#3539 Identifying risk factors for chronic kidney disease progression in sickle cell disease

Abstract Background and Aims Patients with sickle cell disease (SCD) are at high risk of developing renal involvement due to various mechanisms, including chronic microvascular damage from repeated vaso-occlusive events. This damage may lead to progressive chronic kidney disease (CKD). The aim of this study was to evaluate the natural history of kidney disease in SCD patients and identify risk factors for its progression. Method We conducted a retrospective observational study that included all patients diagnosed with homozygous (HbSS) or heterozygous (HbSC) sickle cell disease who were followed in the Hematology clinic at our center between May 2011 and March 2024. We analyzed demographic data, comorbidities, treatments, complications (e.g., vaso-occlusive crises, transfusion requirements, development of hemoglobinuria), and kidney function tests throughout the follow-up period. Glomerular hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) >130 ml/min, as measured by CKD-EPI. The annual rate of eGFR loss was calculated, with rapid progression defined as a loss of >3 ml/min/year. Renal outcome was defined as progression to eGFR <90 ml/min with a decline of >25% from baseline and/or the need for renal replacement therapy. Results The study included 30 patients, with a mean age at the start of follow-up of 26.5 ± 12 years; 60% of whom were women. Of the patients, 23 (76.7%) had HbSS, and 7 (23.3%) had HbSC, with one patient also having alpha-thalassemia. At the start of follow-up, 14 patients (46.7%) exhibited glomerular hyperfiltration, and 5 patients (16.7%) had albuminuria. During follow-up, most patients (86.7%) experienced vaso-occlusive crises, and 7 patients (23.3%) developed hemoglobinuria. Sixteen patients (53.3%) were treated with hydroxyurea, and 4 patients (13%) participated in clinical trials (etavopirat, crizanlizumab). Six patients (20%) received renin-angiotensin system blockade. After a median follow-up of 45 months (IQR 12–113 months), the mean annual eGFR loss was −2.5 ml/min/year (±5.5), with 14 patients (46.7%) showing rapid progression. Three patients (10%) reached the renal outcome: 2 with progression to eGFR <90 ml/min and 1 with progression to end-stage renal disease. The annual rate of eGFR loss was significantly higher in men (−5 ± 4.8 vs. −0.6 ± 5.5 ml/min/year, P = 0.048). Only homozygous patients and those with vaso-occlusive crises developed albuminuria at the end of follow-up (33.3% and 28.6%, respectively) and reached the renal outcome (13% and 11.5%, respectively). Conclusion A significant proportion of patients with sickle cell disease present with glomerular hyperfiltration, and a notable number experience rapid renal function decline, particularly among men, homozygous patients, and those with vaso-occlusive crises. These findings underline the need for prospective studies to analyze the potential benefits of nephroprotective therapies that could improve the natural course of renal disease associated with sickle cell disease.