From the Guidelines
Renal AKI HUS should be managed with prompt recognition, supportive care, and consideration of the latest guidelines for acute kidney disease (AKD) and chronic kidney disease (CKD) prevention, as outlined in the 2017 consensus report by the Acute Disease Quality Initiative (ADQI) 16 workgroup 1. The management of HUS-associated AKI requires a comprehensive approach, including fluid and electrolyte management, blood pressure control, and monitoring for complications.
- Initial treatment includes:
- Fluid management to prevent dehydration and electrolyte imbalances
- Blood pressure control to reduce the risk of cardiovascular complications
- Monitoring for complications such as thrombocytopenia, anemia, and renal failure
- In typical HUS, antibiotics are generally avoided as they may increase toxin release, whereas in atypical HUS, plasma exchange therapy and eculizumab (a complement inhibitor) may be recommended 1.
- Dialysis is often necessary for severe AKI with fluid overload, electrolyte abnormalities, or uremia, and nutritional support should be optimized with adequate protein intake (1-1.5 g/kg/day) while avoiding excessive protein in severe uremia.
- The pathophysiology of HUS involves endothelial damage leading to platelet activation, microthrombi formation, and subsequent kidney injury, highlighting the importance of early recognition and intervention to prevent long-term kidney damage and CKD.
- Recovery from HUS-associated AKI can take weeks to months, and some patients may develop CKD requiring long-term follow-up with regular monitoring of kidney function, blood pressure, and proteinuria, as outlined in the AKD stages proposed by the ADQI 16 workgroup 1.
From the Research
Renal AKI and HUS
- Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure 2.
- Eculizumab, a complement inhibitor, has shown promising results in aHUS, with 80% of patients attaining complete recovery of kidney function and 100% stopping dialysis in one study 2.
- Plasma exchange or plasma infusion (PE/PI) is another treatment option for aHUS, but its efficacy is uncertain, with some studies suggesting lower case fatality rates in the elderly and improved outcomes in children with STEC-HUS treated with PE early in the course 3.
Treatment Options
- Eculizumab has been shown to be more effective than PE/PI alone in the treatment of adult aHUS patients with AKI, with improved kidney function, hypertension, proteinuria, and hematologic values 2.
- The conversion from plasma therapy to eculizumab therapy should be considered in patients with aHUS who show an incomplete response to plasma therapy, as it may improve outcomes 4.
- Combined liver-kidney transplantation with perioperative plasma exchange and use of eculizumab may be a curative treatment option for patients with aHUS associated with complement factor H mutation 5.
Outcomes and Safety
- The use of eculizumab in patients with aHUS has been associated with adverse events such as meningococcal infection, anaphylaxis, and eculizumab-related infusion reactions 4.
- The short-term outcome of patients with STEC-HUS treated with best supportive care, therapeutic plasma exchange, or eculizumab was better than expected, but the efficacy of eculizumab in comparison to plasma exchange alone is uncertain 6.
- Well-performed randomized controlled trials are needed to determine the efficacy of plasma exchange in STEC-HUS and to establish new treatment guidelines 3.