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Introduction Connective tissue diseases, including systemic sclerosis and idiopathic inflammatory myopathies (IIMs), are a very rare cause of thrombotic microangiopathies (TMAs). Whether dysregulation of the complement pathways underlies these secondary forms of TMA and may be targeted by complement blocking agents remains elusive. Methods Kidney pathology and outcomes of 18 critically ill patients with TMA related to inflammatory myopathy flare-up (IIM, n =7) or scleroderma renal crisis (SRC, n =11; biopsy n =9) are assessed. Results IIM-TMA is characterized by acute thrombotic lesions only, whereas SRC-TMA patients also harbored chronic vascular lesions and more interstitial fibrosis. C5b9 deposits, a marker of complement component 5 (C5) cleavage, were observed in the 2 subgroups at the junction of media and intima of arterioles, colocalizing with subendothelial edema. Thus, kidney biopsy distinguished between acute and chronic renal phenotypes that may help to individualize treatment. Treatment of IIM-TMA patients with combined full-code organ support, corticosteroids, B-cell depletion, and complement C5 blocking led to 1-year survival of 72%, compared with 19% in historical cohorts. Treatment of SRC-TMA was more heterogenous and relied on conversion enzyme inhibitor only or with eculizumab ( n =6) and immunosuppressor ( n =5). One-year survival of SRC-TMA patients was 52%, a result similar to historical cohorts. Eculizumab was followed by a rapid dramatic improvement of TMA in all the treated patients. Conclusion C5 blocking may reverse hematologic abnormalities in IIM- and SRC-TMA, and adding an early and aggressive immunosuppressive regimen may improve the survival of IIM-TMA. Underlying chronic vascular and interstitial lesions mitigate renal response in SRC-TMA.

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Intradialytic hypotension can lead to superimposed organ hypoperfusion and ultimately worsens long-term kidney outcomes in critically ill patients requiring kidney replacement therapy. Acetate-free biofiltration (AFB), an alternative technique to bicarbonate-based hemodialysis (B-IHD) that does not require dialysate acidification, may improve hemodynamic and metabolic tolerance of dialysis. In this study, we included 49 mechanically ventilated patients requiring 4 h dialysis (AFB sessions n = 66; B-IHD sessions n = 62). Whereas more AFB sessions were performed in patients at risk of hemodynamic intolerance, episodes of intradialytic hypotension were significantly less frequent during AFB compared to B-IHD, whatever the classification used (decrease in mean blood pressure ≥ 10 mmHg; systolic blood pressure decrease >20 mmHg or absolute value below 95 mmHg) and after adjustment on the use of vasoactive agent. Diastolic blood pressure readily increased throughout the dialysis session. The use of a bicarbonate zero dialysate allowed the removal of 113 ± 25 mL/min of CO2 by the hemofilter. After bicarbonate reinjection, the global CO2 load induced by AFB was +25 ± 6 compared to +80 ± 12 mL/min with B-IHD (p = 0.0002). Thus, notwithstanding the non-controlled design of this study, hemodynamic tolerance of AFB appears superior to B-IHD in mechanically ventilated patients. Its use as a platform for CO2 removal also warrants further research.