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Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia.

ABSTRACT: BACKGROUND:Patients with sickle cell anemia (SCA) have an increased prevalence of nephropathy and mortality from chronic kidney disease (CKD). METHODS:We evaluated the association of hyperuricemia and nocturnal hypertension with lower estimated glomerular filtration rate (eGFR) using cystatin-C in patients aged 10-21 years with the HbSS or HbSB0 form of the disease during a non-acute clinic visit. eGFR and uric acid measurements were obtained in 83 and 81 participants, respectively, and 24-h ambulatory blood pressure monitoring (ABPM) was performed in 44 participants. Annual testing included vital signs, complete blood count, comprehensive metabolic panel, medications, urine microalbumin/creatinine, and lactate dehydrogenase measurements. Hyperuricemia was defined as a uric acid level of ?5.5 mg/dL. Nocturnal hypertension was defined as >25% of nocturnal readings at >95th percentile according to norms established by the American Heart Association Statement on ABPM in children and adolescents. RESULTS:The mean eGFR was statistically significantly lower in patients with hyperuricemia than in those with normal uric acid levels (143 vs. 161 mL/min/1.73 m2, respectively). Of the 44 participants for whom ABPM data were available, 14 (32%) had systolic nocturnal hypertension and 12 (27%) had diastolic nocturnal hypertension. The mean eGFR was statistically significantly lower in participants with nocturnal systolic and diastolic hypertension than in those with normal nocturnal blood pressure. In a regression model, nocturnal hypertension and hyperuricemia were associated with a lower eGFR. CONCLUSIONS:Two risk factors for CKD, i.e., nocturnal hypertension and hyperuricemia, were associated with lower eGFR in older children and adolescent patients with SCA. Long-term studies on their association with progression to CKD in this population are warranted. KEY POINT:Nocturnal hypertension and hyperuricemia are established risk factors for nephropathy in other diseases and may play a role in SCA nephropathy.

SUBMITTER: Lebensburger JD

PROVIDER: S-EPMC5628098 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia.

Lebensburger Jeffrey D JD Cutter Gary R GR Howard Thomas H TH Muntner Paul P Feig Daniel I DI

Pediatric nephrology (Berlin, Germany) 20170405 9

<h4>Background</h4>Patients with sickle cell anemia (SCA) have an increased prevalence of nephropathy and mortality from chronic kidney disease (CKD).<h4>Methods</h4>We evaluated the association of hyperuricemia and nocturnal hypertension with lower estimated glomerular filtration rate (eGFR) using cystatin-C in patients aged 10-21 years with the HbSS or HbSB0 form of the disease during a non-acute clinic visit. eGFR and uric acid measurements were obtained in 83 and 81 participants, respectivel ...[more]

PMID: 28382567

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Project description:There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown.We performed chromosomal microarrays to detect genomic imbalances in children enrolled in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, a longitudinal prospective multiethnic observational study of North American children with mild to moderate CKD. Patients with clinically detectable syndromic disease were excluded from evaluation. We compared 419 unrelated children enrolled in CKiD to multiethnic cohorts of 21,575 children and adults that had undergone microarray genotyping for studies unrelated to CKD.We identified diagnostic copy number disorders in 31 children with CKD (7.4% of the cohort). We detected 10 known pathogenic genomic disorders, including the 17q12 deletion HNF1 homeobox B (HNF1B) and triple X syndromes in 19 of 419 unrelated CKiD cases as compared with 98 of 21,575 control individuals (OR 10.8, P = 6.1 × 10?²?). In an additional 12 CKiD cases, we identified 12 likely pathogenic genomic imbalances that would be considered reportable in a clinical setting. These genomic imbalances were evenly distributed among patients diagnosed with congenital and noncongenital forms of CKD. In the vast majority of these cases, the genomic lesion was unsuspected based on the clinical assessment and either reclassified the disease or provided information that might have triggered additional clinical care, such as evaluation for metabolic or neuropsychiatric disease.A substantial proportion of children with CKD have an unsuspected genomic imbalance, suggesting genomic disorders as a risk factor for common forms of pediatric nephropathy. Detection of pathogenic imbalances has practical implications for personalized diagnosis and health monitoring in this population.ClinicalTrials.gov NCT00327860.This work was supported by the NIH, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute.

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Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia.

Publications

Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia.

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