Introduction: Sickle cell anemia (SCA) is a chronic illness associated with acute and chronic hemolytic anemia, recurrent vaso-occlusion episodes, intense pain, progressive multiple organ damage, and early mortality. Inflammation plays a significant role in the pathophysiology of SCA. Elevated levels of pro-inflammatory cytokines are involved in worsening the degree of kidney damage in SCA patients. Objectives: The present study aimed to assess whether IL1RN VNTR polymorphism is associated with kidney damage in patients with SCA. Patients and Methods: We have investigated 190 SCA patients (104 with Normal kidney function and 86 with kidney damage). Creatinine-based estimated glomerular filtration rate (eGFR) was calculated to assess kidney function. Interleukin-1 receptor antagonist gene (IL1RN) variable number tandem repeats (VNTR) genotypes were analyzed using PCR-electrophoresis. The association between IL1RN-VNTR and kidney damage was evaluated by using χ2 test. Odds ratios (OR) and 95% CI were calculated. The relationship between kidney damage and fetal hemoglobin (HbF) and their interaction with IL1RN-VNTR genotypes, was investigated using a Mantel-Haenszel (M-H) stratified analysis. Results: There were no significant differences in genotype frequencies between SCA patients with or without kidney damage (P=0.107). Furthermore, no significant interactions between IL1RN VNTR and HbF on determining kidney damage were found. Conclusion: These results conflict with the biological plausibility that interleukin levels modulate SCA pathophysiology and may deserve further exploration.