Associação entre variantes de risco do gene APOL1 e hemoglobinas variantes com progressão das doenças glomerulares na Bahia

Abstract

INTRODUCTION: In addition to those traditionally recognized as the main risk factors for kidney disease, increasing emphasis has been placed on the genetic makeup of patients. OBJECTIVE: To estimate the frequency of risk variants of APOL1 and hemoglobin in patients undergoing renal biopsy in Bahia, and to evaluate the association between these variants and the progression of glomerular diseases in these patients. METHODS: Prospective cohort study, including 326 patients undergoing renal biopsy. Hemoglobin variants were defined by high performance liquid chromatography and Apol1 genotypes were determined by DNA sequencing of 304 patients. Patients were followed up for five years to assess disease progression markers. RESULTS: Among the patients, 22.7% had one risk allele and 4.3% had two risk alleles of APOL1. The median age was lower in patients carrying two APOL1 risk alleles, p = 0.04. Among the patients with two risk alleles, 61.5% had focal segmental glomerulosclerosis (FSGS), p < 0.001. The proportion of Interstitial Inflammation, tubulointerstitial fibrosis, global and/or segmental sclerosis and tubular atrophy score was higher in patients with two APOL1 risk alleles (p<0.05 for each of them). There was a progressive decline in the mean glomerular filtration rate between patients with two risk alleles between the time of biopsy and after five years of follow-up: (from 79 ± 51 mL / min / 1.73 m2 to 22 ± 13 mL / min / 1.73 m2, p = 0.004), compared to those with one (from 77 ± 41 mL / min / 1.73 m2 to 194 ± 54 mL / min / 1.73 m2), p = 0.74 or none (from 74 ±47 mL / min / 1.73 m2 to 78 ±45 mL / min / 1.73 m2, p = 0.45) APOL1 risk allele. Renal survival is significantly lower (69%) for individuals with two APOL1 risk alleles compared with 94% and 91% between groups with one and without APOL1 risk alleles, respectively, p = 0.024. The proportion of patients diagnosed with FSGS who progressed to ESRD was significantly higher in individuals with two APOL1 risk alleles (33%) than those with a risk allele (0%) or with no risk alleles (3%), p = 0.04. The frequency of sickle cell trait (HbAS, 4.3%) and hemoglobin C trait (HbAC, 3.7%) was not different from that found in the general population (4.5% and 2.2% respectively). Five years after renal biopsy, the estimated glomerular filtration rate mean was 35 mL / min / 1.73 m2 in patients with sickle cell trait, while in the HbAA and HbAC groups, the estimated glomerular filtration rate mean was 84 mL / min / 1.73 m2 and 103 mL / min / 1.73 m2 respectively, p= 0.01. Patients with sickle cell trait more frequently developed ESRD needing dialysis (31%) compared to those with HbAA (8%) (p = 0.02). CONCLUSIONS: Patients with a high-risk genotype of APOL1 develop a more severe form of FSGS with histological evidence of a worse prognosis and faster progression to the terminal stage of the disease. There is no difference in the frequency of HbAS or HbAC between patients undergoing renal biopsy and the general population. However, patients with HbAS show a faster decline in the glomerular filtration rate, lower renal survival compared to patients with HbAA.