Childhood Kidney Disease Predicts Adult ESRD

— Congenital anomalies of kidney, urinary tract had strongest risk

MedicalToday

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Kidney disease in childhood may have long-term effects on kidney function, a longitudinal study found.

Individuals diagnosed with kidney disease in childhood had a significantly higher risk of end-stage renal disease (ESRD) by adulthood (HR 4.19, 95% CI 3.52-4.99), according to Ronit Calderon-Margalit, MD, MPH, of Hadassah-Hebrew University Braun School of Public Health in Jerusalem, and colleagues.

The results, published in the , showed that this associated risk for ESRD was apparent across all causes of childhood kidney diseases, during a 30-year follow-up period, as follows:

  • Congenital anomalies of kidney/urinary tract: aHR 5.19 (95% CI 3.41-7.90)
  • Pyelonephritis: 4.03 (3.16-5.14)
  • Glomerular disease 3.85 (2.77-5.36)

Action Points

  • Note that this large, Israeli population-based study found that childhood kidney disease was strongly associated with the risk of adult end-stage kidney disease.
  • Be aware that the individuals studied had "resolved" childhood diseases, with normal estimated glomerular filtrating rate on study entry.

"The long-term kidney health outcomes of the broader spectrum of childhood kidney diseases remain largely unknown," the researches wrote, noting that much of the previous literature has focused solely on congenital anomalies of the kidney and urinary tract.

The analysis included 1,521,501 Jewish Israeli adolescents, with a mean age of 17.7 prior to army recruitment. Exclusion criteria included those who had a medical condition that put them at an increased risk for ESRD, which included diabetes, systemic lupus erythematous, cancer, hypertension, impaired renal function, vasculitis, and rheumatic disease.

Among the cohort, 18,592 individuals had a history of childhood kidney disease without proteinuria and with normal blood pressure and serum creatinine levels.

The majority of patients had resolved glomerular disease (n=8,611), defined as a diagnosis of nephrotic syndrome or glomerulonephritis. Pyelonephritis (n=7,231) was the second most common cause of kidney disease in children, defined as a single episode or recurrent pyelonephritis with or without scarring or anatomical malformations. Congenital anomalies of the kidney and urinary tract (n=3,198) were the least common cause of kidney disease, which included congenital single kidney, unilateral renal hypodysplasia, renal ectopia, hydronephrosis, horseshoe kidney, hydroureter, ureterovesical junction stenosis, and ureteropelvic junction stenosis, among other malformations.

By the end of the 30-year follow-up period, 0.75% (n=140) of those who had childhood kidney disease developed ESRD compared with 0.16% (n=2,350) of those without a history of childhood kidney disease. Development of ESRD was considered to be initiation of dialysis treatment or kidney transplantation.

Between the two groups who developed ESRD, those with childhood kidney disease tended to be younger at the time of ESRD onset (mean age, 41.6±10.7 versus 48.6±10.0 years, P<0.001) and had a lower rate of ESRD caused by diabetic nephropathy (14.3% versus 35.4%, P<0.001).

Calderon-Margalit's group suggested that the findings are "consistent with the formulation that low nephron endowment or loss of nephrons can increase susceptibility to chronic kidney disease as a result of the hyperfiltration of residual nephrons.

"Despite the low absolute incidence of ESRD, the interpretation of our findings should take into account that ESRD is estimated to represent only 0.1-2.0% of all patients with chronic kidney disease, which includes earlier stages before ESRD," the team added, emphasizing that this finding of ESRD risk suggests a likely underlying risk even greater for lesser stages of chronic kidney disease in adulthood, which were not measured in the current study.

In an , Julie R. Ingelfinger, MD, of Massachusetts General Hospital in Boston and the journal's deputy editor, called the study "unique" in its ability to follow those with childhood kidney disease with normal renal function at baseline. However, she noted that valuable data on the participants was not available in the study, including their age at childhood kidney disease presentation, use of medication, and history of procedural treatments. She also pointed out that the prevalence of chronic kidney disease is higher in the Israeli population compared with in the U.S. population, although the rate is currently on the rise in the U.S.

The findings "suggest that we need to follow persons who had kidney disease as children throughout life, even if the condition shows apparent resolution," she said. "We also need to find better predictors and methods by which to intervene if we are to prevent ESRD in those at risk."

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

No funding information was provided for the study, and none of the study authors reported having any relevant conflicts of interest.

Ingelfinger reported being employed by the New England Journal of Medicine as Deputy Editor.

Primary Source

New England Journal of Medicine

Calderon-Margalit R, et al "History of childhood kidney disease and risk of adult end-stage renal disease" N Engl J Med 2018; DOI: 10.1056/NEJMoa1700993.

Secondary Source

New England Journal of Medicine

Ingelfinger J "A disturbing legacy of childhood kidney disease" N Engl J Med 2018; DOI: 10.1056/NEJMe1716499.