Urinary Biomarkers for the Assessment of Acute Kidney Injury of Pediatric Sickle Cell Anemia Patients Admitted for Severe Vaso-occlusive Crises.

Sickle cell nephropathy is a progressive morbidity, beginning in childhood, which is incompletely understood partially due to insensitive measures. We performed a prospective pilot study of pediatric and young adult patients with sickle cell anemia (SCA) to assess urinary biomarkers during acute pain crises. Four biomarkers were analyzed with elevations potentially suggesting acute kidney injury: (1) neutrophil gelatinase-associated lipocalin (NGAL), (2) kidney injury molecule-1, (3) albumin, and (4) nephrin. Fourteen unique patients were admitted for severe pain crises and were found to be representative of a larger SCA population. Urine samples were collected at the time of admission, during admission, and at follow-up after discharge. Exploratory analyses compared cohort values to the best available population values; individuals were also compared against themselves at various time points. Albumin was found to be moderately elevated for an individual during admission compared with follow-up ( P = 0.006, Hedge g : 0.67). Albumin was not found to be elevated compared with population values. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and nephrin were not found to be significantly elevated compared with population values or comparing admission to follow-up. Though albumin was found to be minimally elevated, further research should focus on alternative markers in efforts to further understand kidney disease in patients with SCA.

Accuracy of online medical information: the case of social media in sickle cell disease.

The medical needs of individuals with sickle cell disease (SCD) are complex. Patients with SCD experience complications such as recurrent pain episodes and increased hospitalizations. Over 70% of AYA and their parents seek medical information from the Internet; 83% inquire on sites that have interactive/social features, such as Facebook or Twitter, yet accuracy remains unclear. Our objective was to assess the accuracy of the SCD-information posted on social media. We hypothesized that most of the posted information is inaccurate. We coded one month of threads from two common SCD Facebook groups (Sickle Cell Warriors Unity and Sickle Cell Anemia) to identify the purpose of each post and the accuracy of medical information posted. Amongst both social media sites, there were 487 posts. Most of the posts were directed toward socializations (n = 311, 63.8%), while other posts mainly focused mainly on SCD and its management (n = 173, 35.5%). When looking at the medical posts, 44.9% were accurate, whereas 55.1% of the posts included inaccurate information. We found that less than half of the medical information posted on interactive social media is inaccurate. Our findings raise potentially serious implications for individuals with SCD and/or their caregivers who may rely on social media to gather more information about their or their child's disease. Our data highlight the importance of health care providers encouraging patients and parents to ask any questions they may have about SCD, given they may consult social media and Internet site that provide inaccurate information.

Black Americans' willingness to participate in pediatric sickle cell clinical trials: A retrospective, systematic review.

Black individuals are underrepresented in randomized clinical trials (RCTs). Willingness to participate is a frequently cited explanation. However, the few studies that have investigated willingness to participate demonstrated no difference between Black individuals and other groups. We sought to measure willingness to participate by focusing on sickle cell disease (SCD), in which approximately 90% of affected individuals are Black. We conducted an analysis of 17 RCTs. A level of clarity was defined and correlated with each article's transparency in reporting patient enrollment data. Calculated measures of acceptance ranged from 32% to 93.5%. Calculated completion rates ranged from 58.8% to 100%. Weighted measures of acceptance and completion were 59.1% and 83.8%, respectively. Our study is limited by focusing solely on studies pertinent to SCD and only a minority of publications reviewed provided sufficient patient enrollment data. Yet, our results suggest that decreased willingness to participate does not account for underrepresentation of Black individuals.

Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study.

Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality in sickle cell anemia (SCA). Albuminuria is an early manifestation of sickle nephropathy; however, little is known about progression of albuminuria or its correlation with glomerular filtration rate (GFR) decline or CKD. We studied nephropathy progression in 303 SCA participants in a prospective, multicenter, longitudinal study. We collected steady-state urine and serum samples yearly and assessed albumin/creatinine ratio (ACR), estimated GFR (eGFR), and SCA and nephropathy biomarkers. Participants with albuminuria (ACR ≥30 mg/g) for ≥2 annual measurements were classified as having persistent albuminuria (PA). At baseline (mean age, 21 years; range, 2-64 years), 32% had albuminuria. In longitudinal multivariate analysis, ACR was associated with sex, anemia, older age, and higher bilirubin and kidney injury molecule-1 levels. Albuminuria increased with age by 3.5 mg/g per year (P < .0001). Of 175 participants with ≥3 annual samples, 81% with baseline albuminuria ≥100 mg/g developed PA. Decreased eGFR and adult CKD were associated with PA (P = .002 and P = .02, respectively), but not with baseline albuminuria. Rate of eGFR decline was steeper among adults (but not children) with albuminuria, compared with those without (P = .02). Participants with PA were more likely to have rapid eGFR decline compared with those without (P = .03). In this longitudinal study, albuminuria progressed with age, and adults with albuminuria had worse eGFR decline than those without. Albuminuria ≥100 mg/g predicted PA, which was associated with rapid eGFR decline and CKD development in adults with SCA. This trial was registered at www.clinicaltrials.gov as #NCT02239016.

Improving Uptake of Hydroxyurea in Patients with Sickle Cell Disease: A Retrospective Study of a Clinic-based Change in Consenting Practices.

