Friday, June 28, 2024

Opinion: Should we focus on targeted therapy and use less of ACEi/ARB, SGLT2i?

In nephrology, we have traditionally focused on treating CKD and fibrosis, often resorting to "band-aid" therapies for many diseases. Most guidelines suggest starting with ACE inhibitors (ACEi) or angiotensin receptor blockers (ARBs), and more recently, adding SGLT2 inhibitors (SGLT2i). This approach has proven effective for diabetic nephropathy, advanced CKD, and perhaps secondary focal segmental glomerulosclerosis (FSGS). However, is this strategy appropriate for other glomerulonephritides (GNs) and disease states?

For instance, if proteinuria is high, KDIGO recommends ACEi/ARB and conservative management as the first-line treatment for IgA nephropathy (IgAN). Should we not reconsider this approach? Why not prioritize treating the underlying disease with targeted therapies first? If these fail or CKD progression continues, we could then add ACEi/ARB, SGLT2i, and other CKD medications. For example, in lupus nephritis (LN), we initially treat the disease itself. Yet, in many GNs, we start with "band-aid" medications, which often leads to the primary disease treatment being sidelined or neglected.

A paradigm shift is needed in renal medicine, especially as new targeted therapies for conditions like IgAN, C3 glomerulopathy (C3GN), membranous nephropathy, and APOL1-mediated FSGS emerge. We should consider starting with these targeted therapies, and following up with ACEi/ARB and SGLT2i as supportive measures.

I propose adopting a methodology similar to rheumatology and oncology, where disease-modifying agents are used as first-line treatments (supported by RCT data), followed by CKD agents. While there is currently no data to support this approach, a shift in mindset is necessary to design and conduct trials based on this concept. This is a lingering thought from a nephrologist who sees other fields advancing faster than ours.

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