From Pages to Practice

By Karen Sokal-Gutierrez, MD, MPH, FAAP

Published January 31, 2018


A mother brings her 10-year-old daughter to the family physician for follow-up after successful outpatient treatment of an episode of E. coli pyelonephritis. The mother asks, “Is there a chance that this infection might lead to serious kidney problems when my daughter is older?”

The prevalence of chronic kidney disease has been increasing worldwide, often attributed to the widespread prevalence of urinary tract infections and increasing rates of hypertension and diabetes mellitus. Although many children experience one or more episodes of acute kidney disease that resolve with adequate treatment, the question remains about the long-term risk of progression of childhood kidney disease to chronic kidney disease and end-stage renal disease (ESRD) in adulthood.

In this week’s NEJM, Calderon-Margalit et al. attempt to answer this question in a nationwide cohort study of more than 1.5 million Israeli adolescents who underwent baseline medical examinations before compulsory military service in 1967–1997. Those included in the study had normal kidney function and no hypertension in adolescence. Childhood kidney disease was categorized as congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease. Data were linked to the Israeli ESRD registry, and Cox proportional hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease.

During a mean follow-up of 30 years, approximately 0.2% of the cohort developed ESRD. Among individuals with a history of childhood kidney disease, approximately 0.75% developed ESRD. Although the absolute risk of developing ESRD was low, multivariable-adjusted analysis showed that a history of any childhood kidney disease was associated with a hazard ratio of 4.19 for developing ESRD in adulthood. Hazard ratios for ESRD were 5.19 for congenital anomalies, 4.03 for pyelonephritis, and 3.85 for glomerular disease. A history of childhood kidney disease was also associated with a younger age of onset of ESRD than no history (mean age, 41.6 vs. 48.6 years).

The authors concluded that a history of childhood kidney disease, even with normal renal function in adolescence, was associated with a four-fold increased risk of developing ESRD in adulthood. This suggests that early identification and intervention to prevent the progression of chronic kidney disease and its complications is needed.

Returning to the mother and her daughter, the physician can explain that although an episode of pyelonephritis can increase the chance of future kidney problems, the risk is low that her daughter would develop chronic kidney disease. However, if she develops symptoms of urinary tract infection in the future, she should get prompt medical care.

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Karen is a 2017-2018 NEJM Editorial Fellow, Clinical Professor at UC Berkeley-UCSF Joint Medical Program and UC Berkeley School of Public Health, researcher on children’s nutrition and oral health, and member of American Academy of Pediatrics.
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