Transcript
Opening:
You’re listening to GLC on ReachMD. This activity, titled ‘Engaging Adult Patients With C3GN: Shared Decision-Making at the Crossroads of Complement-Targeted Therapy,’ is provided by Global Learning Collaborative.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements, as well as the learning objectives.
Dr. Norouzi:
Hello, I'm Dr. Sayna Norouzi. I'd like to welcome you to our Patient-Clinician Connection focused on shared decision-making in adult patients with C3 glomerulopathy, or C3GN.
C3GN is a complement-mediated disease with the potential for progressive kidney decline. With complement-targeted therapies now available, we have an opportunity to intervene more directly in the disease process. But selecting therapy requires thoughtful discussion, not just about the efficacy but about how complement inhibition may influence long-term kidney preservation and how treatment fits into patients' life.
Today, we'll illustrate how healthcare providers may navigate this conversation in practice with their patients. My colleague, Dr. Brian McDonough, will model a clinical vignette with a patient actor.
So today we're going to discuss a clinical vignette. Patient is Michael, a 38-year-old man. He's been diagnosed with C3GN, and the diagnosis was confirmed by kidney biopsy and also complement-cascade evaluation. He's had persistent proteinuria around 2.1 grams per day, and he's been having eGFR decline from 78 to 62 over the past 12 months. He's currently receiving RAS inhibition, and his blood pressure is well controlled. He has multiple concerns today. He is concerned about the long-term kidney failure, ability to continue working as he travels a lot for his work, and impact on his young family.
Dr. McDonough:
Michael, your blood pressure is optimized on RAS therapy, but your proteinuria remains elevated, and your kidney function has declined over the past year. Before we talk about next steps, what's weighing on you most?
Michael:
I'm 38. I don't want this progressing to dialysis. I want to protect my kidneys as much as possible.
Dr. McDonough:
So long-term kidney preservation is your top priority.
Dr. Norouzi:
Notice how the physician uses open-ended questions, clarifies patient's priorities, and avoids making a premature treatment recommendation. This allows the patient to define their own priorities, which sets the stage for shared decision-making. Let's return to our discussion with Michael so we can discuss next steps.
Dr. McDonough:
Michael, C3GN happens because the alternative complement pathway is overactive. That dysregulation causes inflammation in the kidney filters, leading to protein leakage and gradual scarring.
The newer therapies target specific parts of that complement cascade as we're trying to interrupt the underlying disease mechanism. One therapy blocks complement at the level of C3, which sits at the center of the cascade. Because C3 is central, inhibiting it reduces downstream complement activation more broadly. The other therapy blocks factor B, which is part of the alternative pathway specifically. That approach is more selective in where it acts.
Michael:
So both are going after the source of the problem?
Dr. McDonough:
Yes, both aim to reduce complement-mediated injury. The difference is how broadly they suppress complement activity within the cascade.
Now, let's talk about what we've seen in the studies. With C3 inhibition, we've seen meaningful reductions in proteinuria and signals, suggesting sustained stabilization of kidney function over time. Importantly, in some patients, repeat biopsies have shown reductions in C3 staining in the kidney.
Michael:
What does this mean?
Dr. McDonough:
Your original biopsy shows C3 deposits in the kidney filters. When we see less C3 deposition on follow-up tissue, that suggests we're controlling the inflammatory process at the tissue level. That, along with the drop in the level of protein in your urine, helps us monitor your response to these medications. For someone your age, that may be relevant for long-term kidney preservation.
With factor B inhibition, clinical data also demonstrate proteinuria reduction and kidney function preservation with this approach, though the mechanism involves more selective alternative-pathway inhibition.
Dr. Norouzi:
This exchange provides a clear and simple explanation of the mechanism of action in everyday language. It connects the mechanism of action to outcomes, reduced proteinuria, eGFR stabilization, and potential histopathologic improvement. The histologic response is framed as biologic disease control, not just a lab improvement.
Dr. McDonough:
If you're just tuning in, you're listening to a Patient-Clinician Connection. I'm Dr. Brian McDonough, and today we're speaking about shared decision-making in C3GN.
