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 m 2 , 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.