Sickle cell nephropathy is a severe complication of sickle cell disease (SCD) that has a wide range of manifestations, from asymptomatic microalbuminuria to end-stage renal disease (ESRD). The data on patients with SCD who develop ESRD are scarce. The aim of this study was to explore the course of patients with SCD who developed ESRD and received renal replacement therapy (RRT). The course of patients with SCD who developed ESRD and started dialysis at two centers in the Eastern Province of Saudi Arabia was retrospectively analyzed. Parameters included age at initiation of dialysis, survival until death or kidney transplantation, hospitalization due to pain crisis, disease-related parameters, and requirement for blood transfusion. Sixteen patients with SCD developed ESRD and started RRT with either hemodialysis or peritoneal dialysis. The mean age at initiation of dialysis was 46.6 years. The majority of patients (10 out of 16) were resistant to erythropoiesis-stimulating agents (ESA) and required blood transfusion repeatedly. Pain crises were infrequently encountered. Median survival was 54 months. Four patients received kidney transplantation with good outcome. In conclusion, most patients with SCD who developed ESRD were resistant to ESA and required repeated blood transfusion. The rate of hospitalization due to pain crisis was relatively low. Survival on dialysis was comparable to that of patients with no SCD, and the post-transplant course was relatively benign.