Sex Differences in Clinical Presentation and Outcomes among Patients with Complement-Gene-Variant-Mediated Thrombotic
Christof Aigner1, Martina Gaggl1, Renate Kain2
1Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, 1090 Vienna, Austria.
Insights
Most patients with complement-gene-variant-mediated thrombotic microangiopathy (cTMA) are female. While clinical presentation and renal function are similar between sexes, females more often carry cTMA risk haplotypes.
Area of Science:
- Nephrology
- Genetics
- Immunology
Background:
- Sex differences in complement-gene-variant-mediated thrombotic microangiopathy (cTMA) are not well-defined.
- Understanding these differences is crucial for targeted patient management.
Purpose of the Study:
- To investigate sex-based disparities in the demographic and clinical presentation of cTMA.
- To analyze the association between sex and genetic risk factors in cTMA patients.
Main Methods:
- Retrospective analysis of 51 cTMA patients from the Vienna TMA cohort (1981-2019).
- Comparison of demographic data, clinical features, renal function, and treatment modalities between female and male patients.
- Assessment of complement gene variant (CFH, CD46) risk haplotypes and pathogenic variants in relation to sex.
Main Results:
- The majority of cTMA patients (63%) were female.
- No significant sex differences were observed in age at diagnosis, renal function, or need for renal replacement therapy.
- Females exhibited a higher prevalence of CFH and CD46 risk haplotypes (97% vs. 68%, p=0.01).
Conclusions:
- Complement-gene-variant-mediated thrombotic microangiopathy predominantly affects females in the Vienna TMA cohort.
- Clinical outcomes and renal function do not significantly differ between sexes.
- Females are more likely to carry genetic risk factors associated with cTMA.
Abstract:
Sex differences among patients with complement-gene-variant-mediated thrombotic microangiopathy (cTMA) are not well established. We examined demographic and clinical data from female and male patients with a history of cTMA enrolled in the Vienna thrombotic microangiopathy (TMA) cohort. Follow-up was three years after first presentation with cTMA. In this single-center study, we identified 51 patients with a first manifestation of cTMA between 1981 and 2019; 63% were female (p = 0.09). The median age at diagnosis did not differ between females and males. There was also no disparity between the sexes with regard to renal function or the need for renal replacement therapy at presentation. Furthermore, we observed similar use of plasma or eculizumab therapy and a comparable evolution of renal function of female and male patients. More females showed risk haplotypes of complement factor H (CFH) and CD46 (97% vs. 68%, p = 0.01), but there was no difference in the prevalence of rare pathogenic variants in complement-associated genes with regard to sex. In conclusion, the majority of cTMA patients enrolled in the Vienna TMA cohort were female. Clinical presentation and renal function did not differ between the sexes, but females more frequently presented with cTMA risk haplotypes.
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