Webinar Summary for Doctors: Beyond the Illusion: Unravelling the Puzzle of aHUS

A recent multidisciplinary webinar jointly organized by NephroPlus, the Atypical HUS India Foundation and the Kidney Warriors Foundation, with support from AstraZeneca, brought together leading experts in complement-mediated diseases to examine current challenges, evolving strategies, and systemic gaps in the management of atypical hemolytic uremic syndrome (aHUS). Participants included clinicians with extensive experience in adult and pediatric thrombotic microangiopathies (TMAs) such as Dr. Vivekanand Jha, Dr. Arvind Bagga, Dr. Nicole Isbel, Dr. Aditi Sinha, Dr. Manisha Sahay, Dr. Raja Ramchandran, Dr. Sreebhushan Raju, Dr. Sayali Thakare, Dr. Sandhya Suresh and Dr. Arun. The session aimed to distill global experience, regional realities, and clinical insights into a cohesive framework for improving diagnosis and care of complement-mediated TMA in India.

Diagnostic Complexity in Complement-Mediated TMA

One of the recurrent themes was the inherent diagnostic complexity of aHUS and its frequent misclassification in early stages. The syndrome often presents with the familiar triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury—features that overlap significantly with sepsis, malignant hypertension, shiga-toxin–associated HUS, pregnancy-related disorders, and thrombotic thrombocytopenic purpura (TTP). This overlap leads to delayed recognition in peripheral centers, where supportive care is often initiated without a dedicated evaluation for complement-mediated disease.

Experts emphasized that certain patterns should heighten suspicion for complement-mediated TMA: disproportionately severe AKI relative to systemic illness, persistent thrombocytopenia despite clinical improvement elsewhere, markedly elevated LDH, and schistocytosis. Early ADAMTS13 testing was highlighted as a critical step in distinguishing complement-mediated processes from TTP, and several speakers underscored the importance of not allowing the absence of immediate ADAMTS13 results to delay the initiation of diagnostic pathways or consideration of complement blockade.

Importance of Early Complement Blockade

Timely initiation of C5 inhibition remains the single most important modifiable determinant of renal recovery in aHUS. International registries and national cohorts demonstrate that earlier initiation leads to a higher likelihood of renal salvage, fewer long-term dialysis requirements, and lower relapse risk. Plasma exchange, once a mainstay of therapy, is now recognized as potentially counterproductive once complement blockade is initiated, given its impact on drug clearance.

Neurological involvement, while variably reported in literature, was discussed as a marker of severe endothelial injury. In such situations, early and aggressive complement inhibition may help halt progression. Similarly, postpartum TMAs that fail to improve after several days of supportive care may represent complement-driven endothelial injury rather than classical preeclampsia or HELLP syndrome, warranting reconsideration of therapeutic priorities.

Complement Testing and Genetic Evaluation

The webinar highlighted the dual importance and limitation of genetic testing in aHUS. While genetic variants in complement regulators and effectors—such as CFH, CFI, MCP, C3, and CFHR rearrangements—provide valuable prognostic information, their absence does not exclude complement dysregulation. This is especially true in settings where environmental or physiologic triggers such as pregnancy or infections may unmask latent pathway vulnerabilities.

Experts noted the challenges faced in India: variability in assay quality, limited availability of specialized laboratories, long turnaround times for genetic panels, and frequent preanalytical errors in complement sampling. Proper sample handling—rapid processing, cold-chain integrity, and avoidance of complement activation ex vivo—was emphasised repeatedly. Several speakers highlighted that complement levels may appear normal even in active disease due to dynamic consumption, reinforcing the primacy of clinical judgement.

Management of Anti–Factor H Antibody–Associated aHUS

A detailed pediatric case underscored the complexity of managing anti–factor H antibody–mediated aHUS, a phenotype more prevalent in South Asian populations. These patients often present with severe renal injury, very high antibody titers, and substantial complement activation. Effective management requires an integrated approach: plasmapheresis to remove circulating antibodies, immunosuppression (often multi-agent) to suppress antibody production, and complement inhibition to arrest endothelial injury.

