Patients with lupus nephritis who have a high-risk APOL1 genotype, compared with those who do not, have worse kidney function at diagnosis, more collapsing glomerulopathy, and higher likelihood of progressing to end-stage kidney disease (ESKD), investigators reported at the European Renal Association’s 2023 Congress in Milan, Italy.
Carole Burger, MD, of European Hospital Georges-Pompidou HEGP in Paris, France, and colleagues compared 13 adults who inherited 2 APOL1 risk alleles, G1 and/or G2 (high-risk group) and 86 adults who inherited 0-1 APOL1 risk alleles (low-risk group).
At lupus nephritis diagnosis, median serum creatinine was significantly higher in the high-risk group compared with the low-risk group: 131 vs 66 μmol/L. Serum creatinine exceeding 200 μmol/L also was significantly more common in the high-risk group: (45.5% vs 10.5%) and required acute hemodialysis more frequently (30.8% vs 1.3%). Collapsing glomerulopathy affected 45.5% of the high-risk group compared with 4.5% of the low-risk group.
Chronic kidney disease (CKD) ultimately developed in a significantly greater proportion of the high-risk than low-risk group (33.3% vs 4.9%), with the high-risk genotype significantly associated with 9.6-fold increased odds of CKD, the investigators reported. Median follow-up from lupus nephritis diagnosis to ESKD, last follow-up, or the end of study was 7.9 years. At last follow-up, median estimated glomerular filtration rate (eGFR) was significantly lower in the high-risk than low-risk APOL1 genotype group: 22 vs 99 mL/min/1.73m2, respectively. The risk of ESKD was a significant 6.2-fold higher for the high-risk group after adjusting for kidney response at 12 months.
According to Dr Burger’s team, lupus nephritis prognosis is “heavily driven” by the high-risk APOL1 genotype regardless of kidney response. They noted that APOL1 inhibitors are currently being developed that might treat these patients with primary or secondary forms of collapsing glomerulopathy.
Burger C, Benichou N, Narjoz C, et al. APOL1 genotype is a major determinant of lupus nephritis severity in patients of African ancestry. Presented at: ERA 2023 Congress; 2023 June 15-18; Milan, Italy. Abstract 3155.