{"doi":"10.1002/ajh.26115","title":"Hyperuricemia and abnormal nocturnal dipping impact glomerular filtration rate in patients with sickle cell anemia","abstract":"Patients with sickle cell anemia (SCA) are at increased risk for developing chronic kidney disease (CKD), and progression to end-stage renal disease is associated with increased morbidity and mortality. Identifying modifiable risk factors for CKD in childhood are a vital first step to ameliorate progression. Patients with SCA may have higher risk for CKD due to the unique renal pathophysiology associated with chronic heme exposure and sickling of red blood cells; however, it is important to evaluate established risk factors associated with CKD in non-SCA populations. Hyperuricemia and abnormal ambulatory blood pressure monitoring (ABPM) represent two established modifiable risk factors associated with development of CKD. We performed a cross-sectional study of this cohort at baseline and identified that hyperuricemia and abnormal ABPM were associated with lower eGFR at baseline.1 This prospective study evaluated the annual change in estimated GFR (eGFR) among patients with and without hyperuricemia, nocturnal hypertension, and abnormal nocturnal dipping. As children with SCA experience a rise in eGFR in the first decade of life prior to a decline, we restricted this analysis to the change in eGFR from 10–18 years of age. We hypothesized that hyperuricemia and abnormal APBM would be associated with a decline in eGFR during the second decade of life. The IRB approved, UAB Pediatric Renal SCA cohort enrolled 192 pediatric participants to evaluate the impact of nocturnal hypertension and biomarkers of renal injury on progression of chronic kidney disease (NCT02373241). Participants with HbSS or HbSB0 thalassemia, ages six to 19 years, were eligible to enroll in the study for annual blood and urine studies of chronic kidney disease. Participants were given an option to complete a 24-hour ambulatory blood pressure monitoring (ABPM). We prospectively collected eGFR by cystatin C and uric acid levels at each annual standard of care sickle cell clinic visit; we also abstracted eGFR values retrospectively from annual standard of care clinic visits. Fifty-nine participants older than age 10 completed 24-hour ambulatory blood pressure. Annual decline in eGFR was the primary outcome for this analysis and our predictor variables were hyperuricemia and abnormal nocturnal blood pressure. Pediatric patients with sickle cell anemia experience an elevation in eGFR during the first decade of life, before a decline in eGFR during the second decade of life. For this study of decline in eGFR, we restricted our analysis to 132 SCA participants with eGFR values obtained between 10–18 years of age. We recorded a total of 642 cystatin based eGFR levels during annual SCA clinic well visits. We defined hyperuricemia as a mean uric acid level ≥ 5.5 mg/dL. Nocturnal hypertension was defined as >25% of nocturnal blood pressure (BP) readings >95th percentile. Abnormal nocturnal dipping was defined by a <0% decrease in BP while sleeping (BP increased while sleeping). Attenuated nocturnal dipping was defined by <10% to ≥0% dip in mean BP while sleeping. We defined normal blood pressure dipping by ≥10% dip in mean BP. To compare the change in GFR as a function of age for the different groups, we fitted a random intercept mixed model with age (linear), groups and age by group interaction. If the interaction was not significant, we refit the model with only the main effects of age and groups. We performed analyses using SASv9.4. The mean eGFR was 167 ± 34 mL/min/1.73 m2 with a mean age of 13.9 ± 2.6 years. We identified 39 (30%) participants with hyperuricemia and 93 (70%) without hyperuricemia. We found a significant interaction (P = .003) between age and hyperuricemia group implying that the change in eGFR over time depends on hyperuricemia. At age 10, we identified no significant difference between eGFR among groups. As the participants age, those with hyperuricemia showed a significant decrease in mean eGFR of −2.46 mL/min/1.73 m2/year (P = .002). (Figure 1(A)","journal":"American Journal of Hematology","year":2021,"id":196003,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":366744,"name":"Inmaculada Aban","orcid":"0000-0002-0563-1691","position":1,"is_corresponding":false},{"id":540635,"name":"Lee Hilliard","orcid":null,"position":2,"is_corresponding":false},{"id":247933,"name":"Daniel I. Feig","orcid":"0000-0002-0017-6335","position":3,"is_corresponding":false},{"id":439255,"name":"Jeffrey D. Lebensburger","orcid":"0000-0001-5011-1022","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-18T23:50:11.609550Z","pmid":"33524174","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}