Kidney disease in childhood is associated with an increased risk of end-stage renal disease (ESRD) in adulthood, even if kidney function seems normal in adolescence, according to a new study.

The finding, based on a nationwide, population-based cohort study of 1,521,501 Israeli adolescents examined before compulsory military service in 1967 through 1997, suggests that kidney injury or structural abnormality in childhood has long-term consequences, investigators Ronit Calderon-Margalit, MD, MPH, of Hadassah-Hebrew University Braun School of Public Health, Hadassah Ein Kerem, Jerusalem, Israel, and colleagues reported in the New England Journal of Medicine (2018;378:428-438).

The investigators identified ESRD cases using the Israeli ESRD database. During 30 years of follow-up, ESRD developed in 2490 individuals, yielding an incidence rate of 5.93 cases per 100,000 person-years. A history of any childhood kidney disease was associated with a 4-fold increased risk of ESRD compared with the absence of such a history. The magnitude of increased risk was similar across the types of childhood kidney disease. A childhood history of congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease were associated with a 5-fold, 4-fold, and 3.8-fold increased risk of ESRD, respectively.

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For their primary analysis, the investigators included only conscripts who, at the time of their medical evaluation for conscription, had no evidence of impaired renal function from any cause and no medical conditions considered to confer an increased risk of subsequent ESRD, such as diabetes mellitus and hypertension. The individuals ranged in age from 16 to 25 years and had a mean age of 17.7 years at their initial medical assessment for conscription.

“The current study suggests that mild kidney abnormalities or injury in childhood may confer a risk of ESRD in adulthood, even when there is no overt compromise of renal function in adolescence,” the authors concluded. “This finding is 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.”

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In a discussion of study limitations, the authors noted that, because of their method of data collection, they did not have information on exact age of participants at the time of clinical presentation during childhood, clinical presentation, histopathologic subtype of the childhood kidney diseases, or indication for urologic interventions. “Therefore, we could not perform analyses according to time from diagnosis or according to the severity or subtype of disease in childhood.”

In an accompanying editorial (pp. 470-471), Julie R. Ingelfinger, MD, Chief of the Division of Pediatric Nephrology at Massachusetts General Hospital in Boston, observed, “Findings such as those reported by Calderon-Margalit et al. suggest that we need to follow persons who had kidney disease as children throughout life, even if the condition shows apparent resolution. We also need to find better predictors and methods by which to intervene if we are to prevent ESRD in those at risk.”


Calderon-Margalit R, Golan E, Twig G, et al. History of childhood kidney disease and risk of adult end-stage renal disease. N Engl J Med. 2018;378:428-438.

Ingelfinger JR. A disturbing legacy of childhood kidney disease. N Engl J Med. 2018;378:470-471.