Has the time come to change the treatment criteria for patients with chronic kidney disease? The “hypofiltering nephron” hypothesis

Chronic kidney disease (CKD) has long been regarded as a common category in which patients receive similar treatments, regardless of the underlying causes. However, current evidence indicates that different therapeutic approaches are necessary for patients with CKD based on whether they experience hyperfiltration or hypofiltration of residual nephrons. In diabetic nephropathy (DN), which arises from the progression of Kimmelstiel-Wilson glomerulonephritis, the kidneys exhibit hyperfiltration and albuminuria. In contrast, the nonalbuminuric form of DN sees CKD progression primarily due to glomerular hypofiltration, which is linked to atherosclerotic changes in the medium-sized intrarenal arteries. While renin-angiotensin system blockers and sodium-glucose cotransporter-2 inhibitors have been shown to reduce albuminuria and slow CKD progression in cases of hyperfiltration, these treatments may actually be less effective in cases of hypofiltration, as they can promote the decline in residual nephron function. In such situations, therapies that enhance glomerular filtration or slow the progression of atherosclerotic disease in the kidneys may be more appropriate. We believe it is crucial for future studies to explore this issue further.