Vivante A, Twig G, Tirosh A, Skorecki K, Calderon-Margalit R. Childhood History of Resolved Glomerular Disease and Risk of Hypertension During Adulthood. JAMA. 2014;311(11):1155-1157. doi:10.1001/jama.2013.284310
Most children who develop glomerular disease have a favorable prognosis with complete resolution of all signs and symptoms. Yet the long-term sequelae of resolved childhood glomerular disease are incompletely understood. We assessed whether a medical history of resolved childhood glomerular disease confers a future risk for hypertension.
We conducted a cohort study of young healthy men seen in the Israel Defense Forces Medical Corps Staff Periodic Examination Center (SPEC)1 where periodic examinations of career military personnel are conducted. All men had a baseline evaluation conducted prior to recruitment at age 17 years1,2 during which the diagnosis of resolved childhood glomerular disease was determined. This included childhood acute glomerulonephritis or nephrotic syndrome (Table 1; diagnostic criteria appear in footnote b). We excluded men with baseline diagnoses of unresolved childhood glomerular disease, hypertension, diabetes, active rheumatic diseases, or any other kidney or urinary tract disorders (n = 959).
Participants were followed up from the time of medical assessment during adolescence (1970-1997) through the SPEC visits (1994-2010) until the diagnosis of hypertension (systolic >140 mm Hg or diastolic >90 mm Hg), retirement from service, or December 31, 2010, whichever came first. The definition of hypertension (Table 2; see footnote a) was based on standard protocols as previously described.1
Associations were estimated using Cox proportional hazards models. A second set of analyses counted time from first SPEC visit and excluded diagnoses made before or on the first visit when dates of diagnoses might be inaccurate. Similar analyses were conducted using the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease Study equation; levels below 60 and 70 mL/min/1.73 m2 were used as outcomes.
All analyses were conducted using SPSS software version 21.0 (SPSS Inc). Two-sided P values of less than .05 were considered statistically significant. The Israel Defense Forces review board approved the study and waived the requirement for informed consent.
The study included 38 144 male career personnel, of whom 264 were diagnosed with a medical history of resolved childhood glomerular disease (Table 1). During a mean follow-up of 18 years (mean [SD] age, 35.8 [7.05] years), 2856 participants developed hypertension; 13.6% (n = 36) of participants with a medical history of resolved childhood glomerular disease and 7.4% (n = 2820) of those without such history, yielding a crude hazard ratio (HR) of 1.63 (95% CI, 1.17-2.26) and an HR adjusted for age and body mass index of 1.67 (95% CI, 1.20-2.31). Excluding those diagnosed before the first SPEC visit had a negligible effect on these HR estimates (Table 2).
Creatinine values were available for 76% of the cohort. During follow-up, 2.0% (n = 4) of those with a medical history of resolved childhood glomerular disease and 1.1% (n = 308) of those without such a history had an eGFR below 60 mL/min/1.73 m2, yielding an age-adjusted HR of 1.53 (95% CI, 0.57-4.10). Thirteen percent of those with and 10.4% of those without a history of glomerular disease had an eGFR below 70 mL/min/1.73 m2 (age-adjusted HR, 1.03; 95% CI, 0.70-1.51).
In this study, resolved childhood glomerular disease was associated with subsequent risk of hypertension in a cohort of young healthy adult men. In addition to the selected cohort, the limitations include lack of information on the exact glomerular histopathologic injury during childhood. Nevertheless, all glomerular conditions were clinically resolved and, by the age of 17 years, participants were free of symptoms and signs for at least 2 years. The interpretation is also limited by the young age of the study population at the end of follow-up.
The 2 most common resolved childhood glomerular diseases are acute glomerulonephritis and steroid-sensitive nephrotic syndrome. Previous large case series3- 6 showed excellent long-term prognoses for children with these conditions. In agreement with our findings, 3.5% to 21.1% of patients with glomerulonephritis3,4 and 2.6% with nephrotic syndrome5 have been reported to develop either persistent urinary abnormalities or hypertension.
Our results suggest that glomerular disease during childhood may represent a continuum of kidney injury that begins well before sufficient loss of excretory kidney function can be measured with standard laboratory tests, such that the first manifestation may be adult hypertension.
Corresponding Author: Asaf Vivante, MD, Talpiot Medical Leadership Program, IDF Medical Corps, Sheba Medical Center, Tel Hashomer 52621, Israel (firstname.lastname@example.org).
Author Contributions: Drs Vivante and Calderon-Margalit had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Vivante, Twig, Skorecki, Calderon-Margalit.
Acquisition of data: Vivante, Tirosh, Calderon-Margalit.
Analysis and interpretation of data: Vivante, Tirosh, Skorecki, Calderon-Margalit.
Drafting of the manuscript: Vivante, Calderon-Margalit.
Critical revision of the manuscript for important intellectual content: Vivante, Twig, Tirosh, Skorecki, Calderon-Margalit.
Statistical analysis: Vivante, Tirosh, Calderon-Margalit.
Administrative, technical, and material support: Vivante.
Study supervision: Vivante, Skorecki.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Skorecki reported serving as a consultant to Elsevier. Dr Calderon-Margalit reported receiving travel reimbursement from COST. No other disclosures were reported.
Funding/Support: Access to anonymized databases was provided by the Israeli Defense Forces Medical Corps.
Role of the Sponsor: The Israeli Defense Forces Medical Corps had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Dorit Tzur, MBA (IDF Medical Corps), for technical support and thoughtful comments. She was not compensated for her contributions.