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- Title
APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses.
- Authors
Watanabe, Andreia; Guaragna, Mara Sanches; Belangero, Vera Maria Santoro; Casimiro, Fernanda Maria Serafim; Pesquero, João Bosco; de Santis Feltran, Luciana; Palma, Lilian Monteiro Pereira; Varela, Patrícia; de Menezes Neves, Precil Diego Miranda; Lerario, Antonio Marcondes; de Souza, Marcela Lopes; de Mello, Maricilda Palandi; de Brito Lutaif, Anna Cristina Gervásio; Ferrari, Cassio Rodrigues; Sampson, Matthew Gordon; Onuchic, Luiz Fernando; Nogueira, Paulo Cesar Koch
- Abstract
Background: APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. Methods: Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m2] and slow/non-progressors (eGFR > 30 mL/min/1.73 m2 through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. Results: Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. Conclusions: Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.
- Subjects
BRAZIL; CHRONIC kidney failure; DISEASE progression; RESEARCH; GLOMERULAR filtration rate; NEPHROTIC syndrome; GENETIC polymorphisms; PEDIATRICS; MEDICAL cooperation; RISK assessment; APOLIPOPROTEINS; DESCRIPTIVE statistics; ETHNIC groups; FOCAL segmental glomerulosclerosis; PROPORTIONAL hazards models; DISEASE risk factors
- Publication
Pediatric Nephrology, 2021, Vol 36, Issue 8, p2327
- ISSN
0931-041X
- Publication type
Article
- DOI
10.1007/s00467-021-04960-w