INTRODUCTION: Sickle cell disease (SCD) can shorten lives and may result in severe clinical complications. Hydroxyurea (HU) is inexpensive, widely available, and National Institutes of Health (NIH) recommends HU for SCD. Despite these benefits, utilization of HU is low. Barriers to taking HU include inaccurate perceptions of serious side effects such as hair loss, a significant barrier in the African American community. However, at doses for treating SCD, the incidence of side effects is extremely low. Using a retrospective medical record review, the impact of a revised consent procedure for HU that addressed these barriers was evaluated. METHODS: SCD patients 2-20yo eligible for HU were examined. Patients prescribed HU versus those not prescribed HU were compared one year before and one year after revising consent procedures. RESULTS: Change in clinic practice (including revised consent procedures) resulted in 158% more patients agreeing to HU therapy (p<.001). DISCUSSION: The revised consent procedures are not resource intensive and easy to implement. Future research should address treatment acceptability, intimidation, and cultural sensitivity.

Losartan for the nephropathy of sickle cell anemia: A phase-2, multicenter trial.

Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA = 14, MicroA = 12, MacroA = 6). The primary endpoint was met in 83% of the MacroA group (P < 0.0001) and 58% of the MicroA group (P < 0.0001). Median fold-change in UACR was -0.74 for MacroA and -0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in three participants [leg cramps, N = 1; decline in eGFR >25% (142➝104 mL/minute/1.73 m2 ), N = 1; rise in serum creatinine >50% (0.2➝0.3 mg/dL), N = 1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA.

Cerebral vascular abnormalities in pediatric patients with sickle cell disease after hematopoietic cell transplant.

OVERVIEW: Stroke is a common sequela of sickle cell disease (SCD). Patients with SCD who undergo hematopoietic stem cell transplantation (HSCT) with successful engraftment will not experience sickling. This ameliorates one aspect of stroke risk; however, the significance of preexisting cerebrovascular abnormalities remains unclear. METHODS: We performed a literature search for neurological outcomes following HSCT for SCD. We searched for relevant neuroimaging and neurosurgical protocols. We identified 4 unique studies encompassing 196 patients. Of these, 81 had a history of a stroke, transient ischemic attack (TIA), cognitive dysfunction or cerebrovascular abnormalities identified by pretransplant neuroimaging, achieved stable engraftment, and had long-term follow-up. RESULTS: Of the 81 patients, 1 had peritransplant (10 days prior transplant to 50 days posttransplant) TIA. One had posttransplant TIA within 36 to 72 months. None had strokes. Forty-five underwent cerebral imaging at nonuniform intervals. Among this group, 32 (71%) had stable cerebrovascular abnormalities on imaging, 6 (13%) had improvement, and 7 (16%) showed worsening. CONCLUSIONS: Cerebrovascular abnormalities identified on neuroimaging may stabilize, improve, or worsen in patients after successful HSCT. Some patients may have neurological events such as TIA. Neurological outcomes in children with SCD post-HSCT have been inadequately studied.

The prevalence of hypertension and abnormal kidney function in children with sickle cell disease -a cross sectional review.

BACKGROUND: Renal disease is a known contributor to mortality in adults with sickle cell disease (SCD) and renal abnormalities are evident in childhood. Hyperfiltration (evidenced by elevated glomerular filtration rate, GFR) occurs in children with SCD early in disease. However, the incidence of low GFR (<90 ml/min/1.73 m(2)) suggestive of chronic kidney disease (CKD), is not well established. The prevalence of hypertension is also not well known. The goal of this study was to determine the prevalence of hypertension and CKD in a cohort of children with SCD. METHODS: We performed a retrospective chart review of patients followed at the Rainbow Babies and Children's Sickle Cell Disease Clinic who were seen during routine follow up visits. Inclusion criteria were all patients ages 3-18. Exclusion criteria included recent (within 2 weeks) hospitalization and/or episode of acute chest, pain crises, febrile illness or red blood cell transfusion. Data collected included serum creatinine, blood pressure and history of sickle cell complications (acute chest syndrome, stroke or stroke risk). Estimated GFR (eGFR) was calculated using the updated Schwartz creatinine-based estimating formula. Analysis examined the associations among eGFR, blood pressure and sickle cell complications. The Institutional Review Board at University Hospitals Case Medical Center approved this study. RESULTS: A total of 48 children had complete data available. Mean eGFR was 140 mL/min/1.73 m(2) +/- 34.9 (range 71.9-404.2 mL/min/1.73 m(2)). Four patients (8.3%) had eGFRs < 90 mL/min/1.73 m(2), 35 patients (72.9%) had eGFRs > 120 mL/min/1.73 m(2) and 9 patients (18.8%) had eGFRs in the normal range. Eight patients (16.7%) had evidence of elevated blood pressures (pre-hypertension or hypertension). There was no correlation between eGFR and age, and no association of eGFR with acute chest or stroke risk. CONCLUSION: In this SCD cohort, we identified abnormally low eGFR (suggestive of early CKD) in 8.3% of patients and elevated blood pressure in 16.7%. These findings are in contrast to other published studies that show primarily normal or elevated GFR and the absence of or minimal hypertension. These findings indicate that elevated blood pressure and decreased eGFR are not uncommon in children with SCD, and should be more rigorously studied.