Abstract: TH-PO002

Renal Crisis in Scleroderma: A Renal Complementopathy?

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Ghossein, Cybele, Northwestern University FSM, Chicago , Illinois, United States
  • Kanwar, Yashpal S., Northwestern University FSM, Chicago, Illinois, United States
  • Varga, John, Northwestern University Medical School, Chicago, Illinois, United States
Background

Scleroderma renal crisis (SRC) is an abrupt-onset and unpredictable complication of systemic sclerosis (SSc) generally presenting with acute kidney injury and severe hypertension. Despite the introduction of ACE inhibitors, the 5-yr survival of these patients remains<50%. The pathogenesis of SRC is still incompletely understood. Current paradigms implicate activation of renin- angiotensin system leading to accelerated hypertensive pathophysiology .Recently there has been an enhanced understanding of the role of acquired and/or genetic complement pathway dysregulation in the pathogenesis of thrombotic microangiopathies (TMA) such as in preeclampsia and aHUS. Pathologically SRC shares many similarities to TMA. We hypothesized that complement may play a role in SRC

Methods

We retrospectively reviewed all SRC patients who had a renal biopsy at our institution between the years of 1990 -2015 . 19 renal biopsies of SSc patients with diagnosed SRC, defined as a clinical presentation and pathologic findings consistent with this diagnosis were evaluated. Light microscopy, immunofluorescence and electron microscopy were assessed with specific focus on vascular injury

Results

14 out 19 renal biopsies had C3 deposition in arteriolar walls along with immunoglobulin reactivity. Biopsies with complement staining had active severe vascular lesions.5 out of the 19 renal biopsies showing no complement staining were more likely to have significant interstitial fibrosis with vessel undergoing impending hyalinosis.

Conclusion

C3 small vessel reactivity in renal biopsies of patients with SRC reflects the active role of complement in the pathogenesis of SRC. Once in the chronic phase of the disease, complement is no longer an important component of disease activity. These findings challenge the current dogma for SRC pathogenesis, and raise the possibility of alternative treatment approaches to SRC.

Table 1
 C3+ (n= 14)C3 - (n=5) 
Average Age at SRC onset ( years) 4855 
Male/Female4/100/5p=0.5
Hypertension on presentation (# of patients)104p=0.9
RNA Polymerase 3 + ( # of patients)52p=0.9
>50% interstitial fibrosis (# of patients)24p=0.0173

Funding

  • Clinical Revenue Support