Relapses, often triggered by infections, highlight the need for vigilant long-term monitoring. Decisions regarding B-cell–targeted therapies such as rituximab, or newer agents, depend on persistence or rebound of antibody titers. Persistent proteinuria despite hematologic remission remains an important marker of chronic complement-mediated damage, warranting longitudinal nephrology follow-up.

Pregnancy-Associated TMA: Recognizing the Complement Continuum

Pregnancy-associated TMA surfaced as an especially challenging scenario. The clinical overlap with preeclampsia, eclampsia, and HELLP syndrome complicates early diagnosis. However, recurrent episodes across pregnancies, early-onset severe hypertension, precipitous renal injury, or poor fetal outcomes may point towards underlying complement dysregulation. Several experts noted that pregnancy can serve as a physiologic stressor that unmask latent complement pathway abnormalities.

The group discussed the role of prophylactic measures such as aspirin and hydroxychloroquine, which may reduce endothelial activation but do not directly modulate complement activity. In cases where complement-mediated TMA is strongly suspected, early complement inhibition may interrupt the cascade of endothelial injury and improve both maternal and renal outcomes.

Long-Term Management, Relapse Monitoring, and Withdrawal Strategies

The webinar also explored long-term management strategies, including when and how to consider withdrawal of complement blockade. Decisions must incorporate genetic background, disease severity, organ involvement, presence of anti–factor H antibodies, and patient-specific risk factors. Close monitoring after withdrawal—through regular labs, blood pressure tracking, and symptom surveillance—is critical, particularly in patients with complement gene variants or history of relapse.

Relapse risk is highest in the first year after withdrawal and in individuals with pathogenic complement variants. Several experts advocated for structured relapse action plans that empower patients and clinicians to recognize early warning signs and reinitiate therapy promptly.

Building a Better aHUS Care Ecosystem in India

The session concluded with a forward-looking examination of systemic barriers in India. Key needs include: expanding access to complement assays and genetic testing; improving diagnostic capacity in regional hospitals; establishing national registries to track epidemiology, mutations, and outcomes; and developing designated Centers of Excellence with multidisciplinary TMA teams. Strengthening referral pathways and ensuring equitable access to complement inhibition remain high priorities for improving outcomes nationwide.

Key Takeaways

• Complement-mediated TMA is frequently misdiagnosed; early clinical suspicion is essential.

• Early C5 inhibition significantly improves renal recovery and reduces long-term morbidity.

• Genetic testing informs prognosis but must not delay therapy.

• Anti–factor H antibody–mediated aHUS requires integrated immunosuppression, plasmapheresis, and complement blockade.

• Pregnancy-associated TMA often reflects unmasked complement dysregulation.

• India needs improved diagnostic infrastructure, national referral pathways, and Centers of Excellence.

• Long-term follow-up and structured relapse plans are essential due to ongoing risk.

Webinar Summary for Patients: Beyond the Illusion: Unravelling the Puzzle of aHUS

A recent webinar hosted by NephroPlus, the Atypical HUS India Foundation and the Kidney Warriors Foundation, with support from AstraZeneca, brought together leading kidney specialists to discuss atypical hemolytic uremic syndrome (aHUS). This rare and serious condition affects the blood and kidneys and can be difficult to diagnose. Experts including Dr. Vivekanand Jha, Dr. Arvind Bagga, Dr. Nicole Isbel, Dr. Aditi Sinha, Dr. Manisha Sahay, Dr. Raja Ramchandran, Dr. Sreebhushan Raju, Dr. Sayali Thakare, Dr. Sandhya Suresh and Dr. Arun shared their experiences and offered clear guidance on how care can be improved in India.

Why aHUS Is So Hard to Diagnose

One of the biggest challenges with aHUS is that its early symptoms look similar to many other illnesses. Patients often arrive with anemia, low platelet counts, and kidney problems — symptoms also seen in infections, blood pressure emergencies, and pregnancy-related complications. Because these conditions are far more common, aHUS is often not recognized right away.

