The Pathological Role of LDL in Membranous Nephropathy and Diabetic Nephropathy and the Protective Efficacy of LDL Apheresis: A Narrative Review

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. One-third of patients with DN develop primary glomerulonephritis, and membranous nephropathy (MN) is the most common concurrent glomerulonephritis. Nephrotic syndrome (NS) due to DN and MN is often refractory to immunosuppressants because increased levels of low-density lipoprotein (LDL) not only accelerates kidney injury but also reduce the bioavailability of cyclosporine, a first-line immunosuppressant for MN. Given the pathological role of LDL, especially oxidized LDL, reducing LDL cholesterol levels can help achieve remission of NS and halt the progression of kidney injury. Although some lipoproteins are not excreted by the kidneys, excessive LDL, including oxidized LDL, can be considered uremic toxic-like factors that contribute to the development of NS or DN. We encountered a 74-year-old patient with concomitant DN and MN who achieved complete remission following additional LDL apheresis (LDL-A) with immunosuppressant therapy. Here, we provide a narrative review summarizing the role of LDL, especially ox-LDL, in the progression of DN and glomerulonephritis, including MN, and discuss the therapeutic rationale for LDL-A. We also present a representative case of concomitant MN and DN refractory to conventional immunosuppression who achieved clinical improvement following LDL-A.