Early intervention key to safe kidney transplants for aHUS in India, per study
Favorable outcomes seen for nearly 20% of patients whose disease returned
Written by |
Kidney transplants can result in favorable outcomes for people with atypical hemolytic uremic syndrome (aHUS) in India, even when the disease returns after transplant, provided patients are evaluated before surgery and treated for complications soon afterward if they occur.
That’s according to a new study from the Asian nation that found that, among more than three dozen kidney transplant recipients at a single hospital in Central India, nearly 20% — seven patients in all — developed recurrent thrombotic microangiopathy (TMA), the blood vessel damage underlying aHUS. All seven had disease-causing genetic abnormalities affecting the complement system, a network of proteins that forms part of the immune system.
The team pointed out that this is a common cause of aHUS, although a triggering event is typically necessary. Among these individuals, disease recurrence occurred within one to three weeks after transplant — but all cases were successfully controlled with individualized treatment, the researchers reported.
Importantly, the team noted, each patient’s treatment had been tailored before transplant to take into account the individual’s complement findings and estimated risk of TMA returning.
“Comprehensive pre-transplant complement evaluation and biologic risk stratification are essential for safe transplantation in complement-mediated kidney disease,” the researchers wrote.
The study, “Kidney transplant outcomes in patients with complement dysregulation,” was published in the World Journal of Transplantation.
aHUS is a type of thrombotic microangiopathy or TMA, a group of conditions in which damage to small blood vessels leads to tiny blood clots that can restrict blood flow and damage organs, particularly the kidneys.
TMA in aHUS is driven by abnormal activation of the body’s complement system. This can result from genetic mutations affecting proteins that help regulate the complement system or, in some people, self-reactive antibodies that target complement factor H, a protein that normally helps keep complement activity under control.
Limited resources can hinder kidney transplant success
Generally, when kidney damage in a patient becomes severe enough to cause kidney failure, a transplant may be needed. In people with aHUS, however, kidney transplants can mean a higher risk of TMA coming back and affecting the new kidney.
The widely approved treatment Soliris (eculizumab) can help can help improve kidney transplant outcomes in people with aHUS, but access to the intravenous, or into-the-vein, therapy may be limited in certain regions of the world.
Moreover, a key concern for clinicians in India and other South Asian populations is that most evidence on kidney transplant outcomes in aHUS comes from Western populations. Additionally, the researchers here noted, people in these Asian regions often appear to have a different pattern of disease-causing abnormalities affecting the complement system than other aHUS patients. Given more limited resources in these countries, data on how these differences affect transplant outcomes remain limited.
To learn more, the team set out to examine kidney transplant outcomes in people in India with TMA or suspected aHUS. Their focus was on recurrent TMA and how genetic and antibody findings related to that risk.
Altogether, the team looked back at 335 people evaluated for suspected complement-mediated kidney disease at the single transplant center between 2018 and 2025. Among these individual, 136 had evidence of complement system dysregulation.
The analysis focused on 38 who underwent a kidney transplant. Nearly all — 32 or 84% — were men. The patients’ mean age was 36.3. Approximately three-quarters were receiving dialysis, a treatment that filters waste and excess fluid from the blood when the kidneys can no longer work adequately.
Genetic mutations affecting the complement system were identified in 34 patients. Most (79%) involved the CFHR1 and CFHR3 genes, while seven (18%) involved the CFH gene. Anti-factor H antibodies were detected in 15 people (40%), 11 of whom also carried a mutation in a complement system gene.
95% of patients alive at last follow-up
Before transplant, treatment was tailored to each person’s complement findings and estimated risk of TMA recurrence. Among the treatments was plasma exchange, in which the blood’s liquid part is removed and replaced to eliminate disease-driving complement components. Rituximab, which reduces the number of antibody-producing immune cells, was also given. Two people considered at particularly high risk additionally received a preventive dose of Soliris.
Despite these measures, seven individuals (18%) developed recurrent TMA, all within 1-3 weeks after transplant. All cases were confirmed by kidney biopsy, while other potential causes of TMA, including transplant rejection, medications, and active infection, were excluded.
All seven recurrences occurred in people with a mutation affecting a complement system gene. By contrast, none of the four people who had anti-factor H antibodies but no identified genetic abnormality developed recurrent TMA.
Treatment for recurrent TMS was again tailored to each person and included plasma exchange and rituximab, with other therapies added when needed. One person received Soliris as rescue treatment. Ultimately, TMA was controlled in all seven people, and all maintained functioning transplanted kidneys after treatment, the researchers noted.
Early recognition and timely intervention are critical to prevent recurrence [following kidneys transplants].
At the last follow-up, 95% of the transplant recipients were alive. Two died from severe infections. One other person eventually lost the transplanted kidney due to invasive mucormycosis, a serious fungal infection.
In reporting these data, the researchers cautioned that the study was small, retrospective, and conducted at a single center, with a median follow-up of about one year. As such, larger and longer studies are still needed to determine the risk of TMA returning later after transplant, the team noted.
Still, the findings suggest that “kidney transplantation can be successfully performed in selected patients with [aHUS]-mediated kidney disease when underlying complement abnormalities are identified and appropriately managed,” the researchers wrote, adding that “early recognition and timely intervention are critical to prevent recurrence and preserve graft function.”
Leave a comment
Fill in the required fields to post. Your email address will not be published.