Certain signs should raise suspicion: kidney injury that seems too severe for the illness, low platelet counts that do not improve, very high LDH (a marker of cell damage), and damaged red blood cells on the blood smear. Early testing to rule out other conditions, especially TTP, is essential. Once these are ruled out, doctors can consider aHUS sooner instead of waiting for symptoms to worsen.

Early Treatment Makes a Major Difference

Early treatment with complement-blocking medicines, most commonly eculizumab, can dramatically improve outcomes. These medicines stop the part of the immune system that causes blood vessel damage in aHUS. Patients treated earlier are much more likely to recover kidney function and avoid long-term dialysis.

Once treatment begins, older approaches such as plasma exchange should usually be stopped because they can reduce the effectiveness of these medicines. Severe symptoms such as confusion or seizures suggest rapidly progressing disease and may require quicker treatment decisions. Similarly, if a woman develops blood vessel damage after childbirth and does not improve within a few days, complement-blocking therapy may be needed.

The Role and Limits of Genetic Testing

Genetic testing can help explain why a person developed aHUS and whether they are at higher risk of relapse. However, a negative genetic test does not rule it out. Many patients have normal results but still have strong signs of complement system overactivity.

Access to high-quality testing remains limited in India, and sample handling errors can give misleading results. Doctors emphasized that treatment should be guided mainly by clinical judgement rather than waiting for test results.

Anti–Factor H Antibody–Related aHUS

Some patients, especially children in South Asia, develop aHUS because their immune system produces harmful antibodies against a protein called factor H. This causes sudden and severe kidney problems. These patients usually need plasma exchange to remove the antibodies, immunosuppressive medicines to control them, and complement-blocking therapy to stop further damage.

Viral infections can trigger relapses even after improvement, so long-term monitoring is important. Ongoing protein loss in urine may indicate that the kidneys still have ongoing injury.

Why Pregnancy Can Trigger aHUS

Pregnancy-related aHUS is especially challenging because it closely resembles complications like preeclampsia or HELLP syndrome. Repeated severe issues across pregnancies, sudden kidney failure, or very low platelet counts may indicate underlying complement problems. In such cases, complement-blocking treatment may help prevent permanent kidney injury.

Long-Term Care and Relapse Prevention

Long-term follow-up after an aHUS episode is essential. Some patients may eventually stop complement-blocking therapy, while others may need longer treatment depending on their condition. Relapses can occur, especially within the first year after stopping treatment. Patients and families should be aware of warning signs and know when to seek immediate help.

Strengthening aHUS Care in India

Experts highlighted several areas where care can be improved: expanded awareness among regional hospitals, easier access to complement and genetic testing, national registries to study patterns of disease, and establishing Centers of Excellence to guide diagnosis and treatment. Better referral pathways and faster access to complement-blocking medicines could make a major difference in outcomes for patients across the country.

 

Webinar Recording: Beyond the Illusion: Unravelling the Puzzle of aHUS

A webinar for doctors was held on the 18th November where leading researchers and clinicians from India and Australia spoke on various aspects of the disease. Here is a recording of the webinar:

You can use this link to share as well: https://www.youtube.com/watch?v=NJX65-UPLdg

How you can get access to Soliris (Eculizumab) in India: Government Funding Route

The Government of India has a National Program for Rare Diseases (NPRD) that funds, up to a certain extent, treatment for rare diseases including aHUS. With Soliris (drug name: Eculizumab) now becoming available in India through the company directly, supply should be more reliable. Until now, the drug was available through importers who imported such drugs through unofficial, non-company based channels.

For those who can afford to pay for the drug out-of-pocket, please refer to this post for more details.

This post will outline the steps to take to apply for assistance in procuring the drug through the Government's NPRD.