Let's now talk about the practical ways in which these therapy options differ. One is given as a subcutaneous self-injection twice weekly; the other is taken orally twice daily.
Michael:
The pill sounds easier, especially with my travel schedule.
Dr. McDonough:
That's understandable. The oral option requires consistent twice-daily dosing. Missing doses can allow complement activity to reemerge, so adherence becomes central to maintaining disease control.
With injections, the schedule is structured differently. Some patients prefer a scheduled injection routine rather than remembering twice-daily oral dosing, particularly when they're traveling. The injection does require comfort with self-administration, but we provide training and support to make the process manageable.
I know your job involves travel. Do you think it might be difficult being consistent with the twice-daily dosing when you're on the road?
Michael:
Yes, it might be, and that’s a good point. And if I'm going to be on this long term, what kind of side effect should I expect?
Dr. McDonough:
That's an important question. Because both therapies modulate the complement system, the primary safety consideration is infection risk. Complement plays a role in protecting against certain bacterial infections, so we take vaccination and monitoring very seriously. We'll review your vaccination history and ensure appropriate immunizations are up to date before starting therapy.
With the injectable therapy, some patients experience mild injection site reactions, particularly early in treatment. These are typically manageable and often improve over time. Regardless of which therapy we choose, we'll monitor your labs closely and stay in regular contact. If anything feels concerning, we address it early.
Have you ever had serious infections?
Michael:
No.
Dr. McDonough:
That's reassuring. Vaccination and, in some situations, taking prophylactic antibiotics plus ongoing monitoring are essential with either approach.
Dr. Norouzi:
This exchange demonstrates a clear separation between mechanism and practical decision-making. The physician shifts the discussion from how the therapies work to how they differ in real-world use. Route of administration, adherence expectations, vaccination review, and infection monitoring are presented in straightforward, non-alarming language. The conversation reinforces that both therapies require active participation and monitoring, framing safety and lifestyle considerations as shared responsibilities rather than barriers to care.
Dr. McDonough:
Michael, you've said your main priority is long-term kidney preservation. In someone your age with documented progression, I’d think carefully about how comprehensively we're controlling complement activity. C3 inhibition targets the central component of the cascade and has shown histopathologic signals in addition to proteinuria reduction. That may align well with your goal of being aggressive in protecting your kidneys. How are you feeling about that option now?
Michael:
I'm not thrilled about injections, but if it offers stronger control and better long-term protection, I'm willing to consider it.
Dr. McDonough:
And that's completely reasonable. We'll proceed thoughtfully: vaccination review, injection training, and close monitoring, and we'll reassess responses together.
Dr. Norouzi:
This exchange demonstrates how shared decision-making includes thoughtful physician guidance. The recommendation is explicitly anchored to the patient's stated priority, long-term kidney preservation, and to clinical contexts, including age, documented progression, and the presence of histopathologic response signals.
The role of the nephrologist is no longer simply to prescribe, but to partner. In C3GN, complement-targeted therapies offer meaningful opportunities to reduce proteinuria and potentially preserve kidney function through direct modulation of the complement activity. By eliciting patients' goals, explaining mechanisms clearly, comparing options transparently, and aligning treatment with patient values, we can improve engagement and confidence in care decisions. Shared decision-making is not just communication; it's clinical excellence.
Thank you for joining this Patient-Clinician Connection on shared decision-making in C3GN. Goodbye.
Closing:
You have been listening to GLC on ReachMD. This activity is provided by Global Learning Collaborative.
To receive your free CE credit or to download this activity, visit ReachMD.com/CME. Thank you for listening.
In support of improving patient care, Global Learning Collaborative is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. 
Global Learning Collaborative designates this activity for 0.25 contact hour(s)/0.025 CEUs of pharmacy contact hour(s).
Global Learning Collaborative has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit(s) for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.25 AAPA Category 1 CME credit(s). Approval is valid until 06/18/27. PAs should claim only the credit commensurate with the extent of their participation in the activity. 
