VIDEO: Early diagnosis, prognostic markers among biggest unmet needs in IgA nephropathy

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Nephropathy is a kidney disease with several unmet needs. Some of the most significant unmet needs, in my opinion, include early diagnosis and prognostic markers. Early and accurate diagnosis of IgA nephropathy is challenging. In the US, unfortunately, routine broad urine analysis screening is not supported, so patients are often diagnosed at the later stage leading to a worse prognosis. Now that we have safe and effective treatments and understand the long-term outcomes, early diagnosis is of paramount importance, and stakeholders must revisit their cost-effective analysis on early proteinuria screening.

Further, unfortunately ultimate diagnosis can only be ascertained through an invasive biopsy right now, which is often an additional barrier to early diagnosis. Identifying reliable biomarkers that can diagnose and predict disease progression in response to treatment is needed. Another unmet need is understanding the biology behind divergent treatment responses among patients. A better understanding and ability to predict which patient may respond to which therapy will allow personalized treatment approach based on genetic, molecular, biopsy, or clinical profiles. Combination protocols are another unmet need that will become even more important soon. We now have two drugs approved and many others in the pipeline.

Several distinct therapeutic targets are being studied, yet not in combination, except for endothelium receptor A blocker and SGLT2 inhibitor. Although we believe their affect is additive, and like lupus nephritis, we might be moving toward a multi-targeted approach rather than a succession of individual drug trials and errors, we don't know until we study this rigorously. This is a very slow and costly process. Right now, it is unlikely to be pursued by anyone on a large scale. Our understanding of the biology and pathophysiology of the disease remains elusive and is an unmet need. There is still so much we don't understand about IgA nephropathy. For example, why do some people produce aberrant galactose-deficient IgA while others don't? What triggers its production? Why do some people deposit the aberrant IgA in the kidneys while others don't? Why do many have deposits in the kidney but never develop the disease, while others do? And why does the disease progress faster in stage kidney disease in some, while maintains low level proteinuria and hematuria in their life and don't experience a decline in kidney function?

Many unanswered questions. Further, I would like to highlight the management of comorbidities and application of supportive measures as unmet need. Patients with IgA nephropathy often have comorbid conditions such as hypertension, hyperlipidemia, and obesity. Integrated treatment approaches that effectively address these comorbidities are needed and we need to do better with supportive care. Again and again, we see RAS inhibition, statin, SGL2 inhibitors, and blood pressure control are not as effectively utilized as they could be. Another unmet need is more long-term outcome studies.

Because IgA nephropathy is a rare disease, we need to follow the modest numbers of patient who we can enroll in trials and epidemiological studies over extended periods to see a meaningful change in hard clinical outcomes such as the number of patients starting dialysis or dying due to kidney disease. While proteinuria and GFR are accepted surrogates for often drug approvals, we do want to see long-term patient outcomes ultimately. And lastly, we need to empower our patients with information better and provide them with support and equitable access to care. The IgAN Foundation has done tremendous work in this field, and they have made available many resources for patients with IgA nephropathy, including patient communities, handout and mental health support.

We need to get these to patients and family members earlier and faster. We also need to ensure that all patients have access to specialized care, particularly now that we can entertain multi-target regimens, many new therapeutic options come with infusion and complicated monitoring requirements, and not every nephrologist may have the resources to do so. The GlomCon Network allows patients to find a specialist close to them or find clinical trials available to them.