• Identify the closest Centre of Excellence (CoE) to you. Here is a complete list of CoEs in India
• Visit the CoE campus and meet a senior doctor in the nephrologiy department. You may need to take an appointment by phone or in-person. At the time of enrolment, you will be given a Hospital ID. Keep this handy
• Carry the following with you when you meet the nephrologist:
• ID proof (Aadhaar / PAN / Voter ID) - original and 2 copies - if patient is a minor, also carry ID proof of parent / guardian
• 2 Passport size photographs
• Your medical file that has past prescriptions
• Any hospitalisation discharge summaries
• Current Prescription from the nephrologist treating you
• Recent lab reports - CBP, LDH, Kidney function tests, Urine Analysis etc.
• Genetic Test Reports, if available
• The nephrologist may require some other tests to be done or additional documents may need to be provided. Arrange these as requested by them
• Once all documents are provided, the nephrologist (or their assistant / adminstrator) will enter the details into the NPRD portal. this will include the number of vials, duration of treatment etc. An enrollment number will be generated and given to you. Keep this number safely
• There is a Rare Disease Committee that has been constituted at each CoE. This committee meets periodically and even on emergency basis to review all applications submitted and decides the merits of each application. The committee meets once every 1-3 months (depending on the hospital and the number of cases to review; they may also meet on emergency basis if needed). The committe decides to approve / reject / recomend to modify the application
• Once a decision has been reached, you will be notified of the decision
• Keep in touch with the nephrologist you met about this and any other queries you may have. Sometimes, the nephrologist might put you in touch with another coordinator who would be able to answer any queries you may have
• The committee may request additional documentation including some investigations. Make sure you get these in a timely manner
• Also, if you undergo any doctor consults / investigations after the initial form is submitted, make sure you give this to the doctor / assistant in the CoE to submit in the portal
• Note that approval by the committee might take up to a few months
• Once the application is approved, then the CoE will raise the funding requisition with the government for which you may be asked to sign some consent forms
• Once the funding request is approved, the CoE will procure the drug from the company through their pharmacy
• Once the drug reaches the pharmacy, speak to the nephrologist to discuss the next steps

Please be aware that this is a relatively new process for the CoEs. Even among the CoEs, there are some that are better equipped than others.  Remember, you need to advocate for yourself or your loved one. You will need to keep following up with the relevant stakeholders. Do not expect things to be handed to you on a platter. You will need to push people to help you. Do drop us a line with your experiences and we will do the best we can to help. All the best!

Happy aHUS Awareness Day!

September 24th every year is observed as aHUS Awareness Day. The day was picked because it was around that time that the term "Hemolytic Uremic Syndrome" was first used by Prof Conrad van Gasser in medical literature. The day was decided by the Atypical HUS Alliance, an umbrella group of aHUS patient support groups from various nations. 

This year has been special for aHUS patients in India. After years of hopelessness, we finally have a drug that is approved for sale in India and has been launched in India. Until a year or so back, we would never have imagined this would become a reality. Full credit and much gratitude to AstraZeneca for bringing the drug to India! The aHUS India Foundation has witnessed the team work really hard to make this a reality.

The Government of India also deserves a lot of credit for coming out with a National Policy for Rare Diseases. This is truly a sign of tremendous foresight and consideration for rare disease patients. The aHUS India Foundation commends the Government of India for this step on behalf of all aHUS patients.

We are excited that the times are changing for aHUS patients in India. We hope that drug access will be improved further and challenges in pricing will be overcome. We cannot rest until every aHUS patient in the country has access to a drug that they are able to afford and not have to continue to live a compromised life due to this disease.

Here is a message from the aHUS India Foundation on this occasion:

Changes needed to the National Program for Rare Diseases in India

The Government of India launched the National Program for Rare Diseases (NPRD) a few years back. In its current form, 63 rare diseases (including Atypical HUS) are covered. The program will fund a one time grant of Rs. 50 lakhs to each patient towards treatment. Decisions to fund such treatment will be made by Centres of Excellence (CoE) identified by the government.

Such a policy was unthinkable till a few years back. The debate between spending large sums of money on the treatment of a few people versus spending that money on basic healthcare necessities like preventing infant mortality, basic sanitation and other aspects of primary healthcare which impact several times more people is far from settled. While I may be biased in favour of the former due to my medical history, I do acknowledge that the choice is tricky. I am grateful therefore that the Indian government chose to set up the NPRD which impacts only a few people.

I would still suggest that two changes be made to the NPRD.

