Abstract: Provided are methods and kits for determining predisposition of a subject to develop a kidney disease, by identifying in a sample of the subject at least one APOL1 polypeptide variant which is characterized by a higher trypanolytic activity on Trypanosoma brucei rhodesiense as compared to the trypanolytic activity of wild type APOL1 polypeptide as set forth in SEQ ID NO:1 on the Trypanosoma brucei rhodesiense under identical assay conditions; or at least one APOL1 nucleotide mutation in the APLO1 genomic sequence set forth in SEQ ID NO:3, wherein the at least one nucleotide mutation or polypeptide variant being in linkage disequlibrium (LD) with the S342G mutation in the APOL1 polypeptide set forth in SEQ ID NO:1, wherein presence of the APOL1 polypeptide variant indicates increased predisposition of the subject to develop the kidney disease.