patients receive appropriate therapy services, such as physical, occupational, and speech to ameliorate these effects,” she said.

Individualizing the approach to slow progression

Using the predictive model to stratify patient risk for renal failure can “assist professionals involved in the care of these patients, who may possibly establish appropriate measures for each risk group,” Oliveira said. He noted this could include more intensive preventive measures for those identified as being at high risk for progression to ESRD.

Chand underscored that the multidisciplinary approach used by Oliveira was also key for identifying progression and early intervention in children with kidney disease.

“The authors provide an excellent predictive model of CKD progression. Pediatric nephrology practices can optimize use of the multidisciplinary approach, with maximized education and monitoring of eGFR, proteinuria, and growth,” Chand said. “As with the adult CKD population, progression of proteinuria is a significant contributor to rate of kidney function decline. The authors have highlighted proteinuria and hypertension management as targets for the practitioner. This is critical if prevention of progression is possible.”

Although the predictive model can assist in identification of children at risk, early referral to pediatric nephrologists is vital to improving outcomes in this population. “This is an important point for our general pediatrician colleagues and could prove to be a very valuable concept in the management of these children,” Chand said.

Reference

1. Cerqueira DC, et al. A predictive model of progression of CKD to ESRD in a predialysis pediatric interdisciplinary program. Clin J Am Soc Nephrol. doi: 10.2216/CJN.06630613.

March 2014 (Vol. 6, Number 3)​