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Background: Limited data exist about causes of chronic kidney disease (CKD) and impact on health-related quality of life (HRQoL) in African children. We evaluated types of kidney disease in Ugandan children 0-18 years and compared HRQoL in children with CKD or with benign or resolving kidney disease (non-CKD) to assess predictors of HRQoL., Methods: Demographic, socioeconomic, and clinical data were obtained for this cross-sectional study. Pediatric Quality of Life Core Scale™ (PedsQL) was used to survey 4 domains and overall HRQoL. CKD and non-CKD scores were compared using unpaired t test. HRQoL predictors were evaluated using linear and logistic regression analyses., Results: One hundred forty-nine children (71 CKD, 78 non-CKD; median age 9 years; male 63%) had the following primary diseases: nephrotic syndrome (56%), congenital anomalies of the urinary tract (CAKUT) (19%), glomerulonephritis (17%), and other (8%). CAKUT was the predominant etiology (39%) for CKD; 63% had advanced stages 3b-5. Overall HRQoL scores were significantly lower for CKD (57 vs. 86 by child report, p < 0.001; 63 vs. 86 by parent proxy report, p < 0.001). Predictors of lower HRQoL were advanced CKD stages 3b-5, primary caregiver non-parent, vitamin D deficiency, and anemia., Conclusion: Like other parts of the world, CAKUT was the main cause of CKD. Most CKD children presented at late CKD stages 3b-5. Compared with non-CKD, HRQoL in CKD was much lower; only two-thirds attended school. Vitamin D deficiency and anemia were potentially modifiable predictors of low HRQoL. Interventions with vitamin D, iron, and erythropoietin-stimulating agents might lead to improved HRQoL.