One size does not fit all

Currently, irrespective of the disease and the extremely varied types and durations of treatment, the NPRD stipulates the same grant for every patient. While the Rs. 50 lakhs might be more than enough for some, it is woefully inadequate for others. Even within the same rare disease, the requirements could be different. 

Take my disease, aHUS, for instance. Depending on the age of the patient and specific genetic mutation, the dosage and the duration of treatment with Eculizumab (the only approved drug to treat the disease) could vary. Some people would need only two vials twice a month while others could need three to four vials twice a month. Again, some patients may need it lifelong while others could need it only for a few months.

Keeping this reality in mind, the NPRD needs to allocate different funds for different patients. I understand this could make the decision process extremely complex. Who decides, for instance, which patient gets how much money? A group of experts can be constituted for each disease and a framework can be established to guide such decisions. Other solutions can be explored based on the experience of other nations where these problems have been successfully resolved.

Involvement of CoEs

In the current policy, decisions pertaining to applications for assistance under the NPRD are to be taken by CoEs. One can only imagine the delays this would bring about in getting access to the drugs by patients. The process would involve the treating physician getting the history and the clinical summary ready and then getting this information to the appropriate committee in a CoE close by. The authorities who decide on such applications in the CoE would need to then meet and review the dossier submitted. They might have further questions which would need to be communicated to the treating physician and then if everything is clear, they would decide. 

In diseases such aHUS, time is critical. Quick administration of the drug can mean the difference between remission and progression to kidney failure or even death. In such circumstances, does it really make sense to allow so much delay in deciding on the application?

One possible solution could be to not require a committee but one doctor among a panel of doctors in the CoE to decide on the application. The treating physician should be able to request urgent hearing of the case and decisions should be taken in less than 48 hours. Such models have been adopted in other nations already where similar circumstances exist.

The Government of India has shown amazing foresight and consideration for rare disease patients in coming up with the NPRD. If the kinks mentioned above can be ironed out, it would do tremendous benefits to the intended beneficiaries of this policy. 

How you can get access to Soliris (Eculizumab) in India: Self Pay Route

Now that Soliris is available in India, it is important for patients and their families and doctors to know how to get access to the drug. It is obviously not something that you can walk into a pharmacy and buy.

The drug can be accessed on one of two ways:

1. Paying yourself for it
2. Getting it through the Government's National Program for Rare Diseases (NPRD)

You can get more information of the contours of the NPRD and how it works here.

The Atypical HUS India Foundation has consulted the manufacturers of the drug and understood the steps to be taken by patients or their families to get access to the drug.

Cost of the drug for self-paying patients

The drug comes in vials of 300 mg each. Each vial costs about Rs. 95,000-100,000. Adults require about 3-4 vials each time, typically twice a month at steady state. There is a higher dosage required in the first few weeks. The dosage for children is typically lower. Please consult your doctor to determine the right dosage and frequency.

Steps to follow to get access to the drug

• The first step is to speak to your doctor to prescribe the drug on a prescription note along with the history and the tests conducted to make the decision to prescribe. Your doctor will need to ascertain your clinical condition to confirm if the drug is likely to help you. A lot will depend on your current clinical condition including (and not limited to) the following:
• Are you recently diagnosed and you still retain significant kidney function?
• Have you progressed to kidney failure requiring dialysis?
• Are you a candidate for a kidney transplant?
• Do you have willing related donor?
• Are you on the cadaver transplant list?
• Once the prescription is ready, your doctor will need to contact AstraZeneca. The Atypical HUS India Foundation can also help make this connection. Email us at ahusindia@gmail.com.
• The company's medical team will then speak with the doctor directly to understand the clinical background and requirements.
• The AstraZeneca commercial team will then liaise with the doctor / hospital pharmacy and arrange the drug through the appropriate authorized distributor.
• Escalation for urgent support: If you face challenges in accessing the drug, or if the physician is temporarily unavailable, you can write to med.info3@astrazeneca.com with a cc to ahusindia@gmail.com and oshin.santoshi@astrazeneca.com.

We will soon publish steps to access the drug through the second pathway - through the government's NPRD.