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Hypertensive emergency and hemolytic uremic syndrome
A
B
Figure 5. Renal survival of patients with atypical hemolytic uremic syndrome according to the presence or absence of rare complement variants and hypertensive emergency. (A) Analysis of renal survival without end-stage renal disease or death in patients not treated with eculizumab, log-rank test, P=0.02. (B) Analysis of renal survival in the whole cohort, log-rank test, P=0.001. Follow-up was not available for two patients with hypertensive emergency and atypical hemolytic uremic syndrome. HE: hypertensive emergency; aHUS: atypical hemolytic uremic syndrome; C: complement.
but may suggest that the H3 haplotype in the CFH gene confers an increased risk of HUS only in patients with hypertensive crisis. Altogether, we showed that geneti- cally impaired regulation of complement activation is present in a substantial proportion of patients with HE- aHUS. However, whether a hypertensive crisis acts as a disease trigger in variant carriers or whether complement- mediated endothelium damage induces a secondary HE phenotype remains to be studied.20
The cause of the disease remained undetermined in 60% (46/76) HE-aHUS and 32% (20/61) of noHE-aHUS patients. Notably, we identified no DGKE mutation in the 76 HE-aHUS patients. Moreover, the absence of effect of complement variants in the renal prognosis of HE-
aHUS patients, contrary to patients with noHE-aHUS, suggests the involvement of superimposed factors other than complement in HE-aHUS. A major involvement of the renin-angiotensin system during HE-aHUS has been demonstrated in the stroke prone spontaneously hyper- tensive rat model.21 Interestingly, C3 is involved in the phenotype of this model,22 and renin has been shown to cleave C3, an effect inhibited by a direct renin inhibitor.23,24 Renin-angiotensin system activation is also correlated with hemolysis in HE patients.25 Increased chronic renin-angiotensin system activation could have a deleterious role in the long-term kidney prognosis of HE- aHUS patients.26 Overall, our results suggest that HE- aHUS has a complex pathophysiology involving comple-
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